Carte Engleza

Poisoning
in
Children
Poisoning
in
Children
Third Edition
Utpal Kant Singh MD PhD FRCP (Lond) FCCP FIAP

Professor
Department of Pediatrics
Patna Medical College
Patna (India)
FC Layland DCH (Lond) FRCP (Lond) FRCP Ch (Lond)
Consultant Pediatrician
Wordsley Hospital, West Midland
United Kingdom
Rajniti Prasad MD
Lecturer
Institute of Medical Sciences
BHU, Varanasi (India)
Ex-Assistant Professor
BP Koirala Institute of Medical Sciences
Nepal
Shivani Singh MRCP (UK)
Specialist Registrar
Cambridge University Hospital Trust
Cambridge, UK
Forewords
IC Verma
HPS Sachdev
Panna Choudhury
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Poisoning in Children
2006, Authors
All rights reserved. No part of this publication should be reproduced, stored in a retrieval
system, or transmitted in any form or by any means: electronic, mechanical, photocopying,
recording, or otherwise, without the prior written permission of the authors and the publisher.
This book has been published in good faith that the material provided by authors is
original. Every effort is made to ensure accuracy of material, but the publisher, printer
and authors will not be held responsible for any inadvertent error(s). In case of any
dispute, all legal matters are to be settled under Delhi jurisdiction only.
First Edition : 1998

Second Edition : 2001
Third Edition : 2006
ISBN 81-8061-798-X
Typeset at JPBMP typesetting unit
Printed at Paras
To
My teacher
Late Dr DN Tewari
and
Late Dr P McArther
Foreword
Children are by nature exploratory, and therefore they are liable to

ingest unwanted substances in their environment. Thus poisoning is
a common event. There is no doubt that prevention is best for
poisons, but unfortunately this aspect has been ignored in India. For
example, the covers of the bottles of the medicines are still not
children proof. Once poisoning occurs prompt diagnosis and therapy
is life-saving. The number of poisons is large, and for their manage-
ment a ready reference is required. Dr Utpal Kant Singh has done
a marvelous job in assembling the information on poisonings in
children, in an easy to read format. It is not surprising therefore to
see that the book is popular and has rapidly come to a 3rd edition.
I am confident that the book will enjoy the success that it deserves.
IC Verma
Senior Consultant
Sir Ganga Ram Hospital
New Delhi
Foreword
Poisonings form an inescapable part of pediatric practice. It is not

unusual to be confronted with a child with suspected poisoning in an
emergency situation. Obviously, instantaneous accurate diagnosis and
prompt institution of appropriate therapy is life-saving in this scenario.
However, the diversity of poisonings in different settings and their
variety of presentations can make this daunting task. The need for a
practical handbook on various facets of poisoning in children, especially
in relation to the Indian setting, is obvious. The present monograph
entitled Poisoning in Children fulfills this need admirably. It has been
conceived and edited by eminent personalities led by Dr Utpal Kant
Singh, an accomplished academician.
This monograph provides practical guidelines on the diagnosis
and management of acute poisonings likely to be encountered in
children. There is an additional chapter on animal poisoning due to
snakes and scorpions. This book also provides an outline of the
pathophysiology of poisoning. As a noteworthy innovation, each
chapter concludes with key points in the diagnosis and treatment of
the particular poisoning. This concise book is authoritative and yet
makes easy reading.
This volume will be an ideal companion to students, residents and
pediatricians. It is recommended for all Intensive Care Units and for
all those who regularly treat cases of poisoning.
HPS Sachdev
Professor
Department of Pediatrics
Maulana Azad Medical College
New Delhi
Foreword
The reported incidence of childhood poisonings in India varies from

0.3 to 7.6 percent, while a large number goes unnoticed. Majority of
these cases are brought as pediatric emergencies. Timely intervention
and appropriate therapy are highly rewarding in such situations.
Problem in India, however, is that there are large variety of poisonings
and some poisonings are region specific. There is also a general lack of
sensitization to environmental hazards, which exposes children to a
variety of pesticides, drugs, corrosives and various metals and non-
metals. Identifying the poison remains the most crucial aspect in initial
stages of management. A constellation of signs and symptoms consistent
with ingestion or exposure to a toxin is called toxidrome. Pediatricians
need to recognize toxidrome especially in a sick child without history
of poisoning. Life-saving therapies are available for some of these
situations, which should be an integral part of pediatric emergency set-
up.
It is surprising that on such a vital subject as childhood poisoning
there is a great paucity of dedicated book in our setting. This book by
Dr Utpal Kant Singh and his colleagues precisely fulfills such a
requirement. Initial chapter deal with general signs, symptoms and
management. In later chapters each category of poisonings have been
classified and divided into sections like pathophysiology, diagnosis
and management. Addition of animal poisoning and radioactive hazards
has further enhanced the academic content. For a busy practitioner,
key points in the diagnosis and management of a particular poisoning
given at the end of each chapter whould be an immense help. Popularity
of the book is evidenced from the fact that 3rd edition has come up in
a short span of time. Authors have tried to improve each subsequent
edition with added chapters and new information thus rendering
enormous service in the field of pediatric toxicology.
Panna Choudhury
DCH MD FIAP FRSTMH FIMSA
Consultant Pediatrician
Lok Nayak Hospital associated
Maulana Azad Medical College
New Delhi 110 002
and
Editor-in-Chief, Indian Pediatrics
Preface to the Third Edition
Children are the principal victims of poisoning/intoxications by

chemicals, animals, plants, medicines, etc. in rapidly changing world.
The ongoing research in the field of toxicology inspired us for 3rd
edition.
This edition represents major revision and reorganization. Three
new chapters have been added and matters on scorpion bite,
organophosphorus, iron, acetaminophen, cocaine, kerosene,
pyrethroid, aluminium, cowdung powder and nicotine have been
completely revised. Obsolete materials have been eliminated and
replaced by new text that reflects modern trend in management of
principal victims. However, care has been taken to retain the original
format, style and rapid access to important information.
The new chapters on theophylline, calcium channel blocker and
benzodiazepines should prove immensely useful for undergraduates,
postgraduates, pediatricians and general practitioners. Finally, we
would like to acknowledge the support of Shri JP Vij, Chairman and
Managing Director, and Mr Tarun Duneja, General Manager
(Publishing) of M/s Jaypee Brothers Medical Publishers (P) Ltd, to
bring out this book.
Utpal Kant Singh

FC Layland
Rajniti Prasad
Shivani Singh
Preface to the First Edition
Toxicology is the scientific study of poison, their detection, action and

treatment of their effects. This subspecialty assumes greater
importance in children with proliferation of chemicals, newer
technologies of energy production, and the ever increasing strains
of an overpopulated and rapidly changing world. Out of all poisoned
patients admitted each year, about 40 to 50 percent are children
under the age of fourteen years. It is not surprising that pediatricians
and physicians having first contact with children encounter poisoning
in their day-to-day practice. However, in contrast to adults, poisoning
in children presents unique problems which may pose diagnostic and
therapeutic challenges.
Unfortunately traditional Western books on pediatrics do not
provide comprehensive information on this subject, particularly in the
context of the developing world. Consequently practitioners and
postgraduate students have to go through a number of sources for
updating their knowledge. Realizing the paucity and the problem in
care of poisoning patients, there is ample justification for writing a
separate volume on the subject.
This book is written as a practical guide in the field of pediatric
toxicology and specially styled to provide rapid access to important
information. The format of this book follows the actual clinical
approach to patients.
This volume is intended for the information of pediatricians and
physicians sharing initial contact with emergencies in children as well
as in subsequent critical and intensive care cases. Postgraduate students
will find it of particular help.
Utpal Kant Singh

Acknowledgements
I can never express myself adequately about the inspirations,

encouragement and deep affection that I received from Late
Dr Vijajee Singh, who is the spirit behind this book.
I acknowledge with gratitude to Dr SP Srivastav, Professor and
Head, Department of Pediatrics, (Rtd) Patna Medical College for his
encouragement and valuable suggestions in the true spirit of a genuine
teacher. I owe my gratitude to Dr FC Schwartz, Consultant
Pediatrician, Wordsley Hospital, West Midland, UK, and Dr CAS
Galloway, Consultant Pediatrician, Raigmore Hospital, Inverness,
Scotland, whose inspiration is really unforgettable. I am extremely
grateful to Mrs H Morrison, Dr Rupa Singh, Additional Professor
Pediatrics BPKIHS Nepal, Dr SA Krishna, Professor and Head,
Department of Pediatrics, Nalanda Medical College, Patna, Dr AK
Patwari, Professor of Pediatrics, Lady Harding Medical College,
New Delhi and Dr S Aneja for making the publication of this book
possible.
The last, though not the least, is my life partner, Dr Rita Singh,
whose constant support has made the book see the light of the day.
It would have remained incomplete, if she had not prevailed upon
me to spare time for it.
But for you, my well-wishers, this book would never have reached
the publishers. My ever grateful thanks.
Contents
1. Introduction 1
2. General Symptoms and Signs of Poisoning 3
3. General Management 8
4. Corrosive Poisons 33
5. Metals and Non-Metals 43
6. Animal Poisoning 82
7. Insecticide Poisoning 109
8. Salicylate Poisoning 131
9. Acetaminophen (Paracetamol) 138
10. Barbiturate Poisoning 146
11. Hydrocarbon 150
12. Datura 156
13. Cocaine 159
14. Opioids 162
15. Phenothiazines and Related Neuroleptics 169
16. Cyclic Antidepressant 174
17. Carbon Monoxide 180
18. Ethylene Glycol 183
19. Epidemic Dropsy 186
20. Mustard Gas 191
21. Methanol (Methyl Alcohol) 194
22. Oleander Poisoning 196
23. Miscellaneous 199
24. Theophylline 216
25. Calcium Channel Blocker 220
26. Benzodiazepines 226
27. Fluoride Toxicity 229
28. Radioactive Hazards 233
Index 237
1
Introduction
Toxicology is the branch of medical science which deals with the

sources, pharmacokinetics and pharmacodynamics of poisons, the
clinical manifestations produced by them, their lethal doses and the
therapeutic measures to be employed to counter them. A poison has
been defined as a substance which when introduced into or absorbed
by living organisms, causes injury or death. Thus a variety of substances
may act as poison including the medicines. The law, however,
discriminates poison from potion principally on the basis of intention
with which they are administered.
Poisons are as old as mankind or perhaps even older. Their
description can be found in the ancient Egyptian, Babylonian, Hebrew
and Greek literature. Poisons have been described in Atharva Veda
(1500 BC), Kalpasthana, Chikitsasthana and Uttarasthana of the Shastras
have described symptoms and antidotes of poisons in detail. Susruta
(350 BC) described the procedures for incorporating poisons into foods,
drinks, perfumes, medicine, bathing water, snuff or sprinklers (The
ancient Indians had mastered the art of turning dazzling damsels into
beings capable of delivering death kisses, known as the Vishkanya).
Children being an integral and more vulnerable section of our
society, have been one of the principal victim of all the social ills,
poisoning being no exception. Childhood poisoning run the entire
gamut from accidental ingestion in toddlers and preschool children
falling prey to their own curiosity; to intentional overdoses in the
adolescents. These involve, besides somewhat obsolescent traditional
poisons, the infashion intoxications with recreational drugs as well as
chronic exposure to industrial chemicals.
The peak incidence of accidental overdoses is in the second year
of life and 85 percent of accidental poisoning affect children under five
years of age. The reported incidence of childhood poisoning in India
varies from 0.3 to 7.6 percent. Poisoning accounts for 0.03 percent of
mortality in infants; for 0.16 percent in the one to four years age group
2 Poisoning in Children
and for 0.37 percent of mortality in five to fourteen years age group
as per the statistics projected by Government of India. High incidence
of poisoning in perschool children, is a direct consequence of the
developmental stage of the child. As the infant begins to crawl, creep
and then walk around one year of age, his human instincts lead him
into exploring the environment, putting the objects into his mouth
being a part of this exploration. By two and half to three years of age,
childs motor development and ingenecity make accessible to him
things potentially noxious. The fourth year of life heralds a decline
in the incidence of accidental poisoning, not withstanding a further
motor development and coordination as the child now tends to be
selective in choosing things for purpose of ingestion, putting to good
use his least experiences. Male children predominate the poisoning
accidents accounted for by their greater degree of activity. The incidence
also tends to be higher among children from lower economic strata
of society owing to poor storage facilities in such households and
among children from larger families attributable to parental negligence.
The present day households offer toxic substances at every corner
including caustics, insecticides and medicines that provide an all too
easy setting for childhood inquisitiveness to end in disaster.
2
General Symptoms and
Signs of Poisoning
While supportive therapy is being initiated to maintain physiologic

homeostasis, efforts must be made to ascertain the type and mode of
intoxication, the quantity of toxin involved and the time lapsed since
exposure. Since the history is often unreliable and inadequate, physical
examination assumes greater importance. The physician should pay
close attention to and look for various signs and symptoms based on
which one may unravel the identity of the underlying poison.
Physical examination should initially focus on the vital signs, cardio-
pulmonary and neurologic status to ascertain the need for immediate
supportive management. The effect of a poison on the level of
consciousness is variable. The patient may be comatosed or may come
in an irritable, restless state. The table below lists a differential diagnosis
on the basis of CNS activity and vital signs as affected by particular
poisons.
A. Stimulant poisoning B. Depressant poisoning

1. Sympathomimetic effects 1. Sympatholytic effects
(restlessness, sweating (Bradycardia, hypotension,
tachycardia, dilated pupils, wheezing due to broncho-
flushing, plucking of hair) constriction, sedation,
Amphetamine depression, hallucination).
Caffeine Adrenergic blockers
Cocaine Antiarrhythmics
Decongestants Tricyclic antidepressants
MAO inhibitors Antihypertensives
Theophylline Calcium channel blockers
Digoxin
2. Anticholinergic effects 2. Cholinergic effects
(Tachycardia, warm dry (nausea, vomiting, abdominal
flushed skin, hyperthermia, cramps, diarrhea, involuntary

dilated pupils, decreased defecation and micturition,
bowel sounds and urinary sweating, salivation, lacrima-
retention). Dhatura and other tion, bronchorrhea, blurred
belladona alkaloids, tricyclic vision due to miosis and weak-
antidepressant, antihistaminics, ness) organophosphorus,
antiparkinsonian agents, carbamate, pyridostigmine
antipsycotics, antispasmodics,
mydriatics, mushrooms
3. Hallucinogenic effects: 3. Narcotism
LSD and synthetic analogues, Analgesics
Marijuana. Mescaline and Antispasmodics
synthetic analogues,
phencyclidine
4. Withdrawal syndrome 4. Sedative hypnotic effects
Alcohol Alcohol
Antidepressants Antiepileptics
Beta-blockers Barbiturates
Narcotics Benzodiazepines
Sedative hypnotics Hydrocarbons
Glutethimides
After initial assessment of vital signs, consciousness level and
behavior, quick general survey and neurological examination is done.
In the general survey of the patient, the face may show grimacing
(phenothiazines, butyrophenones), pallor (hemolysis), cyanosis
(hypoxia or methemoglobinemia) or icterus (drug induced hepatic
injury or hemolysis). Acidotic breathing may indicate increased anion
gap, metabolic acidosis (methanol, salicylates) or due to lactic acidosis
(any poison causing hypoxia, hypotension or seizure). The pulse may
reveal an abnormal rate or rhythm. Tachycardia and tachyarrhythmia
(sympathomimetics, anticholinergics) or bradycardia or bradyarrhy-
thmias (digitalis, cholinergic agents). Skin may reveal needle marks,
abscesses (opiates, amphetamines, and cocaine), staining (chronic
exposure to chloride, bromide or similar chemicals) blisters on extensor
surfaces or back (abuse of CNS depressants) or flushing (due to
belladona derivatives, antihistaminics, phenothiazines or tricyclic
antidepressants). Alopecia may be found due to arsenic or thallium.
In the systemic examination, examination of oral cavity may unveil
signs of caustic ingestion. Presence or absence of gag reflex, amount
of salivation, presence of foul odour of breath can be found out which
gives clues for the type of poison involved. Abdominal examination
reveals either hyperperistalsis (cholinergics) or atony (opiates,
anticholinergics and barbiturates).
General Symptoms and Signs of Poisoning 5
The chest may show features of pulmonary edema (carbon

monoxide, cyanide, narcotics, salicylates) or aspiration pneumonia
(hydrocarbons and CNS depression or patient in coma/seizures) or
bronchospasm (cholinergics, beta-blockers and opiates).
Cardiac examination may reveal underlying cardiomyopathy
(alcohol, heavy metals) or endocarditis (opiates, amphetamines) and
also confirm the tachyarrhythmias or bradyarrhythmias found in
general survey.
Evaluation of the nervous system and the eyes, comprise a very
important part of the examination. The level of consciousness must
be assessed repeatedly. It is important to remember that impaired
neurological functions may be caused by direct toxic effect or indirect
effect of electrolyte imbalance or oxygen deprivation). Cerebellar
dysfunction and hyperesthesia may be due to intoxication with heavy
metals or with carbon monoxide. Muscle fasciculations, myoclonic
jerks, and seizures are common in a large number of cerebral intoxicants.
Presence of spasticity (anticholinergics, strychnine and botulinism)
should not be overlooked.
Ophthalmological survey may reveal impaired vision (methanol,
mercury) blurred vision (cholinergics and anticholinergics) yellow
vision (digitalis). Pupillary examination (size and reaction to light) is
very important as mydriasis (anticholinergics, sympathomimetics) or
miosis (cholinergics, opiates and sympatholytics) is an important clue.
Specific signs and symptoms due to poisons involved are given
below.
GENERAL SIGNS AND SYMPTOMS OF POISONING
Signs and Symptoms
Poison
1. Miosis Cholinesterase inhibitors, barbiturates,
nicotine, opium, morphine, parasym-
pathomimetics
2. Mydriasis Cocaine, dhatura, thallium, cyanide, carbon
monoxide, benzene, sympathomimetics
3. Partial or total Methyl alcohol
blindness
4. Blurring of vision Cholinesterase inhibitors, dhatura, alcohol,
ergot
5. Purple-yellow vision Digitalis
Face and Scalp

1. Alopecia Thallium, arsenic, ergot, lead
2. Facial twitching Lead, mercury, phenothiazines
3. Dull and mask like Thallium, bromides, barbiturates
expression
Skin and Mucous Membrane

1. Pallor Aniline derivatives, sympathomimetics,
insulin, pilocarpine
2. Cyanosis Carbon monoxide, morphine, sulphonamide
and drugs causing methemoglobinemia
3. Ashy coloration Ergot, lead
4. Yellow Chlorinated compounds, arsenic other
heavy metals, mushrooms
5. Sweating Physostigmine, cholinesterase inhibitors,
nicotine, pilocarpine
6. Dry, hot skin Dhatura and its allied alkaloids, botulinum
toxin
7. Brown-black Iodine
8. Deep brown Bromide
9. Gray Mercuric chloride
10. White Phenol derivatives
Gastrointestinal Tract
Nausea, vomiting, diarrhea, dehydration, abdominal pain; corrosive acids
and alkalis, heavy metals, nicotine, ergot, phosphorus, phenol, cresol,
mushroom, digitalis, cantharides, morphine, cholinesterase inhibitors,
cocaine and salicylates.
Nervous System
1. Headache Carbon monoxide, phenol, lead, benzene
and its derivatives, cadmium, strychnine,
copper salts, atropine, scorpion sting and
bites of black widow spider
2. Convulsions Carbon monoxide, sodium fluoroacetate,
mushrooms, cyanides, salicylates, copper
salts, nicotine, lead, cholinesterase inhibi-
tors, dhatura cocaine and strychnine
3. Delirium Dhatura, cocaine, lead, arsenic, ergot,
barbiturates, DDT, physostigmine
General Symptoms and Signs of Poisoning 7
4. Coma Salicylates, mushrooms, cholinesterase

inhibitors, insulin, phenol, carbon monoxide,
cyanide, lead, barbiturates, morphine
derivatives and analogues, nicotine
Respiratory Symptoms
1. Tachypnea, cough, hoarseness Nicotine
stridor, dyspnea, retractions
wheezing, chest pain, sooty sputum
2. Pulmonary edema Carbon monoxide, cyanide,
narcotics, salicylate
Cardiovascular Symptoms
1. Bradycardia, AV bock Beta-blockers, antiarrhythmics, Ca ++
channel blockers, carbamates and
organophosphorus, digitalis, tricyclic
antidepressants
2. Ventricular tachyarrhy- Antipsychotic, tricyclic antidepressants
thmias fluorides, heavy metals, lithium,
magnesium
3. Cardiomyopathy Alcohol, heavy metals
4. Endocarditis Opiates, amphetamines
BIBLIOGRAPHY
1. Arena JM. Poisoning, Fourth Edition, Charles C. Thomas, Spring Field Illinois
1979;6-7.
2. Behram RE, Kliegman RM, Arvin AM. In: Nelson Textbook of Pediatrics 15th
edition. WB Saunders Company: 2002-30.
3. Ellenhorn MJ, Barceloux DG. Medical Toxicology: Diagnosis and Treatment
in Human Poisonings. New York, Elsevier, 1988.
4. Vale JA. Reviews in Medicine: Clinical Toxicology, Postgrad Med 1993; 69:19.
3
General Management
Poison management involves domestic intervention as well as hospital

care. The intricacies of management depend upon the nature of
exposure.
The principles of poisoning management are:
i. Removal of the source of poison and/or removal of the patient
from the site of poisoning.
ii. Initial resuscitation and stabilization.
iii. Symptomatic and supportive measures.
iv. Removal of unabsorbed poisons.
a. From gastrointestinal tract.
b. From skin, eye and other body cavities.
v. Hastening the elimination of absorbed poisons.
vi. Use of specific antidote, if available.
vii. Disposition of the patient with advice for prevention.
Initial Resuscitation Stabilization

This includes basic life support measures in the form of management
of:
Airway, Breathing, Circulation

1. A clear airway is maintained by:
a. Proper positioningHead tilt and chin lift.
b. Suction of vomitus, secretions from oropharynx.
c. Removal of obstructing object, if any.
d. Falling back of tongue is prevented by suitable airway tube.
2. Breathing is maintained by:
a. O2 (approx. 60%) via a maskif spontaneous, normal respiration
is maintained.
b. When gag or cough reflex is absent-endotracheal tube inserted.
c. Intermittent positive pressure ventilation with proper monitoring
of blood gases is required when ventilation remains inadequate
by above measures.
General Management 9
d. Respiratory stimulants like Nikethamide and Doxapram are

used for severe respiratory depression. Continuous IV Doxapram
is most effective.
3. Circulation: Proper IV access should be secured in all cases of
severe poisoning. This facilitates.
i. Collection of samples for measurement of plasma concentration
of poisons or substances, if possible.
ii. Initial baseline evaluation of serum electrolytes, blood gases and
other biochemical parameters, if necessary.
iii. Combating hypotension, which is a common feature of drug
overdosage.
iv. Maintenance of fluid and electrolyte balance.
v. Administering IV drugs for treatment.
Symptomatic and Supportive Management

1. Hypotension or hemodynamic support
2. Cardiac dysrhythmias
3. Convulsion
4. Hypothermia
5. Pulmonary edema
6. Stress hemorrhage
7. Rhabdomyolysis
8. Pain
9. Nausea and vomiting
Management of Hypotension or Hemodynamic Support

Hypotension is a common feature of drug overdose and is the result
of the following physiological effects.
i. Expansion of venous bed due to venodilatation,
ii. Inadequate fluid intake in stage of prolonged coma, and
iii. Myocardial depression due to effects of drugs.
Aggravating factors of hypotension in poisoning include:
i. Hypoxia
ii. Acidosis
iii. Hypothermia
Management
The following measures should be taken to combat hypotension.
i. Elevation of foot end of the bed.
ii. Oxygen administration.
iii. IV fluids:
a. Crystalloids
i. Isotonic sodium chloride solution.
ii. Hypertonic sodium chloride solution.
iii. Ringers lactate solution.
b. Colloids
i. Five percent serum albumin in normal saline.
ii. Ten percent dextran40 in 5 percent dextrose.
iii. Hydroxyethyl starch in normal saline.
c. Blood products
i. Whole blood.
ii. Packed red cells.
iii. Fresh frozen plasma.
Fluid Management in Hypotension

Initial fluid of choiceIsotonic crystalloid (Ringers lactate or Normal
saline)
Amount of fluid20 ml/kg over 3-5 mts.
Reassess
No improvement Improved BP
Urine passed
Repeat isotonic crystalloid Continue fluid,

20 ml/kg over 3-5 mts correct the cause
and
Reassess ventilation, Acid-base
balance and electrolytes
No improvement Improvement
Assess cardiac status (CXR, ECG)

and
Monitor CVP (Central venous pressure)
CVP <10 mmHg CVP >10 mmHg CVP>15 mmHg

Repeat isotonic inotropic agents, Diuretics
Crystalloid or e.g. Dopamine
Colloids Dobutamine
(5-10 ml/kg)
iv. Inotropic agents

i. Dopaminedose 5-20 g/kg/mt
ii. Dobutaminedose 2-20 g/kg/mt
iii. Isoproterenoldose 0.1-5 g/kg/mt
The rational choice of inotrope may be made considering that
dobutamine is a pure inotrope whereas dopamine may be a vasodilator
inotrope or vasoconstrictor depending on the dose. Dopamine is usually
the agent of choice and is administered in continuous infusion with
normal saline or 5 percent dextrose in gradual incremental doses.
Infusion beyond 20 g/kg/mt should be avoided because of
predominance of alpha-activity leading to vasoconstriction. Regarding
infusion it is useful to remember that 1 ml of dopamine when dissolved
in 100 ml of fluid gives a concentration 400 g/ml.
For patients who fail to respond to usual incremental doses of
dopamine or dobutamine, more potent cardiotonic agents like
epinephrine, norepinephrine and isoproterenol may be considered.
Correction of Acid-base Disturbances

Intoxication in children result in changes in either HCO3 or PCO2
causing blood pH to shift away from normal and hence acid-base
disturbances. Acid-base disturbances may be metabolic or respiratory
acidosis or alkalosis. The normal arterial blood gas (ABG) values in
childrenpH 7.36 to 7.44, PCO2 35-45 mmHg and total CO2 ;
24-32 mEq/L.
ABG in different situations
Acid-base disturbances pH PCO2 HCO3
1. Metabolic alkalosis
Uncompensated N
Compensated N/
2. Metabolic alkalosis
Uncompensated N
Compensated N/
3. Respiratory acidosis
Uncompensated N
Compensated N/
4. Respiratory alkalosis
Uncompensated N
Compensated N/
Metabolic acidosis: It is defined as reduction in HCO3 that reflects either

the accumulation of acids or loss of alkali with compensatory increase
in ventilation leading to fall in PCO2.
The acidosis must be corrected with parenteral bicarbonate when

pH of blood of patient is less than 7.2.
The correction of acidosis should not be abrupt and total because
over alkalinization can induce tetany, seizures and cardiac arrhythmias
and increased lactate production. Since the distribution of bicarbonate
is about 50 percent of lean body weight, an approximation of the
amount of bicarbonate required to return the serum concentration to
normal can be calculated as follows.
HCO3deficit (mEq) = 0.5 body wt (kg)
(desired HCO3 measured HCO3)
Normally half of this calculated deficit should be given over 6

hours and after reassessment of the acid-base data it may be repeated
if necessary, no further bicarbonate should be given once the pH
reaches 7.2. Since correction of acidosis without correction of a
potassium deficit may lead to profound hypokalemia, potassium
supplementation should be undertaken if serum potassium
concentration begins to fall. Serum calcium should also be monitored
and corrected if necessary as alkalosis may decrease ionized calcium.
Metabolic alkalosis is defined as increase in HCO3 with rise in
PCO2 as a result of compensatory hyperventilation. They may be
either chloride responsive or chloride resistant. In chloride responsive
metabolic alkalosis with urinary chloride less than 10 mEq/L,
administration of normal saline intravenously usually corrects the
alkalosis in majority of patients by reversal of fluid compartment
concentration and increasing distal chloride delivery. The effectiveness
of therapy can be monitored even at bedside by serial measurement
of urinary pH. In patient resistant to saline, acid therapy with O.I N
HCl (100 mEq/L) may be given. The required amount of HCl (mEq)
= 0.5 wt (kg) base excess. The calculated amount is infused with
5 percent dextrose over 6-8 hours. In extreme alkalosis, potassium
chloride (100-150 mEq/L) may be administered intravenously under
electrocardiographic (ECG) monitoring.
In chloride resistant metabolic alkalosis with urinary chloride greater
than 20 mEq/L, underlying causes should be corrected. Potassium
deficits should also be corrected.
Respiratory acidosis: It is characterized by a primary increase in PCO2
due to processes that interfere with pulmonary excretion of CO2 with
a compensatory rise in serum HCO3.
Treatment is directed at improving ventilation by mechanical
ventilators. Administration of bicarbonate to correct acidosis may be
harmful since the low pH is an important stimulus for ventilation.
Respiratory alkalosis: It is characterized by a decrease in PCO2 due to

hyperventilation with a compensatory falls in serum HCO3.
Treatment should be directed at correction of the underlying disorder.
Acute therapy is usually not necessary unless pH is greater than 7.5.
If hypoxemia is not present, symptoms of acute hyperventilation may
be relieved by reassurance and rebreathing into a paper bag. If persistent
hyperventilation occurs, use of CO2 rebreathing apparatus may be
warranted.
Management of Cardiac Arrhythmia

Cardiac arrhythmias are common manifestations of poisoning such as
Tricyclic antidepressant, Phenothiazines, Nicotine, Organophosphorus,
Scorpion bite. The aggravating factors of arrhythmias are hypoxia,
acidosis and hypokalemia. The management of cardiac arrhythmias
is following:
i. Correction of aggravating factors
a. Hypoxia Oxygen
b. Acidosis Intravenous sodium bicarbonate
c. Hypokalemia Oral/IV supplementation of potassium.
ii. Continuous monitoring of the patient with ECG.
iii. Anti-arrhythmic drugs.
a. Ectopic beats: No medication usually required. Beta-blockers
rarely.
b. Atrial fibrillation: Digoxin0.04 mg/kg/day and fluttersDC
cardioversion (treatment of choice).
c. Paroxysmal atrial tachycardia:
i. Vagal stimulation by carotid or occular massage
ii. Verapamil4-10 mg/kg/day tid
iii. Beta blockerPropranolol 0.15 mg/kg/dose IV
iv. Adenosine (Drug of choice).
d. Paroxysmal atrial tachycardia with block:
Potassium supplementation
Phenytoin3-5 mg/kg IV over 3 mts.
e. Ventricular tachycardia:
i. IV lignocaine1 mg/kg/dose
ii. Bretylium tosylate5-10 mg/kg IM/IV 1-2 hourly
iii. DC cardioversion
f. Complete heart block: Atropine0.01 mg/kg/dose SC or IV
Cardiac pacing: Temporary/Permanent.
Management of Convulsion
Convulsion is a common problem in the management of childhood
poisoning. It may occur either early or during terminal phase of
poisoning. The possible causes of convulsion are listed below:
i. Direct effect of the poison on CNS

ii. Hypoglycemia
iii. Hypocalcemia
iv. Hypoxia
v. Cerebral edema, and
vi. Other metabolic defects.
Management
Actions which should be taken immediately:
i. Insert an airway to keep respiratory passage patent and apply
nasopharyngeal suction.
ii. Nurse the patient either on one side or while lying flat on the
back.
iii. Administer oxygen if cyanosis is present.
iv. Establish an indwelling intravenous catheter and draw a blood
sample for biochemical analysis before infusion of 5 percent
dextrose.
v. Correct hypoglycemia/hypocalcemia if present.
vi. Give anti-convulsants.
Anti-convulsant therapy:
Administer Diazepam IV in a dose of 0.2-0.3 mg/kg slowly, may
be repeated if seizure not controlled after 15
mts. If seizures are still not controlled.
Bolus IV Phenytoin 10-15 mg/kg at a rate not more than 50 mg/
mt.
or
Barbiturate IM/IVloading dose 10-15 mg/
kg then maintains on oral therapy (5-8 mg/
kg/day).
If seizures are still Paraldehyde (4% solution)IV 0.1 to 0.15
ml/kg. Rate should be fast enough to control
seizure in 20 mts. Other agents to control
seizures are IV Pentothal sodium and general
anesthetics.
Once seizures get controlled, look for features of cerebral edema,
as it is one of the cause and effect of seizures.
The measures used to reduce the cerebral edema are:
i. Twenty percent mannitolThe dose of mannitol is 0.25-0.5 gm/
kg/dose intravenously over 20 mt, 6-8 hourly. The reduction in
ICP occurs within minutes and effect lasts for about 2-4 hours.
One to two doses are sufficient.
ii. IV Furosemide0.5-1.0 mg/kg IV alone or with 20 percent

mannitol.
iii. DexamethasoneDexamethasone is highly effective against
vasogenic cerebral edema. Dexamethasone in a loading dose of
1mg/kg, then 0.25 mg/kg every 6 hours is generally used.
If above measures are ineffective in reducing ICP, hyperventilation
of patient with PCO2 25-35 mmHg (PO2-80 mmHg) should be done.
Hyperventilation is very effective in reducing ICP.
Management of Hypothermia
Hypothermia is a common problem in poisoning with chlorpromazine
and other neuroleptic agents. Actions, which should be taken to combat
hypothermia, are:
i. Cover the child immediately with a space blanket.
ii. Transfer the patient immediately to a thermoneutral environment.
iii. Give prewarmed IV fluid/Nasogastric fluids at body temperature
(37oC).
iv. If possible inspired gases should also be warmed to 37oC. Direct
heat should never be applied to the patient.
Management of Pulmonary Edema

Pulmonary edema in poisoning occurs due to following causes:
i. Injury to alveolar epithelium with consequent exudation in the
alveoli, e.g. volatile irritant poisoning.
ii. Stimulation of bronchial secretion, i.e. organophosphorus and
related compounds.
Pulmonary edema interfers with the process of gaseous exchange
hence the patient should be treated immediately and vigorously.
i. The patient should preferably be in a cardiac bed.
ii. Administer 100 percent oxygen and intermittent positive pressure
ventilation, if necessary.
iii. IV aminophylline5-8 mg/kg/IV diluted with equal volume of
5 percent dextrose over a period of 20 mts.
iv. IV frusemidedose1-2 mg/kg may be repeated, if required.
v. Prophylactic antibiotics to combat infection.
vi. Atropine IM/IV in cases of poisoning with organophosphorus
which decreases excessive respiratory secretions.
Management of Stress Ulcers

All patients who are unconscious and require intensive care are prone
to develop stress ulcers of the gastrointestinal tract causing hemor-
rhage, which further aggravates the encephalopathy. Measures needed
to prevent stress ulcers include the following:
i. Nasogastric intubation.
ii. Administration of antacids through nasogastric tube.
iii. H2-receptor antagonists: Among the H2-receptor antagonists,
ranitidine oral or IV is the agent of choice. The dose of ranitidine
is 1-3 mg/kg/24 hours, IV or 6-12-mg/kg/24 hours orally in two
divided doses.
Rhabdomyolysis
Rhabdomyolysis may occur either from pressure necrosis in poisoned
patient or may complicate narcotic abuse without coma. It results in
myoglobinuria, which may precipitate acute renal failure. Dehydration
and acidosis further potentiate the risk of renal failure. The measures,
which should be taken for prevention of acute renal failure, include:
1. Ensure adequate urine output to prevent precipitation of myoglobin
in the renal tubules.
2. Correction of dehydration with fluids given through nasogastric
tube or intravenously.
3. Correction of acidosis with IV sodium bicarbonate.
4. Removal of offending factors for rhabdomyolysis.
Management of Pain
Pain is common complain of children with poisoning, e.g. corrosive
poisoning or animal bites. Severe pain may cause reflex vasomotor
collapse and inhibition of normal physiological functions. Pain should
be relieved by analgesics, preferably narcotics or through local
infiltration of xylocaine. Narcotic analgesics are contraindicated in the
following situations.
i. CNS depression
ii. Respiratory depression
iii. Pre-existing liver disease.
Nausea and Vomiting

Nausea and vomiting are common manifestations of poisoning with
corrosives, irritants, etc. Vomiting usually gets relieved by removing
the toxic material by a stomach wash followed by administration of
demulscents. If vomiting continues, it should be treated with antiemetic
drugs to prevent dehydration and acidosis.
Removal of Unabsorbed Poison
Removal of unabsorbed poison is an essential step which aims to

reduce further absorption of the poison.
Removal of Unabsorbed Poison from GI Tract
Prevention of absorption of poison from the GI tract along with the

life support measures are the two most valuable measures taken by
the treating physician.
Methods used
1. Dilution
2. Emesis
3. Gastric lavage
4. Absorption
5. Catharsis
6. Whole bowel irrigation
1. Dilution
i. Though the American Association of Poison Control Centers
condemns it, it is sometimes used as a first aid measure.
ii. Fluid in the form of water or milk and sometimes Vinegar, fruit
juice and carbonated beverages are given to dilute the poison.
iii. Amount given is 15 ml/kg to a maximum of 240-300 ml (Rumack
and Peterson, 1979).
iv. Coma and convulsions are contraindications for fluid
administration.
2. Emesis
This is the most commonly used method to evaluate the stomach
contents. Most effective when done within 6 hours of ingestion.
Emetics - Syrup of ipecac, apomorphine, copper sulfate, zinc sulfate
and salt water.
Syrup of ipecac is the preferred emetic in children and it is used
as outlined below:
[Oral dose of 10 ml in child <18 months, and 15 ml in child > 18
months, one glass (200 ml) of water is given after 5 minutes].
Watch for 15 minutes for emesis

No vomiting

Repeat ipecac 15 ml

Still no emesis
Mechanical stimulation Gastric lavage

With padded tongue blade
Apomorphine acts rapidly by stimulating CTZ causing emesis within

3-5 minutes. It is not preferred in children due to its narcotic and
potent depressant effect on CNS and respiratory system.
Household emetic: One spoonful of mustard powder or two spoonful
of table salt in 200 ml of tepid water is easily available and safe.
However, it is not a reliable method for inducing emesis.
Contraindications for emesis:
1. Hydrocarbon poisoning
2. Corrosive poisoning
3. Comatose patients
4. Convulsing and very sick patient
5. Absent gag reflex
6. Age < 6 months old.
Note: Syrup of ipecac should not be administered routinely in the
management of poisoned patients. In experimental studies, the amount
of marker removed by ipecac was highly variable and diminished
with time. There is no evidence from clinical studies that ipecac
improves the outcome of poisoned patients and its routine
administration in the emergency department should be abandoned.
3. Gastric Lavage
This is the best method for removing poisons from the stomach.
a. Indications:
i. Unconscious patient (emesis inadvisable)
ii. Convulsing patient
iii. Patients with absent gag reflex.
b. Contraindication: Corrosive and hydrocarbon poisoning due to high
risk of gastric perforation and aspiration.
c. Method:
i. Airway must be protected either by intubation or placing the
patient in a head down position.
ii. Biggest tube, which can be safely inserted, should be selected
28 FG for a child below 2 years.
30 FG for a child between 2-4 years.
34 FG for a child above 4 years.
iii. The patient is placed in a left lateral position with head down
position and foot end elevated 15o above horizontal.
iv. The length of the tube inserted should be measured from nose
to xiphoid process.
v. The maximum possible amount of stomach contents should be
aspirated using a large bore syringe.
If there is no aspirate the position of the tube in the stomach
is reconfirmed.
vi. 50 ml of water is pushed inside the stomach and this process

is repeated till returning fluid is clear.
d. Complications:
Aspiration may occur especially if patient is uncooperative. It
can be prevented by means of a cuffed endotracheal tube.
Trauma to esophagus.
Bleeding
Laryngospasm (due to spillage of gastric contents).
Note: Gastric lavage should not be employed routinely in the
management of poisoned patients. In experimental studies, the amount
of marker removed by gastric lavage was highly variable and
diminished with time. There is no certain evidence that its use improves
clinical outcome and it may cause significant morbidity. Gastric lavage
should not be considered unless a patient has ingested a potentially
life-threatening amount of a poison and the procedure can be
undertaken within 60 minutes of ingestion. Even then, clinical benefit
has not been confirmed in controlled studies.
4. Adsorption
Adsorption is the process of rendering the absorbable substance non-
absorbable by means of adsorbants.
Agents used
Activated charcoal
Bentonite
Kaolin
Talc
Exchange resins, etc.
Activated charcoal: It is the only agent currently in widespread use.
Charcoal is prepared by burning various organic substances in the
absence of air and is activated by treatment with steam, various gases
or inorganic acids. Activation removes not only the previously adsorbed
substances but decreases the size of granules thus further increasing
the adsorptive surface area. The place of activated charcoal in
emergency management of the poisoned patient has been disputed
over years. Recently it has been recommended in treatment protocol
for virtually all ingestions except corrosives.
Poisons with significant adsorption to activated charcoal are:
i. Acetaminophen
ii. Arsenic
iii. Barbiturates
iv. Cantharides
v. Chloroquine
vi. Cocaine
vii. Digitalis
viii. Iodine
ix. Isoniazid
x. Kerosens
xi. Organophosphorus
xii. Salicylates
xiii. Narcotics
xiv. Nicotine
xv. Phenothiazines
xvi. Phenytoin
xvii. Sulfonamides
xviii. Tricyclic anti-depressant.
The optimum dose is ten times the ingested poison. In children it
is standardized to 30-60 gm, as the ingested dose of poisons are
unknown. It is given as suspension of 20 percent activated charcoal
in 70 percent sorbitol syrup with optimum benefit when used within
30 minutes. To avoid interference with syrup of ipecac, it should be
with held until after completion of emesis. It may be administered
after completion of lavage.
Contraindications: Corrosive ingestions.
Adverse effects:
i. Nausea
ii. Vomiting
iii. Bronchospasm
iv. Acute airway obstruction.
Activated charcoal is relatively safe and is effective in adsorbing
a wide range of poisons, as it can be conveniently prepared in a
palatable form.
Note: Single-dose activated charcoal should not be administered
routinely in the management of poisoned patients. Based on volunteer
studies, the effectiveness of activated charcoal decreases with time; the
greatest benefit is within one hour of ingestion. The administration
of activated charcoal may be considered if a patient has ingested a
potentially toxic amount of a poison (which is known to be adsorbed
to charcoal) up to one hour previously; there are insufficient data to
support or exclude its use after one hour of ingestion.
5. Catharsis
This method had recently been recommended by American Board of
Toxicology. Cathartics enhance the removal of the poisons via feces
by decreasing the gastrointestinal transit time.
Agents used:
Magnesium citrate
Disodium phosphate
Magnesium sorbitol, and
Milk of magnesia (Magnesium sulphate)
Among them the most commonly used are magnesium sulphate
and sodium sulphate.
Dose: 250 mg/kg to a maximum of 20-50 gm for both magnesium
sulphate and sodium sulphate.
Adverse effects:
Nausea
Vomiting
Electrolyte imbalance
Dehydration
Note: The administration of a cathartic alone has no role in the
management of the poisoned patient and is not recommended as a
method of gut decontamination. Based on available data, the routine
use of a cathartic in combination with activated charcoal is most
endorsed.
Whole Bowel Irrigation

Whole bowel irrigation can be used to physically eliminate highly
toxic substances that are not absorbed by activated charcoal and have
long gastrointestinal transit time. The treatment is based on the enteral
administration of large quantities (30 ml/kg/hr) of osmotically balanced
polyethylene glycol electrolyte solution to induce a liquid stool and
continued till rectal effluent clears. Whole bowel irrigation may be
considered for potentially toxic ingestions of sustained release or enteric
coated drugs. There are isufficient data to support or exlude the use
of whole bowel irrigation for potentially toxic ingestions of iron, lead,
zinc or packets of illicit drugs.
Removal from Skin, Eyes, Other Body Cavities

Copious flushing with water, saline or other available clear fluids is
the initial method of treatment.
i. Saline is preferred for occular irrigation.
ii. Triple wash (water-soap-more water) of the skin is preferred for
decontamination of skin.
iii. Liquid poisons from body cavities, i.e. rectum and vagina is
removed by irrigation.
Hastenting the Elimination of Absorbed Poisons

Considerable absorption of poisons in the bloodstream occurs when
more than six hours has elapsed since ingestion. So enhancement of
elimination of absorbed poison becomes necessary. Techniques
employed for the purpose include.
1. Forced diuresis, i.e. diuresis induced by alteration of urinary pH.
2. Peritoneal dialysis
3. Hemodialysis
4. Hemoperfusion
5. Hemofiltration
6. Plasmapheresis
7. Exchange transfusion.
The choice depends on several factors like type and amount of toxic
substance ingested, expected morbidity and mortality produced by
the poison concerned as well as the availability of the appropriate
equipment and personnel. However, recipes book guidelines are of no
use and demands own judgement. Personal experience and skill is
more important.
Forced diuresis: This is an old method but considered obsolete
nowadays, though it may occasionally be helpful in a few patients.
Principle
The intact renal physiology is a pre-requisite. Drugs and chemical
substance filtered by glomerulus or actively secreted by tubular lumen
if rendered poly-reabsorbable will be excreted in urine at a rapid rate.
This reabsorption is prevented either by changing the concentration
gradient of the substance across the blood or tubular lumen or by
increasing the degree of ionization. So alteration of pH of the urine,
i.e. alkaline pH for acidic drugs and vice versa together with forced
diuresis will enhance elimination.
Two types are described:
a. Forced alkaline diuresis
b. Forced acid diuresis.
a. Forced Alkaline Diuresis

Indications:
i. Salicylate poisoning
ii. Phenobarbitone
iii. Chorphenoxy herbicides, e.g. 2(4-1) MCPA
iv. Isoniazid poisoning.
Methods
Forced diuresis is done by mannitol (20%) in a dose 0.5 to 1 gm/kg
followed by infusion of 10 percent dextrose 300 ml per hour or by
frusemide IV in a dose of 0.5 to 1 mg/kg. The alkalinization of urine
is achieved by adding sodium bicarbonate 1-2 mg/kg in one liter of
0.2 percent sodium chloride solution and infusion at a rate of 0.5-1.0
liter per hour until desired diuresis is obtained. Subsequent infusion
is done at a rate equal to the rate of urine output.
b. Forced Acid Diuresis

This is indicated in cases of poisoning due to:
i. Amphetamine
ii. Phencyclidine
iii. Quinidine
iv. Quinine
Method: Diuresis is achieved as above and is followed by alternating
solution of amonium chloride 1.5 gm in 5 percent dextrose and normal
saline dextrose with a goal to obtain a urine pH of less than 5.5 and
to maintain a normal urine flow.
Complications of forced diuresis:
i. Fluid overload
ii. Pulmonary edema
iii. Cerebral edema
iv. Metabolic acidosis or alkalosis.
The forced diuresis by itself is not life saving but can serve as a
useful adjunct in the absence of other facilities.
Dialysis
Dialysis, the movement of substance against concentration gradient
across semi-permeable membrane, can be accomplished using
physiological membranes (as in peritoneal dialysis) or using artificial
membranes (as in hemodialysis).
The principle and indications of peritoneal dialysis and hemodialysis
are the same.
Indications for dialysis

1. Severe intoxication with unstable vital signs like hypotension
refractory to fluid replacement: Apnea, Hypothermia, etc.
2. A critical level of toxin, in a potentially fatal range.
3. Ingestion and absorption of a potentially lethal dose.
4. A degree of intoxication that hinders the normal route of excretion
of the drug and an underlying disease in the patient that impairs
the function of a major metabolic or excretory organ for that

particular drug.
5. Progressive clinical deterioration while patient is under careful
medical management.
6. Prolonged coma with its attendant hazards such as aspiration
pneumonia, septicemia from infected sites and peripheral
neuropathy secondary to pressure ischemia.
7. Poisoning by agents known to produce delayed toxicity.
Toxins/Drugs where Dialysis is Employed

1. Barbiturate(100/g/ml)
2. Carbon tetrachloride
3. Chloral hydrate (50 mg/ml)
4. Digitalis glycosides (0.1 g/ml)
5. Ethanol (150 gm/ml)
6. Ethylene glycol
7. Glutaraldehyde (40 gm/ml)
8. Salicylates (800 gm/ml)
9. Theophylline (50 gm/ml)
10. Methotrexate
11. Procainamide.
Peritoneal dialysis is technically a simple procedure and does not
require sophisticated equipment and highly trained personnel. It is
preferred when anticoagulation may be dangerous or when the patient
is in shock. Also, it is the preferred method of dialysis in infants.
Hemodialysis is more effective than peritoneal dialysis. It requires
comparatively less time to complete and achieves better total body
solute clearance. Peritoneal dialysis and hemodialysis only have a
selected role in routine management of poisoned patients, emphasis
must first be placed on supportive care.
Complications Associated with Dialysis

a. Metabolic:
i. Water and electrolyte imbalance
ii. Acid-base imbalance
iii. Hypoproteinemia
b. Tecnique related:
i. Peritonitis
ii. Perforation of bowel or blood vessel
iii. Leakage or infiltration of dialysate with hydrothorax
iv. Arrhythmias
v. Pneumonia
vi. Pulmonary edema.
Contraindications for Peritoneal Dialysis

i. Ileus
ii. Acute abdomen
iii. Previous multiple abdominal surgeries
iv. Unsupported marginal respiration
v. Intraperitoneal malignancy, and
vi. Intra-abdominal prosthesis.
Hemoperfusion
The principle of hemoperfusion is that blood flows through activated
charcoal or an appropriate ion exchange resin, which adsorbs the
poisons. Loss of blood cells and activation of clotting mechanism are
largely overcome by coating the charcoal with an acrylic hydrogel
which does not reduce adsorbing capacity, though patient must be
anticoagulated. Indications of hemoperfusion are the same as for
dialysis. This is better for toxins with low water solubility, high affinity
for adsorbate, a fast rate of equilibrium from peripheral tissues to
blood and a low affinity for plasma proteins. Indications are
carbamazepine, barbiturates and theophyllines.
Hemofiltration
Hemofiltration can remove compounds with a high molecular weight
(> 500-40000 RMM). It is of particular value in aminoglycoside and
theophylline overdose. Hemofiltration may be of benefit in iron and
lithium overdose.
Antidotes
Antidotes are substances, which counteract the effect of poisons. They
are used in the following situations.
a. The poison may not have been completely removed by emesis or
gastric lavage or these procedures are contraindicated.
b. Poisoning by parenteral route.
c. Poison already absorbed.
Antidotes are divided into four groups:
1. Physical (mechanical antidotes)
2. Chemical antidotes
3. Physiological or pharmacological antidotes
4. Universal antidotes.
1. Physical Antidotes
These substances tend to impair the absorption of poisons. Physical
antidotes are the following:
a. Demulscents: They prevent absorption by forming a coating on

mucous membrane of stomach. They may be used in heavy metal
poisoning but are contraindicated in phosphorus poisoning, e.g.
oils fats, egg albumin, etc.
b. Starch: This is used for iodine poisoning.
c. Activated charcoal: This is used in poisoning of many chemicals and
alkaloids except cyanides.
2. Chemical Antidotes
These are substances which neutralise the effect of poison by forming
compounds which are insoluble, innocuous or both.
Examples of chemical antidotes (Canned fruit juice is a useful
alternative)
Vinegar or dilute acetic acid for corrossive alkalies.
Soap water, milk of lime, milk of magnesia for corrosive acids.
Potassium permanganate (1% solution) for oxidisable poisons, i.e.
most of the alkaloids, e.g. amidopyrine, anti-pyrine, barbiturates,
phosphorus, cyanides, etc.
Copper sulphate for phosphorus.
Freshly prepared iron oxide for arsenic.
Tannin precipitates a large number of substances such as metals,
alkaloids and glycosides.
Tincture of iodine, about 15 drops given in 100-150 ml of water
precipitates heavy metals and most alkaloids.
3. Physiological or Pharmacological Antidotes

They act at tissue level and produce effects opposite to those of poison.
These reduce or abolish the effects of poisons by one of the following
means:
Receptor stimulations, blockade or bypass
Enzymatic inhibition or reactivation
Displacement of poison from tissue binding site.
Most of them are unreliable in their action. Examples of physiological
or pharmacological antidotes are atropine for pilocapine, nalorphine
for poisoning with morphine and digitalis for ACONITE poisoning.
Chelating agents: Chelating agents are a family of physiological
antidotes effective against heavy metals. They are drugs which complex
metallic ions, forming ring structure within their molecule. The
complexes thus formed are stable, biologically inert and excreted in
urine. They compete with body ligands for heavy metals. British Anti-
Lewisite (BAL) or Dimercaprol, Penicillamine, Calcium Edetate and

Desferrioxamine are some of the common chelating agents. Succeimer
(Dimercapto succinic acid), a derivative of BAL is more potent, less
toxic and orally effective in Hg, Pb and As poisonings. Also, a derivative
of penicillamine, N-acetyl penicillamine (NAP) appears promising for
the treatment of Hg, Cu, Pb poisoning. Pentetic acid (DTPA) is an
antidote for radioactive metals but is of limited use and is still under
investigation. The details of antidotes with their indication, dose and
side effects are summarized in the following tables (page 28).
Universal Antidote
It is used in those where the nature of the ingested poison is unknown
or where a combination of two or more poisons is suspected. It consists
of:
Ingredient Proportion Action
1. Powdered charcoal 2 parts Adsorbs alkaloids

(Burnt toast)
2. Magnesium 1 parts Neutralizes acids
3. Tannic acid (Strong 1 parts Precipitates alkaloids
tea) certain glucosides and
many metals
The mixture is administered in a dose of one teaspoonful dissolved

in 200 ml of water, which may be repeated once or twice. It should
be given soon after ingestion of poison.
Household products that can be used as safe antidotes are strong
liquid tea, starch, milk, flour suspension or mashed potatoes, solution
of soap, and orange or lemon juice or vinegar. It should be borne in
mind that in majority of toxicologic emergencies effective antidotes
are not available. Symptomatic and supportive treatment remain the
mainstay of management.
Prevention
Childhood poisonings are usually accidental unlike in adults where
they are more frequently suicidal or homicidal. This makes childhood
poisoning amenable to prevention with some simple but intelligent
measures. Potentially noxious substances should never be stored in
containers normally used for storing food or beverages. Kerosine oil
and caustic soda in particular should never be kept in tumblers and
beverage bottles. The whole houses especially the kitchen and bathroom
should be periodically screened for poisonous substances and their
Antidotes Mode of action Indication Doses Side effects
28
1. Atropine Blocks muscarinic Cholinesterase inhibitors, 0.05 mg/kg IV repeated Tachycardia, atropine
Cholinoceptors Insecticides, every 10-15 mts till full psychosis, cerebellar
Organosphosphorus atropinization symptoms, dryness of
mouth, blurring of vision
2. N-Acetyl- Replenishes depleted Acetaminophen Loading dose 140 mg/kg Nausea, vomiting,
cysteine glutathione stores (paracetamol), orally followed by 70 mg/ hypokalemia
Chloroform, kg every 4 hrs. Spread over
Carbon tetrachloride a period of 3 days for
additional 17 doses
3. Benztropine Blocks muscarinic Drug-induced movement 1-2 mg IM/IV per day Anticholinergic symptoms
cholinergic receptors disorders
4. Benzyl Displaces toxin from Amatoxin (amanita 3-5 lacs/kg/day IM/IV
penicillin plasma albumin and phylliodes) individed doses
enhances urinary excretion
5. Calcium Chelates lead ions Lead 50-75 mg/kg/day in 4 Hypotension, lacrimation,
edetate divided doses IM or IV nasal congestion, sneezing,
as 0.2-0.4% solution chills, myalgia, renal
damage
6. Calcium Binds or precipitates Hydrofluoric acid, 200-300 mg/kg oral or Cardiac arrest/arrhythmia
gluconate fluoride ions fluorides IV slowly nausea, vomiting, lacrima-
tion and salivation par-
esthesia, muscular aches
and pain
7. Dimer Chelates metal ions Arsenic, copper, gold, 12 to 24 mg/kg/day in 6 Urticaria and rashes,
caprol (BAL) lead, inorganic mercury divided doses IM tachypnea, tremors,
2-3 mercapto- convulsions, coma
propanol
8. Digoxin- Binds free glycoside Digitalis glycosides 40 mg vial =0.6 mg No known side effects
specific FAB- in plasma. Complex digoxin infused over
fragments excreted in urine 30 minutes
Contd...
Contd...
9. Desferrioxamine Chelates ferrous ions Iron 15 mg/kg/hr IV infusion Cataract, retinal damage,
to a maximum of 80 mg/ deafness
kg IV 4 hrs
10. Flumazenil Competes for Benzodiazepines 0.2 mg/mt IV (Max. 0.5 mg) Vomiting, anxiety,
seizures in
Benzodiazepine till patient regains epileptics, precipitates
receptors consciousness withdrawal symptoms
11. Glucagon Bypasses blockage B-blockers 0.25-1.0 mg IM or IV Nausea, vomiting and
of B-receptor, gastrointestinal upsets
stimulates CAMP
with positive cardiac
ionotropic effect
12. Isoprenaline Competes with B-receptors B-Blockers 0.1-0.2 mg/kg/min IV Tremor, flushing, sweating,
Adjust the dose according palpitation, headache,
to the clinical response and diarrhea, tachycardia
monitor heart rate and BP
13. Methionine Replenishes depleted Paracetamol 2.5 gm 4 hrly up to a Nausea, vomiting
glutathione stores maximum total of 10 gm
14. Physostigmine Inhibits acetylcholinesterase Antimuscarinic drugs, 0.5-2 mg IM every 30 mts Muscarinic effect
leading to acetylcholine Dhatura
accumulation at cholinergic
receptor sites.
15. Naloxone Competes for opioid receptors Opioids 0.01 mg/kg/dose Opioid withdrawal
Repeat the dose until symptoms
there is a response or a
General Management
total dose 10 mg has

29
been given
30
Contd...
Contd...
16. Oxygen Competitively displaces Carbon monoxide 100% Retinopathy and

carbon monoxide from bronchopulmonary
dysplasia
binding sites on hemoglobin in premature;
pneumothorax 17. Penicillamine Chelates metal ions
Copper, gold, lead, 20-40 mg/kg/day orally GI upset, impairment of

elemental mercury, zinc taste, thrombocytopenia,
aplastic anemia, allergic,
reaction, nephrotic
syndrome 18. Phytomena- Replenishes Coumarin
(Warferin) and 5-10 mg IM or IV Flushing, breathlessness,
dione (Vit. K1) Vitamin K Inandione anticoagulants hypotension, a sense of
constriction in the chest
19. Pralidoxime Competitively reactivates Cholinesterase inhibitors, 25-50 mg/kg IM or Weakness, blurred vision,
Cholinesterases e.g. organophosphorus IV as 5% solution diplopia headache,
insecticides tachycardia
20. Prussian blue Exchanges for Thallium Thallium (Rodenticides)
(Ferric Ferrocyanide)
21. Protamine Binds ionically to Heparin 2.5-5.0 mg/kg followed Impairment of taste
neutralize heparin by 1.0-2.5 mg/kg IV
4 hrly
22. Propranolol Competes for B-adrenoceptors B-receptor agonist drugs: 0.5-1.0 mg/kg/day orally Cold hand and feet, lack of
ephedrine, theophylline, bid or tid drive, GI upsets,
thyroxine hallucinations
23. Unithiol Chelates metal ions Lead, elemental and Exact dose not known
organic mercury
Contd...
Contd...
24. Methylene blue Leukomethylene blue Methemoglobinemia 1-2 mg/kg/dose IV may

(1 or 2%) reduces methemoglobin Suphemoglobinemia be repeated 6 hrly
to hemoglobin
25. Fomepizole Cytochrome oxidase Methylalcohol Load; 15 mg/kg IV Headache
Ethylene Glycol Maintenance: 10 mg/kg/ Nausea
12 hrly IV, (4 doses) Vomiting
26. Flumazenil Competitive antagonist Benzodiazepines 0.01-0.02 mg/kg/dose Nausea
of Benzodiazepine (Max: 0.125-0.2 mg/kg Vomiting
receptor complex IV, repeated till Facial flushing
desired effect Agitation
Headache
Dizziness
Seizure
27. DMSA Chelation Lead, Mercury 10 mg/kg 8 hrly for Nausea
Arsenic and other 5 days then 10 mg/kg Vomiting
heavy metals 12 hrly for 14 days
28. Diphenhydramine Antihistaminic and Extrapyramidal 5 mg/kg IV or PO Sedation
anti-cholinergic Symptoms, Acute or 300 mg over 24 hrs Paradoxical agitation
dystonic reaction (Max) Ataxia
and other allergic
General Management
reaction
31
29. Ethyl alcohol Inhibits oxidation Methyl alcohol Load: 750 mg/kg IV Nausea
(5 or 10%) Ethylene glycol Maintenance: 80-150 mg/ Vomiting
kg/hrs IV infusion Sedation
inaccessibility to children ensured. Mass media such as television,

radio and newspaper should be harnessed for creating awareness
about the potential hazards and their prevention. Flow chart for
emergency management and necessary facilities and medicines should
be available at all health centers so that treatment may be promptly
instituted.
ALL POISONOUS SUBSTANCES SHOULD BE KEPT OUT OF
REACH OF CHILDREN.
BIBLIOGRAPHY
1. American Academy of Clinical Toxicology and European Association of
Poisons Centres and Clinical Toxicologists. Gastric lavage. J Toxicol 1997;
35:711-19.
2. American Academy of Clinical Toxicologists. Ipecac syrup. J Toxicol 1997;
35:699-709.
3. American Academy of Clinical Toxicology and European Association of
Poisons Centres and Clinical Toxicologists. Single-dose activated charcoal.
J Toxicol Clin Toxicol 1997;35:721-41.
4. Abdallah AH, Tye A. A comparison of the efficiency of emetic drugs and
stomach lavage. Am J Dis Child 1967;113:571-75.
5. Amold FJ, et al. Evaluation of efficiency of lavage and induced emesis in
treatment of salicylate poisoning. Pediatrics 1959;23:286-301.
6. Burke M. Gastric lavage and emesis in the treatment of ingested poisons.
A review and a clinical study of Lavage. Resuscitation 1973;1:91-105.
7. Coriner CS, et al. Rational use of emergency antidotes In: Bayer MJ, Rumack
BH. Poisoning and overdose. Aspen Systems, Rockville, Maryland, 1983;28-
29.
8. Ellenhorn MJ, Barceloux DG. Medical toxicology: Diagnosis and Treatment
in Human Poisonings, New York, Elsevier, 1988.
9. Rumack BH. Poisoning In: Hathway WE, Groothuis JR, Hay WW. Current
Pediatric Diagnosis and Treatment. Appleton and Lange Norwalk, CT, 1993.
10. Rumack BH, Peterson RG. Poisoning prevention of absorption. Tropics Emerg
Med 1979;1:13-18.
11. Watanabe AS, et al. Enhancement of Elimination in poisonings. Tropics
Emerg. Med. 1979;1:19-26.
12. Winchester JF, et al. Dialysis and hemoperfusion of poisons and drugs. Trans
Am Soc Artif Intern Organs 1977;23:762-842.
4
Corrosive Poisons
Corrosives are widely used for industrial, scientific and domestic

purposes. Ingestion by older children and adults is usually made
with a suicidal intent. The children on the other hand consume it
by mistake. Accidental surface burns from breaking or bursting of
the container is far more common. Corrosives may be deliberately
thrown on the face or body of a person (Vitriolage) to cause blindness
or disfigurement.
Poisoning with corrosives is more common among toddlers. The
incidence all over India as computed by different workers varies
from 3 to 5 percent. The incidence at our institution (Patna Medical
College) is 3 to 4 percent. The poisoning is more commonly seen in
children in household of battery, automobile and laundry workers
and for obvious reasons in urban areas.
Corrosives are divided into four groups:
Mineral acids
Sulfuric acids
Nitric acids
Hydrochloric acids
Organic acids
Oxalic acids
Carbolic acid (Phenol)
Acetic acid
Salicylic acid
Vegetable acids
Hydrocyanic acid
Alkalies
Sodium hydroxide
Potassium hydroxide
Ammonium hydroxide
Sites Likely to be Affected by Local Effect

1. Skin of exposed parts of body and the face

2. Mouth, throat
3. Upper gastrointestinal tract
4. Respiratory tract
Effects of Corrosives
Early effects:
1. Burning pain, tingling sensation
2. Vomiting often blood stained
3. Dysphonia due to laryngeal edema
Late effects:
1. Perforation of stomach and esophagus
2. Pulmonary edema or bronchopneumonia
Delayed effects:
1. Laryngeal stricture
2. Esophageal stricture
3. Pyloric fibrosis
4. Pulmonary fibrosis.
MINERAL ACID
Mineral acids in common use are Sulfuric acid, Nitric acid,
Hydrochloric acid. Sulfuric acid is a colorless, odorless, viscid liquid.
Nitric acid is a clear colorless liquid which on exposure to light and
air turns yellowish brown. Hydrochloric acid is a clear colorless
fuming liquid. They are used in industry, laboratories and automobile
battery fluid and for domestic cleaning purpose. The poisoning in
children is usually accidental but may be suicidal or homicidal.
Pathophysiology
Mineral acids corrode and cause tissue destruction by following
three ways:
1. Extraction of water from tissues
2. Coagulation of cellular protein and formation of acid albuminates
3. Conversion of hemoglobin to hematin.
As a result, they cause local irritation, bleeding and sloughing of
mucous membrane and skin. Apart from shock other remote systemic
effects of mineral acids are rare. They usually get concentrated at
the pyloric end of the stomach, causing scarring and stricture
formation. They may damage the esophagus and other areas of the
stomach resulting in necrosis and perforation.
Corrosive Poisons 35
Fatal dose Fatal period

Sulfuric acid 3-7 ml 12-24 hours
Nitric acid 5-10 ml 24-30 hours
Hydrochloric acid 5-15 ml 18-24 hours
Clinical Features
The clinical features depend on the mode of poisoning, concentration
of mineral acid, amount of acid used, duration of contact and age
of child. Following ingestion of mineral acids, severe pain in the
mouth, pharynx, chest and abdomen occurs, followed by hematemesis
and bloody diarrhea. The mucosa of mouth becomes black to brown
with sulfuric acid, yellow with nitric acid and grey brown with
hydrochloric acid. Yellow discoloration with nitric acid is because
of formation of picric acid. Difficulty in breathing occurs with nitric
acid and hydrochloric acid but it is more marked with hydrochloric
acid ingestion due to development of laryngitis, bronchiolitis and
pulmonary edema. The teeth lose their lustre and appear chalky
white with sulfuric acid. The perforation of stomach particularly in
pyloric region leading to peritonitis may occur with sulphuric acid.
Vitriolage, the splashing or throwing of acid on body surface and
face, causes severe burns and sometimes blindness. The color of the
skin turns black (sulphuric acid), yellow (nitric acid), or may change
markedly with hydrochloric acid.
Frequently, profound shock develops with mineral acid poisoning.
Sometimes, metabolic acidosis, liver and renal dysfunction, hemolysis
and DIC may be seen in severe cases. The features of mediastinitis
and peritonitis may develop in surviving children resulting from
early or late esophageal and gastric perforation.
Diagnosis
1. History of ingestion
2. Clinical features
3. Analysis of vomitus or stool
4. RadiologicalLateral X-ray of the soft tissues of neck to evaluate
upper airway compromise and chest and abdominal X-rays should
be done to look for signs of esophageal or gastric perforation in
severe cases.
5. EndoscopyEsophagoscopy and gastroscopy are diagnostic proce-
dures of choice in all documented or suspected cases of corrosive
ingestion to assess the extent and severity of the injury. To avoid
perforation these procedures are performed in the first 24 hours
and if possible within the first hour of poisoning.
Key Points Treatment
Management After giving proper care to

airways, circulation and breath-
1. Care of airways, breathing and circula-
ing, the dilution should be done
tion
2. Gastric lavage is contraindicated immediately. The diluent of
3. Dilution with milk or milk of magnesia choice is milk of magnesia.
4. If patient is unable to swallow-feeding Emetics and gastric lavage are
through gastrostomy or IV hyper- contraindicated. A soft stomach
alimentation tube or Levine tube can be
5. Corticosteroids: Orally or parenteral
6. Supportive management
passed with care within an hour
7. Surgery for sequelae of ingestion and milk of
magnesia is administered to
neutralize the corrosive acids. If milk of magnesia is not readily
available, lime water, wood-ash or soap and water may be used. If
the patient develops respiratory distress, endotracheal intubation,
positive pressure ventilation, cricothyrotomy or tracheostomy may
be done accordingly and patency of airway should be maintained.
For hypotensive patient IV crystalloid fluid is infused and CVP
monitoring is done. Oral fluids are given through mouth only after
the patient is able to swallow his saliva. Patients unable to swallow
are maintained either by feeding through gastrostomy or by intra-
venous hyperalimentation.
The early administration of steroids is advocated in an attempt
to decrease the incidence or severity of stricture formation and
respiratory tract obstruction from laryngeal edema. It should be
started preferably within 48 hours. The steroid of choice is
prednisolone in a dose of 2 mg/kg/day. If the patient is unable to
tolerate oral medication, an equivalent parenteral dose of
dexamethasone or methylprednisolone should be given as an
alternative. The duration of steroid therapy is recommended for
atleast 2 weeks or until esophagus and/or stomach heals. Antacids
should be used for burns of the stomach. Prophylactic antibiotic may
be used in a patient with steroid therapy to prevent suppurative
complications. Otherwise, the use of antibiotics should be reserved
for specific signs of infection.
Esophageal dilatation: Esophageal stricture or gastric outlet
obstruction may require subsequent dilatation and bougienage. In
order to avoid perforation, esophageal dilatation should be delayed
4 to 6 weeks until healing is complete.
Surgery: Retrograde dilatation through a gastrostomy may be
required if it is impossible to dilate from above. This is possible
because the lower end of stricture is always conical as opposed to

the proximal end where the opening is often placed eccentrically and
may be difficult to define.
A radical surgical intervention is ultimately required in 40 percent
of cases due to complete stenosis, fistula formation, failure of
bougienage to provide an adequate lumen, non-compliance of patient
with bougienage.
Types of operations
i. Local excision of stricture if it is short
ii. High esophagogastrostomy
iii. Cervical esophagogastrostomy
iv. Colon or jejunum interposition.
For burns of the skin, wash the skin with large amount of water
and soap or dilute solution of sodium or potassium bicarbonate.
Later, thick paste of magnesium oxide is applied. The raw surface
is treated with soframycin or povidone iodine ointment. When the
eyes are involved they should be washed immediately with large
amount of water followed by irrigation with 1 percent sodium
bicarbonate solution. A few drops of olive oil is then instilled into
eyes. Eyedrops containing antibiotics and steroids are useful.
PHENOL (CARBOLIC ACID)

Carbolic acid, a coal tar in pure form, occurs as long, colorless,
prismatic needle like crystals with a sweet taste and characteristic
phenolic odour. It is water-soluble but demonstrates better solubility
in alcohol, ether, chloroform and glycerine. Phenol or related
compounds like cresol, hexachlorophane, hydroquinone and resorcinol
are used as antiseptics, caustics, preservatives, surface anesthetics and
germicides. In children, intoxication is usually accidental but may be
suicidal in adolescents and rarely homicidal.
Pathophysiology
It is well absorbed from skin, lungs and gastrointestinal tract. Phenol
is a protoplasmic poison, i.e. poison kills cell by denaturing and
precipitating proteins. It, therefore, causes necrosis and sloughing of
tissues. It has mild corrosive and anesthetic action on the skin and
mucous membrane. When it is applied to the skin, it causes necrosis
and gangrene. The local nerve endings are stimulated and then
paralyzed, resulting in anesthesia. After absorption, it causes
widespread capillary damage and clotting in superficial vessels. It
also affects the central nervous system, heart and kidneys. In small
doses it stimulates respiratory centre, causing respiratory alkalosis.

Higher centers are also affected producing giddiness and rapid loss
of consciousness.
Fatal dose: 10-15 gm but 20 drops of pure phenol may cause death.
Fatal period: 3 to 4 hours.
Clinical Features
The usual mode of intoxication is ingestion, therefore, burning pain
occurs from mouth to stomach with corrosion of lips, mouth and
tongue. The corroded area may have a characteristic dead-white
appearance. The pain is not so intense owing to its anesthetic property.
The cheeks and chin may be burnt due to dribbling of phenol from
angle of mouth. Hematemesis and bloody diarrhea may occur. The
skin is cold, pulse feeble and barely preceptible, pupils contracted
and pinpoint, temperature subnormal and breathing labored. After
initial phase of hyperpnea due to stimulation of respiratory center,
stupor, coma, convulsions, pulmonary edema and shock may develop.
The initial respiratory alkalosis is followed by acidosis which results
from renal excretion of base during alkalotic stage, acidic nature of
phenol, and from disturbances in carbohydrate metabolism. If children
survive the acute stage, acute tubular necrosis may lead to oliguria
and anuria. Since phenol is hepatotoxic also, it may lead to jaundice.
The urine in cases of phenol poisoning becomes dark smoky green
(carboluria) on exposure to air. Death may occur due to paralysis
of respiratory or cardiac center.
Diagnosis
1. History of ingestion and characteristic odour of phenolic
compounds.
2. Clinical feature
3. Investigations: Shows presence of carbolic acid.
Add few drops of ferric chloride to urine. The color of urine in
presence of carbolic acid changes to violet or blue.
Treatment
This is the only corrosive poisoning in which gastric lavage should
be done immediately by passing a soft stomach tube because of mild
corrosive action and hardening of tissues. Gastric lavage is done with
either plain water or 10 percent solution of glycerine in water. If
available, magnesium sulphate (solution of 10%) should be added to
the plain water until washings no longer emit phenolic odour. About
10-20 ml should be left in stomach after lavage is complete. Demulscents

like egg white or milk may be useful. Supportive therapy should be
instituted if necessary. Airway patency is maintained by intubation
or tracheostomy.
If the child recovers from acute stage and develops oliguria or
anuria, further management should be conservative with restriction
of fluid and salts and daily monitoring of input and output. If
necessary peritoneal dialysis or hemodialysis may be instituted.
Surface burns should be washed with water followed by local
application of castor oil. If castor oil is not available, burns may be
mopped with soap and water.
HYDROCYANIC ACID AND ITS SALTS

Hydrocyanic acid is a colorless gas with penetrating odor of bitter
almond. This is an extremely potent and rapidly acting poison.
Cyanides are widely used in industry and for fumigation in homes,
for silver polishes and in photography. Cyanide poisoning may result
from the inhalation of hydrocyanic acid, ingestion of soluble inorganic
cyanide salts or related substances like cyanamides, cyanogen chloride
and nitroprusside. Seeds of some stone fruits like choke berry,
cherry, plum, peach, apricot, bitter almond, roots of cassava, the
leaves of elder berry and ill paste of hydranga contains substances
(amygdalin) which on ingestion release cyanide. The intoxication
with cyanides and hydrocyanic acid is usually suicidal but may be
accidental in children.
Pathophysiology
Hydrocyanic acid and cyanides are protoplasmic poison. They react
with trivalent iron of cytochrome oxidase, inhibiting the system for
electron transport, hence oxygen utilization in cells, resulting in
cellular dysfunction and death.
Fatal dose: Less than 60 mg of pure hydrocyanic acid (the exposure
of children to concentration of 0.15 mg of hydrocyanic acid per liter
of air for a period of 20-30 mts, is dangerous to life).
100-200 mg of cyanide of potash
60 drops of crude oil of bitter almond
Fatal period: Usually 2-10 minutes for hydrocyanic acid, death may
occur immediately in children.
30 minutes for sodium or potassium cyanide.
Clinical Features
The clinical features depend upon the mode of intoxication. Inhalation
of hydrocyanic acid or swallowing Key Points

of large doses may even cause
sudden death but symptoms usually Diagnosis
appear at an interval of about one- H/o Inhalation or ingestion
minute. The first feature is an Characteristic breath
increase in rate of ventilation because Odor of bitter almonds
Clinical features
of blockage of oxidative metabolism Hyperventilation
in chemoreceptor cells. As more Cyanosis, headache,
cyanide is absorbed, there is head- inosomnia, hypotension
ache, dizziness, nausea, drowsiness Dyspnea
and hypotension, followed by Convulsions
Coma
dyspnea, coma and convulsions. The
Dilated pupils
odor of breath is of bitter almond.
Cyanosis is usually absent unless Management
respiratory depression supervenes.
1. Administer 100% oxygen
Pupils are dilated. A small quantity 2. Antidote
of fine froth may appear at the Amyl nitrate inhalation
corner of the mouth. The jaw may Sodium-thiosulphate for
be tightly clinched. There may be further detoxification
epigastric pain and vomiting. Alternative antidote-
hydroxy cobalamin
(subject to availability)
Diagnosis Supportive treatment
1. History of inhalation or ingestion
2. Characteristic breath odor with clinical features.
Treatment
Oxygen (100%) should be given immediately followed by specific
antidote. The objective of the treatment is the production of
methemoglobin by amylnitrite inhalation. The methemoglobin
competes with cytochrome oxidase for cyanide ions. The cytochrome
oxidase cyanide complex dissociates restoring the enzymatic and
respiratory functions. Further detoxification is achieved by adminis-
tration of sodium thiosulphate. The enzyme rhodonase catalyses the
reaction of thiosulphate with cyanide liberated by dissociation of
cyanmethemoblogin; thiocyanate which is relatively non-toxic, is
formed and excreted in urine.
Amyl nitrate capsule should be broken under childrens nose for
30 sec of each minute till freshly prepared sodium nitrate solution
is administered IV at a dose of 0.33 ml/kg (10 mg/kg) to maximum
dose of 10 ml/patient with normal hemoglobin. Sodium thiosulphate
25 percent solution is administered IV next at a dose of 1.65 ml/kg
to a maximum dose of entire ampoule.

An alternative antidote, which is not freely available, is hydroxy
cobalamin. Apart from specific antidotes, acidosis, shock, coma and
respiratory failure should be managed effectively. The usual cause
of death of children is respiratory paralysis.
CAUSTIC POTASH AND SODA
Caustics act as corrosive poisons when concentrated and simple

irritants when dilute. These are used as household cleaning agents.
In children, accidental poisoning is common due to easy accessibility
whereas suicidal and homicidal poisoning are rare.
Pathophysiology
Caustics are rapidly absorbed from mucous membrane and combine
with fat and protein forming soaps and proteinates. Thus caustics
produce soft, deeply penetrating necrotic areas on contact with
tissues.
Fatal dose: Uncertain, average dose is 5 gm.
Fatal period: Death within 24 hours from shock and collapse or
within a few weeks from exhaustion.
Clinical Features
The child has burning pain from mouth to stomach with complaints
of strong soapy, nauseating taste, vomiting then follows. The vomitus
is frothy, containing slimy mucous and may be blood stained. The
mucous membrane of mouth is swollen, translucent and soaplike and
mucilaginous slough may be present. Tongue and lips turn brown
and swell extensively. Swallowing becomes increasingly difficult.
Respiratory distress is present when pharynx is affected. There is
diarrhea with tenesmus and stool contains blood stained mucous. As
with other corrosives, shock may occur within cold clammy skin, pale
anxious face, sunken eyes dilated pupils, rapid feeble pulse and sighing
respiration. If the children survive the initial shock, they may develop
esophageal stricture and atrophy of gastric mucosa.
Treatment
As with other corrosives, emetics and gastric lavage are
contraindicated. However, a soft stomach tube or Levine tube can
be passed cautiously within one hour of ingestion. Weak acids such
as vinegar, lemon or orange juice should be given to neutralize the
alkali. Dilution with water should be done very cautiously since they
liberate a considerable amount of heat. Shock, respiratory distress

and perforation when present should be managed as with other
corrosives.
Complications like esophageal stricture should be treated by
internal bougienage. The patients who develop atrophy of gastric
mucosa are at a high risk for developing carcinoma of stomach.
BIBLIOGRAPHY
1. Haller JA, Andrews HG Write JJ, et al. Pathophysiology and management
of acute corrosive burn of esophagus. J Pediatr Surg 1971;6:578-84.
2. Modi. Textbook of Medical Jurisprudence and Toxicology, 20th edn. Bombay.
EM Tripathi Pvt. Ltd., 1977;485.
3. Narayan Reddy KS. The Essential of Forensic Medicine and Toxicology
1984; 389-95.
4. Penner GE. Acid Ingestion: Toxicology and Treatment. Ann Emerg Med
1980; 9:374-97.
5
Metals and Non-Metals
IRON POISONING
Iron is an essential nutrient that is a common content of numerous
vitamin preparations and tonics. Iron poisoning is a common pediatric
emergency. It is listed as one of the top ten substances ingested by
children younger than five years. Its high incidence in childhood is
related particularly to the prevalence of iron containing tablets and
tonic in home and the resemblance of many tablets to candy. Accidental
iron ingestion is not uncommon in children and has become a leading
cause of unintentional pharmaceutical ingestion fatality. Accidental
ingestion of iron is the leading cause of poisoning deaths in children
under 6 years in United States despite child resistant packaging. Since
1986, over 110,000 such incidents have been reported leading to 33
deaths. Almost 17 percent of childrens death reported to poison control
centers in USA between 1988 and 1992, were due to iron poisoning.
Chronic iron intoxication occurs due to repeated blood transfusion as
required in cases of Thalassemia. Though there have been several
reports of acute iron poisoning in children in India, the exact incidence
and mortality is not known either due to scarcity of reports or lack
of effective reporting system.
Accidental iron poisoning in children is common because of the
following facts about iron.
1. Iron supplements are found in many homes with small children.
Iron is freely available in numerous over-the-counter and
prescription tablets and liquids. It is also found in many
multivitamins preparations of both children and adults. Pregnant
women are often prescribed prenatal vitamins that have high
amounts of iron and often kept around house even after stops
taking them.
2. Unawareness of people that iron can be dangerous.
3. Attractiveness of iron tablets: Various chewable children tablets of
vitamins with iron are often in cartoon shapes with various colors
and fruit flavors. The much more dangerous adult formulations

contain more iron and often look like brightly colored candies to
young children.
4. Illiteracy and carelessness of parent.
Pathophysiology
Although iron is an essential mineral physiologically but in excess it
acts in the body as metabolic poison. Normally it is absorbed in
ferrous form into mucosal cells of duodenum and jejunum by saturable,
carrier mediated uptake. Further it is oxidized to ferric form,
transported by protein transferrin and utilized for synthesis of
hemoglobin, myoglobin, catalase, cytochrome oxidase or stored in
liver and bone marrow, bounds to proteins as ferritin or hemosiderin.
In acute overdose, normal mechanisms of absorption are exceeded
and iron is absorbed by a passive first order process. Factors that
enhance iron absorption from gastrointestinal tract are presence of
valine and histidine, ascorbic acids, succinate, pyruvic acid and citric
acid in diet. Furthermore iron toxicity is also influenced by serum
copper, phosphorus and vitamin E level, and associated diseases such
as primary hemochromatosis, thalassemia, liver diseases that in turn
enhance toxicity.
Ferritin is a unique iron storage protein, the production of which
is directly related to amount of iron in the baby. Ferritin is greatly
abundant in heart and livers, therefore large amount of accidentally
ingested iron rushes in to these organs for storage. Excess build up
of iron in these organs causes tissue destruction. With acute iron
poisoning much of damage to gastrointestinal tract and liver may be
a result of high localized iron concentration and free radical production
leading to hepatotoxicity via lipid peroxidation and destruction of
hepatic mitochondria. Various mechanisms of iron toxicity have been
suggested.
1. It exerts a direct corrosive effect on gastrointestinal tract leading
to hemorrhagic necrosis and cause nausea, vomiting diarrhea and
abdominal pain. The ferrous remains stable in acid pH and cause
direct irritation of gastric mucosa whereas in duodenum it gets
converted into insoluble iron complexes causing further mucosal
damage.
2. Free iron crosses cellular membranes and at sub-cellular level tends
to concentrate around mitochondrial cristae and may act as an
electron sink shunting electron away from electron transport
system. A switch to anaerobic metabolism and increased lactic acid
production results in metabolic acidosis.
Metals and Non-Metals 45
3. Reduction oxidation reactions of excess iron may lead to excessive

production of free radicals in the body which cause damage to cells
of various organs by peroxidation of lipids and proteins. The
pulmonary damage manifests as ARDS, respiratory failure and
acidosis.
Fe++ + H2O2 Fe++++ OH + OH
Free iron also acts on vascular system causing post-arteriolar
dilatation and increased capillary permeability leading to venous
pooling, decreased blood volume and reduced cardiac output due
to release of histamine and serotonin.
4. Excess free iron leads to functional, reversible and concentration
dependent impairment of coagulation within first few hours,
probably as a consequence of susceptibility of serine proteases to
non-transferrin bound ferric ion.
Acute iron intoxication exerts its primary effects on GI tract,
liver and cardiovascular system. Pathological changes in various
organs are mentioned in Table 5.1.
Table 5.1: Pathological changes in iron poisoning
Esophagus: Ulceration, edema, hemorrhage

Stomach: EarlyUlceration, venous thrombosis, gastritis, necrosis and
perforation
LateStricture/obstruction
Liver: Swelling, hemorrhagic periportal necrosis, iron deposition in
Kupffer or parenchymal cells
Lung: Vascular congestion, edema, atelectasis
Heart: Fatty degeneration of cardiac muscles
Kidneys: Fatty degeneration of renal tubules
Pancreas: Hemorrhagic necrosis
Gastrointestinal tract: On autopsy, commonly observed lesion is

hemorrhagic necrosis of proximal GI tract. Lesions identified are
corrosive mucosal lesions of stomach and proximal small intestine and
segmental infarction of the distal small bowel. Pyloric stenosis and
intestinal obstruction are late sequelae.
Liver: The severity of liver damage may vary from no change to
swelling, hemorrhagic portal necrosis and fatty degeneration with
Kupffer or parenchymal cells deposition of iron. Severe mitochondrial
injury is seen at sub-cellular level. Liver damage may lead to hepatic
encephalopathy, coagulopathy and death.
Cardiovascular: On postmortum examination, myocardial damage
and stainable iron has been observed. Myocardial dysfunction is
mediated by lipid peroxidation of membranes due to iron-catalyzed
free radical generation. Myocardial depression could be secondary to

metabolic acidosis.
Other systems: Secondary changes may be observed due to shock,
hypotension and acidosis. Pancreas may show hemorrhagic necrosis.
Hemorrhage in the lungs and kidneys with focal pulmonary atelectasis
and fatty degeneration of renal tubules may occur.
Ingestion of elemental iron more than 20 mg/kg produces
gastrointestinal toxicity while more than 60 mg/kg results in systemic
toxicity.
Toxic Doses
The lowest reported lethal dose for children was 600 mg. However,
iron ingestion less than 20 mg/kg body weight though considered
sub-toxic will rarely produce even mild symptoms, 20-60 mg/kg body
weight is considered potentially serious and more than 60 mg/kg
body weight, potentially lethal.
Clinical Features
Five stages may be observed in the clinical and pathological evolution
of acute iron intoxication. These are:
Stage Time
since ingestion
1. Gastrointestinal 30 min - 2 hours
2. Apparent recovery 2-6 hours
3. Circulatory failure 12 hours
4. Hepatic necrosis 2-4 days
5. Gastric scarring 2-4 weeks
1. Gastrointestinal Stage
This stage usually appears 30 minutes to 2 hours after ingestion of iron
containing preparations. The clinical manifestations during this phase
is the result of local necrosis and hemorrhage at the site of contact.
The usual manifestations during this stage are nausea, vomiting, bloody
diarrhea, abdominal pain and hematemesis. Sometimes pallor or
cyanosis, lassitude, drowsiness, hyperventilation due to acidosis and
severe hypotension or cardiovascular collapse may occur.This stage
lasts for 6-12 hours.
2. Stage of Apparent Recovery (Relative Stability)

This is a poorly defined stage during which child appears better. In
this stage iron accumulation continues in mitochondria and various
organs. The careful observations reveal ongoing problems which are

manifested as hyperventilation, oliguria, poor tissue perfusion and
vague gastrointestinal symptoms.
3. Stage of Circulatory Failure

This stage is characterized by shock, which is usually multifactorial
in origin. Gastrointestinal fluid or blood loss, increased capillary
permeability, loss of postarterial and venous tone are the main
contributing factors. These are further exacerbated by co-existing
metabolic acidosis and coagulopathy. Clinical manifestations during
this stage are tachycardia, pallor with cold extremities, decreased
central venous pressure and later hypotension, oliguria, depressed
sensorium and severe acidosis. Acute renal tubular necrosis, pulmonary
hemorrhage and pancreatic necrosis may occur in severe cases.
4. Stage of Hepatic Necrosis

This stage usually seen 2-4 days after ingestion is rarely encountered.
It is characterized by severe hepatic necrosis with elevation of AST,
ALT, prothrombin time and serum bilirubin.
5. Stage of Gastric Scarring

This appears 2-4 weeks after acute episodes of iron ingestion and
clinical features are those of gastric outlet or intestinal stenosis due
to scaring. Stenosis occurs in the pyloric region due to local irritative
action during first phase. An overgrowth of Yersinia enterocolitica with
sepsis is an infrequent complication.
Table 5.2: Clinical manifestations of iron poisoning
Gastrointestinal: Anorexia, nausea, vomiting, hematemesia, diarrhea, tarry

stools, scarring of stomach and bowels in serious cases
Cardiovascular: Hypotension, tachycardia
Nervous system: Drowsiness, lack of desire to do anything, coma
Respiratory: Tachypnea, pulmonary edema, ARDS, respiratory failure
Skin: Bluish colored lips and finger nails, jaundice
Other: Dehydration, hypothermia, hypoglycemia, oliguria
Problems Resulting from Iron Toxicity

There are many problems that may result from iron toxicity. These
include anorexia, diarrhea, hypothermia, diphasic shock, metabolic
acidosis and death. In addition to these, the patient may experience
vascular congestion of GI tract, liver, kidneys, heart, brain, spleen,
adrenals and thymus.
As a result of iron storage disease, the liver becomes cirrhotic and

incidence of hepatoma, primary cancer of liver increases several fold.
Also when siderosis becomes severe in young people, myocardial
disease is a common cause of death. Impotence may occur in young
male and amenorrhea may occur in adolescent girls. Both of these
sexual related problems are due to iron loading in the anterior pituitary.
Diagnosis
2. Clinical features as mentioned above
3. Laboratory diagnosis.
Free serum iron estimation: This is the best way to determine the
potential for toxicity and is done by assessing total serum iron and
total iron binding capacity. Peak serum iron levels are usually seen 2-
6 hours after ingestion.
Free iron in serum = Total serum iron total iron binding capacity.
a. If free serum iron is less than 50 mg/dl toxicity unlikely.
b. If free serum iron is 50 mg/dl or more toxicity manifests.
c. Total serum iron 350 mg/dl or more toxicity evident.
i. Plain X-ray abdomen: Demonstrates the presence of remaining
iron tablets. Radiographs are most useful when obtained in first
2 hours of ingestion. Negative X-rays do not rule out poisoning.
ii. Total leukocyte count: Usually greater than 15,000/mm (Polymor
phonuclear leukocytosis).
iii. Serum glucose: Usually more than 150 mg/dl.
iv. ABG (Arterial blood gas): If facilities exist for metabolic acidosis
and increased anion gap.
v. Coagulation profile: Prothrombin time usually prolonged.
vi. Electrolyte estimations: Serum calcium, sodium, potassium,
chloride and bicarbonate.
vii. Liver function test: Serum transaminases (AST, ALT) may be
increased in severe intoxication.
viii. Renal function test: BUN and serum creatinine may be raised.
ix. Qualitative test for iron ingestion: If iron ingestion is suspected
but exact history is not available, rapid qualitative test can be
performed by mixing 1 ml of gastric fluid with 2 drops of
30 percent hydrogen peroxide and deferoxamine (125 mg/ml).
Any color change, compared to gastric content and hydrogen
peroxide alone is considered positive for iron.
Treatment
When a child presents in emergency with acute iron intoxication the
following measures should be promptly started. The algorithm for
management of iron poisoning is mentioned in Figure 5.1.
Dose of elemental iron ingested
Do not know > 20 mg/kg < 20 mg/kg
Yes
Serum iron estimation GI symptoms
2-6 hours, postingestion
No
Observe the patient
500 g/dl 300-500 g/dl 300 g/dl
Abdominal X-ray/
Glucose/TLC/TiBC/ Yes
Clinical features GI symptoms
Any One positive No
No Decontamination Observe the

Chelation therapy patient
supportive care
Fig. 5.1: Algorithm for management of iron poisoning
Decontamination (Removal of Unabsorbed Iron)

This should be done as rapidly as possible. Emesis may be induced
with ipecac syrup, if patient is alert and co-operative and ingestion
occurred within 30 to 60 minutes or if an abdominal X-ray shows the
presence of tablets in the stomach. However, ipecac does not
consistently remove all iron tablets from stomach. Gastric lavage should
be done in all cases irrespective of previous vomiting either spontaneous
or induced.
Gastric lavage should be done with a large bore tube using saline.
Following lavage, 100 ml of milk of magnesia or 50-100 ml of 5 percent
sodium bicarbonate solution may be left within the stomach. These
compounds will form complex iron to prevent further absorption and
also decrease the corrosive effects of stomach acid upon a denuded
gastric mucosa. Oral administration of desferrioxamine has been shown
experimentally in humans and in some animal models to promote the

absorption of iron from GI tract and therefore, this should not be used.
Whole bowel irrigation using PEG-ELS solution should be used as
an alternative to emesis, lavage and cathartics, particularly if large
numbers of tablets are visible on X-ray past the stomach. Activated
charcoal does not bind iron and should not be given unless coingestants
are involved that may be bound by charcoal. An abdominal X-ray
should be performed to determine the presence of any remaining
tablets following GI decontamination.
In a small number of cases where X-ray has shown as bezoars of
iron tablets in GI tract, surgical removal of the tablets (gastrotomy)
may be done. This should be considered if a clump of tablets can be
seen on X-ray and they fail to move or break-up with the usual
procedures. Endoscopy has rarely been successfully used to break-up
clumps of tablets in the stomach.
Definitive Therapy
The definitive therapy of iron poisoning is chelating agent
desferrioxamine. Desferrioxamine a chemical produced by siderophore
bacteria with high affinity for iron in the plasma resulting in excretion
of ferrioxamine complex via urine which typically becomes Vinrose
(pink) in color. It can bind free iron at subcellular level by crossing
the cell membrane.
Indications of Chelation Therapy
1. Clinical manifestation like lethargy, hypotonia, tachypnea and
tachycardia.
2. If free serum iron more than 50 g/dl or total serum iron more than
350 g/dl.
3. Abdominal radiograph showing large mass of remaining tablets.
4. Total leukocyte count more than 15,000/cumm.
5. Serum glucose >150 mg/dl.
Routes and Dosage of Desferrioxamine

For acute cases, continuous intravenous infusion is preferred while in
less severe cases it can be given intramuscularly. The dose of
desferrioxamine is 15 mg/kg/hour for intravenous infusion and 50
mg/kg (maximum 1 gm per dose) given every 4 hours by intramuscular
route. Total dose of desferrioxamine should not exceed 6.0 gm IV or
IM. For practical purposes, it is useful to remember that 1 gm of
desferrioxamine chelates about 90 mg of elemental iron. It is available
as injection Desferal, a white powder in doses of 500 mg. It is diluted
by adding 5 ml of distilled water for injection to each 500 mg vial to

produce 10 percent solution. It is further diluted with normal saline
or one fifth glucose saline and administered as a continuous infusion.
The clinical improvement can be seen in an hour or two.
Preparation Available
A powder form is available in vials containing 500 mg which is to be
diluted in water for injection to produce 10 percent solution. This
solution is further diluted in 0.8 percent saline or 0.25 percent saline
in 5 percent dextrose for continuous intravenous infusion.
Effectiveness and Duration of Therapy

The effectiveness of chelation therapy is judged by passage of red
colored or port wine urine. The duration of continuous infusion still
remains a debatable issue. Traditionally a change in urine color to pink
or vin rose is interpretated as an indicator of high iron load and
treatment is continued till urine is clear for 24 hours. However,
occasionally urine color may not change despite serum iron level of
more than 500 g/dl. Therapy is continued till the urine color becomes
normal or serum iron falls to less than 300 g/dl. In severe poisoning,
additional 12-24 hours chelation therapy is recommended. Recently
Yastscoff RW et al have suggested an objective criteria for cessation
of desferrioxamine therapy based on urinary iron to creatinine ratio,
if facilities are available.
Acute reactions such as hypersensitivity reactions and anaphylaxis
may develop. In higher dose, hypotension may occur due to histamine
release. Pulmonary edema and ARDS have been reported in patients
receiving desferrioxamine infusion for more than 65 hours. Optic
neuropathy, hearing loss and cataracts have been reported after long-
term use.
Supportive Therapy
Attention to airway and ventilation is important in patients who
developed altered sensorium. Shock must be treated with IV fluid and
ionotropic support with frequent monitoring of CVP. Blood transfusion
may be given if there is significant hemorrhage. Persistent acidosis
may require correction with sodium bicarbonate. Liver and renal
failure should be managed as per hospital standard protocols.
Dyselectrolytemia and hyperglycemia associated with stage III and IV
should be managed effectively. Sometimes patient may develop gram-
negative septicemia especially due to Yersinia enterocolitica or Listeria
Key Points monocytogens either due to

free iron induced mucosal
Diagnosis damage or desferrioxamine
1. History induced growth of these
2. Clinical features: Vomiting, abdominal organism.
cramps, hematemesis, diarrhea, circu-
latory failure, rarely jaundice (2-4 days
Other Measures
later)
3. Investigations: Hemodialysis as such has no
i. Plain X-ray of abdomen shows pre- role to play but is indicated
sence of unabsorbed tablet/ capsule.
ii. Free Serum iron > 50 mg/dl
in patients with oliguria to
iii. Total Serum iron > 350 mg/dl remove ferrioxamine. Ex-
iv. Leukocytosis change transfusion along with
desferrioxamine may increase
Management clearance of free irons as much
1. Emesis with Syrup ipecac as 30 fold as compared to
2. Gastric lavage desferrioxamine alone. How-
3. Supportive and symptomatic treament ever, it is indicated only in
4. Chelation therapy: Desferrioxamine - cases where serum iron levels
Continue infusion for severe cases until exceed 1000 g/dl and no
urine color turns normal or serum iron
concentration falls. Intramuscular injec-
response to routine treatment.
tion in mild cases Charcoal hemoperfusion may
5. Dialysis with chelation - In renal failure not be very useful since char-
6. Very severe casesExchange trans- coal has poor affinity for iron.
fusion hastens removal of iron by 20-30 Experimental modalities of
times. Charcoal hemoperfusion with
therapy include IV adminis-
simultaneous chelation
tration of liposomal encapsu-
lated desferrioxamine and high molecular weight derivatives of
desferrioxamine, i.e. desferrioxamine covalently attached to high
molecular weight carbohydrates such as dextran and hydroxyethyl
starch.
Prognosis
Children with iron poisoning usually respond very well to conservative
management and chelation therapy. The prognosis is directly related
with development of shock and hypotension. Untreated children with
shock have almost 100 percent mortality compared to those received
chelation 10 percent.
Prevention
The reduction of risks of iron intoxication in children requires a
multifactored approach. Education of parents, restriction of over
counter prescription of iron, safe packaging and conspicuous warning

about dangers of accidental over ingestion in children is important
steps. Simultaneously, additional resources should be directed towards
identification, testing and marketing of improved antidotes.
LEAD POISONING
Lead, a heavy steel grey metal is virtually ubiquitous in the environment
as a result of its natural occurrence, presence in a number of alloys
and its use for various domestic, industrial, and medicinal purposes.
Prolonged exposure or ingestion of its soluble compounds may result
in accumulation of lead in the body.
Lead and its inorganic compounds like lead acetate, lead monoxide,
lead chloride, lead bromide, lead iodide, lead sulphite, lead nitrite,
lead carbonate, lead sulphate and lead chromate are poisonous.
Acute lead poisoning is rare. In children it is usually chronic due
to exposure to inorganic lead over a prolonged period. Children in the
age group of 1-6 years are commonly affected. The usual sources of
exposure are ingestion of contaminated food stored or cooked in
tinned vessels or swallowing of lead paints on pencils, toys, windows,
walls of old houses or storage batteries. Sniffing of gasoline (Tetra
Ethyl lead) by older children and adolescents causes organic lead
poisoning. The major pathway of lead entry into circulation is by
intestinal absorption.
Pathophysiology
Although lead can be absorbed through the skin and mucous
membrane, major routes of absorption are gastrointestinal tract and
respiratory system. Gastrointestinal absorption of lead is more common
in children in comparison to adults as the former absorb upto
40 percent while the latter absorb only about 10 percent of the ingested
lead. After absorption lead is distributed mainly in the skeleton (95%),
teeth and hair and only a small quantity is present in viscera and body
fluids. The mechanism of deposition, mobilization, and excretion of
lead is the same as that of calcium. The conditions, which favor
deposition of calcium in bones also, favor the deposition of lead.
Conversely stored lead is mobilized and returned to circulation by
conditions, which remove calcium from bone. In normal person, the
fecal content of lead is 0.4 mg/day and urinary content is 0.08 mg/
liter.
Lead combines with essential sulfhydryl (SH) groups of certain
enzyme, e.g. those involved in prophyrin (heme) synthesis and
carbohydrate metabolism. The enzymes of heme system, inhibited in
lead poisoning are ALA (Aminolevulinic acid) synthetase, ALA

dehydratase and ferrochelatase and porphobilinogen synthetase. It
affects membrane permeability and interferes with mitochondrial
oxidative phosphorylation. It also causes degenerative changes in
extensor muscles of extremities and peripheral nerves. The principal
toxic effects occur in the central and peripheral nervous system,
erythroid series of the bone marrow and the kidney. Abnormal cardiac
conduction and thyroid function have also been reported in severe
cases. Lead causes inhibition of hemoglobin synthesis as well as
hemolysis of mature red blood cells through direct action. Deposition
of lead sulphide along gum margins causes a lead line (Burtonian
line). Lead also induces increased density in the metaphyseal ends of
the long bones in children.
Fatal dose: Lead acetate20 gm
Lead carbonate30 gm
Fatal period: 1 to 2 days
Clinical Features
Based on duration and mode of presentation, lead poisoning may be
acute, subacute, and chronic.
Acute Lead Poisoning

Acute lead poisoning is rare and results from inhalation of lead vapors
or ingestion of soluble lead compounds. The manifestations are metallic
taste, salivation, diarrhea or more usually constipation, intestinal colic,
headache, formication, insomnia, convulsions, circulatory collapse and
coma. The kidneys may be affected resulting in Fanconis syndrome
and nephropathy with hyperuricemia. Lead intoxication also affects
the liver. Death may occur in 2-3 days. Most children recover slowly
or develop signs of chronic poisoning. The blood level in acute poisoning
is usually more than 150 mg/dl.
Sub-acute poisoning results from inhalation or ingestion of small
amounts of lead. The manifestations are weight loss, anorexia,
salivation, metallic taste, constipation and intestinal colic. Black line
on the gums, muscle cramps, tremor, insomnia, muscular paralysis,
ataxia, visual and auditory disturbances and hypertension may be
present. Vascular spasm may cause gangrene. Delirium, stupor and
coma usually precede death.
Chronic Intoxication
Chronic lead poisoning or plumbism results from continued absorption
of lead from gastrointestinal tract and respiratory tract. The presentation
of chronic lead poisoning are encephalopathy, peripheral neuropathy,

developmental dysfunction, abdominal syndrome, nephropathy and
hematological disturbances. Encephalopathy is usually more common
among children, while abdominal syndrome is more prevalent in
adults.
Encephalopathy
This is the most dangerous manifestation of lead poisoning. The onset
is insidious. In toddlers, early manifestations are anorexia, irritability,
refusal to play and projectile vomiting. In older children, early features
are abnormal behavior and headache. After a period of 4-6 weeks,
there is altered sensorium, persistent vomiting, ataxia, and convulsion.
The child rapidly goes into coma. Transient paresis, dysphasia,
paresthesia and deafness may be present. Lead encephalopathy often
mimics tuberculous meningitis. There may be paralysis of recurrent
laryngeal nerve causing hoarseness of voice and phrenic nerve palsy,
which may result in sudden death. The involvement of 2nd, 3rd and
6th cranial nerves lead to visual defect, strabismus, ptosis, diplopia
and lateral gaze paralysis.
Neuromuscular Effects and Peripheral Neuropathy

Neuromuscular effects include pain especially in calf muscles and
weakness and paralysis of extensor muscles of forearm, wrist and
fingers. Paralysis is associated with degeneration of nerve and atrophy
of muscle, which is due to interference with the resynthesis of
phosphocreatinine. The paralysis initially affects the dominant hand
but eventually both hands are affected. Lower limbs are rarely involved.
Easy fatiguability may be the only preceding symptom. Acute
paralysis like wrist drop and foot drop appears much later. Sensory
involvement is relatively uncommon.
Developmental Dysfunction
There is regression of milestones in children after first 12-18 months
of normal development. Children present with steady loss of motor
skills and speech and are hyperkinetic and aggressive. They have
impaired learning due to lack of sensory perception. Blood levels of
30-50 gm/dl are associated with incidence of hyperkinetic behavior
and poor IQ.
Abdominal Syndrome
It is an early manifestation and often the first symptom that raises
suspicion of chronic lead poisoning. Children present with anorexia,
nausea, vomiting, metallic taste, abdominal discomfort and constipation

or rarely diarrhea. There is periumbilical rigidity and tenderness.
Abdominal colics or lead colics are due to intestinal spasm and attacks
are paroxysmal and excruciating. There may be gingivitis, stomatitis,
and 70 percent children have a dark line (Burtonian line) at gum
margins more frequently seen on the mandibular gum in the incisor
region. It is bluish-black line due to sub-epithelial deposition of lead
sulphide granules particularly in the vicinity of teeth having caries or
infection.
Hematological Manifestations
Initially, there is polycythemia, polychromasia, reticulocytosis and
basophilic stippling. In basophilic stippling or punctate basophilia;
many dark colored spots are present in the cytoplasm of erythrocytes.
These are due to aggregation of ribonucleic acid in the RBC, which
takes basic dyes. Hypochromic microcytic anemia develops due to
impaired heme synthesis and increased hemolysis. Anisopoikilocytosis,
nucleated red blood cells, thrombocytopenia, neutropenia and mild
reticulocytosis have also been observed. The erythrocyte osmotic
fragility is decreased and bone marrow shows erythroid hyperplasia
with stippling of nucleated red cells.
Renal Manifestations
Tubular transport processes promote the accumulation of lead within
renal cells, particularly proximal convoluted tubule leading to tubular
degeneration and atrophy. Lead nephropathy is associated with
ischemic changes in glomeruli, fibrosis of small arterioles and focal
areas of cortical scarring. Thus lead nephropathy, classically occurs in
two forms:
i. Reversible renal tubular disorder
ii. Irreversible interstitial nephropathy
The clinical manifestations are oliguria, Fanconis syndrome,
hypertension, hyperuricemia, albuminuria, hematuria and casts in
urine.
Clinical Features of Chronic Lead Poisoning (Table 5.3)

Encephalopathy
Irritability
Refusal to play
Vomiting
Headache
Table 5.3: Diagnosis of lead poisoning
Acceptable Increasing Risk of CNS toxicity
I II III IV
1. Pb B (gm/dl) < 10 10-24 25-39 40-60 60

whole blood
2. FEP (g/dl) 5020 92-197 198-444 445
Erythrocytes
3. Erythrocyte < 35 > 35 35-75 76-169 170
protoporphyrin
(gm/dl whole blood)
4. PBGS 75% 30% 10-15%
Altered sensorium
Ataxia
Convulsions
III, IV, VI cranial nerve palsy.
Neuromuscular
Easy fatiguability
Paralysis of extensor muscles of forearm and hand (dominant hand)
Wrist-drop, rarely foot drop.
Developmental
Regression of milestones
Impaired motor skills and speech
Impaired sensory perception
Hyperkinetic behavior
Poor IQ.
Abdominal
Nausea, vomiting, anorexia
Metallic taste
Lead-line on gum
Abdominal colics.
Hematological
Hypochromic microcytic anemia
Basophilic stippling
Decreased osmotic fragility of RBC.
Renal
Oliguria
Hematuria
Hyperuricemia
Fanconis syndrome.
Diagnosis of Lead Poisoning

1. History of exposure to lead
2. Clinical manifestations
3. Lab diagnosis.
Where facilities are available, whole blood lead level, free
erythrocyte porphyrin, Erythrocyte protoporphyrin, -aminolevulenic
acid and porphobilinogen synthetase should be estimated to confirm
diagnosis and to estimate the risk of associated encephalopathy. The
normal whole blood lead level is 6 gm/dl. Blood lead level exceeding
25 gm/dl and free-erythrocyte prophyrin levels exceeding
35 gm/dl are diagnostic of lead poisoning.
In emergency, diagnosis of lead poisoning may be considered in
the presence of two or more of the following:
a. Hypochromic microcytic anemia with stippling of erythrocytes.
b. Abdominal X-rays showing radiopaque foreign bodies in the bowel,
and X-rays of long bone (knee and leg) showing broad, dense,
bands at the metaphyses.
c. Glycosuria, aminoaciduria and hypophosphatemia.
d. Raised pressure and protein in CSF with mild pleocytosis.
e. Coproporphyrinurianormal value is 60-280 mg in 24 hrs.
f. Urinary ALA estimation shows several fold increased value. Normal
value being 2 mg in 24 hrs.
g. Normally the lead content of urine is less than 0.08 mg/liter but
in poisoning it may be as much as 0.15-0.30 mg/liter.
Management
Management of lead poisoning includes supportive therapy to combat
complications and specific treatment.
Supportive Treatment
The cornerstone of the therapy is removal of the child from sources
of lead followed by timely reduction of lead hazards in home
environment. Gastric lavage with a dilute solution of magnesium
sulphate is helpful only in acute poisoning from oral ingestion. Fluid
and electrolyte, management is critical in lead encephalopathy. After
an initial infusion of 10 percent dextrose in water to establish urine
flow, continuous IV infusion should be restricted to match the
requirement. If the features of raised intracrainal pressures are present,
this should be managed with IV mannitol (20%) and dexamethasone.
Seizures should be controlled initially with diazepam and thereafter
with repeated doses of paraldehyde until level of consciousness
improves significantly.
Long-term anticonvulsant therapy with phenytoin or pheno-

barbitone should be given. Children with abdominal colic are treated
with IV calcium gluconate in a dose of 2 ml/kg under cardiac
monitoring. Smooth muscle relaxants, atropine and nitrite may also
be used effectively.
When the lead poisoning results from ingestion of lead paint,
effective long-term management requires the cooperative efforts of
local health personnel, medical-social worker, the psychologist or
psychiatrist and pediatrician. The childhood habit of putting objects
in the mouth and pica is very difficult to control although behavioral
modifications may help.
Specific Treatment
Specific treatment includes enhancing the elimination of lead from the
body either through urine or stool and chelation therapy.
Elimination of lead from body is hastened by giving potassium or
sodium iodine, sodium bicarbonate, and magnesium or sodium
sulphate. Potassium or sodium iodide when given in a dose of 20-30
gm/day in four divided doses converts the insoluble tribasic lead
phosphate into soluble dibasic lead phosphate and thus enhances the
elimination of lead in urine. Magnesium and sodium sulphate change
the unabsorbed lead salts into insoluble lead sulphate and hasten its
elimination in stools.
Chelation Therapy
The commonly used chelating agents are:
1. Calcium EDTA
2. DMSA (meso, 2, 3-dimercaptosuccinic acid)
3. BA L (British Antilewisite or Dimercaprol)
4. D-penicillamine.
Indications of chelation therapy
1. Acute encephalopathy
2. Whole blood lead level >90-100 micro gm/dl
3. Coproporphyrinuria
4. Urinary lead over 0.15-0.3 mg/liter
5. Albuminuria and increase in plasma concentration of amino-
levulenic acid.
Dose CaEDTA is available in the market as ampoules, which contain
200 mg/ml. It is given intramuscularly at a daily dose of 1000 mg/
sqm in two divided doses for five days. The total daily dose should
not exceed 75 mg/kg and total therapeutic dose should not exceed
500 mg/kg. Repeat courses Key Points

of CaEDTA are often indi-
Diagnosis
cated in children with
higher lead burden. Strict 1. History
monitoring of urine output 2. Intestinal colic, constipation, headache,
formication, circulatory collapse, coma
is mandatory because
3. Investigation:
chelated lead complex is i. Hypochromic microcytic anemia.
nephrotoxic. Side effects ii. Abdominal X-ray showing radiopaque
with CaEDTA are hyper- foreign body
calcaemia, elevation of iii. Raised CSF pressure with increased
protein and pleocytosis
blood urea nitrogen levels,
iv. Coproporphyrinuria
acute zinc depletion, nasal v. Urinary lead >0.8 mg/liter
congestion and rigors.
DMSA, as compared to Management
CaEDTA can be given
1. Supportive and symptomatic treatment
orally, has no serious 2. Magnesium and sodium sulphate: Eliminate
adverse effect and does not lead through stool
induce acute zinc deple- 3. Potassium or sodium iodide: Eliminate
tion. DMSA is more effec- through urine.
4. Chelation therapy by:
tive in reducing the lead
i. Calcium EDTA-1000 mg/sqm IM in
content of brain, kidney divided doses for five days
and blood. It is indicated ii. DMSA
for the treatment of asymp- iii. BAL
tomatic patient and mildly iv. D-penicillamine - 20-40 mg/kg/day for
symptomatic patients. The 3-6 months
usual duration of therapy is up to four weeks.
BAL is available in ampoules containing 50 mg/ml as oily solution for
intramuscular use. In patients with acute encephalopathy, it is used
with CaEDTA. The dose of BAL is 500 mg/sqm/24 hrs and for
CaEDTA, 1500 mg/sqm/24 hrs. The drugs are injected simultaneously
at separate IM sites in six divided doses for five days after an initial
one dose of BAL only. Side effects of BAL include vomiting,
hypertension, tachycardia, headache, abdominal pain, burning
sensation in mouth, lips, throat and penis. Intravascular hemolysis in
G6PD deficient patient and sterile abscesses at injection site. The side
effects usually disappear on discontinuation of therapy.
D-Penicillamine a metabolite of penicillin that contains SH groups
and competes with enzymes for lead and removes lead not only from
soft tissues but from bone also. The dose is 20-40 mg/kg/day to a
maximum of 1 gm for a period of 3-6 months until body lead burden
is depleted. To avoid allergy, start the therapy with one quarter of the
total dose which is given for one week, then the starting dose is
doubled on weekly basis until full dose is reached.
Massive doses of vitamin B complex, splitting massage and electrical
stimulation may be required for the management of paralysis and
contracture.
Prognosis The mortality rate in untreated cases is 65 percent and
neurologic sequelae occur in majority of survivors. Sequelae include
seizure disorders, mental impairment and attention deficit, blindness,
hemiparesis and dystonia musculorum deformans.
The cause of death in acute poisoning is gastroenteritis leading to
shock while in chronic cases, malnutrition, intercurrent infection, hepa-
tic failure, respiratory or renal failure and lead encephalopathy can
cause death.
MERCURY POISONING
Mercury, also called quick silver, is a volatile liquid metal with a bright
silvery lustre at room temperature. It is a common heavy metal poison
due to its widespread use in various forms for household, agricultural,
medicinal and industrial purposes.
Elemental mercury, salts of mercury and organic mercurials are
three major toxic chemical forms of mercury. Elemental mercury is
volatile and highly toxic. It is used in thermometers, sphygmomano-
meters, and dental amalgams. There are reports of neonatal exposure
to faulty mercury switches in incubators leading to elevated serum
mercury levels. Inorganic salts of mercury are used in manufacturing
of plastics, fungicides, germicides, foodstuffs and topical medicines.
Mercury chloride is still used in some antiseptic skin creams. Mercurial
diuretic has been employed in roentgenographic scanning of kidney
and brain. Phenylmercuric compounds have been used extensively as
fugicides and poisoning results from ingestion of bread made from
contaminated wheat. Extensive use of mercuric salts in industries has
led to the problems of environmental contamination, particularly by
methyl mercury which is avidly taken up by plankton, algae and is
ultimately concentrated in fish via the food chain. Ingestion of
contaminated fish causes mercury poisoning in epidemic proportions,
as occurred in Minamata, Japan.
Mercury poisoning can lead to either acute or chronic toxic
manifestations. In acute poisoning the gastrointestinal tract and kidney
bear the burnt while in chronic poisoning, central nervous system and
skin are affected.
Pathophysiology
Mercury and its compounds cause tissue damage usually by their
direct toxic action. Renal toxicity, cerebral toxicity particularly of visual
cortex and granular layer of cerebellum, pulmonary toxicity and
mucosal damage at the site of absorption are most frequently encoun-
tered effects of mercury poisoning. In inorganic mercury poisoning
renal glomerular injury may be indirectly mediated by immune-
complex formation.
Elemental mercury gets vaporized and is absorbed primarily through
lungs. Gastrointestinal absorption of elemental mercury is low but
organic mercury is readily absorbed. The inorganic and organic forms
may both be absorbed through the skin. After absorption it gets
concentrated mainly in the kidney but is also distributed to the liver,
erythrocytes, bone marrow, spleen, lung, intestine, CNS and skin. Free
passage through blood-brain barrier and secretion through breast milk
are due to the lipid soluble nature of methyl mercury. Excretion is via
urine and faeces. The half-life of elemental, inorganic and organic
mercury is 60,40 and 70 days respectively.
Clinical Manifestations of Acute Mercury Poisoning

Clinical manifestations depend on the mode of intoxication. Exposure
to mercury vapor may cause weakness, chills, nausea, vomiting
diarrhea, abdominal pain and headache. Pulmonary manifestation
includes cough, dyspnea, a feeling of tightness in chest and interstitial
pneumonitis. Ingestion of mercury causes stomatitis, gingivitis,
esophagitis, gastroenteritis, metallic taste, nausea, vomiting, intense
abdominal pain and bloody diarrhea. Severe fluid loss may result in
hypovolemic shock and death. Renal involvement may cause anuria,
albuminuria and uraemia and may be fatal in some cases. Neurological
manifestations include ataxia, slurring of speech, numbness of hands
and feet, visual and hearing impairment, delirium, tremor, and
paralysis.
Clinical Feature of Acute Mercury Poisoning (Table 5.4)

Diagnosis of mercury poisoning is based on following criteria:
1. History of exposure to mercury
3. Lab investigation:
a. Estimation of concentration of mercury in blood: > 4 g/dl
(0.20 UM) is considered to be abnormal.
b. Estimation of total mercury in erythrocytes: It is a better
indicator of organic mercury poisoning.
Table 5.4: Clinical features of acute mercury poisoning
A. Inhalation of mercury vapor

Respiratory Cough
Dyspnea
Feeling of tightness of chest
Pneumonitis (Interstitial)
GI tract Nausea
Vomiting
Diarrhea
Abdominal pain
Misc. Weakness
Chills
Headache
B. Ingestion of mercury salts
GI tract Stomatitis
Gingivitis
Nausea
Vomiting
Gastroenteritis (bloody stool)
Abdominal pain
Renal Albuminuria
Oliguria, anuria
Uremia
Neurological Ataxia
Slurring of speech
Numbness of hands and feet
Visual and hearing impairment
Tremor
Delirium and
Paralysis
Misc. Metallic taste
Shock (Hypovolemic)
Death
c. Estimation of concentration of mercury in urine: > 25 g/L

or 0.12 M is considered to be abnormal.
Management
Treatment is aimed at reducing further absorption, protecting vital
organs and eliminating the absorbed mercury. If poisoning has occurred
through ingestion, unabsorbed poison is removed by inducing emesis
with syrup of ipecac and gastric lavage, first with milk and then
repeated with 2.5 percent sodium bicarbonate. Fluids and electrolyte
imbalance is corrected using appropriate IV fluid to prevent peripheral
vascular collapse. Hydroxyzine and chlorpromazine may be used for
restlessness. If there is tachycardia, tolazoline may be given.
For elimination of absorbed poison, drugs used are dimercaprol

(BAL) and D-penicillamine. Dimercaprol is administered IM as 10
percent solution in a dose of 5 mg/kg for the first injection followed
by 3 mg/kg every 4 hours for first two days. Thereafter 3 mg/kg is
given every 6 hours for one day and eventually every 12 hours for
seven days. Dimercaprol if given within three hours of poisoning,
protects against renal damage. Side effects include nausea, vomiting
and fever. D-penicillamine is indicated in those patients who have
adverse reactions to dimercaprol necessitating its withdrawal. D-
penicillamine is given in a dose of 100 mg/kg, orally in four divided
doses to a maximum of 1 gm in 24 hours.
Newer chelating agents like dimercaprol succimer (2-3-Dimercap-
tosuccinic acid: DMSA) and 2, 3 Dimercaptoporprane-1-sulphonate:
(DMPS) are under trial and appear promising for the treament of
mercury poisoning. Recently, a derivative of penicillamine N-acetyl-
D-penicillamine (NAP) is also emerging as more effective chelating
agent for treatment of mercury poisoning. If acute renal failure has
developed, peritoneal dialysis and hemodialysis should be carried out
in addition to chelation therapy.
Chronic mercury poisoning is rare in children. However, both
acrodynia and Minamata disease are important clinical conditions in
children in which CNS and skin are most frequently involved.
Acrodynia (Pink Disease, Dermatopolyneuritis)

Acrodynia is a Greek word, which means painful extremities. Most
of the cases of acrodynia occur due to repeated contact with ingestion
of mercury in products such as diaper rinses, teething powders,
vermifuges, wall papers and house paints. Acrodynia usually occurs
in infant and young children. The interval between mercury exposure
and onset of symptoms may vary from one week to several months.
Pathology
Pathological changes mainly occur in CNS, which include degeneration
and chromatolysis of the cerebral and cerebellar cortex.
Clinical Manifestation
The disease runs a prolonged natural course. The affected child becomes
listless, restless and irritable and loses interest in surroundings. Early
in the disease, tips of the fingers, toes and nose become pink and later
hands and feet become dusky pink with patchy areas of ischemia and
cyanotic congestion. Frequently the cheeks and the tip of nose acquire
a scarlet color.
As the disease progresses, sweat glands become enormously dilated

and enlarged and perspiration becomes profuse. Secondary infection
may lead to pyoderma. There is superficial desquamation of palms
and soles. The fingers and toes become edematous due hyperplasia
and hyperkeratosis of skin. Constant pruritus with excruciating pain
in hand and feet is present. There may be severe burning sensation.
The nails become dark and often drop off. Gangrene of the toes and
fingers may develop. Hair tends to fall out and is often pulled out by
the child. Trophic ulcers may develop. The child may have photophobia
without any evidence of local inflammation of the eyes. Ligaments are
lax resulting in hypotonia. Neurological manifestations include neuritis,
mental apathy and irritability. Tendon reflexes are either normal or
increased early in the disease but later pass into an areflexic state. There
is no motor weakness but due to soft flabby musculature the child
remains hypotonic, listless and
Key Points
hypomotile. Normal sleep gets
disturbed because of severe Diagnosis
pain. The child with acrodynia 1. H/O exposure to mercury
does not play or smile but 2. Clinical features:
appears dejected and melan- Ingestion: Stomatitis, gingivitis, eso-
cholic. phagitis, gastroenteritis, severe abdo-
minal pain and bloody diarrhea,
In extreme cases, teeth may circulatory collapse
be lost. Necrosis of the jaw Inhalation: Headache, cough, dyspnea,
bones may occur. Gums are nausea and vomiting
inflamed and swollen. Exces- Concentration of mercury in blood,
sive salivation may be present. erythrocytes and urine
Anorexia accompanies poly- Management
dipsia. There may be diarrhea
Emesis with syrup of ipecac and gastric
and prolapse of rectum. lavage preferably first with milk and sub-
Hypertension and tachycardia sequently with 2.5% sodium bicarbo-
may occur. nate
Correction of fluid and electrolyte imba-
Laboratory Investigation lance.
Hydroxyzine or chlorpromazine for
1. EyeSlit-lamp examina- restlessness.
tion shows a lenticular grey Tolazoline for tachycardia
Chelation
or red-brown reflex.
1. Dimercaprol (BAL)-5 mg/kg initially
2. Urineproteinuria. followed by 3 mg/kg IM qid
3. Features of nephrotic 2. D-penicillamine -100 mg/kg orally qid
syndrome may be present. 3. Newer agents
i. 2,3 DMSA
Treatment ii. 2,3 DMPS
iii. N-acetylderivative of peniclll-
Dimercaprol is an effective amine
antidote when given early in iv. Peritoneal/hemodialysis
the disease. The doses and side effects are same as for acute poisoning.
Currently D-penicillamine is recommended for treatment of acrodynia.
The effective dose is 30 mg/kg/day in 2-3 divided doses for 4 weeks
or until symptoms improve.
For irritability and pain, barbiturates, paraldehyde, hydroxyzine or
chlorpromazine may be used. A well balanced diet containing proteins,
minerals, vitamins should be given. If there is severe anorexia,
nasogastric feedings should be initiated, IV fluids and electrolytes
should be given to combat dehydration. If there is any evidence of
secondary infection of skin and urinary tract, coverage by appropriate
antibiotics should be resorted to.
Prevention
The withdrawal of mercury from various household products,
avoidance of mercurial drugs in pediatric practice and avoidance of
food contaminated by agricultural processes and industrial wastes are
best measures for prevention of acrodynia in infants and children.
Minamata Disease
Minamata disease is another form of chronic mercury poisoning that
occurred in children living in towns facing Minamata way, Japan from
1953 to 1966. Minamata disease was caused by methylmercury, released
as industrial waste and absorbed into the body by ingestion of
contaminated fish and shelfish. Methylmercury may cross the placental
barrier and cause congenital Minamata disease.
Pathology
There is marked degeneration and loss of granular cells in the cortex
of the cerebellum. Central convolutions become prominent. In
congenital variety, severe and widespread damage to nerve cells in
cerebral and cerebellar cortices occurs.
Clinical Manifestations
In infantile variety, the principal manifestations are disturbances in
hand coordination, gait and speed. Difficulty in mastication and
swallowing and visual blurring also occur. Numbness, pain in
extremities and involuntary movement may occur in some infants.
Tremor, clouded consciousness, convulsions and rigidity of the
extremities may occur. Some infants may have impaired hearing and
constricted visual field.
In congenital variety, the principal manifestations are physical
retardation, severe mental disturbances, abnormal movements and
delayed milestones.
Investigations
1. Hair content of mercury usuallymore than 20 PPM in Minamata
disease.
2. EEGabnormal.
3. Visual fieldsusually constricted
4. In congenital variety
Abnormal pneumoencephalogram
Cortical atrophy
Microcephalus.
Treatment
Dimercaprol is effective in removal of systemically absorbed poison.
In chronic inorganic mercury poisoning, dimercaprol is ineffective. D-
penicillamine is the drug of choice. The investigational drug N-acetyl-
D-penicillamine (NAP) is more effective than either dimercaprol or
penicillamine. The diet of the affected children should contain high
amount of proteins, vitamins and minerals. In severe cases, nasogastric
feeding should be done. Anticonvulsants are indicated if seizures
occur. Since the damage to brain is irreversible, survivors require
extensive rehabilitation, re-education and long-term care.
In case of ingestion of mercury salts, initial treatment consists of
inducing emesis or gastric lavage to remove unabsorbed poison. Later
chelating therapy using dimercaprol and penicillamine is instituted.
ARSENIC POISONING
Elemental arsenic is non-poisonous but its various inorganic and organic
compounds are toxic to human body. Due to its small fatal dose and
high toxic potential, arsenic poisoning in children is particularly
dangerous. Poisoning in children occurs usually due to accidental
ingestion of its inorganic compounds. Inorganic compounds of arsenic
such as its trioxide and pentaoxide and sodium and potassium arsenite
and arsenate are used as insecticides, rodenticides, fungicides and
herbicides, wood preservatives and also in glass manufacturing. Traces
of its trioxide are found in some soil water sources such as wells.
Epidemics of arsenite poisoning due to consumption of such
contaminated water have been reported from Eastern India especially
West Bengal. It also gets concentrated in shellfish and crustaceans after
contamination. Organic arsenicals are found in environment
particularly in industrial areas and in the past these have been used
in the treatment of syphilis, epilepsy, psoriasis and amoebiasis.
Arsenic toxicity can be acute or chronic. The former being mainly
accidental due to ingestion of its inorganic compounds but it can be
suicidal or homicidal. Chronic poisoning is due to long-term low dose

industrial exposure or consumption of contaminated food, water or
medications.
Pathophysiology
Arsenic is absorbed through the skin, lungs, and gastrointestinal tract.
Inorganic compounds are absorbed more readily than organic. Arsine,
a gaseous hydride of arsenic, is efficiently absorbed through the lungs.
It is distributed from blood to liver, lungs, and spleen within 24 hours
of ingestion and within two weeks to skin, hair and bone. Due to high
sulfhydryl content of keratin, it has a specific predilection for storage
in hair and nails.
It is also deposited in bones and teeth and remains there for long
time because of its chemical similarity to phosphorus. Inorganic
compounds are found in high levels in leukocytes. Inorganic arsenic
does not cross the blood-brain barrier but can cross the placenta. It
is mainly excreted via urine (90-95%) and a small portion (5-10%) is
also excreted in faeces. Arsenic may be detected in urine for 7-10 days
following ingestion of single dose.
Arsenic produces its toxicity by binding with tissue sulfhydryl
groups (SH) of various enzymes, particularly pyruvate dehydrogenase.
It also causes capillary injury particularly of splanchnic and renal
circulation. It causes uncoupling of mitochondrial oxidative
phosphorylation. It is toxic to liver cells causing fatty degeneration,
central necrosis and ultimately cirrhosis. Renal capillaries, tubules and
glomeruli may be damaged. The peripheral nerve and spinal cord
may also be involved. Diffuse degenerative changes of cerebral cortex
(Encephalopathy) may be seen with trivalet organic arsenicals.
Myocardial damage and stomatitis may occur. Arsenic combines with
hemoglobin in RBC to produce severe hemolysis with anemia,
hemoglobinuria and subsequent gross hematuria. Dermatological
manifestations include vasodilation, hyperkeratosis and hyperpigmen-
tation.
Clinical Features and Acute Arsenic Poisoning

Clinical manifestations following ingestion of arsenic appears within
15-30 minutes but may be delayed if taken concomitantly with food.
Gastrointestinal
Initial symptoms are nausea, faintness and burning pain in throat and
abdomen, followed by retching and vomiting which becomes severe,
continuous and persistent. Vomitus initially contains stomach contents

but later becomes blackish or greenish in color and finally consists of
mucous mixed with altered blood in varying quantity. The child usually
complains of throat constriction and difficulty in swallowing. The
major gastrointestinal manifestations are diarrhea accompanied by
tenesmus. The stools are tinged with blood, and resemble the rice
water stools of cholera. It frequently contains shreds of mucous
membrane and fragments of poison. Intense thirst is a constant feature.
The breath of the child has garlic odour. Jaundice may occur.
Cardiovascular
Cardiovascular manifestations are cyanosis, difficulty in breathing,
hypotension and cardiovascular collapse with cold clammy skin, pale
anxious face, sunken eyes, rapid feeble pulse and deep sighing
respiration.
Neurological
Delirium, coma and seizures are usually present in acute cases. A
peculiar type of peripheral neuropathy with a glove and stocking
distribution of dysesthesia may occur.
Respiratory
Inhalation of dust causes coryza, perforation of nasal septum, acute
pharyngitis and pulmonary hemorrhages.
Renal
Acute tubular necrosis with pain in loin, albuminuria, hematuria, and
eventually anuria.
Hematological
Hemolysis leading to anemia, slight to moderate leukopenia,
eosinophilia and anisocytosis may be present. Rarely, bone marrow
depression may also occur.
Ophthalmological
When it comes in contact with eyes causes severe conjunctivitis,
chemosis, keratitis and corneal ulceration.
Dermatological
When arsenic is applied to skin in concentrated form burning pain,
erythema and corrosion occur. There is a raindrop pigmentation of
skin.
Clinical Manifestation of Chronic Arsenic Poisoning

Chronic poisoning usually takes 2-8 weeks to manifest after ingestion.
Dermatological manifestations are erythroderma, uriticaria,
hyperkeratosis, hyperpigmentation, exfoliative dermatitis and Aldrich-
Mees line on the nails. Inflammation of nailbeds and deformities of
nails may be present. There may be hyperkeratosis of palm and sole.
Chronic gastroenteritis with anorexia, nausea and diarrhea may be
present. Laryngitis, tracheitis and bronchitis may occur. One to three
weeks following ingestion, polyneuritis develops and is characterized
by paresthesia, anesthesia, trophic changes and weakness of small
muscles of hand and feet. Progressive weakness, coryza, edema of
lower eyelids and face, loss of weight, anemia and general ill health
occur. The liver may be enlarged with jaundice and eventually cirrhosis
may occur. Depression of bone marrow results in disturbed
erythropoiesis and myelopoiesis resulting in anemia, leukopenia,
thrombocytopenia and basophilic stippling. Rarely megaloblastic
anemia due to folic acid deficiency may be found as arsenic inhibits
enzymatic conversion of folic acid into biologically active derivatives.
An increased incidence of basal cell carcinomas, squamous cell
carcinomas and Bowens disease as well as lung carcinomas has been
associated with chronic arsenic exposure.
Differentiating Features Between Arsenic Poisoning and Cholera
Symptoms Arsenic poisoning Cholera
1. History History of ingestion (+) nt History of epidemic (+) nt

2. Pain in throat Before vomiting After vomiting
3. Vomiting Precedes diarrhea Follows diarrhea
4. Vomitus Contains mucus, bile and Watery or like whey
streaks of blood
5. Stools Like rice-water in early Like rice-water throughout
stages and later bloody
6. Tenesmus and Marked Not so prominent
Anal irritation
7. Appearance Eyes congested No congestion of eyes
8. Voice Hoarse Not affected
9. X-ray of abdomen Barium like radio- No such appearance
paque shadow
10. Lab. tests Arsenic can be isolated Vibrio cholerae can be
from vomitus, stool and urine isolated from stools by
cultures
Investigations
1. X-ray abdomen: Barium like radiopaque shadow of arsenic
present.
2. Determination of arsenic content of urine, hair and nails. Normal

arsenic content of urine is not more than 0.04 mg/day but in arsenic
poisoning, daily urinary excretion of arsenic per day is more than
0.1 mg. The normal hair contains arsenic in the range of 0.025-0.088
mg/100 gm and even 0.1 mg/100 gm is abnormal.
3. Liver function testabnormal.
4. Hematological
Anemia
Leukopenia
Hemoglobinemia
Thrombocytopenia (rarely)
5. Urine
Proteinuria
Hematuria
Hemoglobinuria and
Key Points
Urinary casts
6. ECG Diagnosis
QT prolongation and T- 1. History
wave inversion. 2. Clinical features:
i. Continuous vomiting, tenesmus, rice
Treatment water and bloody stool
ii. Anaemia, Dyspnoea, Tachycardia,
Children with acute arsenic Shock
poisoning should be hospitali- iii. Delirium, Seizure, Coma
iv. Stocking-glove dysesthesia
zed as early as possible and
v. Rain drop skin pigmentation
kept recumbent. If patient is 3. Investigations:
alert, emesis should be induced X-ray abdomen showing radio-
with syrup of ipecac and if opaque shadow
obtunded gastric lavage is indi- ECG-QT prolongation and T-wave
cated. Freshly prepared hyd- inversion
rated ferric oxide prepared by
Management
adding one tsf of tincture of
ferric chloride to a quarter glass 1. Emesis
2. Gastric lavage
of milk of magnesia may be
3. Freshly prepared ferric oxide orally.
given orally as an antidote. The 4. Dimercaprol (BAL)2-5 mg/kg im 6
resulting precipitate should be hourly for first 24 hrs then 12-24 hourly.
removed as completely as 5. DMSArecently discovered to be a very
possible by stomach wash. effective agent
Cathartics are contraindicated. 6. D-penicillamine /Ca EDTAcan be
used.
Dehydration and electrolyte
7. Renal failurehaemodialysis
imbalance should be managed 8. Supportive measures
with appropriate IV fluids. If 9. Exchange transfusion and forced
the patient is unconscious or alkaline diuresis for arsine gas
has difficulty in swallowing, intragastric feeding should be done. The

circulatory collapse and breathing difficulty should be managed
effectively.
To hasten the removal of absorbed arsenic, Dimercaprol (BAL) or
penicillamine should be given. Dimercaprol chelates arsenic by
producing insoluble complexes that are excreted in urine. For mild
symptoms and elevated serum/urinary level dimercaprol in a dose
of 2-3 mg/kg dose is given intramuscularly every 6 hours for 24 hours
and then every 12-24 hours for 10 days. For patients with severe
symptoms and significantly elevated arsenic level in blood/urine, 3-
5 mg/kg/dose of dimercaprol is administered following a similar
regime. Dimercaprol is effective for dermatitis, encephalopathy and
hepatitis. Toxic manifestations of dimercaprol are hypertension,
tachycardia, nausea, vomiting and headache, burning sensation in
lips, irritation of mucous membrane and convulsions.
D-penicillamine is very effective in chronic arsenic poisoning. In
acute cases, it is given with dimercaprol. It is administered in dose
of 20-40 mg/kg/day orally in 4-6 divided doses to a maximum of 1
gm per day. Side effects of penicillamine include skin rashes, leukopenia,
eosinophilia, thrombocytopenia and nephrotoxicity.
Calcium EDTA (0.2-0.4% solution) in a dose of 50-75 mg/kg/day
in four divided doses IM or IV is also useful in removing absorbed
arsenic.
Recently, succimer (2,3-dimercaptosuccinic acid: DMSA), a water-
soluble analogue of dimercaprol appears to be an extremely promising
agent for treatment of arsenic poisoning.
If renal failure develops, hemodialysis is preferred. Hemodialysis
removes arsenic with a clearance of 80-90 ml/minute.
Exchange transfusions and forced alkaline diuresis are treatment
of choice for arsine gas poisoning.
PHOSPHORUS POISONING
Phosphorus exists in four allotropic forms black, white, red and yellow,
the latter two being commonly encountered in day to day practice.
Red phosphorus is innocuous to the human body. On the other hand
yellow phosphorus is highly toxic and when exposed to air it gives
dense white fumes of phosphorus pentaoxide leaving behind a waxy
luminous mass with garlic like odor. It is soluble in ether, carbon-
disulphide and oil but insoluble in water.
Phosphorus is used in the chemical industry, fire cracker works,
match works and as an insecticide and rodenticide. Phosphorus
poisoning in children is usually accidental due to ingestion of insecticide
and rodenticide preparation and firecrackers available in most

households. Suicidal as well as homicidal poisoning is rare.
Pathophysiology
Ingestion of phosphorus causes corrosion of the mucosa of upper
gastrointestinal tract. After absorption, it remains in the blood in
elemental form for few days and is then oxidized to hypophosphorus
and phosphorus acid. Both acids interfere with cellular oxidation, and
produce widespread fatty degeneration of the liver, heart, kidney,
muscle, vascular wall and nervous system. Chronic absorption of
phosphorus increase bone formation under epiphyseal cartilage and
also impairs blood circulation in bone by causing bone formation in
Haversian canals which ultimately leads to necrosis and sequestration
of bone, particularly of jaw (phossy jaw). It produces severe skin
burns, when it comes in contact. On inhalation as during wartime, it
leads to inflammation of respiratory mucosa.
Fatal dose: 5 mg/kg-body weight.
Fatal period: Death may occur from vascular collapse within 24
hours but usually the symptoms last for several days and the patient
may remain alive for 6-7 days.
Clinical Features
Clinical manifestations of acute phosphorus poisoning are divided
into three phases.
a. Primary Phase
Primary phase is due to its local irritant effect on gastrointestinal
mucosa. Clinical features include burning pain in the throat, esophagus,
and stomach, garlic taste in mouth and garlic odor of the breath.
Other symptoms may be nausea, vomiting often dark colored,
epigastric discomfort, intense thirst and diarrhea. The vomitus and
stool are often dark, luminous and offensive. Vascular collapse and
myocardial damage resulting in death may occur. This phase lasts for
2-6 hours.
b. Latent Phase
The primary phase is followed by a symptom free period (latent
phase) for 2-3 days. The children may complain of minor symptoms
such as nausea, thirst and eructations. Death may, however, occur
during this phase from vascular collapse and myocardial damage.
c. Secondary Phase
Children, who survive the primary and latent phase, land up in
secondary phase. It is characterized by reappearance of primary
symptoms. Jaundice often with pruritus, as well as other features of
hepatic failure appears. Abdomen may become distended. Vomiting
and diarrhea are much more distressing. Purpura and epistaxis may
occur due to hypoprothrombinemia. Weakness and anemia may be
present. Urine is scanty in amount, concentrated and acidic in nature,
and contains blood, albumin, bile and sometimes sugar and crystals
of tyrosine, leucine and cystine.
Neurological manifestations are frontal headache, tremor, insomnia,
tinnitus, impaired vision, formication, cramps and paralysis. Priapism
is frequent. Myocardial damage may be evident in ECG, convulsion,
delirium, and coma precede death. The cause of death is hepatic and
renal insufficiency.
Chronic poisoning in children is very rare.
Treatment
When phosphorus poisoning is suspected, gastric lavage should be
done without delay if patient is seen within 5 hours of ingestion.
Lavage is done with a weak (0.5%)
Key Points
solution of potassium permanga-
nate repeatedly till no more smell Diagnosis
of garlic remains. Potassium 1. H/O exposure to chemicals
permanganate acts as a chemical 2. Clinical features:
antidote. It oxidises phosphorus into Garlic odour and taste
harmless compounds, phosphoric Intense thirst, vomiting, epi-
gastric discomfort
acid and phosphates. A dilute
Muscular cramps
solution of copper sulfate (0.1%) Jaundice
may be used instead of potassium Vascular collapse
permanganate. The children should Formication
be kept on high carbohydrate and Priapism
low fat diet. IV crystalloid solution Phossy jaw
should be used to combat shock and
Management
vasopressor agents may be used if
required. Close monitoring of fluid Gastric lavage with 0.5 percent
potassium permanganate
intake and output should be done
Copper sulfate 0.1 percent
to detect impending acute renal solution
failure. IV glucose with supple- Supportive treatment
mentary vitamin B complex should High carbohydrate and low fat diet
be given if jaundice appears. Vitamin K parenterally if prothrom-
Vitamin K should be given paren- bin time prolonged
terlaly if prothrombin time is prolonged. Proper care of airways should

be taken during period of stay in hospital.
The treatment of phosphorus burn is difficult. The area should be
first washed with copious amount of water and kept wet. The area
is then irrigated with 2 percent solution of sodium bicarbonate to
neutralize phosphoric acid. Subsequently, the area is washed with 1
percent solution of copper sulfate. The wound, if required, should be
debridged.
Chronic Phosphorus Poisoning

It usually results from inhalation of fumes of phosphorus. Teeth of
susceptible persons should be periodically examined especially those
with caries teeth. Following preventive measures should be taken to
reduce the effects of chronic phosphorus poisoning:
1. Alkaline gargle with sodium bicarbonate is prescribed.
2. Filling of carious tooth.
3. Clean and proper working conditions.
4. Air of the working place should be saturated with turpentine
vapor.
IODINE
Iodine occurs as blackish violet crystals with a metallic lusture,
characteristic odour and acrid taste. It is commonly employed as a
disinfectant (tincture iodine, povidone iodine), antiseptic, an emetic
and for treatment of thyroid disorders. It is also used in chemical
industry, photography and dye manufacturing. Poisoning in children
is usually due to accidental ingestion of iodine solution at home.
Poisoning may be suicidal in older children. Homicidal poisoning is
very rare due to its bad taste.
Iodine is both a corrosive and irritant poison. It directly damages
the cells by precipitating proteins.
Clinical Features
As with other corrosives and irritants, clinical manifestations include
brownish discoloration of lips and oral mucosa, pain in mouth and
unpleasant taste, intense thirst and abdominal pain with vomiting and
diarrhea. Vomitus and stool may be dark colored with peculiar odour
of iodine. Micturition is painful and there may be oliguria or anuria.
Marked depression, feeble pulse, delirium and collapse may occur.
Injection of iodine compound may cause sudden fatal collapse due
to hypersensitivity reaction. Inhalation of iodine vapors causes
edema of glottis and death from asphyxia. The classical features of

idiosyncratic reactions are headache, acute coryza, bronchial catarrh,
conjunctivitis and edema of face and eyelids, which clear up when
drug is withheld.
Skin contact causes erythema, desquamation and sometimes
vesication.
Key Points
Treatment
Diagnosis
Gastric lavage should be done
1. History
immediately when iodine poi- 2. Clinical features: Pain in mouth, abdo-
soning is suspected with 1 men with brownish discolouration of
percent starch solution or 5 oral mucosa, sudden collapse, dysuria.
percent solution of sodium Management
thiosulphate. At the end of the
1. Gastric lavage with 1 percent starch
lavage demulscents like starchy or 5 percent sodium thiosulphate
foods, eggs, milk, oils, etc. solution.
should be left in the stomach. IV 2. Starchy food left in stomach.
hydrocortisone and anti-hista- 3. IV hydrocortisone and antihistaminics
minics should be given till symp- along with other symptomatic treat-
ments.
toms abate. IV hydrocorti-
sone reduces edema of glottis. If respiratory distress occurs, tracheo-
stomy may be done. The rest of the treatment should be done along
the general lines.
ALUMINIUM TOXICITY
Aluminium is a trivalent metal found in its ionic form in most animals
and plant tissues and in natural waters everywhere. It is the third most
prevalent element and the most abundant metal in the earths crust.
Dietary aluminium is ubiquitous but present in such small quantities
that it is not a significant source of concern in persons with normal
elimination capacity. Urban water supplies may contain a greater
concentration because water is treated with the element before
becoming part of the supply. Subsequent purification processes that
remove organic compounds take away many of those same compounds
that bind element in its free state, further increasing the aluminium
concentration.
The actual incidence of toxicity is unknown. The greatest incidence
is seen in patients with any degree of renal insufficiency. A higher
incidence is observed in populations who have aluminium-
contaminated dialysate or who are taking daily oral phosphate binding
agents. Patients who require long-term parenteral nutrition (TPN) are
at increased risk as well. Recently, there have been case reports
implicating the use of oral aluminum-containing antacids during

pregnancy as a possible cause for abnormal fetal neurologic
development. There is no evidence of a preponderance of aluminium
toxicity in any one geographic region or country.
Pathophysiology
Approximately 95 percent of absorbed aluminium becomes bound to
transferrin and albumin intravascularly and kidneys then eliminate it.
It is absorbed from the GI tract in the form of phosphate and parenterally
via dialysate or TPN contamination. It is also absorbed during peritoneal
dialysis. Lactate, citrate, and ascorbate facilitate GI absorption. If there
is a significant load that exceeds the bodys excretory capacity, the
excess aluminium is deposited in various tissues, including bone,
brain, liver, heart, spleen, and muscle. It is this accumulation that
causes morbidity and mortality through different mechanisms.
The toxic effects are dependent upon the amount of metal ingested,
rate of entry, tissue distribution, concentration achieved, and excretion
rate. Mechanisms of toxicity include inhibition of enzyme activity and
protein synthesis, alterations in nucleic acid function, and changes in
cell membrane permeability. There is no known physiologic need for
aluminium; however, due to its atomic size and electric charge, it is
sometimes a competitive inhibitor of several essential elements such
as magnesium, calcium, and iron.
Aluminium toxicity usually occurs in patients with impaired renal
function. Acute intoxication is extremely rare; however, in persons in
whom aluminium clearance is impaired, it can be a significant source
of pathology. Aluminium causes an oxidative stress within brain tissue,
leading to the formation of Alzheimer-like neurofibrillary tangles.
Aluminium also has a direct effect on hematopoiesis. Excess aluminium
has been shown to induce anemia. Daily injections of aluminium into
rabbits produced severe anemia within 2-3 weeks. The findings were
very similar to those found in patients suffering from lead poisoning.
Aluminium may cause anemia through decreased heme synthesis,
decreased globulin synthesis, and increased hemolysis. Aluminium
may also have a direct effect on iron metabolism. Patients with anemia
from aluminium toxicity often have increased reticulocyte counts.
The typical presentations include anemia, proximal muscle weakness,
bone pain, multiple nonhealing fractures particularly of the ribs and
pelvis, acute or subacute alteration in mental status, mutism, seizures,
dementia and premature osteoporosis. In aluminium-related disease,
the predominant features are defective mineralization and osteomalacia

that result from excessive deposits at the site of osteoid mineralization.
In children bony deformity is due more commonly to the increased
rate of growth and remodeling. Children also may express varying
degrees of growth retardation. The areas of deformity in children
usually involve the epiphyseal plates (i.e. femur, wrist). These patients
almost always have some degree of renal disease. Most patients are
on hemodialysis or peritoneal dialysis. Some studies have shown a
direct correlation between aluminium levels and intensity of uremic
pruritus. In children, special awareness must be made in those who
require parenteral nutrition so as not to give excessive amounts of
aluminium in the TPN.
Investigations
1. Serum aluminium level: Unreliable, as most of the bodys stores are
bound in tissue and are not reflected in the serum value.
2. Deferoxamine infusion test: It liberates aluminium from tissues by
chelating it and will lead to an increased serum level compared to
one taken prior to infusion. The combination of a baseline
immunoreactive parathyroid hormone level less than 200 mEq/ml
and a change in serum aluminium of 200 ng/ml after deferoxamine
is 90 percent specific and has a positive predictive value of 85
percent for aluminium toxicity.
3. Peripheral smear: Microcytic anemia (hypochromic, normochromic),
anisocytosis, poikilocytosis, chromophilic cells, and basophilic
stippling. Aluminium also can be found in bone marrow
macrophages.
4. Radiographs: Looser zones, lines of radiolucency parallel to the
plane of growth in long bones, may be seen in severe cases.
Pathological fractures may also be observed. Bone scintigraphy
shows a characteristic pattern in aluminium toxicity.
5. Bone biopsy from iliac crest: Histological findings in aluminium related
osteomalacia reflect the decrease in mineralization of newly formed
bone matrix. There is an increase in the surface covered by osteoid
and an increase in the osteoid seams. There is also an increase in
osteoid volume and thickness. In histologic sections stained with
eosin, the areas of greater mineralization tend to appear violet or
blue, whereas the osteoid seams appear pink.
Treatment
Treatment of aluminium toxicity includes elimination of aluminium
from diet, TPN, dialysate, medications, and an attempt at the
elimination and chelation of the element from the bodys stores.

Avoidance of aluminium is achieved easily once the need to do so is
recognized. Elimination is accomplished through the administration
of deferoxamine through any of several routes.
Deferoxamine, an iron chelating agent isolated from the bacterium
streptomyces pilosus, is used for acute and chronic iron toxicity and
aluminium toxicity. It has a high affinity for ferric iron and does not
affect iron in hemoglobin or cytochromes. Metals are excreted in the
urine and bile. A hematologist and a neurologist may be able to assist
with the patients care. Since dietary aluminium is ubiquitous, there
are no specific dietary guidelines for its avoidance. Special diets should
be maintained for specific associated disease entities (e.g. diabetes,
renal failure).
Activity modification may not be necessary unless the patient is
at risk for frequent falls, in which case a home attendant or family
member should assist activities of daily living. The goal of
pharmacotherapy is to reduce morbidity and prevent complications.
Avoid all aluminium containing antacids, dialysate, and TPN
solutions.
Prognosis
Depending upon the degree of dementia, majority of patients improve
with deferoxamine therapy. However, few succumb to their underlying
disease processes prior to any noticeable improvement in mental status
or anemia. It is unknown whether aluminium toxicity itself is fatal.
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6
Animal Poisoning
SCORPION STING
Scorpion sting is very common in tropical countries particularly in
rural and coastal areas such as Maharashtra, Tamil Nadu, Bihar, etc.
They inhabitat commonly in the crevices of dwellings, underground
burrows, under logs or debris, paddy husk, sugarcane fields, coconut
and banana plantations. Scorpions retreat in the crevices of dwellings
during the day to emerge at night; thus most stings are reported at
night. India harbours 99 species of scorpion but only two, mesobuthus
tamulus (the common red scorpion) and palamnieus swammerdami
are piosonous. Scorpions have crab-like appearance with long, fleshy,
five segmented, tail-like post-abdomens, ending in a broad sac and
a prominent hollow sting. The venom containing glands are present
in teleson, the last tail segment and the venom passes by a duct
attached to these glands. Envenomation is usually harmless in adults
but causes toxicity in children. Maximum incidence of scorpion bite
occurs in summer and rainy season (breeding season).
Scorpion stings are primarily due to accidental contact. It does not
always inject venom when it stings, since it can control its ejaculation.
Thus stings can be total, partial or non-existance. Numerous
envenomations are unreported; hence true incidence is not known.
Case fatality rates of 3 to 22 percent were reported among children
hospitalized for scorpio stings in India, Saudi Arabia and South Africa.
Venom
The venom of scorpion is acidic, species specific and contains complex
mixtures of short neurotoxic proteins. It contains numerous free amino
acids, appreciable quantities of serotonin, hyaluronidase, various
enzymes such as proteinases, phospholipases (both hematotoxic and
myotoxic) and various polypeptides, i.e toxalbumin (neurotoxic),
cardiotoxins and charybdotoxin which is a specific inhibitor of high
conductance calcium activated potassium channel. Alpha and beta
Animal Poisoning 83
toxins act on sodium channels. Scyllatoxin, charybdotoxin and tityus

toxin act primarily by inhibiting calcium dependent potassium channels
and also causes opening of sodium channels at presynaptic nerve
terminals;thus initiating autonomic storm. Alpha-receptor stimulation
by toxins plays keys role in pathogenesis of scorpion stings.
Pathophysiology (Flow Chart 6.1)

Scorpion venom, in addition to local irritant effect by serotonin, acts
as a powerful stimulus for:
1. Massive release of catecholamines.
2. Suppression of insulin secretion.
3. Elevation of plasma angiotensin II level.
The pathologcal changes metabolic disturbances and cardiovascular
manifestations produced by scorpion venom toxicity can be explained
with these above events. The unopposed action of alpha-receptors
stimulation lead to suppression of insulin secretion, hyperglycemia,
hyperkalemia, increased free fatty acids and free radical accumulation,
which are injurious to myocardium. Excess of catecholamines results
in increased myocardial oxygen consumption due to its positive
inotropic and chronotropic effect, coronary and peripheral vasocons-
triction and increased after-load.
Reduction of insulin secretion leads to hyperglycemia, lipolysis
and increased FFAs concentration, altered RBC ATPase activitiy and
osmotic fragility, DIC, depletion of glycogen store of atria, ventricle,
skeletal muscle and liver.
Elevation of plasma angiotensin II level is responsible for reduced
arterial partial pressure of oxygen and HCO3, changes in pH due to
increased lactic and keto acids. It also causes coronary and peripheral
vasoconstriction and also potentiates the effect of catecholamines.
Increased FFA concentration is an important factor for arrhythmias
and heart failure in scorpion sting victims. Utilization of excess FFAs
results in increased oxygen consumption, which could aggravate the
ischemic injury to myocardium. It increases the susceptibility of the
ventricles to the disorganized electrical behavior and ectopic beats. It
also produces inhibition of sodium and potassium stimulated ATPase
activity and sarcolemmal defects. Free fatty acids alter the function
of platelets leading to an increased tendency for intravascular
thrombosis and DIC.
Cardiac sarcolemmal defects, depletion of glycogen content of heart,
liver, skeletal muscles were observed in experimental animals with
acute myocarditis produced by Indian red scorpion. Acute pancreatitis
through the intrapancreatic conversio of trypsinogen to trypsin has
been reported from of Tityus trinitatis in Trinidad.
Flow chart 6.1: Pathophysiology of scorpion sting
The clinical severity of scorpion stings is directly correlated with level

of cytokines. Increased levels of IL-I alpha, IL-6 and IFN-alpha were
observed in all patients with scorpion stings from Egypt.Increased
levels of inducible NO(iNO) in response toproinflammatory cytokines
may result in direct tissue injury but further studies are needed.
The clinical manifestations are either local or systemic. Species
differences, venom dose/weight determines the toxicity and clinical
picture. Cardiac manifestations are more common in Indian red
scorpions, whereas severe hemolysis, tissue necrosis, pancreatitis and
neurological manifestations are common with other species.
The local manifestations are intense local pain with screaming,
swelling, ecchymosis, and rarely tissue or bone necrosis. Children
appear irritable and excitable. The site of bite may be confirmed by
tap test, i.e.tapping of the sting site causes severe shock like pain.
Serotonin found in scorpion venom is thought to contribute pain.
Animal Poisoning 85
Neurological
Autonomic Nervous System

These are the earliest and most prominent manifestations, also known
as the autonomic storm. The features of cholinergic stimulation
merge imperceptibly into those of adrenergic stimulation and include
the followings:
Profuse perspiration
Tachypnea
Excessive salivation
Vomiting
Lacrimation
Mydriasis
Frequent passage of stool and urine
Priapism and ejaculation.
Positive correlation between occurrence of priapism in male patients
and later development of cardiac manifestations after scorpion sting
has been observed. Salivation and vomiting can worsen respiratory
compromise.
CNS
CNS manifestations are infrequently encountered but invariably fatal
and includes.
Encephalopathy
Convulsions (focal or generalized)
Hemiplegia and other focal neurological deficits
Transient blindness (amaurosis fugax).
Cardiovascular
Tachycardia in scorpion sting is usually seen within 4 hours and
persists for 24-72 hours. This is an earliest sign of myocardial injury.
Hypertension usally lasts 4-8 hours and is due to outporing of
catecholamines. It is prolonged in some children due to direct
stimulation of sympathetic centers in medulla. Hypertensive stress on
myocardium, direct myocyte injury and increased catecholamine
contribute to rhythm disturbances and left ventricular failure in
significant proportion of children. Hypotension and bradycardia may
be encountered within 1-2 hours of sting because of cholinergic
stimulation but in later stage (4-8 hours) hypotension and tachycardia
is due to left ventricular dysfunction. Fluid loss due to vomiting,
salivation and perspiration further aggravate hypotension. Scorpion
envenomation is a risk factor for development of dilated cardio-

myopathy in later life.
Hypertension/Hypotension
Arrhythmia
Gallop rhythm
Varying degrees of conduction-block
Apical systolic murmur
Focal myocardial infarction
Myocarditis
Congestive heart failure
Shock
LDH
ECG Changes
Inchildren with myocarditis, serial ECG is helpful. Changes may be
asfollows:
ST segment - normal or depressed
T wave - flat or inverted or peaked in precordial leads
Deep Q-wave in lead I and aVL
Various degrees of heart block
Arrhythmia (Atrial or ventricular)
Low voltage complexes throughout the record and left anterior
hemiblock indicate poor prognosis.
Echocardiography: Myocardial dysfunction either focal or generalized
and ventricular dilatation with regional wall motion abnormalities.
Respiratory
Pulmonary edema may develop within 30 minutes to 3 hours after
sting and is mainly due to myocardial dysfunction. This is life-
threatening condition characterized by orthopnea, cyanosis, cough
with blood stained expectorations and moist rales in the chest.
Radiological changes suggestive of pulmonary edema are usually
seen within 3 hours of sting. Noncardiogenic pulmonary edema due
ARDS has been reported from Brazil in scorpion sting. Death within
30 minutes in some children may occur due to ventricular arrythmias.
Dyspnea
Cyanosis
Hemoptysis
Pulmonary edema
Gastrointestinal
Abdominal pain
Animal Poisoning 87
Hematemesis
Malena
Pancreatitis
Pseudopancreatic cyst
Raised serum amylase
Metabolic
Metabolic acidosis
Hyperglycemia, hyperkalemia
Free fatty acids
Cholesterol and triglycerides
PaO2
PaO2
pH
HCO3
Serum lactate
Renal
Hematuria
Oliguria
Acute renal failure
Hematological
Increased erythrocyte fragility
Disseminated intravascular coagulation
Hepatobiliary
The dilatation of branches of hepatic artery and vein, focal hydropic
degeneration and focal necrosis of liver had been observerved in some
patient with scorpion envenomation.
Raised transaminases ( AST, ALT)
Raised bilirubin
Dilatation of branches of hepatic artery and vein
Intravascular thrombosis
Subcapsular hemorrhage
Focal hydropic degeneration and
Focal necrosis
Miscellaneous
Muscle fasciculation
Tetany like contractures
Diagnosis
Scorpion envenomation is diagnosed on the basis of:
1. History of scorpion sting and positive tap test
3. Lab. investigations
Urine analysis
Blood glucose
Estimation of serum amylase, lactic acid, AST, ALT and LDH
Blood gas analysis Key Points
ECG
Diagnosis
Management of Scorpion 1. History of bite
Sting 2. Clinical features:
Intense pain at the site
Management of scorpion sting Profuse perspiration
has been divided into two Restlessness
groups, i.e. local management Myocarditis
and systemic management. Arrhythmias
Shock
Priapism and ejaculation (rarely)
Local Management
Management
A ligature should be applied
immediately proximal to the 1. Local treatment:
Wash with plain water, ammonia or
site of sting to delay absorp-
borax
tion of toxins. The ligature Application of ice packs
should be released at frequent Infiltration of 2 percent xylocaine
intervals in order to allow relieves pain
small amounts of toxin to 2. Systemic treatment:
reach the circulation, which Prazosin (Alpha-blocker) - 0.4 mg/
kg/day bid orally
can be eliminated by the Digoxin orally or parentally 0.04 mg/
detoxifying mechanism of the kg if sinus tachycardia/ pulmonary
body. The wound should be edema
washed with plain water, IV frusemide if pulmonary edema
ammonia, borax or potassium 1-2 mg/kg
Corticosteroid contraindicated
permanganate followed by
Lytic cocktail consisting 50 mg
cooling of the affected part chlorpromazine, 50 mg prometha-
with ice. Immobilization of zine and 100 mg pethidinenow
affected part should be done. disputed
The affected area should be Recently insulin - 0.1 to 0.2 IU/kg
infilterated with a local anes- SC thrice daily
Supportive treatment
thetic agent preferably 3. Specific treatment:
2 percent xylocaine hydrochlo- Antivenom of scorpion-not freely
ride to alleviate pain. If the available
Animal Poisoning 89
child has been previously immunized against tetanus one dose of

tetanus toxoid should be administered.
Systemic Management
The management of scorpion sting envenomation is chiefly directed
at neutralizing the toxin by anti-serum and supportive therapy for
complications. Many workers have differently advocated anti-venom
therapy. Though majority of investigators consider anti-venom, the
only specific treatment, there are a few who deny its efficacy in the
prevention and abolition of cardiovascular manifestations. Adminis-
tration of anti-venom effectively neutralizes, prevents and reverses the
cardiovascular, hemodynamic, metabolic and electrocardiographic
changes induced by scorpion venom. It should given wthin 30 minutes
to be maximally effective. As the venom rapidly accumulates in cardiac
tissues and act indirectly through the release of autopharmacological
substances, treatment with sympatholytic agents ( or -blockers)
may be more effective and rapid.
In the past the most widely used lytic cockail consisted of
chlorpromazine (50 mg), promethazine (50 mg) and pethidine (100
mg) in 50 ml of 5 percent dextrose in a dose of 0.3 ml/kg/hour IV.
It was once considered to be the mainstay of therapy because it induces
a state of suspended animation, thereby reducing the cerebral
metabolism and further ensuring complications.
Since cardiovascular and pulmonary complications following
scorpion bite are due to excessive release of catecholamines, the alpha
and beta-blockers can prevent myocardial damage. Although beta-
blocker (propranolol) protects against sinus tachycardia, it does not
prevent either A-V block or pulmonary edema.
Alpha-blocker (prazosin) antagonises the effects of catecholamines
and thus prevents further damage of myocardium but it cant reverse
the damage. Prazosin reduces preload, after load and blood pressure
without rise in heart rate and rennin secretion. Since it is also a potent
inhibitor of phosphodiaesterase, it causes accumulation of cGMP a
second messenger of nitric oxide in vascular endothelium and
myocardium and inhibits the formation of inositol triphosphate. Thus
it results in blunting of catecholamine action on myocardium. Prazosin
also activates venom inhibited calcium dependent potassium channels
and increases insulin secretion resulting in correction of hyperglycemia,
hyperkalemia and help to salvage anoxic myocardium. Prazosin
stimulates gastric acid secretion, hence aggravating the existing
subclinical or clinical acute pancreatitis. Thus prazosin is a cellular
and pharmacologic antidote to the actions of scorpion venom. The
dose is 30 microgram/kg/dose and should be given as immediate

measure in all children irrespective of blood pressure but evidence of
autonomic storm. It should not be given as prophylaxis in children
when pain is the only symptom. After administration children should
not be allow to move and stand to prevent the effects of First dose
phenomenon of prazosin. The dosages should be repeated at end of
3 hours and later every 6 hours till extremities are warm, dry and
peripheral veins are easily visible. Most of children do not require
more than 4 doses. Blood pressure, pulse rate and respiratory rate
must be monitored every 30 mts for 3 hours, 60 mts for next 6 hours
and every 4 hours till improvement. Prazosin is used alone or along
with sodium bicarbonate and/or insulin.
Recently insulin has been recommended for the treatment of
scorpion sting, and is being widely used. The dose of insulin is 0.1
to 0.2 IU/kg/day intravenously or sub-cutaneously in three divided
doses with frequent monitoring of blood sugar to prevent hypoglycemic
attacks. Administration of insulin antagonizes the metabolic changes
produced by excessive catecholamines and it increases the glycogen
content of heart thereby protecting the heart from the effects of hypoxia.
It helps to restore the myocardial contractility after ischemic insult and
increases the cardiac output. Insulin also stimulates sarcolemmal Na+-
K+- ATPase activity, inhibits Ca+-K+- ATPase activity and stabilizes
lysosomal membrane. Since insufficient surfactant is one of the possible
causes of pulmonary edema and ARDS, insulin, by increasing the
surfactant synthesis in alveoli, can counter the development of these
complications. Thus the use of insulin is justified in the effective
management of scorpion sting.
Nifedipine, slow calcium channel blockers causes selective
vasodilation of resistance vessels and enhances coronary blood flow.
It causes reflex sympathetic stimulation with tachycardia and negative
ionotropic effects. Thus irrespective of control of blood pressure, the
patient developed myocardial failure and acute pulmonary edema.
Hence for this reason it is recommended in scorpion bite.
Cardiac glycosides are not effective in pulmonary edema in the
presence of sinus tachycardia and normal cardiac size since both
cardiac glycosides and venom inhibit Na+-K+- ATPase activity in
myocardium.
Diuretics should not be used in scorpion bite even in the presence
of pulmonary edema because of their dehydrating effect, alteration in
blood viscosity and stimulation of rennin-angiotensin system.
Atropine should not be given routinely for profuse perspiration,
vomiting and increased salivation because it may aggravate the
tachycardia and other sympathetic effects of venom. It also aggravates
Animal Poisoning 91
hypertension and the severity of pulmonary edema. The only real

indication of atropine is the presence of severe bradycardia with or
without hypertension.
Glucocorticoids are contraindicated in the treatment scorpion
evenomation because of their catabolic and anti-insulin action, which
only aggravates the complications. It also stimulates rennin-angiotensin
system; hence glucocorticoids are contraindicated in non-cardiogenic
pulmonary edema.
Hypertension should be controlled with calcium channel blockers,
vasodilators and ACE inhibitors. ACE inhibitors are particularly
effective because of elevated angiotensin-II lavel in patients with
scorpion sting. Peripheral circulatory failure should be effectively
managed with low dose dopamine (5-20 g/kg/mt) along with
supportive therapy. If the patient has developed pulmonary edema,
it should be managed with 100 percent oxygen, dobutamine
(5-15 microgram/kg/mt) with vasolidator; sodium nitropruside
(0.3-5 microgram/kg/mt) or nitroglycerine (5 mg/mt) infusion, insulin
and ventilatory support. Inpatient with pulmonary edema, fluid
resuscitation under CVP monitoring is essential. Intravenous calcium
gluconate is indicated, if fasciculations and tetany like muscular
contractions develop.
Convulsions are managed as per convention. Children who have
developed defibrination syndrome, acro-osteolysis or encephalopathy
should be managed conservatively. Fluid loss due to excessive sweating
and vomiting is often overlooked,so whenever possible should be
corrected with oral or IV fluid.
Prevention
In scorpion endemic area protective items like boots, socks and trousers
may prevent scorpion sting. Spraying with 10 percent DDT kills the
scorpion. Other measures include clearance of debris and trash from
areas of habitat and inspection of boots, clothing and bedding prior
to use. Children should be advised not to explore into places one can
not see.
SNAKE BITE
There are more than 3500 known species of snakes but only 300 are
poisonous. All poisonous snakes belong to five families, i.e. Colubridae,
Actractaspididae, Elapidae, Viperidae and Hydrophiidae. Snake bite
is an important problem all over the world particularly rural tropics,
India, Pakistan, Nepal, Sri Lanka, Bangladesh, South Africa. The exact
incidence is not known but approximately 20 percent of these result
in no evenomation and 10 percent result in death. Most of deaths are
due to cobra bites particularly in South-East Asia.
Most snake bites are accidental and inflicted on lower limbs of high
risks population such as children working in field, plantation, herdsman
and hunters in rural tropics. Snakes do not bite without provocation
but this may be inadvertent tread or touch. Some species such as Asian
Kraits and African spitling cobras may enter dwelling at night and
bite people who are asleep. Seasonal peaks in incidence are associated
with onset of rainy season, flooding and rice harvesting season and
occasionally during construction of new buildings and irrigation and
hydroelectric schemes in forest areas. Snake bite or injection of venom
procoagulant have been used therapeutically for severe bleeding.
Classification
All medically important species are classified into following groups:
1. Colubridae, e.g. Boomslang, Bird snakes
2. Atractaspididae, e.g. Address, Natal black snakes
3. Elapidae, e.g. Cobras, Mambas, Krait, Coral snakes and Garter
snakes
4. Viperidae, e.g. Pit vipers, Russels viper, Rattle snakes
5. Hydrophiidae, e.g. Sea snakes
Morphology of Some Important Snakes
Color Length Characteristics
Cobras Brown 2 meters 1. Hood with a mark like

spectacle
2. A white band at the
junction of body and hood
3. Undersurface of hood bears
2 dark round spots and 3
dark band
King Cobras Yellow, green, 3-4 meters 1. Hood but no mark on it
brown or black 2. Yellowish white cross bands
on the body
Common Krait Black-brown 1.5-2 meters 1. Alternating black and
yellow band on the back
2. Black mark on neck
3. Tail ends bluntly and is
swellen at its tip
Russels Viper Light brown 1.5 meters 1. Vshaped mark on its
head
2. Belly is white
3. Three rows of black spots
along its back
Saw-scaled Viper Brown Less than 1. Wavy white line on each
1 meter flank of the back
2. Diamond shaped areas
between these two lines
Animal Poisoning 93
Poison Gland
There is one pair of poison gland, a modified salivary gland situated
behind the eyes on either side surrounded by compressor muscles.
Fangs
All poisonous snakes have two fangs. There are cannulated curved
teeth situated on the maxillary bones and are connected with the sac
of the gland. After bite, poison is poured into the wound. The average
quantity of venom injected at a strike is approximately 60 mg in N
naja, 13 mg in E carinatus, 63 mg in D russeli and 32 mg in V palaestinae.
Wallace jF (1991) observed that interfang distance may help in
assessment of size of snake (< 8 mm - small, 8-12 mm - intermediate
and >12 mm - large size).
Venom
Snake venom may contain 20 or more components. More than 90
percent of dry weight is protein, in form of enzymes, non-enzymatic
polypeptide toxins and non-toxic proteins. Non-protein ingradients of
venom include carbohydrate and metals, often in form of glycoprotein
metalloprotein enzymes, lipids, free amino acids, nucleotides and amino
acids. The role of enzymes in envenoming is most clearly seen in case
of venom procoagulants, e.g. Russels Viper, RVV-x, a glycoprotein
activates factor X by calcium dependent reaction and also acts on
factor IX and protein-C. RVV-V, an arginine ester hydrolase activates
factor V, Eccarin activates prothrombin. Serine protease cleaves
fibrinopeptide-A from fibrinogen molecules.
Phospholipase -A2 is the most widespread venom enzymes. In
experimental states, it damages mitochondria, red blood cells
leukocytes, platelets, skeletal muscles, vascular endothelium and other
membranes by producing lysolecithin, pre-synoptic neurotoxicity,
opiate like sedative effects and auto pharmacological release of
histamine this contribute to myotoxicity, neurotoxicity, cardiotoxicity,
hemolysis and increased vascular permeasibility. Hyaluronidase
promotes the spread of venom through tissues. Hydrolases may be
responsible for local changes in vascular permeability leading to edema,
blistering and bruising and to necrosis. L-amino oxidase of some
Vipers may have digestive functions.
Polypeptide toxins are low mol weight non-enzymatic protein found
exclusively in Elapid and Hydrophiid venoms. Postsynaptic ()
neurotoxins, i.e. -bungarotoxin and cobrotoxin bind to acetylcholine
receptors at the motor and plate. Presynaptic () neurotoxins, i.e.
-bungarotoxin, crotoxin and tiapoxin and phospholipase-A2 sub-unit

block the release of acetylcholine at neuromuscular junctions. Biogenic
amines such as histamine, 5-hydroxytryptamine and kinins found
particularly in Viper venoms may contribute to local pain and
permeability changes at sites of a snake bite.
Absorption of Venom
The neurotoxins of Elapidae and Hydrophiidae are rapidly absorbed
into bloodstream where as larger molecules of Viperidae are taken up
slowly through lymphatics. Venoms can be absorbed through mucous
membranes and intact cornea. After systemic absorption venoms get
concentrated and bound in kidneys and hence eliminated in urine.
Crotaline venoms are selectively bound in lungs, concentrated in liver
and excreted in bile whereas neurotoxins, i.e. -bungarotoxin are
fightly bound at neuromuscular junctions. The most venom components
do not cross blood-brain barrier.

The swelling and bruising in bitten limb result from increased vascular
permeability induced by proteases, phospholipases, membrane
damaging polypeptide toxins and endogenous autacoids released by
venoms such as histamine, 5-hydroxytryptamine and kinins. Venoms
of some species of Viperidae cause generalized increase in vascular
permeability resulting in pulmonary edema, serous effusions,
hypovalemia, hemoconcentration conjunctival and facial edema. Tissue
necrosis near the site of bite is caused by myotoxic and cytolytic
factors, ischemia resulting from thrombosis, intra compartmental
syndromes and tight torniquet. Profound hypotension by release of
vasodilating autacoids, inhibition of bradykinin-deactivating enzymes
and angiotensin converting enzymes, hypovolemia and myocardial
dysfunction.
Snake venoms may cause hemostatic defect by activating clotting
cascades by procoagulant and endogenous plasminogen system at
various sites, direct degradation of fibrinogen by fibrinogenases and
damage of vascular endothelium by hemorrhagics. It also causes
inhibition of platelet aggragation in vitro and thrombocytopenia. The
combination of defibrination, thrombocytopenia and vessel wall
damage can result in massive bleeding a common cause of death from
viper bites. Although most snake venoms are hemolytic in vitro,
clinically significant intravascular hemolysis, apart from mild micro-
angiopathic hemolysis associated with disseminated intravascular
coagulation is seen only by Russel Viper, Australian Elapid and colubrid
Animal Poisoning 95
species. Elapid and Viperid venoms activates complement via alternate

and classical pathways respectively.
Renal failure is a rare complication of severe envenoming and is
major cause of death following bites by Russel Viper and Sea Snakes.
Acute tubular necrosis may be caused by prolonged hypotension,
disseminated intravascular coagulation, direct effect of venom on the
renal tubule, hemoglobinuria, myoglobulinuria secondary to
generalized rhabdomyolysis and hyperkalemia.
The neurotoxic polypeptides and phospholipases of snake venoms
block transmission at neuromuscular junction causing bulbar or
respiratory paralysis. In such patients anti-cholinesterases may lead
to dramatic improvement in paralytic symptoms. Paralytic symptoms
are characteristic of most Elapids. Excessive drowsiness in absence of
respiratory or circulatory failure may be due to release of endogenous
opiates by a venom component or binding to an opiate receptor.
Generalized rhabdomyolysis with release of myoglobin, muscle
enzymes and potassium is an effect in man of pre-synaptic neurotoxins.
tubule
l
and
a
Hemolysis
Flow chart 6.2: Pathophysiology of snake bite

Factors Affecting Severity of Snake Bite

1. Age: Younger the age, more serious will be outcome.
2. Location of bite: Bite on face, neck, trunk and over superficial vessels
of extremities is more dangerous than those on extremities.
3. Size of snake: Large the snake, severe the convenomation.
4. Secondary injection: Presence or absence of clostridia and/or
anaerobic organisms in the wound or skin of the victim, increase
the morbidity and mortality.
5. Post snake bite activity: Exercise or running after the bite increases
the rate of absorption of venom and hence severity of envenomation.
Colubridae (Boomslang, Bird Snakes)

Children with severe envenoming develop nausea with repeated
vomiting, colicky abdominal pain and headache hours after bite. There
is bleeding from old and recent wounds such as venepuncture sites
and spontaneous gingival bleeding, epistaxis, hematemesis, melena,
sub-arachnoid hemorrhage, hematuria and extensive ecchymosis.
Intravascular hemolysis and micro-angiopathic hemolysis have also
been described. Majority of cases had died of renal failure many days
after bite local effects of venom are usually trivial but some have
showed some local swelling with blood filled bullae. Investigations
revealed incoagulable blood, defribination, increased fibrin degradation
products, severe thrombocytopenia and anemia.
Atractaspididae (Natal Black Snakes, Address)

The local effects of envenoming are pain, swelling blistering, necrosis,
tender enlargement of local lymph nodes and in some cases local
numbness or paresthesine in areas conforming to distribution of
cutaneous nerve. The common systemic manifestations are fever,
repeated attack of vomiting, profuse salivation and finally lapsing into
coma. Violent gastrointestinal symptoms (nausea, vomiting and
diarrhea), anophylaxis (dyspnea, respiratory failure) and electro-
cardiographic changes (A-V block, ST, T-wave changes) have been
described in patients bitten by A. engaddensis.
Elapidae (Cobras, Krait, Mambas, Coral Snakes)

The envenoming by elapids cause tender local swelling with regional
lymphadenopathy, blistering within 24 hours of tenat the edge of a
demarcated pale or blackened anesthetic area of skin and superficial
Animal Poisoning 97
necrosis which may be extensive. The lesion smells putrid and

eventually breaks down with loss of skin and sub-cutaneous tissue.
Prolonged morbidity may occur and some patients may lose a digit
or affected limb if there is secondary infection. However, venoms of
elapids are best known for their neurotoxic effect. The earliest symptom
of systemic envenoming is repeated vomiting. Early preparalytic
symptoms include contraction of pontalis muscle, blurred vision,
paresthesiae especially around mouth, hyperacusis, headache,
dizziness, vertigo and signs of autonomic nervous system stimulation
such as hypersalivation, congested conjunctivae and goose-flesh.
Paralysis is first detectable as ptosis and external ophthalmoplegia
as early as 15 minutes after bite but sometimes delayed for 10 hours
or more. Later, facial muscles, palate, jaws, tongue, vocal cords, neck
muscles and muscles of deglutition may become paralyzed. Repiratory
failure may be precipitated by airway obstruction by paralyzed tongue
or vomitus at this stage or later after paralysis of intercostal muscles
and diaphragm. Intercostal muscles are affected before the limbs,
diaphragm and superficial muscles. In patients with generalized flaccid
paralysis, slight movements of digits may be possible. The loss of
consciousness and convulsions are usually explained by hypoxemia
consequent to respiratory paralysis. Neurotoxic effects are completely
reversible either acutely in response to anti-venom or anti-cholinesterase
or may bear off spontaneously in 1 to 7 days.
In absence of anti-venom, patients supported by mechanical
ventilation recover sufficient diaphragmatic movement to breath
adequately in 1 to 4 day. Occular muscles recover in 2-4 days and
usually full recovery of motor function in 3-7 days. Intractable
hypotension may develop.
Envenoming by Australian elapids produces neurotoxicity,
hemostatic disturbances and rarely generalized rhobdomyolysis and
renal failure. Painful regional lymph nodes are a useful signs of
impending systemic envenoming but local signs are usually mild.
Early symptoms include vomiting, headache and syncopal attacks.
Venom Ophthalmia
Spitting elapids may result venom ophthalmia. There is intense pain
in eye, blepharospasm, palpebral edema and leukorrhea. Corneal
erosions may be evident in slit-lamp or fluorescein angiography in
more than 50 percent patients. Rarely venom may be absorbed into
anterior chamber causing by popyon and anterior uveitis. Secondary
injection of corneal abraisions may lead to permanent opacity causing
blindness or panophthalmitis with loss of eye.
Hydrophiidae (Sea Snake)

The bite is usually painless and teeth are frequently present in the
wound. There is no local swelling or involvement of local lymph
nodes. Early symptoms of envenoming include headache, a thick
feeling of the tongue, thirst, sweating and vomiting. 30 minutes - 3.5
hours after bite, there is generalized aching, stiffness and tenderness
of muscles. Trismus is common, later there is generalized flaccid
paralysis as in elapid neurotoxicity. Generalized rhabdomyolysis is
the dominant feature. Myoglobinemia and myoglobinuria appears
3-8 hours after bite and is suspected when serum/plasma appears
brownish and urine dark reddish brown (coca-cola colored). Myoglobin
and potassium released from damaged skeletal muscles can cause
renal failure while hyperkalemia may lead to cardiac arrest.
Viperidae (Pit Vipers, Russels Viper, Rattle Snakes)

Evenoming by viperids usually produce more severe local effects than
other snake venoms. Swelling may appear within 15 minutes but
sometimes may be delayed for several hours. The swelling spreads
rapidly and may involve the whole limb and adjacent trunk. There
is associated pain, tenderness and enlargement of regional lymph
nodes. Bruising especially along the path of superficial lymphatics
and over regional lymph nodes is commonly seen. Swollen limb can
accommodate many liters of extravasated blood leading to hypovole-
mic shock. Blisters may appear at the site of bite which may be filled
with clear or blood stained fluid and extend to the whole of bitten
limb. The necrosis of skin, subcutaneous tissue and muscle may develop
in approximately 10 percent of admitted patients. Bites on digits and
in areas draining into the tight fascial compartments such as anterior
tibial compartment are likely to cause necrosis. Severe pain associated
with tense swelling, subcutaneous anesthesia and pain on dorsiflexion
of foot should raise the possibility of raised intracompartmental
pressure. Sudden severe pain, absence of arterial pulses and a
demarcated cold segment of limb suggest thrombosis of a major artery.
The absence of detectable local swelling 2 hours after a viperbite
usually means that no venom was injected.
Hemostatic abnormalities are characteristic of envenoming by
viperidae. Persistent bleeding from fang puncture wounds, venepunc-
ture or injection sites, other new and partially healed wounds may be
the first clinical evidence of bleeding diathesis spontaneous systemic
hemorrhage is most often detected in gingival sulci. Epistaxis
hematemesis, cutaneous ecchymoses, hemoptysis, hematuria, sub-
conjunctival, retroperitoneal and intracranial hemorrhages are also
Animal Poisoning 99
reported. Bleeding into anterior pituitary (Seehans syndrome) has

been reported in patients bitten by Indian anb Burmese vipers. Severe
headache and meningism suggest sub-arachnoid hemorrhage where
as hemiplegia, irritability, loss of consciousness and convulsions in
absence of cardiorespiratory failure suggest intracranial hemorrhage.
Abdominal distension, tenderness and peritonism with signs of
hemorrhagic shock but no external blood loss suggest retroperitoneal
or intraperitoneal hemorrhage.
Intravascular hemolysis causing hemoglobinemia (pinkish plasma)
and black or greyish urine (hemoglobinuria or methemoglobinuria)
has been reported in patients bitten by Srilankan Russels viper.
Progressive severe anemia and renal failure may result. Hypotension
and shock are a common result of extravasation of fluid into the bitten
limb. The central venus pressure is usually low and pulse rate rapid.
Evenoming by Burmese Russels viper show evidence of generally
increased vascular permeability which manifests as conjunctival edema,
serous effusions, pulmonary edema and a fall in serum albumin
concentration. Patients may develop transient recurrent syncopal
attacks associated with features of an autopharmacological or
anaphylactic reaction such as vomiting, sweating, colic, diarrhea, shock
and angioedema of face, lips, gums, tongue and throat. These symptoms
may appear as early as minutes or as late as many hours of bite. Renal
failure is the major cause of death. Patients may become oliguric
within few hours of bite and have loin pain and tenderness suggesting
renal ischemia, 3-4 days later the patient may become irritable, comatose
or convulsing with hypertension and evidence of metabolic acidosis.
Neurotoxicity similar to elapid bite may occur in envenoming by few
species of viperidae. There is evidence of generalized rhabdomyolysis.
The progression to respiratory or generalized paralysis is unusual.
Clinical Manifestations of Snake Bite

A. Local: Presence of fang mark, pain, swelling, ecchymosis, bullae,
serosanguinous discharge, bleeding and gangrene of sub-cutaneous
tissue and regional lymphadenitis.
B. General systemic features: Fever, headache, muscle cramps,
diaphoresis.
C. GIT: Nausea, vomiting, colicky abdominal pain and rarely jaundice.
D. Hematopoietic: Bleeding diathesis, bleeding from site of bite,
venepuncture and gums. Epistaxis, hematemesis/malena. DIC
severe anemia.
E. Neurological: Numbness and tingling around mouth, scalp and digitis
muscle fasciculations, drowsiness, ptosis, strabismus, paralysis of
tongue and larynx, paralysis of intercostal muscles and diaphragm,

motor weakness; hemiplegia, paraplegia, seizures and coma.
F. Renal: Acute tubular necrosis, glomerulonephritis, renal infarction
and acute cortical necrosis.
G. Cardiac: Arrhythmias, cardiac asystole and shock.
H. Respiratory: Pulmonary edema and respiratory failure.
Laboratory Findings
A. Blood/serum:
Neutrophil leukocytosis (total count > 20,000/cumm)
Hematocrit may be increased initially because of hemocon-
centration, later on decreased markedly due to excessive
bleeding.
Peripheral film: Fragmented erythrocytes, i.e. schistocyte or
helmet cells present and thrombocytopenia.
Coagulations disturbances: BT, CT, PT, Fibrin degradation
products.
Renal function:
Blood urea, serum creatinine
ALT, AST
Serum myoglobulin, hemoglobinemia
Potassium
B. Urine: Colorblack, brown, pink or red
RBC casts (+) nt, blood or hemoglobin (+) nt.
C. ABG changes:
i. Lactic acidosis: anion gap
ii. Metabolic acidosis: pH, HCO3, PaO2
iii. Respiratory acidosis (Respiratory paralysis):
PH, PCO2, PaO2
D. Electrocardiography: ECG changes unusual but are the followings:
i. Sinus bradycardia
ii. ST-T changes
iii. Various degrees of A-V block
iv. Evidence of hyperkalemia
E. EXR- Evidence of pulmonary edema, intrapulmonary hemorrhage
and pleural effusion are present.
F. Immunodiagnosis
The immunological detection of venom antigens in victims body
fluids has improved diagnosis, understanding of pathological
mechanisms, assessment of first aid methods and control of anti-
venom treatment. Radioimmunoassay (RIA) is highly sensitive and
specific but ELISA is most widely used. High venom antigen
Animal Poisoning 101
concentration can be detected. Within 15-30 minutes from wound

aspirate on swabs. For retrospective diagnosis including forensic
purpose, tissues among fang punctures, wound and blister aspirate,
serum and urine should be stored for ELISA or RIA.
Treatment
It is of prime importance to determine whether the patient has been
actually bitten by a poisonous snake. Look for fang marks, presence
of local pain, edema, numbness or weakness and bleeding. Their
absence speaks against snake venom poisoning. Treatment can be
divided into three parts, i.e. first aid, immediate management and
specific treatment.
First Aid
Assure the patient to prevent exertion and vasovagal syncope, allay
anxiety. Immobilize the limb. Apply a tourniquet or crepe bandage
above the bite mark about 5 cm above the upper limit of edema or
fang mark and shift it proximally every 15 minutes, if swelling spreads
further. Torniquet should be tight enough to obstruct lymphatic flow
but not the venous drainage and can be applied only if snake bite
occurs on the limbs. Clean the wound with sterile saline and cover
with a sterile dressing.
Controversial First Aid Methods

The procedures which inflict further trauma or other interference such
as cauterization, incision or excision, amputation of bitten digits, suction
by mouth, vacuum pumps or venom extractor, instillation of chemical
compounds such as potassium permangnate, cryotherapy (cooling
with ice) and electric shocks are potentially harmful. Incision will lead
to uncontrolled bleeding, damage nerves, blood vessels or tendon and
introduce injection. Suction, chemicals and cryotherapy cause necrosis
of tissues. The danger of tight torniquets and other occlusive methods
include ischemia and gangrene if applied for more than 2 hours,
damage to peripheral nerve, increased fibrinolytic activity, congestion,
swelling, increased bleeding and local effects of venom and shock or
rapid life-threatening systemic envenoming after their release.
Immediate Management
Establish IV line and administer fluids and plasma expanders or blood
transfusion to restore intravascular volume. Care of airways and
breathing should be given first priority. If there is any evidence of
respiratory failure, early endotracheal intubation and mechanical

ventilation may be used. Inject tetanus toxoid, single dose if child is
immunized previously. Appropriate antibiotics must be given to patient
to cover both gram positive and negative organism because secondary
injection of necrotizing wound may lead to septicaemia. In case of
viper bite, sedative may be given. Pain may be relieved by NSAID.
Oral paracetamol is preferable to Aspirin as Aspirin commonly causes
gastric erosions and could lead to persistent bleeding in patients with
incoagulable blood. Severe pain can be treated with pethidine or
pentazocine.
Vomiting is a common early symptom. Children should lie on their
side with head down to avoid aspiration. Persistent vomiting can be
treated with IV chlorpromazine in a dose of 1mg per kg body weight.
Children with features of syncopal attack or of an autopharmaological
reaction with angioneurotic edema, abdominal colic and diarrhoea
should be given IV or IM chlorpheniramine (0.2 mg/kg). Hypotension
or broncho constriction can be treated with adrenaline (0.1%) in a dose
of 0.01 ml per kg by sub-cutaneous or intravenous injection.
Glucocorticoids may be given for prevention of allergic reactions.
Irrigation of eyes with large volume water is indicated if there is snake
venom ophthalmia.
Specific Therapy
Species specific anti-venom is the specific therapy but due to high
cost and non-availability and difficulty in identifying the species,
polyvalent anti-venom is commonly used. Polyvalent anti-venom is
derived by hyper-immunizing horses with venoms of four common
poisonous snakes: Cobra, common krait, Russels viper and saw-scaled
viper.
Indications of Anti-venom
A. Systemic manifestations
1. Hemostatic disturbances - spontaneous systemic bleeding,
Incoagulable blood or prolonged clotting time, elevated fibrin
degradation products, thrombocytopenia.
2. Cardiopulmonary: Hypotension or shock, abnormal ECG,
Cardiac arrhythmias, cardiac failure, pulmonary edema and
respiratory failure.
3. Neurotoxicity.
4. Generalized rhabdomyolysis.
5. Impaired consciousness.
6. Definite signs of local enve- Key Points

noming with following labo-
Management
ratory findings.
i. Neutrophil leukocytosis First aid
Immobilization of limbs, cleaning
ii. CPK, ALT, AST
of wound with sterile water
iii. Uremia or hypercrea- Supportive
tininemia Care of airways, breathing
iv. Hypoxemia IV fluid
v. Acidosis Fresh frozen plasma or fresh
B. Local manifestations blood
IV dopamine and dobutamine
1. Local swelling involving more for circulatory collapse
than half of the bitten limb
Specific
2. Extensive blistering or Anti-venom, polyvalent or
bruising monovalent
3. Rapid spread of swelling even Neostigmine methyl sulphate
without evidence of systemic (50-100 g/kg) and atropine
envenoming 4 hourly for neurotoxic enve-
nomation
4. Any evidence of systemic
Mechanical ventilation
spread of venom including
tender regional lymph nodes.
5. Swelling extending up the forearm or leg within 2 hours of bite.
Reconstitution of Anti-venom
Each anti-venom vial is diluted with 10 ml of distilled water or isotonic
saline and than given at the rate of 4 ml/minute. Reconstituted anti-
venom can, however, also be diluted with 3 volumes of normal saline
and infused first very slowly and then with increased rate if well
tolerated over next 1-2 hours. There after depending on clinical response
3-5 vials may be added every 2 hour till all systemic signs and symptoms
disappear or the progression of swelling ceases.
Dosage Guidelines for Anti-venom
Severity of Clinical features Amount of

envenomation anti-venom (vials)
Mild Progressive local swelling with or without 5 vials

lymphadenitis and local ecchymoses/purpura
Moderate Mild systemic signs or coagulation defect or 5-15 vials
hematological changes or nausea, vomiting
and bradycardia
Severe Rapidly progressive swelling with extensive 15-20 vials
local effect, systemic signs and symptoms, DIC,
encephalopathy, shock, paralysis
Anti-venom Reactions
Patients with anti-venom reactions manifest with anaphylaxis,
hypotension, bronchospasm and angioneurotic edema. Anti-venom
reactions occur in 3-34 percent patient within 10-180 minutes. This
should be managed with SC or IV adrenaline (0.01 ml/kg), steroids
(hydrocortisone - 6 mg/kg), anti-histaminic injection and dopamine
as vasopressor. As precautionary measure, a small test dose of anti-
venom should precede the full therapeutic dose.
Stop anti-venom for some period till the reaction subsides. If
envenomation is severe, anti-venom can be readministered even in the
presence of reaction under cover of adrenaline, hydrocortisone and
anti-histaminics. The clinical improvement is often seen immediately
after administration of anti-venom. There is improvement in Glasgow
Coma Scale (GCS) of patient and normalization of blood pressure. The
neurological manifestation may improve either within 30 minute or
may take hours. Bleeding stops by 15-30 minute and coagulation
profile returns to normal within 6 hours.
Neurotoxic envenomation leading to respiratory paralysis is
managed by anti-cholinesterases. Patients who respond to atropine
sulphate (50 g/kg) and edrophonium chloride (0.25 mg/kg IV) should
be given neostigmine methylsulphate (50-100 g/kg) and atropine
4 hourly or by continuous intravenous infusion.
Contraindications to Anti-venom Therapy

1. History of atopic disorders
2. Sensitive to equine anti-serum.
Supportive Management
IV crystalloids, fresh blood, fresh frozen plasma and dopamine infusion
should be used to combat hypotension and shock. Acute renal failure
should be managed with restriction of fluid and electrolytes and as
hospital protocols. If patient develops pulmonary edema or respiratory
failure, it should be managed with assisted ventilation and 100 percent
oxygen.
Prevention
In snake infested area, use of boots, socks, trousers and torchlight at
night may prevent from snake bite. Venomous species of snake should
not be kept as pets. On encountering a snake, it should not be disturbed,
attacked or handled even if thought to be harmless.
Venom toxoids (venoids) have been used to protect high-risk groups

but results are not encouraging. In future recombinant technology
may result in non-toxic and protective antigens suitable for use as
vaccines.
BEE AND WASP STING

Bees and wasp have stings attached to the abdomen and are connected
by a duct to venom gland. The venom of both contains histamine,
hyaluronidase and phospholipase A and B. In addition, wasp venom
contains serotonin and kinins and bee venom mellitin, apamin, and
peptides. Venoms are neurotoxic, hemolytic and hypersensitizing.
Histamine, serotonin and kinins cause pain and increased vascular
permeability. Reactions are severe in young children and those who
have been stung before.
Clinical Features
At the site of sting, there is intense pain, itching, wheal and erythema.
In areas with loose connective tissues such as eyelids and genitalia,
severe edema may be present. Local reactions usually subside in a
few hours and sometimes in a day or two. Stings on head, tongue,
face and neck are very serious. Massive edema of face, tongue, pharynx,
larynx and glottis with immediate death from respiratory obstruction
may occur. Injection of venom directly into a nerve may cause paralysis.
Bells palsy has been reported with bee sting in the facial nerve. If the
venom is innoculated directly into a vein, immediate death may result.
Multiple stings may cause hypotension, respiratory distress and
hemoglobinuria. Acute renal failure is also known to occur.
In children who are sensitized earlier, a sting may cause anaphylaxis
with uriticaria, itching, nausea, abdominal cramps, asthmatic attacks,
edema of face, lips and glottis, cyanosis, hypotension, convulsions,
and coma leading to death. This is more common in children with
history of atopic dermatitis, and hypersensitivity reactions with
previous stings.
Treatment
In general palliative treatment alone is sufficient. The wasp usually
removes the sting but the sting of bee remains in site. Hence, sting
along with attached venom sac must be scrapped off carefully without
introducing more venom into the wound. The bee venom is acidic
and should be neutralized by application of alkaline solutions of

ammonia, soda or methylene blue and wasp venom, being alkaline,
should be neutralized by acid vinegar or lemon juice. Local application
of ice packs will retard absorption of venom as well as release of
histamine from damaged cells. Topial application of antihistamine are
useful in allaying local irritation. Acute allergic reactions should be
treated with SC or IM adrenaline and IV hydrocortisone. Anti-
histaminics may be given parenterally at the same time. Hydrocortisone
is also useful for preventing laryngeal edema and bronchospasm.
Aminophylline may be used for relieving bronchospasm. Hypotension
and shock should be combated with IV crystalloids, and vasopressor
amines like dopamine and dobutamine. Artificial respiration and
oxygen are indicated in the presence of respiratory failure.
Tracheostomy and endotracheal intubation may be required.
SPIDER BITES
The majority of spider bites are not dangerous but are painful. A few
species of spider like L. mactans (black widow spider), atrax robustus
and loxosceles reclusa (hairy brown spider) are dangerous. Black widow
spiders, which are often found in tropical region, are most dangerous.
Death may occur in up to 6 percent cases of spider envenomation in
young children.
Clinical Features
At the site of bite, there is a burning sensation after envenomation.
After an hour generalized muscular spasm, nausea, vomiting, pain,
tenderness and rigidity of abdomen occurs, which mimicks an acute
attack of appendicitis, pyrexia, sweating and shock may occur later.
Treatment
The site of bite is thoroughly washed with hot water, which gives
prompt although temporary relief. Infusion of 10 percent calcium
gluconate solution as slow intravenous injection is effective in transient
relief of the muscular spasm/cramps. Muscular spasms may also be
treated by diazepam or a 10 percent solution of methocarbamol. If
severe systemic toxicity is present, anti-venom, if available, should be
given intravenously in a dose of 2.5 ml diluted in 50 ml of saline over
15 minute and may be repeated if symptoms recurs. Shock, if occurs
is treated with IV crystalloids and vasopressor amines.
LIZARD BITE
Out of the 3000 species of lizards worldwide, only two, i.e. Gila
monster (Heloderma suspectum) and Mexican beaded lizard are
venomous. Both of these varieties are not found in India. Many people
believe that even the breath of a lizard is poisonous particularly
regarding a species called biskhopra. There is no need for any
treatment except reassurance to the person bitten by lizard in India.
Envenomation by poisonous variety occur by contamination of the
wound with venom which is neurotoxic in nature. Envenomation
results in tissue injury, excruciating pain, massive edema and patchy
erythema. Systemic symptoms are nausea, vomiting and hematemesis,
blurring of vision, dyspnea, dysphoia and profound weakness. Systemic
manifestations usually last for 3-4 days. Hyperesthesia in the bitten
extremity may persist for several weeks. There is no anti-venom available.
Treatment comprises of constriction band application, incision and
suction, cooling of the bitten area, measures to prevent or combat
infection including tetanus toxoid and supportive measures. Local
anesthetics should be infiltrated to relieve pain.
CATERPILLAR
Caterpillars are larval stage of butterflies and moths. More than 50
species possess specialized hairs containing venom. The hairs of
catterpillar get scattered by the wind and on dermal contact leads to
localized dermatitis of urticarial type, manifested by severe pain,
erythema and papular eruptions. Ocular contact causes conjunctivitis
and inhalation leads to respiratory disturbance. Other features are
nausea, vomiting, shock and convulsions.
Caterpillar hair envenomation requires local antihistaminic
application, apart from decontamination with water and removal of
hair for local reactions. Parenteral injections of antihistamine and 10
percent calcium gluconate are needed for systemic manifestations.
BIBLIOGRAPHY
1. Arnold R. Treatment of snake bite. JAMA 1976;236:1843-46.
2. Bartholoneu C. Acute scorpion pancreatitis in Trinidad. BMJ 1970;1:666-68.
3. Bhawaskar HS, Bhawaskar PH. Prazosin in management of cardiovascular
manifestations of scorpion sting. Lancet 1986;1:510-11.
4. Chandha JS, Levia A. Hemolysis, renal failure and local necrosis following
scorpion sting. JAMA 1979;241:1038.
5. Clark RE, Wethern, Kestner S, Vance MV. Clinical presentation and treatment
of black widow spider envenomation. Ann Emerg Med 1992;21-182.
6. Gaitonde BD, Jadhav SS, Bhawaskar HS. Pulmonary edema after scorpion
sting. Lancet 1978;1:445-46.
7. Gueron M, Weizman S. Catecholamines and myocardial damage in scorpion

sting. Am Heart J 1969;75:716-17.
8. Mahadevan S, Choudhury P, Puri RK, Srinivasan S. Scorpion envenomation
in children and the role of lytic cocktail in its management. Indian J Pediatr
1981;48:757-59.
9. Malasit P, Warrel DA, Chanthavanich P. Prediction, prevention and
mechanism of early antivenom reactions in victims of snake bites. BMJ
1986;292:17.
10. Murthy RK, Bhakil AR, Yeolekar ME. Reversal of metabolic and electro-
cardiographic changes induced by administration of insulin, alpha-blocker
and sodium bicarbonate. Indian J Med Res 1988;88:450-53.
11. Murthy RK. Reduced insulin secretions in acute myocarditis produced by
scorpion venom injections in rabbits. Indian Heart J 1986;38:467-69.
12. Philip E. Scorpion sting. Indian Pediatr 1986;23:185-86.
13. Raab W. Key position of catecholamines in functional and degenerative
cardiovascular pathology. Am J Cardiol 1960;12:571-73.
14. Radhakrishna MK, Zolfogharian H, Medhi JD. DIC and disturbances in
carbohydrate and fat metabolism in acute myocarditis produced by scorpion
venom. Indian Med Res 1988;87:318-20.
15. Rao AV, Ramaswamy VN. Toxic myocarditis with resultant arrhythmias due
to scorpion sting. J Assoc Phys India 1981;9:481-83.
16. Reisman R. Insect sting. N Engl J Med 1994;331:523.
17. Reid HA, Theakston RDG. The management of snake bite. Bull WHO
1983;63:885-96.
18. Saini RK, Singh S, Gupta VK. Delayed polyvalent anti-venom serum therapy
in viper bites. J Phys India 1984;3:874-75.
19. Smith C, Philips M, Miller C. Purification of charybodotoxin, a specific
inhibitor of high conductance calcium activated potassium channel. J Biochem
1986;261:145607-13.
20. Thomas PP, Jacob J. Randomized trial of anti-venom in snake envenomation
with prolonged clotting time. BMJ 1985;91:177-78.
21. William WF. More on snake venom and insect venom extractors. N Eng J
Med 1993;328:516-17.
7
Insecticide Poisoning
Chemicals have been employed to kill insects and protect crops since
1800 AD. In 1940s, chlorinated hydrocarbon DDT was introduced to
control vectors of insect borne diseases. Following successful
containment of typhus and malaria epidemics, DDT was held as the
final solution to all worldwide attempts to eradicate pests. Eventually,
evidences to suggest that DDT accumulated in human and animal
tissues and had deleterious ecological effects. Substitutes for DDT and
its chlorinated derivative were tried and introduced. Two newer groups
of insecticides used widely as replacement for DDT and its chlorinated
compounds are the carbamates and organophosphates.
Organophosphates and carbamates have been reported to account
for almost 10 percent of deaths due to poisoning. The potential for
poisoning with these products is high as they are used in domestic
and commercial sprays, in flea collar, flypaper, bugbombs and in
ointments and powder for ridding animals as well as humans of
insects. All of them have been responsible for human poisoning in
some way or another.
The incidence of poisoning due to organophosphorus, gammexane
and other insecticides in our country varies from 13 to 15 percent, the
incidence at our institution being 13 to 14 percent. Children from rural
areas are the principal victims.
Classification of Insecticides
1. Insecticides of vegetable origin:
Nicotine
Pyrethrin
Rotenone
2. Chemical insecticides
Inorganic Chemical Insecticides

Phosphorus and antimony compounds
Arsenic
Barium
Mercury
Thallium
Zinc phosphide
Fluorides
Organic Chemical Insecticides

a. Chlorinated hydrocarbons
i. Chlorobenzene derivatives, e.g. DDT
ii. Indane derivatives, e.g. Chlordaine, Heptachlor Aldrin,
Dieldrin, Endrin, Diendrin
iii. Benzene derivatives, e.g. Lindane, Gammexane
iv. Chlorinated camphenes, e.g. Taxaphene, Strobane
b. Phosphate Esters, e.g. Organophosphates
c. Carbamates, e.g. Temik, Baygon, Sevin, Furaxdam, Metacil.
Based on the potential of toxicity, insecticides may also be classified as
below:
a. Virtually Harmless
1. Phenoxyacetic acid plant hormones, e.g. MCPA,DCPA, TCPA
They are used for dock and thistle control
2. Fungicides, e.g. Copperoxide and Oxychlorides
3. Orchard Fungicides, e.g. Lime Sulfur washes
4. Orchard Insecticides, e.g. Petroleum washes
5. Orchard Ovicides, e.g. Tar Oil Emulsion
b. Comparatively Harmless
Sulfuric acid (20%) used as weed killer, sodium chlorate used as mass
herbicides for road and rail tracks.
c. Mildly Toxic
Chlorinated hydrocarbon insecticides: DDT, Gammexane, Metho-
xachlor, Chlordane, Aldrin and Dieldrin, Chlorinated hydrocarbons
are used to control fly, louse, tick which infest cattle and act as
agricultural pests.
d. Highly Toxic
1. Arsenical compoundsSodium arsenite, lead and calcium arsenate,
Paris green, are used as weed killer and orchard insecticides.
Insecticide Poisoning 111
2. Horticultural insecticides, e.g. Nicotine, Sulfates and Tannates.

3. Disinfestors and raticidesHydrocyanic acid and its derivatives,
KCN and NacN.
4. Dinitro-compoundsThey are used as selective weed killers,
ovicides and insecticides, e.g. DNP (Dinitrophenol), DNOC (Dinitro-
orthocresol).
5. OrganophosphatesThey are used as insecticides and acaricides,
e.g. HETP, TEPP, OMPA, Parathion, Malathion.
ORGANOPHOSPHORUS POISONING
Organophosphates are compounds of phosphoric acid with alkyl,
alkoxy or alkylmamino side-chains. The important members are:
1. Cholorothion
2. Diazinon (Diazion, Tik-20)
3. DEP (di-isopropyl fluorophosphate)
4. Malathion (kill bug, bugsolime 20)
5. Methyl parathion (metacide)
6. OMPA (Octa Methyl pyrophosphoramide)
7. Parathion (Follidol, ekatox, killphos)
8. TEPP (Tetraethyl pyrophosphate)
9. THIO-TEPP
10. HETP (Hexaethyl tetraphosphate).
All these except chlorothion and malathion are highly toxic and
humans. They are extensively used as pesticides for protection of
vegetable and fruit crops. Accidental poisoning may result from the
inhalation of spray or absorption through the skin. Fatal but
unsuspected poisoning may result from contaminated clothing and
food articles. It is the most popular suicidial poison throughout the
world. Children and women are being the usual victims. Accidental
poisoning is rare in children but adolescents consume it with suicidal
intention. Homicidal poisoning is rare.
The world health organization estimates that approximately 3
million pesticide poisoning occurs worldwide and causes more than
220,000 deaths. The developing countries like India and Sri Lanka
report alarming rates of toxicity and death. The incidence of organo-
phosphorus poisoning in India as reported by various workers is a
staggering 10 to 11 percent, the incidence at our institution being 6
to 7 percent. Most cases hail from rural areas.
The toxic properties of organophosphates were first recognized in
1932, when king and Krueger observed poisoning in rats. Saunders
developed di-isopropyl fluorophosphate as nerve gas for World War
II. Schroder(1952) was the first to discover the pesticide properties of
organophosphates and developed first organophosphate pesticide

Tetraethyl pyrophosphate.
Pathophysiology
Organophosphate compounds are absorbed by inhalation, transder-
mally, transmucosally and via gastrointestinal tract. The respiratory
route of absorption usually leads to a more rapid onset of symptoms.
Organophosphates bind irreversibly to enzyme acetylcholinesterase
at the histidine-serine hydroxyl group site and enzyme system, thus
preventing the enzymatic breakdown of acetylcholine. The
accumulation of unhydrolyzed acetylcholine at the site of cholinegic
transmission initially stimulates but then paralyzes neural transmission
in cholinergic synapses. The majority of signs and symptoms of organo-
phosphate poisoning are attributable to cholinergic overload, i.e.
Muscarinic, nicotinic and central nervous system action of acetylcholine.
Clinical features appear when cholinesterase activity falls to 25 to 30
percent of normal. They are similar to those resulting from over doses
of acetylcholine, pilocarpine, physostigmine or muscarine.
Thus organosphosphates have three types of action, i.e. Muscarine-
like effect, Nicotine-like effect and action on central nervous system.
1. Muscarine-like Effect
It stimulates post-ganglionic cholinergic (parasympathetic) nerve
ending. The smooth muscles of the eye, bronchial tree, intestinal tract,
Urinary bladder and ureter contract and the heart and exocrine glands
such as sweat, salivary and lacrimal gland stimulated. They may
cause vascular endothelial damage and myocarditis. Severe
bronchospasm and bronchorrhea may mimick an attack of acute
bronchial asthma.
Pneumonic: SLUDGE S: Salivation, L: Lacrimation, U: Urination,
D: Defecation G: Gastrointestinal cramping, E: Emesis, and DUMBELS
D: Diarrheas, U: Urinary incontinence, M: Miosis and muscle
fasciculations, B: Bronchorrhea, bronchospasm and bradycardia,
E: Emesis, L: Lacrimation, S: Salivation.
2. Nicotine-like Effect
It first stimulates, and then causes paralysis of pre-ganglionic and
somatic motor nerve fibers resulting in twitching of muscles, muscle
cramping, weakness and paralysis (eyelids, tongue and facial muscle).
Fatigue and muscle cramps are usually followed by neuromuscular
block and paralysis. Diaphragmatic weakness may result in respiratory
difficulty and respiratory failure. Preganglionic sympathetic nerve

stimulation leads to tachypnea, dyspnea, cyanosis, tachycardia,
hypertension, pallor, mydriasis and re-entrant dysrhythmias and
cardiorespiratory arrest.
3. Action on CNS
It causes stimulation followed by depression leading to tremors,
restlessness, dizziness, loss of memory, ataxia and malaise, followed
by seizures, coma and cardiorespiratory depression. Headache can be
intense and speech slurred. Unusual features like hypothermia,
hyperglycemia, hyperamylasemia, pulmonary edema and all types of
cardiac arrhythmias are also observed. CNS manifestations may
contribute to the mortality by causing seizures, hypoxia, hyperthermia
and seizure induced rhabdomyolysis with acute tubular necrosis.
The usual cause of death from organophosphate poisoning is
respiratory failure, resulting from weakness of respiratory muscles
and cetral depression of respiratory drive. This may be aggravated by
hypoxia because of bronchospasm and bronchorrhea. Those
organophosphates requiring hepatic metabolism for activation are
also hepatotoxic.
Fatal dose:
TEPP : 50 mg IM or 100 mg orally
OMPA : 80 mg IM or 175 mg orally
Parathion : 80 mg IM or 175 mg orally
HETP : 60 mg IM or 350 mg orally
Malathion and diazinon : 1 mg orally
HETP is the least toxic whereas TEPP is the most toxic as well as
the fatest acting organophosphorus compound.
Fatal period: This ranges from 1-24 hours depending on the particular
compound. In non-fatal cases the acute effects last for 6 to 30 hours
which may sometimes persist for two weeks. Complete recovery occurs
in 2-3 months.
Clinical Manifestations (Table 7.1)

The clinical manifestations begin within to 1 hour and reach the
peak in 2 to 8 hours. Signs and symptoms appear when the
cholinesterase activity drops to 30 percent of its normal. The respiratory
and gastrointestinal symptoms are predominant depending on the
route of entry. The clinical features usually appear in the following
order:
1. Nausea, vomiting, abdominal cramps, diarrhea and excessive

salivation.
2. Headache, giddiness, vertigo and weakness.
3. Rhinorrhea and a feeling of tightness in the chest especially after
inhalation.
4. Constricted pupils, dimness of vision, increased tear formation,
muscle spasm, loss of accommodation and ocular pain. Dilatation
of pupil is rarely seen.
5. Loss of muscular co-ordination, slurring of speech, twitching of
muscles and weakness.
6. Mental confusion, disorientation and drowsiness.
7. Difficulty in breathing, excessive bronchial secretion, frothing,
cyanosis, pulmonary edema and hypertension.
8. Jerky movements, bowel and bladder incontinence, convulsions
and coma. Prophyrinemia, resulting in chromolacryorrhea
(shedding of red tears), due to accumulation of prophyrin in lacrimal
gland is very rarely seen. Death occurs due to respiratory failure
and cardiac arrest.
Table 7.1: Clinical manifestations of organophosphate poisoning
Respiratory Rhinorrhea, bronchorrhea, bronchoconstriction, wheezing, dyspnea,

pulmonary edema, respiratory arrest
Cardiac Bradycardia, hear blocks, cardiac arrest
CNS Headache, giddiness, coma, convulsions, loss of reflexes
Gastrointestinal Nausea, vomiting, diarrhea, abdominal cramps
Eye Miosis, blurred vision, lacrimation, papilledema
Skin Sweating, dermatitis
Others Fasciculations, flaccidity, salivation, urination, delirium, psychosis
Intermediate Syndrome
This phase begins 48-96 hours after intoxication. Complete recovery
occurs within 4-18 days if adequate ventilatory support is provided.
It occurs in 20-68 percent of organophosphate poisoning. Two probable
mechanisms for this syndrome are:
a. Long lasting cholinesterase inhibition: de Blecker and collegues
had observed that such patients exhibited prolonged red blood cell
cholinesterase inhibition and prolonged excretion of metabolites in
urine. The intermediate syndrome may result from inadequate
treatment of acute episode, i.e. inadequate amount and time of
administration of oximes, inadequate assisted ventilation.
b. Prolonged transmitter receptor interaction leads to excessive entry
of calcium ion into the muscle producing muscle necrosis. This
syndrome exhibits clinical and electromyographic hallmark of
combined pre- and postsynaptic impairment of neuromuscular

transmission. In both cholinergic and intermediate phases muscles
of respiration may be affected and lead to death from respiratory
failure. Weakness is also observed in areas of motor cranial nerves,
neck flexors and proximal limb muscles. Deep tendon reflexes are
depressed but characteristically fasciculations are absent.
Chronic Effects
The delayed sensorineural polyneuropathy occurs following an
apparent recovery from acute symptoms, usually 7-14 days after
exposure to an organophosphate agent. Although not associated with
death, it results in motor disability due to symmetrical peripheral
muscle weakness causing flaccidity, atrophy of distal limb muscles,
spasticity and ataxia. Some patients experience symptoms ranging
from numbness and tingling in their extremities to permanent paresis.
This is due to delayed distal axonopathy. The phosphorylation of an
enzyme (neuropathy target esterase; NTE) in nerve tissue is considered
to be responsible for polyneuropathy. Nerves that are primarily affected
are sciatic, peroneal and tibial nerve. Long ascending and descending
tracts of spinal cord are also affected. Muscles of respiration and brain
are characteristically spared. Cranial nerve palsy (VIth and VIIth) or
diaphragmatic paralysis may occur rarely. Pyramidal tract degeneration
and Guillain-Barr syndrome have been observed. Postexposure
tiredness, insomnia; inability to concentrate and depression may occur
in next few weeks.
Pregnant women exposed to organophosphates need special
precautions as congenital malformation and precipitation of labor
may occur in first and last trimester respectively. Since atropinization
may increase fetal heart rate, cesarean section should be considered
immediately under regional anesthesia rather than waiting for normal
delivery. Baby may develop hypoxia and may require intubation and
assisted ventilation. Drugs causing reduction in cholinesterase activity
such as barbiturates, diazepam, narcotics, phenothiazines, amniophyl-
line, ephedrine, etc. should be avoided.
Diagnosis
The diagnosis is based on the:
1. History of exposure
2. Signs, and symptoms consistent with organophosphate exposure
3. Response to atropine in a normal person, 2 mg of atropine causes
marked degree of atropinization but in organophosphate poisoning,
symptoms are relieved without atropinization.
4. The diagnosis is confirmed by estimating RBC cholinesterase

activity. The cholinesterase activity of blood and plasma fall by 22
to 88 percent. The average normal values are 77 to 144 in the red
cells and 41 to 140 in the plasma. The plasma cholinesterase activity
is more sensitive and will fall more rapidly and precede that in red
cells. Thus, if there is dissociation of the two, i.e. if the plasma value
is lower and red cell relatively little changed, the amount of exposure
is less than if they were both down. The plasma value will reach
normal in 7 to 10 days. The red blood cell cholinesterase has to be
reduced to 20 percent of normal values for severe symptoms to
appear. Values less than 50 percent of normal enzyme activities
indicate exposure but clinical signs and symptoms may be absent.
The cholinesterase estimation is difficult and not freely available.
Neonates and infants have baseline cholinesterase activity lower
tha adults. The difference between RBC and plasma cholinesterase
are mentioned in Table 7.2.
Table 7.2: Differences between RBC and plasma cholinesterase
Red blood cholinesterase Plasma cholinesterase
Advantage Better reflection of synaptic Easier to assay, declines

inhibition faster
Site CS, gray matter, RBC, motor CNS white matter, plasma,
end plate liver, pancreas and heart
Regeneration (treated) 1% per day 25-30% in first 7-10 days
Normalization (untreated) 35-49 days 28-48 days
Use Unsuspected prior exposure Acute exposure

with elevated plasma
cholinesterase
False depression Hemoglobinopathies, perni- Liver dysfunction,

cious anemia, antimalarial hypersensitivity reactions,
treatment, oxalate tubes malnutrition, drugs and
pregnancy
5. Estimation of urinary P-nitrophenol radical (PNP) is useful for the

diagnosis of parathion, methyl parathion and chlorothion, which
contains this radical.
6. Electromyographic pattern consistent with decremental conduction
with repetitive nerve stimulation and acute cholinergic illness.
7. Development of ascending sensorimotor polyneuropathy with
electromyographic pattern consistent with axonal degeneration.
8. Ancillary investigations:
Increased leukocyte countstress leukocytosis

High hematocrit hemoconcentration from large fluid loss
Anion gap poor tissue perfusion
Increased glucose ad decreased potassium and magnesium
catecholamine excess
Blood urea nitrogen, creatinine and urine specific gravity
patients hydration status.
Management Key Points
The patient is removed from Diagnosis

the source of exposure and after 1. History
removal of the clothing the skin 2. Clinical featuresbronchorrhea,
is washed with copious rhinorrhea, bronchospasm, bradycar-
dia, miosis, blurred vision, sweating,
amounts of water and soap,
fasciculation, twitching
Abrasions must be avoided. 3. Symptoms relieved by atropine
The skin is then swabbed with administration
ethyl alcohol to remove excess 4. Decreased RBC cholinesterase activity
of insecticides. The eyes are
irrigated with physiological Management
saline if contaminated. If the 1. Removal from the source of poison
poison is ingested or inhaled 2. Wash the skin
induce vomiting or gastric 3. Gastric lavage with potassium per-
manganate
lavage with 1:5000 potassium
4. Cathartics
permanganate solution within 5. Atropine: 0.05 mg/kg IV repeated every
30-60 minutes of exposure. 5-15 min until all secretions become
Administer activated charcoal, dry
1gm/kg orally, unless emesis 6. Pralidoxime: 25-50 mg/kg IV as a 5
prevents this. Cathartics should percent solution
7. Symptomatic and supportive treatment
be avoided. including mechanical ventilation if
required
Management of Airways
In life-threatening exposure, risk of airway compromise is very high.
Seizures, loss of diaphragmatic activity, bronchorrhea, and
bronchospasm contribute further to increased risk. Airways may be
maintained by proper positioning, regular suctioning and in severe
cases by intubation. Early administration of atropine helps in better
airway management by drying respiratory secretions and broncho-
dilation. Artificial ventilation may be needed in patients with
diaphragmatic paralysis and respiratory failure.
Management of Seizure
If seizures develop oxygenation and large dose of benzodiazepines
along with antidotal therapy is usually sufficient. Rarely patient may
require phenobarbitone. Phenytoin is contraindicated because of its
membrane stabilizing and autonomic effects. It can also suppress
cardiac activity and physiologic autonomic response.
Atropine Sulphate
Atropine is the key to successfull treatment. It acts by competitive
inhibition of acetylcholine at mucarinic postsynaptic membrane and
in CNS. However, it is not effective against nicotinic effects. Atropine
may be administered in a dose of 0.05 mg/kg intravenously initially
and may be repeated at 5-15 minutes intervals until all secretions are
dry (to a maximum of 10-12 mg in 24 hours). Intratracheal nebulization
of atropine sulphate, 2 mg every six hours have been tried and reported
very useful. Pupils may not dilate with atropine therapy and this effect
should not be used as an end point.
A large dose of atropine may be required depending on the severity
of the clinical condition. Mild atropinization is maintained as long
as necessary.
Useful clinical signs of atropinization include flushed face, dry
mouth, fast pulse and dry skin.
Atropine with dosage used for treatment can cause delirium and
altered behavior. Patients with no evidence for central anticholinergic
syndrome and initial clear sensorium, glycopyrrolate (0.05 mg/kg IV)
can be substituted for atropine, as it does not cross the blood-brain
barrier. Isolated pulmonary manifestation may respond to local
administration of nebulized atropine or ipratropium bromide.
Cholinesterase Regeneration Compounds

These include a class of compounds, oximes, which are capable of
regenerating active enzymes from organophosphate-cholinesterase
complex. They include Pralidoxime (PAM), Diacetylmonoxime (DAM)
and Obidoxime. H-series of oximes H16 and HLO7 are the most
effective newer oximes.
Organophosphates inactivate acetylcholinesterase by a process of
alkylphosphorylation. The nucleophillic oximes bind to the phosphate
to form an oxime phosphate complex, which splits off from the
acetylcholinesterase to leave the regenerated ezyme. With time
phosphorylated regenerated acetylcholinesterase forms more stable
complex which is resistant to effect of pralidoxime.
Pralidoxime is a cholinesterase reactivator which primarly

counteracts the nicotinic effects. Since it regenerates acetyl cholin-
esterase at all sites, it may be useful even if only muscarinic effects
are present. Earliest the better, preferably within 12 hours following
exposure but it continues to be effective even if given several hours
after intoxication. The dose of PAM is 25 to 50 mg/kg IV as a 5 percent
solution in isotonic saline over 5 to 10 minute and 7.5 mg/kg/hour
by continuous infusion after initial bolus dose 4 hours apart. The
dosage may be repeated or prolonged in case of intermediate syndrome.
It is more effective against parathion poisining. Intravenous fluid
must be used with caution to prevent pulmonary edema. Avoid atropine
in cyanosed patients as it may cause ventricular fibrillation. In this
situation artificial ventilation must precede atropinization. Diazepam
is preferred as a tranquilizer instead of phenothiazines as the later
potentiates the effect of organophosphorus compounds. Thiamine
administered intravenously at 100 mg/hr for 2-3 hours prolonged
half-life, increased volume of distribution and decreased renal clearance
of pralidoxime experimentally.
Pralidoxime, a quaternary ammonium compound, does cross blood-
brain barrier. To improve its effect on central nervous system,
dihydropyridine derivative of pralidoxime was synthesized. The sugar
derivatives of pralidoxime also has better CNS penetration. Obidoxime
and H series of oximes have better CNS penetration than pralidoxime.
Purified human cholinesterase and histidine along with
phospheridon to reverse the inhibition of acetylcholinesterase activity
are undergoing experimentations for their efficacy.
Magnesium: Ventricular premature contractions due to organo-
phosphate poisoning can be successfully terminated with IV
magnesium sulfate. In experimental models magnesium infusion were
used with excellent results in decreasing tachycardia associated with
organophosphate poisoning and atropine without producing
hypertension. Magnesium has an additional benefit of inhibitory effect
on acetylcholine release. Hence, it reverses the neuro-electro-
physiological defects induced by organophosphate.
Clonidine: Clonidine inhibits the release of acetylcholine from central
and peripheral cholinergic neurons. Its administration increased the
survival rate to 50 percent following poisoning with physostigmine.
The respiratory paralysis induced by neostigmine, a selective peripheral
anticholinesterase, is not affected by Clonidine therapy. The central
cholinergicneurons involved in regulation of respiration and fine motor,
but not peripheral motor neurons are inhibited by action of Clonidine
on alpha-receptors.
Muscle relaxants metabolized by plasma acetylcholinesterase such

as succinylcholine, mivacurium have a increased duration of action
and should be avoided whereas non-depolarizing muscle relaxants,
e.g vecuronium, pacuronium may be resistant to their effects.
Hemodialysis may be required in seriously ill patents. Close
monitoring of the child, as relapse may occur even after full apparent
recovery.
Monitoring of Patient
Majority of children requiring treatment for organophosphate poisoning
require hospital admission for continued monitoring and therapy. The
patients should be observed for 24 hrs after last dose of atropine is
give delayed respiratory arrest following inadequate treatment may
occur. Patients requiring continuous airways and neuromuscular
monitoring should be managed in ICU. Pulse, blood pressure, ECG,
SaO2, respiration and level of consciousness should be monitored
regularly. Monitor patient during administration of atropine and
pralidoxime until Q-T interval become normal.
Prophylaxis
1. Protective clothing consisting of white cotton, a white cloth hood
to cover the head and neck, rubber apron, gloves and boots, eye-
shields and respiratory.
2. The hands and face should be thoroughly washed after spraying
with soap water.
3. Not more than 2 hours spraying a day should be done by a worker
and he should work for more than 6 successive days on spraying.
4. A person suffering from cold and bronchitis should not be engaged
in spraying operation.
5. The worker should not smoke, chew or drink in the spraying area.
6. Spraying machines, tanks containers, etc. should be thoroughly
washed, at the end of work.
In one case, one drop of parathion falling on the skin of forearm,
which was not washed for 2 minutes, caused death.
A child of nine weeks died after having been deliverately given
two drops of parathion.
CARBAMATES
Carbamates are widely used as insecticides against a wide range of
insects for their muscarinic effects. They are marketed as dusts or
solutions. Carbamates which are available in the market are the
following:
Common Name Brand Name

Aldicarb Temik
Aminocarb Platacil
Bufen carb Bux
Carbaryl Sevin
Carbofuran Furadan
Dioxy carb Elocron
Iso carb Etrofolan
Oxamyl Vidate-4
Propoxur Baygon
The absorpion of carbamates occur through all routes. Their mode
of action is similar to organophosphates in producing toxicity. They
inhibit the enzyme, acetylcholinesterase reversibly by carbamylation
of esteric site of the enzyme analogous to its phosphorylation by
organophosphate. However, carbamates usually have a shorter
duration of action and are somewhat less toxic than organophosphates.
Symptoms and signs of poisoning with carbamates are similar to those
of organophosphates, but less severe as they do not effectively penetrate
the central nervous system. Hemolytic anemia has been reported but
delayed peripheral neuropathy induced by organophosphates has not
been observed with carbamates.
The treatment of carbamate poisoning is similar to that for
organophosphate but the use of cholinesterate reactivator, pralidoxime
is contraindicated as inhibition with cholinesterase is transitory and
reversal occurs rapidly. Currently atropine is the transitory
recommended as an antidote. The popular pesticide SEVIN contains
naphthyl methylcarbamate as the main ingredient. It is non-toxic to
human beings. Methoxythioacimidate is a new cholinesterase inhibitor
similar in action to carbamates.
PYRETHRINS
This insecticide is extracted from flowers of plant Chrysanthemum
cinerariafolium. It is mainly cultivated in Shimla and Kashmir in
India. The active principles of the flowers, Pyrethrins and Cinerins are
highly potent nerve poisons capable of eliminating various insects
instantly on mere contact. As 20 percent extract of the flowers in
soyabean oil or kerosene oil is used in agricultural or household
sprays. Severe poisonings from Pyrethrins are rare. In sensitive
individuals dermal contact with pyrethrins causes erythema, papular
and vasicular eruptions and occassionally asthma. The inhalation or
ingestion of dust or spray solutions causes nausea, vomiting, diarrhea,
headache, tinnitus, tremors, incoordination, muscular paralysis and
death from respiratory failure. The treatment is palliative and
conservative only. No specific antidote is available.
ROTENONE
Rotenone is derived from ground roots and extracts of roots of plants,
Derris elliptica and Lonchocarpus. Dusts of Rotenone are widely used
against animal ectoparasites and as agricultural and household sprays.
Lotions and emulsions are used for treatment of head lice and scabies.
Rotenone on contact with skin and eye cause dermatitis and
conjunctivitis. On inhalation, it causes rhinitis and pharyngitis and on
ingestion it causes nausea and vomiting. Following absorption it first
stimulates and then depresses the respiratory and vasomotor centers.
The cause of death is respiratory and cardiac failure. Treatment is
largely symptomatic. Milk and oily purgatives are contraindicated
because they increase gastrointestinal absorption.
DDT (DICHLORODIPHENYLTRICHLOROETHANE)
DDT is a white crystalline powder, insoluble in water, moderately
soluble in mineral and vegetable oils and readily soluble in organic
solvents. DDT is both insecticidal and parasiticidal. In low
concentration, it is lethal to mosquitoes, houseflies and lice and to
many other arthropods. DDT is easily available as dusting powder or
as a solution. Accidental poisoning due to ingestion, transdermal
absorption or inhalation is common in adolescents.
Pathophysiology
As a powder it is poorly absorbed from the digestive tract and not
at all from the skin. As a solution it is readily absorbed from
gastrointestinal tract and gets accumulated in fat (adipose tissue). The
concentration falls gradually over several months. The motor cortex
of cerebrum and the cerebellum are the main sites of action. It first
stimulates and then depresses the central nervous system. It also
sensitizes the myocardium to catecholamines. On chronic exposure,
it causes focal liver necrosis, renal tubular degeneration and
degeneration of myocardium and voluntary muscles.
Fatal period: Death usually takes place in 1-2 hours and rarely after
1-2 days.
Fatal dose: The lethal dose is approximately 150 mg/kg body
weight of pure DDT.
Clinical Features
Intoxication of DDT may occur following ingestion, extensive
contamination of skin or prolonged inhalation. Following ingestion,
salivation, nausea, vomiting and abdominal pain may occur within
an hour. After absorption by inhalation or through skin, it causes

irritation of eyes, nose, throat, dermatitis and dilated pupils, blurring
of vision, cough and pulmonary edema. With mild poisoning headache,
anorexia, fatigue and aching of limbs, irritability and mental apathy
may occur. Moderate and severe intoxication cause symptoms of
hyperexcitability of CNS such as twitching of eyelids, muscular tremors
and fibrillations, myoclonus, convulsions (may be generalized) and
incoordination. The symptoms of hyperexcitability is followed by
CNS depression, paralysis of limb muscles, cyanosis, labored respiration
and coma. Death results from respiration failure or ventricular
fibrillation. Prolonged exposure to DDT results in anorexia, emaciation,
mild anemia, headache, blurring of vision, ataxia, convulsions and
coma and clinical features are those of damage to vital organs like
heart, liver and kidneys. Experimental evidences suggest that long-
term exposure may lead to neoplastic changes at various sites.
Treatment
In mild intoxication, the clinical manifestations usually pass off rapidly
without any treatment. In moderate and severe intoxication treatment
should be begun immediately.
Gastric lavage should be done to remove unabsorbed poison, if
intoxication occurs by accidental ingestion. This should be followed
by saline catharsis, oily purgatives such as castor oil and oils fat and
milk should be avoided because these enhance the absorption. In case
of skin contamination, wash the skin with soap and water, change the
clothing to prevent skin irritation and further absorption. Airway
should be maintained and oxygen should be administered in the
presence of cyanosis. In severe cases artificial respiration may be
required.
The signs of hyperexcitability of CNS should be treated with either
parenteral barbiturates or diazepam.
Adrenaline and other sympathomimetic drugs should be avoided
as they induce ventricular fibrillation. If ventricullar fibrillation occur,
they should be treated with lidocaine or defibrillators. The other
conservative measures should be employed if necessary.
In chronic intoxication, the treatment is symptomatic and all
measures should be taken to prevent further exposures. If there is liver
and kidney damage, low fat, high carbohydrate and protein diet
should be given together with appropriate conservative management.
Phenobarbitone 4-6 mg/kg/day in two divided doses may be given
for tremor and convulsions and antibiotics are indicated in the presence
of infection.
Prognosis
In mild intoxication, the recovery is complete and rapid. In moderate
and severe intoxication, presence of severe and protracted convulsions
indicate bad prognosis and recovery is unlikely. If the symptoms
remain confined only to tremors, recovery is complete within one to
two months.
ENDRIN
Endrin including chlordaine, heptachlor, aldrin, dieldrin, diendrin are
Indane derivatives, i.e. polycyclic polychlorinated hydrocarbons. They
are soluble in organic solvent but insoluble in water. Of all the
polychlorinated insecticides, endrin is the most toxic and most popular
insecticide used against pests that infest paddy and other plants. It
is used in the form of dust or solutions and its wide spectrum of
activity justifies its alternative name, plant penicillin. Endrin is
available in the market as 20-50 percent solution in petroleum
hydrocarbon such as aromax, which smells like kerosene. Absorption
occurs through all routes. Its pharmacological actions are similar to
DDT.
Fatal dose: Toxic symptoms appear with a dose of 0.5 to 1 gm and
the lethal dose is 3 to 6 gm.
Fatal period: The fatal period ranges from 30 minutes to several
hours, majority die within an hour or two.
The onset of symptoms and signs is very rapid. The principal
manifestations are vomiting, abdominal pain, tremors, convulsions,
oozing of fine white froth Key Points
occasionally blood stained from
both mouth and nostrils and Diagnosis
severe dyspnea. With passage 1. History
of time, the convulsions become 2. Clinical featuresmild bodyache,
severe and continuous, follo- irritation of eyes, nose, throat, blurred
wed by coma, respiratory vision, cough, pulmonary edema,
myoclonus, convulsions.
failure and death.
Management
Treatment
1. Decontamination of skin
Treatmet is palliative. External 2. Gastric lavage
contamination should be 3. Saline cathartics
washed off with copious 4. Other symptomatic and supportive
amount of water. Soiled clothes measures
5. 10 percent calcium gluconate IV for
should be removed imme-
endrin poisoning.
diately. Proper care of airways
should be taken. Parenteral barbiturates and dazepam should be used

to control convulsion. Calcium gluconate 10 percent solution
intravenously should be given as it decreases the toxicity of endrin.
Prognosis depends on the time taken for the onset of convulsion with
if appear later than one hour or are readily controlled carry the best
prognosis.
GAMMEXANE
Benzene hexachloride exists in several isomeric forms and gamma
isomer is known as Gammexane. It is mixed with inert clay and used
widely as a spray or dust for killing insects. Dry powders are poorly
absorbed from digestive tract while in solutions they are readily
absorbed from skin, gastrointestinal and respiratory tracts. The
pharmacological action and clinical manifestations are the same as
with DDT, indane derivative and endrin. It produces aplastic anemia.
Inhalation of dust causes irritation of respiratory mucosa while
conjunctivitis, rhinitis and dermatitis may result from local contact
with eyes and skin. The treatment is symptomatic.
ZINC PHOSPHIDE
Zinc phosphide is a steel gray crystalline powder with a garlic odour,
widely used as a rodenticide. Inhalation of dust, accidental or suicidal
ingestion can give rise to fatal poisoning in children. Zinc phosphide,
on contact with dilute acid in stomach and on exposure to moisture
liberates phosphine gas which is a very potent respiratory poison.
Fatal dose and fatal period: The fatal dose is 5 gram and fatal period
is upto 24 hours.
Clinical Features
Early features of intoxication are nausea, vomiting and diarrhea owing
to irritant effect of phosphine on GI tract and development of diffuse
gastroenteritis. Abdominal pain, fever, cyanosis and respiratory distress
may occur later. Peripheral vascular collapse may result from
arrhythmias and myocarditis due to phosphine. In survivors the healing
of gastrointestinal tract may be associated with strictures of esophagus
or pylorus.
Treatment
Removal of unabsorbed poison should be done immediately by gastric
lavage with a 1:1000 solution of potassium permanganate. Gastric
lavage is followed by saline catharsis, oil-based cathartics being
contraindicated. Fluid and blood loss should be corrected to prevent

peripheral vascular collapse. The patient should be monitored carefully
for hepatic and renal function. The needful symptomatic and supportive
treament should be administered.
SODIUM FLUOROACETATE
It is commonly used rodenticide and is also applied as spot bait in
cereal or vegetable fields. It is marketed as compound 180, which is
colorless, odorless and tasteless. Secondary toxicity usual occurs in
human beings but acute intoxication may occur following ingestion.
Sodium fluoroacetate is well absorbed through gastrointestinal tract
and poorly absorbed through gastrointestinal tract and poorly absorbed
through skin and respiratory routes.
Following absorption, it is excreted mainly via urine and small
amount is excreted through respiratory tract. In the body, substitution
by fluoroacetate occurs in the citric acid cycle where normal acetate
is replaced by fluoroacetyl Co-A. This eventually inhibits the conversion
of citrate to isocitrate thus blocking citric acid cycle. The predominant
effect is on myocardium.
The clinical manifestations usually occur after one hour. Principal
cardiovascular manifestations are chest discomfort, palpitation and
arrhythmias. Central nervous system may be affected, in the form of
generalized convulsions followed by central nervous system
depression.
Management
If the patient is alert, emesis should be induced to prevent absorption
of remaining poison. If the patient develops CNS depression or
convulsions, then endotracheal intubation should be performed and
gastric lavage is done with activated charcoal. This should be followed
by a cathartic such as magnesium sulphate. Convulsions should be
treated symptomatically with parenteral diazepam, 0.1-0.3 mg/kg/
dose. Patient should be closely monitored for cardiovascular changes
and treated appropriately. The toxic symptoms and signs usually
subside within 24 hours.
NICOTINE
Nicotine is an alkaloid of tobacco plant (Nicotiana tobaccum) cultivated
in tropical regions of many parts of the world and is an ingradient
of several insecticides. Nicotine poisoning results either from cutaneous
absorption or inhalation of nicotine dust or spray. The dried and

processed leaf of tobacco is used for cigarettes, cigars and bidi. Tobacco
is chewed with Paan and in the powder from it is used as snuff.
Tobacco ingredients and nicotine are used as insecticides. Agricultural
workers who handle such insecticides may exhibit symptoms of
poisoning due to inhalation of dust or spray or due to cutaneous
absorption. Poisoning is mostly accidental but suicidal and homicidal
cases have been reported. Accidental poisoning results due to ingestion,
excessive smoking or application of leaves and juice on the wound
or skin. Tobacco leaves are soaked in water for some hours and placed
in axilla at bedtime for malingering. The symptoms of poisoning
appear next morning.
Mode of action: It acts on the autonomic ganglia and causes initial
stimulation followed by depression and blockage at later stage.
Fatal dose: 60 mg of nicotine (15 to 30 gm of crude tobacco or 3
to 4 drops of the alkaloid) may prove fatal. It rivals cyanide as a
poison apable of producing rapid death.
Fatal period: 5 to 15 minutes.
Clinical Features
In nicotine poisoning burning sensation develops from mouth to
stomach following ingestion. Nausea, vomiting, excessive salivation
and purging also occurs. Dizziness, headache, perspiration and general
weakness may be present. Numbness, mental confusion, depression
and audiovisual disturbances
develop rapidly in acute Key Points
poisoning. Patients may get
attacks of convulsion. Tremor Diagnosis
and cardiovascular collapses 1. History
may appear and child may 2. Clinical features: Burning from mouth to
ultimately go in coma. Pupils stomach, numbness, confusion, convul-
sion, cardiovascular collapse and coma.
are at first constricted and
Initially pupillary constriction followed by
later becomes dilated. Initially, dilation.
pulse is slow but later
becomes rapid. Cardiac arrhy- Management
thmias may occur. Initial rapid 1. Skin decontamination
and labored respiration is 2. Stomach wash with potassium perman-
followed by a stage of dep- ganate
ression, which is characterized 3. Oral activated charcoal
by slow and sighing res- 4. A purge and colonic washout
5. Symptomatic and supportive manage-
piration. Death occurs from
ment.
Treatment
1. Stomach wash with warm water containing potassium perman-
ganate, Tannic acid or iodine. This should be followed by oral
activated charcoal.
2. For skin contamination, remove soiled garments, and wash skin
with copious amount of waters.
3. Purgation and colonic wash may be needed.
4. If respiration is impaired, artificial respiration with positive pressure
ventilation and respiratory stimulants are indicated.
FLUORIDES
Sodium fluoride, a white powder is used as a poison to kill rats and
cockroach. Powders like sodium silicofluoride, fluoroacetamide and
fluoroacetate are used as rodenticides. Careless handling may result
in accidental poisoning when sodium fluoride is mistaken for baking
powder. It may be used as a suicidal poison. Fluoride compounds
react with acid in the stomach forming highly corrosive hydrofluoric
acid. After absorption fluoride ions bind with calcium, potassium and
magnesium ions and cause hypocalcemia, hypokalemia and
hypomagnesemia. Fluoride ions inactivate proteolytic and glucolytic
enzymes and act as a general protoplasmic poison.
Fatal doses: 5 mg/kg body weight.
Clinical Feature
Acute poioning by ingestion is characterized by severe burning pain
in the mouth, throat and epigastrium, thirst, salivation, nausea,
vomiting, diarrhea, hematemesis and hematuria. Death may occur
within minutes from respiratory and cardiac failure.
Treatment
1. Stomach wash with limewater or milk.
2. Skin contamination with vomitus should be washed with calcium
chloride solution. Calcium orally or 10 percent calcium gluconate
should be given intravenously.
3. Parenteral fluids, potassium and magnesium supplements may be
required. Intravenous lidocaine and defibrillation may also be used
in cardiac arrhythmias.
PYRETHROID
Pyrethroids, a common insecticides are ubiquitous in modern
households. This is widely available in market as mosquito coil, mats
and liquid form as mosquito repellant or as killer and considered as

safe for human beings.
Pathophysiology
Pyrethroids are generally considered to be safe in humans because of
their rapid biotransformation in body by ester hydrolysis and their
hydroxylation to their inactive acids and alcohol components.
Pyrethroids are of two types, i.e. type I: Allethrin and type II:
deltamethrin and felvalerate. Allethrin, which lacks a cyano group,
causes repetitive discharges in nerve fibers by acting on sodium channel
leading to hyperexcitation where as deltamethrin and felvalerate causes
nerve membrane depolarization and block leading to paralysis. In
addition Allethrin also acts on calcium channel and causes blockage.
The exact fatal dose is still unknown but ingestion one coil/ mat may
be fatal in children. In children poisoning is usually accidental but
may be suicidal in adolescent.
In toxic doses, it may causes ataxia, loss of coordination, hyper-
excitation, tremor , unconsciousness and seizures. Seizures are usually
generalized and may lead to sudden respiratory arrest and death.
Clinical manifestations usually last for 24-36 hours.
Diagnosis
1. H/O of ingestion
2. Characteristic clinical manifestations
There is no definite diagnostic test for diagnosis but gastric aspirate
sample should be sent for analysis of chemical examination.
Treatment
Treatment is usually symptomatic and supportive. Care should be
taken for airway, breathing and circulation. Stomach wash should be
done if children are brought in emergency within 6 hours of ingestion.
If patient have ongoing seizures, seizures should be controlled
preferably with benzodiazepines, i.e. diazepam, midazolam or
lorazepam. Phenobarbiturates should be avoided. No specific antidote
is available till date for Allethrin, deltamethrin and felvalerate
BIBLIOGRAPHY
1. Davis JH. Occurrence, diagnosis and treatment of organophosphorus
poisoning in man. New York Academy of Sciences Symposium on Biological
effects of Pesticides, 1967.
2. Dipalma Joseph R. Human toxicity from rat poisons. Am FAM Physician

1981;24:186-89.
3. Eto M. Organophosphorus pesticides: Organic and biological chemistry
Cleveland CRC Press 1974;218.
4. Garg P. Mosquito coil(Alletrin) poisoning in two brothers. Indian Pediatr.
2004;41:1177-78.
5. Godoth N. Late onset neuromuscular blocks in organophosphate poisoning.
Ann Intern Med 1978;88(5):654.
6. Koelle GB. Anti-cholinesterase agents In: Goodman L, Gilman A: The
pharmacological Basis of Therapeutics, New York 1975;442-63.
7. Mishra D, Singh H. Cypermethrin poisoning in a pediatric patient. Pediatric
Today 2003;6:322-24.
8. Namba T. Poisoning due to organophosphate insecticides. Acute and chronic
manifestations. Am J Med 1971;50(4):47592.
9. Peardon DL. New Selective Rodenticide Pest Control, 1974;42:14-27.
10. Quinby GE. Further therapeutic experience with pralidoxime in organic
phosphorus poisoning. JAMA 1984;137:202-06.
11. Repkin R, et al. Organophosphate Insecticide Poisoning Pediatric Conference.
1971;14(2):6-7.
12. Rumack BH. Poisindex Englewood, Co. Micromedex Inc. Publishers, 1981.
13. Wadia RS. Neurological manifestations and organophosphate insecticide
poisoning. J Neurol 1974;37(7):841-47.
14. Zavon MR. Poisoning from pesticide diagnosis and treatment. Pediatr
1974;54:332-36.
8
Salicylate Poisoning
Salicylate poisoning is one of the most common and dangerous forms

of poisoning in children. It may result from (i) overdosage in an
already sick child, accidental ingestion or deliberate self-poisoning,
(ii) use of oil of wintergreen, salicylate powder or ointment on broken
skin. In neonate and infants, salicylate intoxication may occur
inadvertantly through placental transfer, breast milk or by application
of teething gels to gums.

The primary pathophysiological effects of salicylate intoxication include
direct stimulation of the central nervous system, the respiratory center,
and uncoupling of oxidative phosphorylation. There is inhibition of
Kerbs cycle enzymes, stimulation of gluconeogenesis, and increased
tissue glycolysis. Lipid metabolism is stimulated while there is
inhibition of amino acid metabolism and interference with hemostatic
mechanism. Secondary and tertiary effects of salicylate intoxication
include respiratory alkalosis with excretion of acid, Impaired glucose
metabolism and fluid and electrolyte loss. The respiratory stimulation
caused by salicylate intoxication is characterized by increase in both
the depth and rate of respiration which results in increased exhalation
of CO2 and decreased pCO2 leading to an increase in blood pH and
a compensatory increase in renal excretion of bicarbonate. Thus early
in the course of salicylate intoxication, there is respiratory alkalosis
and urine becomes alkaline. Concurrently other mechanisms are at
work that lead to metabolic acidosis. Inhibition of Kerbs cycle enzyme
results in accumulation of both pyruvic and lactic acids. Increased
metabolism and peripheral demand for glucose, then stimulates lipid
metabolism which leads to increased formation of ketone bodies,
inhibition of aminotransferases causes an increase in level of amino
acids and aminoaciduria. Taken together these changes produce a
decrease in plasma pH and excretion of organic acids (aciduria).
Children under 4 years may develop poisoning due to prolonged

therapy hence, initial phase of respiratory alkalosis is less prominent
whereas metabolic acidosis is readily detected.
Fluid and electrolyte imbalance is frequently associated with
salicylate intoxication and results from increased metabolism and heat
production leading to increase cutaneous insensible loss, organic
aciduria accompanied by increased excretion of sodium, potassium
and water, gastrointestinal loss due to emesis, increased pulmonary
insensible loss due to increased respiratory rate. In severe intoxication,
the child may loss 4-6 liters/m2 of fluid.
The poisoning may be associated with coagulation disorders
especially hypoprothrombinemia due to warfarin like effect on vitamin
K1 epoxide cycle. Normally vitamin K is converted to vitamin 2,3-
epoxide and then reconverted to vitamin K, by reductase enzyme,
which is inhibited competitively by warfarin and salicylate. Thus results
in deficiency of vitamin K1 dependent factors II, VIII, IX and X as
vitamin K1 is essential for post-transational Y-carboxylation of glutamyl
residues.
Fatal dose: 200 mg/kg body weight is always toxic (less than 100
mg/kg-body weight is usually safe).
Fatal period: Usually symptoms appear after 1-3 hours in acute
intoxication but the fatal period varies from a few minutes to several
hours. A 5 months old infant died within 10 hours after ingestion of
2 gm aspirin.
Clinical Features
Young children are more severely affected. A mixed acid-base
disturbance occurs with respiratory alkalosis followed by metabolic
acidosis. It can affect all the systems of the body.
General Features
The face is red and swollen. There is profuse sweating. The temperature
is either subnormal or raised (due to increased metabolism). Paresthesia
and muscle weakness may occur.
Gastrointestinal
Nausea, vomiting, epigastric pain, hematemesis, malena due to
irritation of gastric mucosa.
Respiratory
Tachypnea and hyperpnea initially followed by acidotic breathing (to
direct stimulation of respiratory center).
Salicylate Poisoning 133
Catecholamines
Flow chart 8.1: Pathophysiology of salicylate intoxication
CNS
Headache, vertigo, lethargy, drowsiness, excitement, talkativeness,
mental confusion, convulsion and coma. The mental changes are termed
as salicylate jag.
Cardiovascular
Tachycardia (weak and rapid pulse) due to direct paralysis of vasomotor
center.
Vision and Hearing

Tinnitus, deafness and blurring of vision.
Renal
Oliguria or anuria.
Fluid and Electrolyte Disturbances

Dehydation, hyper or hyponatremia are common due to profuse
sweating, vomiting and overbreathing.
Coagulation System
There is bleeding tendency due to decreased platelet aggregation and
defective prothrombin synthesis.
Metabolic Disturbances
Initially respiratory alkalosis due to stimulation of respiratory center,
followed by metabolic acidosis. Sometimes hypo/hyperglycemia and
glycosuria have been noticed.
Clinical features and lab investigations
Usual Unusual Lab investigation
Disorientation Bleeding Hypoglycemia/hyperglycemia

Nausea, vomiting Pulmonary edema Hyponatremia/hypernatremia
Dehydration Acute tubular necrosis Hypokalemia
Hyperpnea
Hyperpyrexia Hepatotoxicity Acidemia
Oliguria Nephrotoxicity Hypoprothrombinemia
Tinnitus Hemolysis Abnormal liver function tests
Bronchospasm Altered renal function test
Complications of Salicylate Intoxication

Complications are acute drug induced hepatitis, Reyes syndrome,
cerebral edema and acute renal failure. GI bleeding, severe
cardiovascular collapse and respiratory failure.
Laboratory Investigations
For accurate assessment of the severity of salicylate intoxication, blood
level determination should be done at 6 hours or more after ingestion
of the salicylate. The blood salicylate level is one of the best indicator
of severity of the intoxication.
Blood salicylate level Severity of poisoning

(at 6 hours)
<50 mg/dl Mild

50-100 mg/dl Moderate
>100 mg/dl Severe
Serial salicylate levels estimation at 4 to 6 hours interval should be

done. There may be hypoglycemia, or hyperglycemia, hyponatremia
or hypernatremia, hypokalemia, elevated pyruvate and lactate,
acidemia, hypoprothrombinemia, abnormal liver and renal functions.
Treatment
The basic principles of poisoning management are applied with
salicylate intoxication also these include stabilization of airway,
restoration of circulation, removal of drug from the body and correction
of acidosis and the related complications.
Gastric emptying is done by using syrup of ipecac as an emetic.
If emesis is not successful, then gastric lavage is done and at the end
of lavage, activated charcoal along with cathartic is left in the stomach.
Since there is no specific antidote available for salicylate, supportive
therapy plays a vital role in the management of salicylate intoxication.
The primary objective is correction of metabolic imbalances and
enhancement of drug elimination.
Fluid therapy in a patient of salicylate intoxication is crucial, the
guidelines of fluid therapy is given in the following table.
Composition of fluid (mEq/L)
Rate of administration
ml/kg/hour Duration Na+ K+ Cl HCO3 Dextrose
Initial hydration 10-15 1-2 hours 75 0 50 25 5-10%

Subsequent hydration 4-8 3-8 hours
Until salicy-
late level
becomes
therapeutic *40 35 50 *20 5-10%
Maintenance 2-3 As per necessity 25 20 25 20 5%
* In case of persistent acidosis, these constituents should be increased by addition of 15

mEq/liter NaHCO3
Note: For severe acidosis (pH < 7.15) give an additional 1-2 mEq/kg
NaHCO3 every 1-2 hours. Usual fluid loss approximates 200-300 ml/
kg. Suggested minimum urine flow 5-10 ml/kg/hour.
If the above solution if not available then 0.25 percent normal saline
with appropriate addition of sodium bicarbonate can be used. Fluid
administration must be monitored carefully to avoid pulmonary
edema or fluid retention. Shock is treated with 5 percent albumin or
plasma in a dose of 10 ml/kg. Since neuroglycopenia may occur even
in the presence of normal blood glucose, glucose administration is
essential.
For elimination of absorbed Key Points

salicylate, forced diuresis
coupled with alkalinization of Management
urine is essential. This is achie- 1. Gastric emptying preferably by emesis
ved by administration of high 2. Activated charcoal
doses of sodium bicarbonate 3. Catharsis
(1-2 mEq/kg) over 1-2 hours 4. Fluid and electrolyte therapy
with adjustment of dose and 5. Correction of acid-base disturbances
6. Glucose administration
careful monitoring of the urine
7. Alkalinization of urine
to maintain the pH at level of 8. Diuresis
8.0 or more. This enhances 9. Hemodialysis, hemoperfusion or peri-
urinary excretion and decreases toneal dialysis
serum level of salicylates.
Unfortunately this urine pH is very difficult to achieve with sodium
bicarbonate unless it is combined with acetazolamide. Close monitoring
of fluid and electrolyte status must be maintained during forced diuresis.
Seizures should be controlled with phenobarbitone (5 mg/kg) or
diazepam (0.2 mg/kg/dose). Hypocalcemic tetany is treated by 10
percent solution of calcium gluconate and prolonged prothrombin
time by parenteral administration of vitamin K. Naloxone should be
given parenterally if there is history of associated opioid ingestion. For
patients with cardiogenic pulmonary edema, digitalis is the drug of
choice. If the patient develops respiratory failure, supportive ventilation
may help.
Indications for Hemodialysis or Hemoperfusion

1. Clinical features:
i. Renal failure
ii. Persistent CNS manifestations
iii. Non-cardiogenic pulmonary edema
iv. Progressive deterioration of patient.
2. Unresponsive acidosis (pH < 7.1).
3. Blood salicylate level: Initial level 90 mg/dl and 100 mg at 6 hours
after ingestion.
Hemodialysis is preferred over hemoperfusion or peritoneal dialysis,
if facilities are available. The unfavorable prognostic indicators of
salicylate intoxication are prolonged seizures, severe respiratory
acidosis, hypoglycemia and life-threatening bleeding.
BIBLIOGRAPHY
1. Anderson RJ, Potts DE, Gabow PA, et al. Unrecognized adult salicylate
intoxication. Ann Intern Med 1976;85:445.
2. Done AK, Temple AR. Treatment of salicylate poisoning. Med Treat 1971;
8:528-51.
3. Done AK. Salicylate intoxication. Significance of measurements of salicylate
in blood in cases of acute ingestion. Pediatr 1960;26:800-07.
4. Lawson AA, Proudfoot AT, Brown SS, et al. Forced diuresis in the treatment
of acute salicylate poisoning in adults. QJ Med 1969;38:31-48.
5. Temple AR. Acute and chronic effects of aspirin toxicity and treatment. Arch
Int Med 1981;141:364-69.
9
Acetaminophen
(Paracetamol)
Acetaminophen is the most widely used antipyretic and analgesic.

It is a combination agent in approximately 125 medications that has
been deemed safe and effective when used within recommended
dosage. Its therapeutic safety in children has been directly related
to absence of significant cumulative kinetics. In USA, 203,930 cases
of acetaminophen overingestion were reported to US Poison centers
between 1998 and 1999, making it the leading pharmacologic agent
associated with toxicity. It is freely available in the market and its
use is widely known to general public. Careless approach of family
members towards its use and storage results in high incidence of
accidental overdose in children particularly below the age of 6 years,
less common but potentially more devastating is the suicide attempt
as manipulative episode in the adolescent.
Experience with acetaminophen overdosages further indicates a
considerable difference between children under age 6 years and
adolescent. Following ingestion of sufficient acetaminophen to produce
potentially toxic blood level, an adolescent is six times more likely
to develop evidence of hepatotoxicity than in a child under age of
6 years. Adolescents are two times more likely to develop potentially
toxic blood levels. The course following overdose in adolescents is
indistinguishable from that of adults.
Pathophysiology
The prime target organ of acetaminophen toxicity is liver. In addition
to hepatotoxicity, renal tubular damage and hypoglycemic coma may
also occur due to toxic action of active intermediate metabolities.
Acetaminophen is rapidly absorbed after therapeutic dose and
produces peak plasma level in half of one hour. In overdose, this
Acetaminophen (Paracetamol) 139
absorption may be delayed as long as 4 hours. The volume of

distribution and half life of acetaminophen with normal liver function
are 1 L/kg and 1 to 3 hours respectively. The drug is metabolized
in liver with less than 2 percent being excreted unchanged in urine.
In children, between 9 to 12 years of age, Acetaminophen is
primarily metabolized in the liver to the sulfate or glucuronide
conjugates, which are metabolically inert. The remaining 2 to 4
percent is metabolized through cytochrome p450 mixed functions
oxidase system, which conjugates it with glutatione to produce
mercaptopuric acid, a non-toxic product. The lower incidence of
toxicity in young children may be related to lesser metabolism via
p450.
With acetaminophen overdose, when hepatic stores of glutathione
are depleted to less than 70 percent of normal, the highly reactive
intermediate toxic metabolites bind with hepatic macromolecules
and cause hepatic necrosis. Hepatic enzyme induction by barbiturates,
narcotics, hydantoin and histamines may increase the formation of
reactive metabolites, predisposing the patient to hepatic damage
even if a minor overdose of acetaminophen is ingested. Co-ingestion
of ethanol and acetaminophen is cytoprotective in both adults and
children, probably as a result of competition at p450 site but ethanol
is not recommended as therapy.
Chronic acetaminophen poisoning is rare as approximately 98
percent of the drug is metabolized by liver, children receiving
therapeutic doses of acetaminophen over a long time should have
no difficulty in managing the small load of toxic metabilites with
constantly regenerating glutathione stores in liver. Therapeutic
accumulation to plasma levels of 40 g/dl which is still under that
required for hepatotoxicity may occur if the highest recommended
dose of 15 mg/kg is given every 4 hours for extended period, child
abuse or intentional overdose must be considered in children who
develop high plasma levels at therapeutic overdose. Severe liver
damages occurs in most of the patients with plasma concentration
of acetaminophen greater than 300 g/ml at 4 hours or 45 g/ml at
15 hours after ingestion of the drug.
Fatal dose: 20-25 gm.
Fatal period: 2-7 days.
Clinical Features
Children with overdose of acetaminophen usually present with
features of hepatic cell damage, renal tubular necrosis and
hypoglycemic coma. They pass through following four stages of

toxicity, if left untreated.
Stage I This stage lasts for first 24 hours after ingestion. Average time
of onset of symptoms is 6 hours after ingestion and all symptoms
develop usually by 14 hours. In this stage the child presents with
anorexia, nausea, vomiting, malaise, pallor and diaphoresis. Children
less than 6 years of age rarely
show diaphoresis but present Biochemical and hemotological
with early vomiting. Laboratory abnormalities in paracetamol poisoning
investigation such as SGOT, Biochemical:
SGPT, serum bilirubin and ALT/AST
prothrombin time are normal in Bilirubin
this stage. Blood sugar
Lactase
Stage II This stage lasts for next Amylase
24 hours after stage I. It is Creatinine
Phosphate
characterized by resolution of
symptoms of stage I with upper Hematological
quadrant abdominal pain and Thrombocytopenia
tenderness. Mild hepatomegaly Prothrombin time
and jaundice may also be present. Clotting factors II, V, VII
Laboratory investigations show
elevated serum bilirubin, AST, ALT and prothrombin time. Some
children may develop oliguria.
Stage III This stage is seen 48 to 96 hours after ingestion. Maximum
liver function abnormalities are seen during this period.
Hepatotoxicity due to acetaminophen is characterized by elevated
transaminases, increased serum bilirubin level and prolonged
prothrombin time.
Plasma AST level in excess of 1000 IU/L, prolongation of
prothromption time and serum bilirubin more than 4 mg/dl, on third
to fifth day after ingestion are indicators of severe hepatotoxicity.
Acute renal failure may also occur in some patients. Anorexia, nausea,
vomiting, malaise may reappear during this stage. Less than 1 percent
of patients in stage III develop fulminant hepatotoxicity and eventually
die of hepatic failure, if not treated specifically. Liver biopsy in this
stage reveals centrilobular necrosis of hepatocytes with sparing of
periportal area.
Stage IV This is the stage of resolution and extends from four days
to two weeks. It is characterized by resolution of hepatic dysfunction

although AST may remain elevated for few more days. On follow-
up of patients with hepatotoxicity, usually no sequelae is revealed
either clinically or on liver biopsy, three months to one year later.
Diagnosis
3. Laboratory investigations:
a. Plasma level of acetaminophen: to assess the severity of
hepatotoxicity. Serum concentrations greater than 200, 100
and 50 ug/ml at 4, 8 and 12 hours after ingestion respectively,
or any concentration above the values leveled on the Rumack
Mathew normogram indicates a potential risk of hepato-
toxicity.
b. Plasma AST level greater than 1000 IU/L.
c. Bilirubin more than 4 mg/dl.
d. Prolonged prothrombin time.
Management
Assessment
In children with acetaminophen overdose, efforts should be made
to determine the amount of drugs or other co-ingestants which may
also have been involved. Acetaminophen alone will not produce any
alteration in the sensorium in first 24 hours and usually will not
produce such an alteration unless patient develops hepatic encephalo-
pathy. Thus if a patient comes with a significant change in sensorium,
some other agents should be considered in addition to or instead
of acetaminophen care of airways, breathing and circulation should
be done properly. A sample of blood should be drawn and sent for
laboratory investigations including serum acetaminophen level.
General Measures
When a child presents with a history acetaminophen overdose within
4 hours, gastrointestinal decontamination should be done. Emesis
should be induced with syrup of ipecac to get rid of remaining
acetaminophen. Gastric lavage must be done with normal saline.
Activated charcoal is effective in adsorbing acetaminophen. In
physiological pH range, adsorption is rapid and pH independent.
The dose of activated charcoal is 10 times the ingested dose of

acetaminophen. Activated charcoal appears to reduce the number of
patients who achieve toxic acetaminophen concentrations and thus
may reduce the need for treatment and hospital stay. For maximal
effect, activated charcoal should be administered within 30 minutes
of ingestion. However, in vitro experiments, activated charcoal
effectively adsorbs both methionine and N-acetylcysteine, concurrent
administration of both would markedly diminish their anti-dotal
effectiveness.
Specific Measures
N-acetylcysteine is the specific antidote and drug of choice for
prevention of hepatotoxicity. Other drugs like methionine, cysteamine
are available but are not popular due to their side effect. Oral or
intravenous N-acetylcysteine mitigates acetaminophen induced
hepatorenal damage as demonstrated by prevention of elevation of
serum transaminases, bilirubin and prolongation of prothrombin
time, if given within 10 hours but becomes less effective thereafter.
In vivo, N-acetylcysteine forms L-cysteine, cystine, L-methionine,
glutathione and mixed disulfides; L-methionine also forms cysteine
thus giving rise to glutathione and other products. The beneficial
effects of N-acetylcysteine include improvement of liver blood flow,
glutathione replenishment, modification of cytokine production and
free radical oxygen scavening.
The oral dosage schedule of N-acetylcysteine is 140 mg/kg of
body weight as loading dose followed by subsequent doses of 70
mg/kg body weight at 4 hourly interval for an additional 17 doses.
If the patient vomits within an hour of administration of dose, it
should be repeated. If there is persistent vomiting, a nasogastric tube
should be inserted, preferably into the duodenum. The optimal route
and duration of administration of N-acetylcysteine are controversial.
On the basis of selected Post-hoc analysis, oral N-acetylcysteine was
found superior to intravenous route in presentations later than 15
hours. However, the differences claimed between oral and
intravenous N-acetylcysteine regimes are probably artifactual and
relate to inappropriate subgroup analysis. A shorter hospital stay,
patient and doctor convenience and the concerns over the reduction
in bioavailability of oral N-acetylcysteine by charcoal and vomiting
make intravenous N-acetylcysteine preferable for most patients with
acetaminophen poisoning. The administration of activated charcoal
before oral N-acetylcysteine in acetaminophen overdose does not
reduce the efficacy of N-acetylcysteine and may provide additional
hepatoprotective benefit. Key Points

However, some workers have
Management
suggested increment of
loading dose by 40 percent or i. Gastric lavage.
from 140 to 235 mg/kg body ii. Specific treatment: N-acetylcysteine,
Oral N-acetylcysteine: Loading:
weight.
140 mg/kg. Maintenance 70 mg/kg
Intravenous preparation of at interval of four hours for 17 such
N-acetylcysteine is also doses.
available but it is indicated only Intravenous-acetylcysteine:
when recurrent vomiting Loading 150 mg/kg IV.
In 5 percent Dextrose (200 ml) over
precludes the oral
15 min.
administration. The loading Maintenance: 50 mg/kg in 5 percent
dose is 150 mg/kg in 200 ml 5 Dextrose
percent dextrose, given over (500 ml) over 4-8 hours for 3 doses.
15 min followed by 50 mg/kg iii. Supportive treatment
diluted in 500 ml of 5 percent a. Correction of hypoglycemia
b. If prothrombin time ratio 3.0 pro-
dextrose administered over 4- phylaxis to combat hepatic ence-
8 hours for three doses. phalopathy.
Complications associated with c. If acute renal failurehemo-
IV use are anaphylactic dialysis.
reactions and hypokalemia. If d. Charcoal hemoperfusionrole and
efficacy, not proved.
patient develops wheezing,
flushing and hypotension, then
infusion should be stopped, hydrocortisone and an antihistaminic
should be given parenterally. IV infusion may be restarted later on
at slower rate.
As unpleasant odour and frequent vomiting is associated with its
use, the concentration of N-acetylcysteine should be diluted to a final
concentration of 5%(w/v) and to mask the unpleasant flavor, citrus
fruit juices or carbonated beverages should be added with intra-
venous preparations. Loading dose should be given with 200 ml of
5 percent dextrose over 15 mts followed by subsequent doses in 500
ml dextrose over 4-8 hours.
Nausea, vomiting and diarrhea may also occur as results of oral
N-acetylcysteine administration. Anaphylactoid reactions including
angioedema, bronchospasm, flushing, hypotension, hypokalemia,
nausea/vomiting, rashes, tachycardia and respiratory distress may
occur 15-60 minutes after N-acetylcysteine infusion in upto 10 percent
of patients. A reduction in the loading dose of N-acetylcysteine may
reduce the risk of adverse reactions while maintaining efficacy. Oral
therapy with N-acetylcysteine or methionine for acetaminophen
poisoning is contraindicated in presence of coma or vomiting or if
activated charcoal has been given by mouth. Hemodynamic and

oxygen delivery and utilization parameters must be monitored
carefully during delayed N-acetylcysteine treatment of patients with
fulminate hepatic failure, as unwanted vasodilatation may be
deleterious to the maintenance of mean arterial blood pressure.
The administration of N-acetylcysteine for longer period might
provide enhanced protection for patients in whom acetaminophen
absorption or elimination is delayed. N-acetylcysteine may also have
a role in treatment of toxicity from carbontetrachloride, chloroform,
1, 2-dichloropropane and other compounds.
Methionine acts by replenishing cellular glutathione stores or
more probably through generation of cysteine and/or glutathione.
It acts also as a source of sulphate and so unsaturate sulphate
conjugation. Methionine is more effective when given orally than IV.
The initial oral dose is 2.5 gm than 2.5 gm 4 hourly to a total of 10
gm over 12 hours.
During the course of treatment laboratory investigations should
be repeated. If the liver function tests begin to become abnormal,
proper measures should be taken. Once the hepatic failure occurs,
use of N-acetylcysteine is contraindicated and it shold be managed
along conventional line with lactulose, vitamin K, mannitol and
appropriate IV fluids. Renal function should be evaluated periodically
and necessary measures should be taken, if deterioration occurs.
Forced alkaline diuresis is of no therapeutic value. Haemodialysis
or charcoal hemoperfusion enhances elimination of acetaminophen
but not the toxic intermediate.
Prognosis
The poor prognostic factors in established paracetamol induced hepatic
failure are pH below 7.3, serum creatinine above 300 mmol/L and
prothrombin time above 100 secs in grade III to IV encephalopathy.
However, factor VIII to factor V ratio above 30 is the best poor
prognostic indicator.
BIBLIOGRAPHY
1. Buckley NA, Whyte IM, OConnell DL, Dawson AH. Activated charcoal
reduces the need for N-acetylcysteine treatment after acetaminophen
overdose. J Toxicol Clin Toxicol 1998;37:753-57.
2. Buckley NA, Whyte IM, OConnell DL, Dawson AH. Oral or intravenous
N-acetylcysteine: Which is the treatment of choice for acetaminophen
(paracetamol) poisoning? J Toxicol Clin Toxicol 1991;37:759-67.
3. Chamberlain JM, Gorman RL, Oderda GM, Klein-Schwartz W, Ktein BL.
Use of activated charcoal in a simulated poisoning with acetaminophen: A
new loading dose for N-acetylcysteine? Ann Emerg Med 1993;22:1398-1402.
4. Clark J. Acetaminophen poisoning and the use of intravenous N-

acetylcysteine. Air Med J 2001;20:7-16.
5. Flanagan RJ, Meredith TJ. Use of N-acetylcysteine in clinical toxicology. Am
J Med 1991;91:131-39.
6. James O, Lesna M, Roberts SH. Liver damage after paracetamol overdosage:
Comparison of liver function tests, fasting serum bile acids and liver
histology. Lancet 1975;2:579-81.
7. Jones AL. Mechanism of action and value of N-acetylcysteine in the treatment
of early and late acetaminophen poisoning: A critical review. J Toxicol Clin
Toxicol 1998;36:277-85.
8. Klein-Schwartz W, Oderda GM. Adsorption of oral antidotes for acetamino-
phen poisoning (methionine or N-acetylcysteine) by activated charcoal. Clin
Toxicol 1981;18:283-90.
9. Lich Lai MW, Sarnaik AP, Newton JE. Metabolism and pharmacokinetics of
acetaminophen in severely poisoned young child. J Pediatr 1984;105:125-28.
10. Miller RP, Robert RJ, Fisher LJ. Acetaminophen elimination kinetics in
neonates, children and adults. Clin Pharmacol Ther 1976;19:284-94.
11. Mitchell JR, Thorgeirsson SS, Potter NZ. Acetaminophen induced hepatic
injury. Clin Pharmacol Ther 1974;16:676.
12. Nahata Mc, Powel DA, Durell DE. Acetaminophen accumulation in a pediatric
patient after repeated therapeutic doses. Eur J Clin Pharmacol 1984;27:57-
59.
13. Peterson RG, Rumack BH. Age as variable in acetaminophen overdose.
Arch Intern Med 1981;141:390-93.
14. Riper W, Piperno E, Mosher AH, Berrssenbruesse DA. Pathophysiology of
acute acetaminophen toxicity: Implication for management. Pediatrics 1978;
62:880-89.
15. Rumack BH, Mathew H. Acetaminophen poisoning and toxicity. Pediatrics
1975;55:871-70.
16. Rumack BH, Peterson RC, Koch GG. Acetaminophen overdose: 662 cases
with evaluation of oral acetylcysteine treatment. Arch Intern Med 1981;
141:380-85.
17. Rumack BH. Acetaminophen overdosage in young children, treatment and
effects of alcohol and additional ingestions in 417 cases. Am J Dis Child 1984;
138:428-33.
18. Rumack BH. Acetaminophen overdose in young children. Am J Dis Child
1984;138:428-33.
19. Smilkstein MJ, Knapp GL, Kuling KW, Rumack BH. Efficacy of oral N-
acetylcysteine in the treatment of acetaminophen overdose. Analysis of
national multicenter study (1976 to 1985). N Engl J Med 1988;319:1557-62.
10
Barbiturate Poisoning
Barbiturates, white crystalline substances with bitter taste, are used

as hypnotic, sedative, anti-convulsant and short-term anesthetic agents.
They are so freely prescribed and easily available that they are ready
at hand when the impulse to commit suicide arises. Poisoning in
children is uaually accidental from over dosage. An uncommon type
of accidental poisoning, involuntary suicide or barbiturate
automatism, occurs in children who are taking usual dose of
barbiturate. The doses may be repeated several times in succession
due to mental confusion produced by the drug ultimately resulting
in fatal overdosage. The incidence in India has been variously reported
as 11 to 13 percent, it being 10 to 12 percent at Patna Medical College.
Based on duration of action, Barbiturates are classified into four
groups:
a. Long acting 8-12 hours Fatal dose 3-4 gm

Phenobarbitone
Barbitone sodium
Barbitone
Methyl phenobarbitone
b. Intermediate acting 4-8 hours Fatal dose 2-3 gm
Allobarbitone
Amylobarbitone
Aprobarbitone
Butobarbitone
Pentobarbitone
c. Short acting 2-4 hours Fatal dose 1-2 gm
Cyclobarbitone
Hexobarbitone
Quinalbarbitone
Quinal with amylobarbitone
d. Ultra-short acting For anesthetic purpose Fatal dose 1 gm
Pentothal sodium
Hexabarbital sodium
Kemittal sodium
Thiamylal sodium
Barbiturate Poisoning 147
Pathophysiology
Barbiturates decrease the excitability of all cells of central nervous
systems. Reticular formation of thalamus and midbrain are particularly
affected. Large doses depress respiratory and vasomotor centers. The
renal function may be impaired secondary to fall in blood pressure.
Barbiturates stimulate the production of ADH by neurohypophysis
and thus prevent diuresis. The basal metabolism and intestinal motility
are reduced.
Barbiturates are rapidly absorbed from gastrointestinal tract and
subcutaneous tissues. Then they are stored in liver for a short time
and later evenly distributed in body fluids. In general the long acting
ones are excreted in urine while the short acting stable compounds
are detoxified in the liver.
Lethal Blood Levels

1. Long acting - 10 mg/dl
2. Intermediate acting - 7 mg/dl
3. Short acting - 3 mg/dl
Fatal period: Usually ranges from 1-2 days.
Clinical Features of Acute Barbiturate Intoxication

The clinical features depend upon the amount and type of drug ingested
and the time elapsed since ingestion. In general, larger doses of long
acting preparations are required to produce the depth of unconscious-
ness comparable to that produced by short acting compound.
Mild Poisoning
The patient is drowsy and can be readily aroused by shaking or calling
name. There may be mild mental confusion, impairment of judgement,
emotional lability, disorientation, slurred speech, nystagmus and ataxia.
The reflex activity, blood pressure and aspiration are not affected.
Moderate Poisoning
The patient is usually in coma and can be aroused only by vigorous
stimuli. Reflexes, except corneal and pharyngeal ones, are depressed
or absent. Respiration is shallow.
Severe Poisoning
The patient is in deep coma and cannot be aroused. Respiration is slow
and shallow and may be Cheyne-Stokes type in character. Cyanosis
and pulmonary edema may be present. There is marked hypotension

due to direct action of barbiturate on cardiac and smooth muscles of
blood vessels. In presence of severe anoxia, rigidity of limbs, exaggerated
reflexes, ankle clonus and decerebrate rigidity are present. Involuntary
movements in the form of tremor and spasm may occur. Pupils are
contracted or even unequal. Skin lesions such as patches of erythema
and blisters may occur. In 6-8 percent cases bullous lesions occur on
the pressure area but are also found on the hand and feet. Fixed drug
eruptions and exfoliative dermatitis may occur. There may be jaundice
and hypothermia. Urine output could be severely reduced due to a
number of factors such as hypotension, anoxia and toxic action of
barbiturates on renal tubular cells.
The cause of death is usually respiratory failure. If recovery occurs,
headache, dizziness somnolence, diplopia, ptosis, ataxia and
hypotension may be present for several days.
Diagnosis
The diagnosis is based on history, clinical features and circumstantial
evidences like presence of tablets or capsules in gastric contents. The
poisoning resembles glutethimide intoxication except that pupils are
fixed and child has conversion reactions. It must be differentiated
from head injury, cerebrovascular accidents, brain tumors, meningitis,
encephalitis, hyper/hypoglycemic coma, uremia and narcotic
poisoning.
Investigations
1. Serum estimation of barbiturate: If the serum level of long acting
and intermediate acting barbiturates are more than 10 mg/dl and
33 mg/dl respectively they reflect a severe degree of intoxication.
2. EEG: The electroencephalogram provides useful evidence of
poisoning.
Mild Intoxication
The normal activity is replaced by fast activity in the range of 20-30
Hz, which appears first in frontal regions and spreads to parietal and
occipital regions as toxicity increases.
Severe Intoxication
The fast waves become less regular and are interpersed with 3 to 5
Hz slow wave activities.
In extreme overdosage, all electrical activity cases and EEG records
show a flat line.
Barbiturate Poisoning 149
Treatment Key Points

Children with mild to mode- Diagnosis
rate intoxication require no
1. History
vigorous treatment.
2. Clinical features: Confusion, drowsi-
Gastric lavage should be ness or coma according to degree of
done if the drug has been poisoning. Dilated pupil, extensor
ingested within 4-6 hours. The plantar reflexes, bullous skin eruptions.
patient is then watched for 3. EEG initial 20-30 Hz fast activity
signs of impending coma, the appearing in frontal region.
presence of which necessitates Severe cases - fast activity followed
by slow 3-5 Hz waves.
treatment for severe intoxi-
Extreme overdosage - isoelectric
cation. EEG.
Children with severe intoxi-
cation constitute pediatric Management
emergency. The aim of treat-
1. Gastric lavage
ment is to maintain adequate 2. Active supportive measures:
perfusion and pulmonary gas i. Circulatory collapse: IV crystalloid,
exchange and prevent compli- blood and dopamine,
cations. If ventilation is inade- ii. Inadequate ventilation: Artificial
quate or if the respiratory rate respiration.
3. Alkaline diuresis,
falls below 12 per minute,
4. Hemodialysis
artificial ventilation, preferably 5. Charcoal hemoperfusion
positive pressure ventilation
should be started. Circulatory collapse calls for IV administration of
crystalloid, plasma or whole blood. Pressor agent of choice is dopamine
which should be infused if necessary at a rate of 5-10 g/kg/min.
Continuous monitoring of rectal temperature and urine output is
mandatory. The urine may be alkalinized by giving sodium bicarbonate
to maintain urine pH in the range of 7.5-8.0, which facilitates excretion.
Hemodialysis and charcoal hemoperfusion are useful in removing the
drug from circulation. If the child remains in coma for more than 24
hours, prophylactic antibiotics should be given to prevent secondary
bacterial infections like hypostatic pneumonia.
On recovery, some children suffer a short period of Psychosis. They
may become hyperactive or agitated and sustain injuries from falls.
Continued supervision by a nurse or an attendant is essential.
Paraldehyde may be used to control agitation.
BIBLIOGRAPHY
1. Bireridge CW, Lanson AAH. Occurrence of bullous lesions in acute barbiturate
intoxication. BMJ 1975;1:835-37.
2. Narayan Reddy KS. The essentials of forensic medicine and toxicoloty. 1984;
444-46.
11
Hydrocarbon
With modern society baking, burning and running on hydrocarbon,

literally, the high incidence of hydrocarbon poisoning should hardly
raise an eyebrow. What follows is a partial list of commonly ingested
hydrocarbons with recommendations for their treatment (Table 11.1).
Table 11.1: Various groups of hydrocarbon
Viscosity Example Mode of removal
1. Very low Mineral sea oil Emesis

(furniture polish) contraindicated
2. Low Benzene, toluene Gastric lavage
aniline, nitrobenzene indicated
pine oil, camphor,
chlorinated hydrocarbons
pesticides with hydrocarbon
3. Low viscosity Gasoline, kerosene, lighter oil Gastric lavage not
Middle contraindicated but
often
hydrocarbon unnecessary
4. High viscosity Lubricating greases and Gastric lavage not
oils, motor oil required
Petroleum jelly,
Paraffin wax
Pathophysiology of Hydrocarbon Poisoning

Pulmonary damage is the principal threat associated with hydrocarbon
ingestion and inhalation. Hydrocarbons are potent-respiratory irritants
and contact with respiratory mucosa initiates a strong inflammatory
response. A bronchiolar exudate containing primarily polymorpho-
nuclear leukocytes may be found within hours of aspiration. This
may clinically manifest as bronchospasm, cough, rales and radiographic
changes. Another postulated mechanism of pulmonary damage is the
loss of surfactant with resultant increase in alveolar surface tension.
Pneumatoceles following hydrocarbon ingestion generally occur in
Hydrocarbon 151
the areas of lung where densest infiltrates are seen. The two
mechanisms postulated for pneumatocele formation are either necrosis
of pulmonary tissue or local obstruction leading to overdistension
and rupture of alveoli.
Hydrocarbons act as gastrointestinal irritants and may result in
an increase in peristalsis. Clinically this may manifest as nausea,
vomiting, abdominal pain, and diarrhea. However, gastrointestinal
bleeding is uncommon.
Arrhythmias after hydrocarbon ingestion, although rare, are
probably secondary to hypoxia, acidosis or the presence of toxic
substances in hydrocarbon base. Hydrocarbons also sensitize the
myocardium to endogenous catecholamines.
The CNS depression is related to anesthetic property of certain
hydrocarbons and other CNS manifestations are secondary to hypoxia.
Renal and hematological toxicity is usually the result of long-term
exposure.
Clinical Presentations
a. Asymptomatic
b. Features of pulmonary aspirations:
Cough, chest pain, tachypnea, wheeze
cyanosis and respiratory distress.
c. Fever: The presence of fever does not indicate bacterial infection.
This usually subsides after 24-48 hrs.
d. Gastrointestinal: Tender abdomen with hyperactive bowel sounds,
vomiting, diarrhea and rarely gastrointestinal hemorrhage.
e. Cardiovascular: Cardiac arrhythmias and congestive heart failure.
f. Neurological: CNS depression, euphoria, headache, vertigo and
ataxia.
g. Miscellaneous: Renal and hepatic damage, leukocytosis.
Admission Criteria following Hydrocarbon Ingestion

1. Admit immediately, if the patient has significant respiratory
symptoms or an abnormal chest radiograph.
2. Admit, if patient has significant CNS depression, severe gastro-
intestinal symptoms or has ingested a significant amount of
hydrocarbon.
3. Admit after observation, if respiratory symptoms are worsening
or if the chest radiograph is becoming progressively worse.
General Principles of Emergency Management of Hydrocarbon

i. Determine exactly the product ingested and the time elapsed
since ingestion.
ii. Record vital signs, mental status and pulmonary and gastro-
intestinal findings.
iii. Rule out pulmonary aspiration.
iv. If there is evidence of aspiration suggested either by history
or physical examination, order chest radiograph. If infiltrates
are demonstrated, admit the patient.
v. If the initial chest radiograph is normal, repeat two hours after
ingestion. If even this is normal and the patient remains
asymptomatic, the patient may be discharged. If however, the
repeat radiograph is abnormal, the patient should be admitted.
vi. There is no need of gastric emptying for commonly ingested
hydrocarbon not containing toxic additives.
KEROSENE OIL POISONING

Accidental kerosene oil poisoning continues to be a childhood menace
in India and other developing countries. The reported incidence of
kerosene oil poisoning varies from 33 to 60 percent amongst poisonings
in childhood and is the commonest accidental poisoning in India. The
high incidence of kerosene oil poisoning is obviously due to its easy
availability in most households more so in the poor households and
developing countries. Storage of K-oil in containers meant for drinking
water, easy accessibility and carelessness on the part of parents and
factors responsible for such as staggering incidence of K-oil poisoning.
Toddlers (1-3 years) are at greatest risk due to their natural curiosity.
Poisoning by these hydrocarbon results mainly from ingestion and
because of its low surface tension, this can easily be aspirated into
the lungs while vomiting and eructation. K-oil poisoning can also
result from inhalation of vapors and through transdermal route.
The principal threat from K-oil poisoning is aspiration, which can
occur during initial ingestion or following vomiting. There is no
correlation between aspiration and the amount of K-oil ingested.
Absorption through gastrointestinal tract is negligible unless large
volumes are ingested. Following aspiration, chemical pneumonitis
develops which may progress to atelectasis, pneumothorax or pleural
effusion. Interference with gaseous exchange in the lungs leads to
hypoxia, which is the reason for involvement of central nervous
system and other vital organs.
Fatal dose: 30 ml
Fatal period: 24 hours.
Clinical Features
After ingestion, there is usually burning pain in the throat, sensation
Hydrocarbon 153
of choking, cough, nausea, vomiting, colicky abdominal pain and

diarrhea. Other symptoms include breathlessness, fever, cardiac
arrhythmias, hemolysis, acute renal failure, gastrointestinal hemor-
rhage, seizures, cyanosis, drowsiness and coma. On auscultation
rhonchi and crepitations are heard. The pupils are first constricted
but become dilated later when coma supervenes. The breath, vomitus
and urine have peculiar odor.
On basis of clinical manifestations, Gupta et al devised a scoring
system to determine outcome and severity of kerosene poisoning.
They have taken account of four parameters and scored as follows:
Parameter Absent Present Others
Fever 0 1 -
Severe malnutrition 0 1 -
Respiratory distress 0 2 4 (presence of cyanosis)
Neurological symptoms 0 2 4 (presence of convulsion)
The score may range from 0 to 10 in a particular patient. If score

is 4 or more; significant risk and patients should to treated in a
hospital with facility for advanced life support. A score of 7 or less;
likely to survive whereas score 8 or more; risk of death several fold
higher. The predictive value of this scoring system is about 85
percent.
Key Points for K-oil Poisoning
Radiological Findings
Diagnosis
Chest X-ray exhibits fine, punc-
tate mottled densities in 2. Clinical features: Cough, tachypnea,
perihilar areas in early stage and chest pain, cyanosis, wheeze and a
latter patchy ill-defined densities characteristic breath odor.
may develop. Pneumonitis Arrhythmias and congestive heart
involves both lungs particularly failure.
Tender abdomen with hyperactive
the lower lobes. There may be bowel sounds. Seizure and coma.
evidence of pneumatoceles and 3. Radiological: Fine punctate mottled
later pneumothorax. densities in perihilar areas/pneumo-
nitis of lower lobes.
Management
The management is largely sup- Management
porative and includes care of Supportive therapy
respiration, circulation and Oxygen administration
sensorium. Oxygen adminis- Gastric lavage contraindicated
Antibiotics if there is evidence of
tration through hood or mask infection
should be given, if there are Observation for at least 24 hours.
respiratory symptoms and tachypnea. Gastric lavage is contraindicated,

except in a deeply comatosed child. Activated charcoal, cathartics,
steroids, mineral oil and olive oil have no role and are not
recommended in the management of K-oil poisoning. Antibiotics
should only be used when there are signs of pneumonia, in debiliated
children and if there are signs of acute infection. Routine prophylaxis
with antibiotics is not necessary.
Observation for at least 24 hours is essential as an initially
asymptomatic child may develop full-blown picture of K-oil poisoning
upto 24 hours after ingestion.
SOLVENT SNIFFING
The substances that may be sniffed include glue, polystyrene, cement
cleaning fluids, paints and varnishes, nail polish remover, petrol,
lighter fuel and aerosols.
Diagnosis
There may be physical signs of glue sniffing like smell of acetone
or papules and vesicles around the mouth and nose. Typical behavioral
effects like disinhibition, dizziness, ataxia, dysarthria, hallucinations
are also found. Prolonged and repeated inhalations may cause
convulsions, coma, cardiac dysrrhythmia, hepatic, renal and
Management
1. Treatment of the complications discussed above.
2. Detailed psychiatric evaluation and rehabilitation.
PETROLEUM AND DERIVATIVES

Petroleum derivatives include paraffin, paint thinner and their
substitutes. The worst effect of poisoning is pneumonitis, which
either starts immediately after ingestion due to concomitant inhalation
or upto 24 hours later due to absorption.
Management
1. Observe the child for 24 hours
2. Do not perform stomach lavage
3. If evidence of pneumonitis (cough, tachypnea crepitations) are
present, suitable antibiotics and steriods are recommended.
BIBLIOGRAPHY
Hydrocarbon 155
1. Baldachin B, Melmed RN. Clinical and therapeutic aspects of kerosene

poisoning. BMJ 1964;2:28-30.
2. Beamon RF, Siegil CJ, Landus G. Hydrocarbon ingestion in children: A six-
year retrospective study. JACEP 1976;5:771.
3. Burnners, Rovsing H, Wolf H. Roentgenographic changes in the lungs of
children with kerosene poisoning. Am Rev Res Dis 1964;89:633.
4. Eade NR, Taussing LM, Marks MI. Hydrocarbon pneumonitis. Pediatrics
1974;54:351.
5. Geehr E. Management of hydrocarbon ingestions. Topics in Emergency
Medicine 1 1979;3:110-97.
6. Gupta P, Singh RP, Murali MV, et al. Prognostic score for kerosene oil
poisoning. Indian Pediatr 1992;29:1109-12.
7. Mc Nally WD. Kerosene poisoning in children. J Pediatr 1956;48:296-99.
8. Rumack BH. Hydrocarbon ingestion: An opinion. National Cleaning House
for Poison Control Centers Bulletin, May-June, 1976.
9. Shirkey HC. Treatment of petroleum distillate ingestion. Modern Treatment
1971;4:697.
12
Datura
Datura, commonly growing in the wild all over India belongs to

Solanaceae family. Common members include Datura alba, Datura
niger and Datura stramonium (thorn apple). All parts of Datura are
poisonous but seeds and fruits are the most noxious. The active principle
is known as Dhaturine and contains the alkaloids, levohyoscyamine.
Hyoscine or scopolamine and traces of atropine. In India, Datura is
mainly employed as a stupefying poison mostly for criminal purposes
such as robbery and rarely for kidnaping and rape. In children
accidental poisoning may occur due to ingestion of Datura fruits,
mistaking them for edible fruits or capsicum seeds. Accidental cases
are also seen from use of Datura seeds by quacks for treatment of
various ailments. The incidence of Datura poisoning in India varies
from 3 to 5 percent.
Pathophysiology
On ingestion of Datura fruits or seeds, its alkaloids get absorbed from
intestine and antagonize the muscarinic actions of acetylcholine. The
chief sites of action of alkaloids are cholinergic muscarinic receptors
of post-ganglionic parasympathetic nerves and cortical and subcortical
levels in the brain. Cholinergic nicotine receptors at neuromuscular
junctions remain unaffected in Datura poisoning. The lethal dose for
alkaloids is 4 mg and death usually occurs within 24 hours.
Clinical Features
The clinical manifestations of Datura poisoning is summed up by the
statement, Hot as a hare, blind as a bat, dry as a bone, red as a beet
and mad as a hen.
On ingestion clinical features appear usually within half an hour.
They may be broadly divided into peripheral and central antimuscarinic
effects.
Datura 157
Peripheral Antimuscarinic Effects

The blockadge of muscarinic receptors in the post-ganglionic
parasympathetic pathways result in excessive thirst, blurring of vision
and difficulty in swallowing. The most consistent sign of Datura
poisoning is tachycardia. Its absence would suggest poisoning with
an unrelated agent. The skin and mucous membranes are dry. There
is flushing of skin and symmetrical pupillary dilatation. Ingestion of
large quantities may lead to fever or even hyperpyrexia. Urinary
retention, hypertension and diminished bowel sounds. Hypertension
and arrhythmia may occur terminally.
Central Antimuscarinic Effects

The children usually present with agitation, confusion, disorientation,
ataxia, visual incoordination and auditory or visual hallucination.
Seizures and coma may follow with terminal cardiorespiratory failure.
There may be vomiting followed by giddiness and unsteady gait.
The children are first restless and confused and later become delirius.
The patient keeps on muttering indistinct words, hence the condition
is aparently known as muttering delirium. The patient may be
noisy, violent and may have dreadful auditory and visual halluci-
nations. The child appears to grasp at imaginary objects, picks at his
clothings and tries to pull imaginary threads from nail beds. The acute
delirium begins to wane off in an hour and is followed by state of
drowsiness. There may be appearance of a scarlatiniform rash. In
fatal cases drowsiness passes into stupor, followed by coma and
death from respiratory paralysis.
Investigations
The mydriatic test is used to detect the presence of alkaloids like
atropine, present in Datura. The suspected material (aspirated gastric
content) is processed and a solution is prepared. A drop of solution
is instilled into one eye of cat, keeping another eye as control. The
pupil dilates in about half an hour, if Datura is present. However, a
negative test does not rule out the possibility of Datura poisoning.
Diagnosis
2. Mydriatric test from gastric content
3. Therapeutic physostigmine test.
Treatment
All children with mild poisoning exhibiting only peripheral features
should be observed in hospital for 28-48 hours and complete recovery
occurs without the need of treatment. Cases with severe poisoning
require gastrointestinal deconta- Key Points

mination, appropriate supportive
Diagnosis
care and use of specific antidotes
to reverse the action of alkaloids. 1. History of ingestion
2. Clinical features, peripheral and
Gastrointestinal Decontamination central anticholinergic effects
3. Positive mydriatic test
Gastric lavage with normal saline 4. Therapeutic physostigmine test
is useful upto 48 hours after positive.
ingestion especially if there are Management
clinical features of adminished 1. Gastric lavage
gastrointestinal tract motility. 2. Activated charcoal 1-2 g/kg to be left
On completion of lavage, in the stomach
activated charcoal in a dose of 1- 3. Supportive treatments
2 g/kg is left in the stomach. 4. Antidote - physostigmine 0.5 mg
IV repeated every 10 minutes upto
Supportive Care a dose of 2 mg
The care of airways, breathing and circulation must be given proper

attention in comatose/unconscious patients. Secure an IV line to deal
with any emergency. Hyperpyrexia is managed by cold sponging.
Since hypertension is usually transient, it does not require any anti-
hypertensive drug. Hypotension is managed with IV fluids and
vasopressor amine like dopamine. If the patient has developed seizure,
IV diazepam is administered in a dose of 0.2 mg/kg slowly. The cases
not responding to diazepam may respond to specific antidotes. Forced
diuresis and dialysis have no role in the management of Datura
poisoning.
Antidote
The specific antidote of Datura poisoning is physostigmine.
Physostigmine crosses the blood-brain barrier reverses both peripheral
and central antimuscarinic effects of Datura. The indications for its
used are presence of hallucinations, seizures or supraventricular
tachycardia. The dose is 0.5 mg IV slowly over a period of 3-5 minutes
and may be repeated every 10 minutes to a maximum of 2 mg. Side
effects are uncommon and can be effectively controlled with atropine
0.5 mg SC for each mg of physostigmine administered.
BIBLIOGRAPHY
1. Lampe KE. Systemic plant poisoning in children. Pediatr 1974;54:347-51.
2. Laurence DR, Bennet PN. Clinical Pharmacology, 6th edn. Edinburgh the
English Language Books Society, Churchill Livingstone 1987;470-74.
3. Mikolich RJ, Paulson GW. Acute anticholinergic syndrome due to jimson
seed ingestion. Ann Int Med 1975;83:321-25.
4. Weiner N. Atropine: Scopolamine and antimuscarinic drugs. In: Goodman
and Gilmans. The pharmacological bais of therapeutics, 7th edn, Macmillan
Publishing Company 1985;130-44.
13
Cocaine
Cocaine is an alkaloid derived from coca, the dried leaves of the plant
Erythroxylum coca. It is a colorless crystalline substance, which has a
bitter taste and is soluble in water and alcohol. Cocaine is now a
common abused drug in adolescents. Cocaine use may lead to violent
fatal injuries in part because of its neurobehavioral effects. Cocaine is
absorbed from all mucous membranes and from gastrointestinal tract
and genitourinary tract. Crack cocaine is most potent and addictive
form. It is also form that small children may ingest and result in fatal
intoxication. Acute intoxication may arise following inhalation with
boric acid, ingestion or injection. Infants and neonates may also be
exposed to cocaine from breast milk or via passive inhalation of vapors
from adults smoking crack cocaine.
Pathophysiology
Cocaine is rapidly absorbed from all mucous membranes and
metabolized by plasma and hepatic cholinesterases into water-soluble
renally excreted metabolites, i.e. benzoyl ecognine and ecognine methyl
ester. Because cocaine is rapidly metabolized and having short half-
life, serum level is of generally little use and do not correlate with
clinical manifestations.
Cocaine blocks the reuptake of norepinephrine, dopamine and
serotonin from synaptic cleft in presynaptic nerves and leads to
accumulation of these neurotransmitters and causes effects on
peripheral and central nervous system. Norepinephrine and
epinephrine act on -adrenergic receptors and results in tachycardia,
increased myocardial contractility, tremor, diaphoresis and mydriasis.
The tachycardia increases myocardial oxygen demand and reduces
coronary perfusion. The action on -adrenergic receptors causes
vasoconstriction and hypertension. In experimental animals,
vasoconstriction may result from impairment of the peripheral
endothelial nitric oxide system. Centrally-mediated dopamiergic effects
include mood elevation and movement disorders while serotonin-

induced stimulation results in exhilaration, hallucination and
hyperthermia. It causes coronary artery vasospasm by stimulation of
peripheral nervous system by 5-HT receptors.
Cocaine also stimulates and activates platelet aggregation and
causes an increase in both platalet factor 4 and beta-thromoglobulin.
It also blocks sodium channel and results in prolongation of action
potential and thus QRS interval. The combined adrenergic stimulation
and sodium channel blockade may result in tachyarrhythmias which
include wide complex arrhythmias, VT and VF.
Clinical Features Key Points

The clinical features of acute Diagnosis
intoxication are euphoria, excite-
1. History of ingestion/inhalation
ment, restlesness, feeling of 2. C/F
grandeur, vomiting, pyrexia, i. Euphoria, excitement, halluci-
mydriasis, delirium, tremor, nation, delirium or convulsion
convulsions and hyper-reflexia. ii. Tachycardia or ventricular arrhy-
Hypertension, hypotension, thmias
iii. Hyperventilation and respiratory
tachycardia, ventricular arrhyth-
failure.
mias, cardiac failure are the
cardiovascular manifestations. Management
Hyperventilation and respiratory
1. Supportive
failure may occur. 2. Stomach wash with dilute potassium
The manifestations of chronic permanganate or tannic acid
poisoning are anorexia, loss of 3. Activated charcoal
weight, weakness, tremors, 4. Barbiturates
impotence, moral degradation 5. Cardiorespiratory stimulants
6. Artificial respiration
and insanity which is characte-
7. De-addiction.
rized by delusions of persecution
and hallucinations chiefly visual and tactile as if grains of sand are
lying under the skin or small insects (cocaine bugs) are creeping on
the skin.
Management
The management is chiefly symptomatic and supportive. If ingested,
stomach wash is carried out with dilute solution of potassium
permanganate or tannic acid. Activated charcoal may be administered
after completion of stomach wash. The principle of management
includes oxygen administration, continuous ECG monitoring, benzo-
diazepines and administration of aspirin and heparin. Benzodiazepines
have both aticonvulsant and CNS-depressant effect. It also reduces
Cocaine 161
heart rates, systemic arterial pressure and attenuate toxic myocardial

and CNS effects of cocaine. Phenothiazines and butyrophenones have
no benefit and may be harmful to patients.
Children with cocaine-induced chest pain and myocardial ishemia
should be treated with oxygen, nitroglycerin and aspirin. Benzodiaze-
pines are an important adjunct to this therapy. Avoid -blockers in
children with hypertension and sinus tachycardia because it results
in pardoxical increase in blood pressure and coronary artery constriction
due to its antagonistic effects on cocaine induced -adrenergic receptor
stimulation. Coronary vasospasm may respond to nitroglycerin that
is also effective in pulmonary hypertension. The dose is 0.25 to 0.5
mcg/kg/min titrated upto 1-3 mcg/kg/min: maximum 5 mcg/kg/
min at 20 to 60 minutes interval by continuous infusion. The drug
recommended for treatment of hypertension in children is phentola-
mine, an alpha-blocker in a dose of 0.05 to 0.1 mg/kg IM or IV
up to a maximum of 2.5 to 5 mg. Lidocaine should not be used to treat
arrhythmias as it also acts by blocking sodium channel. In addition
both have additve effects on GABA current in CNS, thus increasing
likelihood of seizure activity. Epinephrine may exacerbate cocaine-
induced arrhythmias and is contraindicated.
Sodium bicarbonate is effective in treatment of cocaine toxicity. It
reverses cocaine-induced ECG changes, i.e. prolonged PR, QT and
QRS interval. It also counteracts acedemia associated. The dose is
1-2 mEq/kg IV slowly.
Seizures should be controlled preferably with benzodiazepines such
as diazepam, lorazepam and midazolam but must monitor for
respiratory depression while administration. Cardiorespiratory
stimulants and artificial ventilation may be required. A chronic addict
should be sent to de-addiction center, where proper rehabilitation may
be carried out.
BIBLIOGRAPHY
1. Blaho K, Logan B, Winbery S, Park L, et al. Blood cocaine and metabolite
concentrations, clinical findings and outcome of patients presenting to an
ED. Am J Emerg Med 2000;18:593-98.
2. Havlik DM, Nolte KB. Fatal crack cocaine ingestion in an infant. Am J
Forensic Med Pathol 2000;21:245-48.
3. Heesch CM, et al. Cocaine activates platelets and increases the formation of
circulating platelet containing micoaggregates in humans. Heart 2000;83:688-
95.
4. Lange RA, Hills LD. Cardiovascular complications of cocaine use. N Eng J
Med 2001;345:351-58.
14
Opioids
The term opiate has been used for natural alkaloids (morphine and
codeine) of opium and opioid for the agents having similar action.
Opium is obtained from milky juice of poppy, Papaver somniferum.
Opioids are used as analgesic, tranquilizer, antitussive and anti-
diarrheal. The incidence in India varies from 2-8 percent, the incidence
being more in western India. Opiates and opioids are capable of
producing euphoria as well as psychological and physical dependance
when taken in high doses over a prolonged period of time. The natural
and synthetic opiates are classified as follows:
Classification of Opioids
a. Pure agonist
1. Natural morphine
Codeine
2. Semi-synthetic
Heroin (diacetylmorphine)
Hydromorphone
Oxymorphone
Oxycodone
Hydrocodone
3. Synthetic
Propoxyphene
Diphenoxylate
Methadone
Meperidine (pethidine)
b. Mixed agonistantagonist
Butorphanol
Levallorphan
Nalorphine
Pentazocine
Opioids 163
c. Pure antagonist
Naloxone
Naltrexone.
Pathophysiology
Opioids are easily absorbed from gastrointestinal tract, the lungs and
muscles. The most rapid and pronounced effects occur following
intravenous administration and least intense actions are seen after oral
administration. Opoids are metabolized primarily in the liver through
the conjugation with glucuronic acid and small amounts are excreted
directly in urine and feces. The plasma half-life ranges from
2.5-3 hours for morphine to more than 22 hours for methadone.
Opioids interact with opiate receptors located throughout the body
including central nervous system. Endogenous opioid peptides,
enkephalin, endorphin and dynorphin are the neurotransmitter in
complex pain-inhibitory systems. These endogenous peptides attach
to specific opioid receptors, mu, kappa, delta and sigma and mediate
the action of exogeous opioids via neuronal sodium and calcium
channels. Tolerance and dependance on opioids are mainly due to
complex mechanism of endogenous opioid system and partly due to
changes in intracellular modulators such as adenyl nucleotide, calcium-
related substances as well as alteration in neutrotransmitter including
acetylcholine, serotonin and catecholamines. The direct effects on opioid
receptors located in medulla (vomiting), spinal cord, thalamus and
peri-aqueductal grey region (analgesia), limbic system (euphoria/
dysphoria) and reticular activating system (sleep) are responsible for
the neurological manifestations. They also decrease the intestinal
motility resulting in constipation and anorexia. Acute administration
may result in decrease in leutinizing hormone with subsequent decrease
in testosterone and decreased sex-drive. Other hormonal changes
include decrease in the release of thyrotropin (TSH) as well increase
in prolactin and possibly growth hormone. Opioids also cause
respiratory depression, which results from decreased response of the
brainstem to carbon dioxide.
Clinical Manifestations of Opioids

The principal manifestations of opioid on different system are the
following:
Central Nervous System (CNS)

1. Depression of CNS
Analgesia
Respiratory depression
Supression of cough reflex
Sleep
2. Excitation of CNS
Nausea
Vomiting
Miosis
Hyperactive spinal cord reflexes, convulsion
3. Change of mood
Euphoria/dysphoria
4. Dependance.
Adulterants
Adulterants of the opioids may cause:
Peripheral neuropathy
Ambylopia
Myelopathy
Leukoencephalopathy.
Smooth Muscle of Various System

They cause spasm of smooth muscles of GI system, biliary tract,
respiratory tract and urinary tract leading to following features:
GI tract
Decreased peristalsis
Decreased segmentation
Constipation
Biliary tract
Biliary colic
Increased intrabiliary pressure
Respiratory tract
Bronchospasm due to histamine release
Urinary tract
Urinary retention
Cardiovascular
Orthostatic hypotension
Bradycardia
Dilatation of arterioles and veins
Miscellaneous
Sweating, pruritus
Piloerection
Decreased sex-drive
Prolonged labor.
Opioids 165
Opioid Overdose
The high doses of opioids taken intentionally or by the street abuser
who has misjudged the potency of injected substance can result in
overdose with potentially lethal outcome. The typical manifestations
occur immediately with intravenous route or within an hour with oral
administration. The manifestations are analgesia, nausea, drowsiness,
shallow respiration, miosis (mydriasis once anoxia develops),
bradycardia, hypothermia, decreased persistalsis, urinary retention
and absence of responsiveness to external stimuli. If patient is not
treated immediately, cyanosis and death may occur from respiratory
depression and subsequent cardiorespiratory arrest.
Opioid Withdrawal
The time of onset as well as intensity and duration of acute withdrawal
are influenced by a number of factors including drug half-life dose
and chronicity of administration. The initial manifestations of opioid
withdrawal are pupillary dilatation, piloerection, yawning profuse
sweating, rhinorrhea, myalgias cramps, lacrimation and anorexia. In
more advanced forms, restlessness, insomnia, hyperthermia,
tachycardia and tachypnea occur. In severe form of withdrawal,
vomiting, diarrhea, hyperactive bowel sounds and hypertension occur.
Twitching of muscles and convulsion may occur.
Opioid Withdrawal in Newborn

The newborns of opioid addicted mothers develop addiction in 80-90
percent babies and carry a mortality of 3-30 percent. If not treated,
when prominent signs are apparent. The clinical manifestations of
opioid withdrawal usually begin on third day. The babies usually
present with irritability, excessive crying, tremor (80%), increased
reflexes, tachypnea, diarrhea and hyperactivity (60%) vomiting (30%).
The babies usually have a low birth weight.
Complications of Opioid Abuse

Cardiovascular
Thrombophlebitis
Vasculitis
Bacterial endocarditis
Lymphedema
Orthostatic hypotension
Central nervous system
Respiratory arrest
Altered sensorium
Post-hypoxic encephalopathy
Transverse myelitis
Spinal epidural abscess
Endocrinal
Amenorrhea
Sterility
Hypoglycemia/hyperglycemia
Gastrointestinal
Ileus, constipation
Hyperamylasemia
Hyperlipasemia
Hepatitis
Dermatological
Cellulitis
Abscesses
Ulcers
Musculoskeletal
Trauma
Myalgias
Septic arthritis
Osteomyelitis
Rhabdomyolysis and compartment syndrome
Genitourinary
Urinary retention
Delayed ejaculation
Decreased libido
Proteinuria/myoglobinuria
Glomerulonephritis
Pulmonary
Aspiration pneumonitis
Pulmonary edema Key Points
Pneumothorax Diagnosis
Tuberculosis 1. History of drug abuse and needle
Eye marks on skin
Endophthalmitis 2. Clinical manifestations
Toxic ambylopia 3. Laboratory findings
Infections a. Arterial blood gas
Tetanus Hypoxia
Hypercapnia
Tuberculosis
b. Hyperglycemia/hypoglycemia
Hepatitis c. Hyperamylasemia/hyperlipase-
Malaria mia
CMV d. Positive toxicological analysis of
Veneral diseases, etc. blood and urine for drugs
Opioids 167
Management of Opioid Overdose
General Management
This should emphasize on appropriate maintenance of airways and
oxygen administration, if necessary positive pressure ventilation.
An intravenous line should be secured with normal saline and
blood samples obtained for estimation of blood glucose, electrolyte,
hamatocrit and toxicological analysis. The blood pressure should be
maintained with IV crystalloids and vasopressor-amines. This is
followed by gastric lavage to remove any remaining drug with care
taken to use a cuffed endotracheal tube to prevent aspiration if the
patient is not alert.
Activated charcoal in a dose of 1-2 g/kg should be left in the
stomach after completion of lavage to prevent further absorption of
the drug.
Specific Management
The specific management, antidote, should be given immediately. The
antidote of choice is naloxone in a dose of 0.01 mg/kg IM or IV and
may be repeated in 3-10 minutes, if no response occurs. A clinical
response, i.e. improvement in mental status, respiration, enhanced
bowel sounds or even frank withdrawal is noted within 1-3 minutes.
Since the effects of this drug diminish within 2-3 hours, it is important
to monitor the individual for atleast 24 hours after a heroin overdose.
The major complications associated with naloxone is withdrawal
syndrome which occurs almost exclusively in narcotic dependent
patient. Other antidotes are nalorphine, lavallorphan and naltrexone.
Nalorphine and lavallorphan are not in use today as they have mixed
agonist and antagonist action. Naltrexone, a pure antagonist of opioid
receptors is effective in rehabilitation of the patient as it has longer
duration of action (24 hrs). A 50-mg dose of naltrexone blocks
approximately 15 mg of heroin. No known withdrawal symptoms
occur with use of naltrexone. For effective rehabilitation, the patient
should be free of opiates for a minimum period of five days.
The convulsions and cardiac arrhythmias should be managed with
appropriate anticonvulsants and antiarrhythmic drugs respectively.
Appropriate antibiotics are given if there is any evidence of infections.
Management of Opioid Withdrawal

The proper physical examination of the patient like assessment of liver
function, neurological and for local and systemic infections should be
done. Proper nutrition is given and rest is advised. The effective
treatment of withdrawal requires Key Points

readministration of sufficient (Acute Opioid Overdose)
opiate on day one to decrease Diagnosis
symptoms followed by a more
gradual withdrawal of the drug Nausea, vomiting
Shallow respiration, analgesia, mio-
usually over 5-10 days. Metha- sis, bradycardia, urinary retention,
done is the opioid of choice and respiratory depression.
the first dose is estimated from Coma
the previous history of amount
ingested. Methadone 1 mg is Management
approximately equivalent to 1. Gastric lavage
3-mg morphine, 1-mg heroin and 2. Activated charcoal
20-mg meperidine (pethidine). 3. Specific antidote: Naloxone - 0.01 mg/
kg/IM/IV
The equivalent dose of metha-
4. Symptomatic and supportive treat-
done is given in two divided ment, social rehabilitation.
doses. After several days of
stabilization, the original dose of methadone is tapered by 10-20 percent
each day.
Clonidine, an alpha-2 adrenergic agonist may be used in part to
decrease sympathetic overactivity. It is effective in relieving discomfort
and pain. Clonidine is often not well-tolerated because it produces
high levels of sedation and orthostatic hypotension. The dose of
clonidine is 5 g/kg to a maximum of 0.3 mg in 2-4 divided doses.
Successful patient management demands excellent psychiatric and
social support for the patient requiring a comprehensive program for
rehabilitation.
BIBLIOGRAPHY
1. Deneav GA, Mule SE. Pharmacology of opiates. In: Lowinson JH, Ruiz P:
Substance abuse clinical problems and perspectives, 1st edn. Baltimore:
Williams and Wilkins 1981;129-39.
2. Gold Frank LR, Bresnitz EA, Weisman R. Opioids. In: Gold Frank L: Toxicology
emergencies: A comprehensive handbook in problem solving, 2nd edn. New
York: Appleton Century Croft 1982;125-37.
3. Jaffe JH, Martin WR. Opioid analgesics and antagonists. In: Gilman AG,
Goodman LS, Gilman A: The pharmacological basis of therapeutics, 6th edn.
New York: MacMillan Publishing Company 1980;494-34.
4. Ream NW, et al. Opiate dependance and abstinence. In: Richter RW Medical
aspects of drug abuse, 1st edn. New York: Harper and Row Publishers 1975;
81-123.
15
Phenothiazines and
Related Neuroleptics
Phenothiazines and related neuroleptics are widely used in outpatient
treatment of psychiatric illness, which have shown a steep rise in last
few decades because of increasing urbanization and fast changing
lifestyles of people. Although these drugs are used primarily in
psychotic illnesses, they also find some use in treatment of nausea and
vomiting, intractable hiccoughs, preoperative adjuncts in anesthesia
and as antidepressants. Overdosages in children are either due to
accidental ingestion of drugs available in home when one of the family
members is taking drugs or inappropriate doses advised by unqualified
practitioners. Overdosages account for approximately 1 percent of all
drug ingestion overdosage and less than 1 percent of death.
Classification of Phenothiazines and Related Neuroleptics
a. Phenothiazines
1. Aliphatic
Chlorpromazine
Promazine
Promethazine
Triflupromazine
2. Piperidine
Thioridazine
Mesoridazine
3. Piperazine
Fluphenazine
Trifluoperazine
Prochlorperazine
b. Thioxanthenes
Chlorprothixene
Thiothixene
c. Butyrophenones
Haloperidol
Droperidol
d. Dihydroindolones
Molindone
e. Dibenzoxazepines
Loxapine.
Pathophysiology
On ingestion they are absorbed completely from GI tract. Peak plasma
levels occur in 2-3 hours and are rapidly distributed to tissues with
preferential distribution to brain and lungs. The volume of distribution
is approximately 20 L/kg and is predominantly protein and tissue
bound making dialysis and charcoal hemoperfusion ineffective in the
management of overdose. The major source of elimination is
metabolism of drug by liver through a combination of hydroxylation,
demethylation, oxidation and conjugation with glucuronic acid. The
metabolites are excreted both in urine and feces.
Phenothiazines and related compounds are similar in structure to
dopamine, thus blockade of dopamine receptors occurs in brain
predominantly in limbic system and basal ganglion. When dopamine
receptors in limbic system are blocked it results in amelioration of
psychotic symptoms whereas in basal ganglia it gives rise to an
imbalance between dopaminergic and cholinergic system causing
cholinergic side effects. They also block peripheral and central alpha-
adrenergic receptors resulting in orthostatic hypotension and reflex
tachycardia. The decrease in CNS autonomic reflexes and direct
depressant effect on the heart also contribute to hypotension. They
have also quinidine like effects resulting in conduction disturbances.
Phenothiazine lowers the threshold for seizure activity and hence
overdose caries a high risk for development of seizure. In the
hypothalamus it decreases the production of growth hormone and
increases the prolactin release, which may lead to galactorrhea. They
also alter the temperature control system resulting hypothermia or
Phenothiazines and Related Neuroleptics 171
hyperthermia. Idiosyncratic reactions lead to jaundice leukopenia,

agranulocytosis and dermatitis.
Clinical Features
The toxic effects are generally more apparent and serious following
an overdose but may also occur during the normal course of treatment.
Signs and symptoms are described below:
Cardiovascular
Tachycardia
Hypotension
Ventricular arrhythmias and
Complete heart block.
Central Nervous System

Indifferences to environmental stimuli
Lethargy
Coma
Convulsions
Hypothermia or hyperthermia with rhabdomyolysis.
Extrapyramidal Symptoms
Acute dystonic reactions
Akasthisia
Pseudoparkinsonism
Tardive dyskinesia
Choreiform movements of trunk or limbs
Neuroleptic malignant syndrome (rigidity, hyperthermia and stupor
or coma).
Autonomic Nervous System

Tachycardia
Hypertesion
Diaphoresis
Dyspnoea and
Incontinence.
Pulmonary
Usually tachypnea
Rarely respiratory depression.
Gastrointestinal Key Points

Nausea Diagnosis
Vomiting
Decreased bowel sounds. 2. ECG changes
Eye 3. Plain X-ray abdomen-radio-opaque
tablets
Blurring of vision 4. Urinalysis - phenistix strip is dipped
Miosis in patients urine, deep purple shade
Eye pigmentation. of strip occur immediately in the
presence of phenothiazines. A false
Skin positive reaction may occur in pre-
sence of salicylates or large quantities
Dry and pigmented or ketones.
Dermatitis. 5. Estimation of blood level of the drug.
Allergic and Idiosyncratic Management
Jaundice 1. Secure airway and establish
Leukopenia adequate ventilation.
Agranulocytosis. 2. Establish IV line using a largebore
cannula.
ECG 3. All comatose patients should receive.
a. Naloxone, 0.02 mg/kg
1. Flattening and inversion of
b. 25 percent IV dextrose, 2 ml/kg.
T-waves 4. Gastric lavage or emesis with syrup
2. Prominent U-wave of ipecac, depending upon the level
3. ST-depression of consciousness.
4. Prolonged PR, QRS and QT 5. Activated charcoal through lavage
intervals. tube, 1-2 g/kg.
6. Cathartic: Magnesium sulfate 250 mg/
Specific Treatment kg orally.
a. Hypotension
1. IV normal saline or lactated Ringers
2. Trendelenberg position
3. MAST pants if available
4. Levarterenol, 0.1-0.2 mg/kg/min IV
Adjust as necessary to maintain blood pressure
(Epinephrine dopamine, isoproterenol, dobutamine are
contraindicated).
b. Arrhythmias
1. Put the patient on cardiac monitor
2. Sodium bicarbonate IV to normalize pH
3. Lidocaine 1 mg/kg IV in bolus followed by 0.03 g/kg/min
drip gm/kg/min drip
4. Phenytoin 1 mg/kg over a period of 5 min to a maximum of
10 mg/kg
5. Propranolol 0.1 mg/kg to a maximum of 1 mg may be repeated
after 5 min
Phenothiazines and Related Neuroleptics 173
6. Physostigmine 0.5 mg Key Points

slows IV
Diagnosis
7. Cardiac pacemaker for
completes heart block Clinical features: Dyskinesias, convulsion
(Procainamide, quinidine or coma, hypo- or hyperthermia.
Tachycardia, hypertension and arrhy-
and disopyramides are thmias.
contraindicated). ECG Flat or inverted T wave, pro-
c. Respiratory insufficiency: longed QT, PR and QRS.
Airway protection and venti- Urine analysis: Phenistix strip test
latory assistance. positive.
d. Seizures: Diazepam 0.2 mg/
kg IV slowly, phenobarbitone Management
loading doses 5 mg/kg IV 1. Gastric lavage and emesis according
slowly may be repeated in to level of consciousness
20 min. 2. Activated charcoal through lavage
tube
e. Temperature control: Hypo-
3. Catharticsmagnesium sulphate
thermia or hyperthermia 4. Dyskinesiasdiphenhydramine
should be managed accor- 5. Naloxone for comatosed patients
dingly. 6. HypertensionMAST pants, levar-
f. Extrapyramidal side effects: teranol
Diphenhydramine 1 mg/kg 7. Arrhythmias:
i. Alkalinization
IM or IV. The resolution of
ii. Lidocaine, phenytoin, propranolol,
symptoms occurs within 20- physotigmine
30 minutes following IM iii. Cardiac pacing.
therapy and immediately (NoteProcainamide, quindine
after IV injection, if extrapyra- and disopyramide are contra-
midal symptoms does not indicated).
resolve after treatment, alter- 8. Symptomatic and supportive mana-
gement.
native diagnosis such as teta-
nus, hypocalcemia, encepha-
litis, meningitis, hysteria or drug reaction should be considered.
As with any overdosage of medication, a reason for the occurrences
should be sought and corrected.
BIBLIOGRAPHY
1. Barry D, Meyskens FL, Becker CE. Phenothiazine poisoning. California
Medicine 1973;118:1-5.
2. Byck J. Drugs and the treatment of psychiatric disorders. In: Goodman L,
Gilman A: The pharmacological basis of therapeutics. McMillan 1980;391-
48.
3. Caroff SN. The neuroleptic malignant syndrome. J Clin Psychiatry 1980;
41(3):79-83.
4. Habibzadeh MA. Cardiovascular Effects of Phenothiazines: A review. Arizona
Medicine 1979;36(7):518-20.
5. Ott D, Goeden S. Treatment of acute phenothiazine reaction. IACEP 1979;
8:471-72.
16
Cyclic Antidepressant
Cyclic antidepressants are widely used in treatment of depressive

disorders. Other uses include the management of childhood enuresis
and more recently in the treatment of chronic pain syndromes.
Children account for approximately 20 percent of tricyclic intoxications
either due to overdose of the drug prescribed or accidental ingestion
of drugs at home. Amitryptiline and imipramine are the two most
commonly prescribed and hence most commonly implicated in
toxications.
Cyclic Antidepressant
Structure Generic name CNS toxicity CVS toxicity
Tricyclic Amitryptiline ++++ ++++

Amoxapine ++++ +
Clomipramine ++++ ++++
Desipramine ++++ ++++
Doxepin ++++ ++++
Imiramine ++++ ++++
Loxapine ++++ +
Nortriptyline ++++ ++++
Tetracyclic Maprotiline ++++ ++++
Mianserin Sedative dose Less cardiac
not inhibit risk
amine pump agranulo-
cytosis
Bicycle Viloxazine Less sedative ?
Zimetidine ? ?
Misc Trazodone + +
Pathophysiology
Tricyclic antidepressants are rapidly absorbed from gastrointestinal
tract and undergo a major first pass metabolism in liver. They are
highly lipid soluble and are rapidly distributed to body tissues such
as myocardium as well as celular ultrastructures including
mitochondria.
Cyclic Antidepressant 175
Only a small amount of the absorbed drug remains in the blood,

of which 85 to 95 percent is bound to plasma proteins. Extensive
binding to tissues and plasma proteins explain the ineffectiveness of
forced diuresis and dialysis techniques in the removal of these drugs.
They are eliminated (expect amoxapine) mainly by hepatic metabolism
and minimally by renal excretion. In the liver, they are metabolized
by monodemethylation poducing active metabolites, desipramine,
and nortryptiline. Subsequently, following ring hydroxylation and
demethylation, these metabolites undergo an enterohepatic circulation
and a final stage of glucuronidation before being excreted by kidney.
The elimination of amoxapine is primarily renal.
Cyclic antidepressant, particularly tricyclics are structurally similar
to phenothiazines and have similar anticholinergic, adrenergic and
alpha-blocking properties. They block neuronal reuptake of
norepinephrine, serotonin or dopamine and cause drowsiness and
impair concentration and thought process even in therapeutic doses.
They also block H 1 receptor, which explains its sedative and
antihistaminic properties. Peripheral anticholinergic effects are
mydriasis, dry mucous membrane, tachycardia, urinary retention
and decreased intestinal peristalsis while the central effects include
confusion, agitation, hallucination, myoclonus, choreoathetosis and
seizures. Trazodone inhibits the neuronal reuptake of serotonin and
has anti-serotonergic and alpha-adrenergic blocking properties.
Fatal dose: The average lethal dose is 30 mg/kg but as little as 8
mg/kg may be fatal.
Wide ranges of clinical manifestations are seen in children intoxicated
with cyclic antidepressants. Initial manifestations, usually anticholi-
nergic, include tachycardia, mydriasis and dryness of mucous
membranes, urinary retention, hallucinations and flushing. Fever
may occur as a drug effect but raise the possibility of aspiration
pneumonia particularly in comatose paient. Hypothermia may also
occur at times.
CNS toxicity is prominent feature of tricyclic toxicity and includes
alteration in mental status, depression, lethargy and hallucination.
Myoclonus and choreoathetosis occur variably. Major seizures occur
in upto 20 percent of patients typically in first 12 hours and may
progress to status epilepticus. Seizures are more frequent with
amoxapine and maprotiline overdosage. Coma may occur which
rarely lasts for more than 48 hours, persistence beyond this period
should suggest the ingestion of additional drugs or development of
complications.
Common cardiovascular manifestations of cyclic antidepressant
overdose and intoxication are arrhythmias. Most common arrhythmia
is sinus tachycardia, others include supraventricular tachycardia,
premature atrial and ventricular fibrillation. Various conduction
disturbances like right bundle-brand block (RBBB) and left bundle-
branch block (LBBB), various degrees of A-V block including complete
heart block is uaually associated with seizures, coma, respiratory
depression and arterial hypotension. Electrocardiographic change
include widening of QRS complex, prolongation of QT interval with
flattening or inversion of T-wave, ST-segment depression and evidence
of RBBB, LBBB and complete heartblock.
A withdrawal syndrome occurs in neonates born to mohers who
have been taking tricyclics. The features of withdrawal syndrome
are tachypnea, irritability and restlessness, which last for first month
of life. Amoxapine causes a higher incidence of seizures and coma.
Exposures to tetracyclics are associated with higher incidence of
cardiovascular effects as compared to tricyclics. Bicyclics are similar
to tetracyclics but it causes less cholinergic toxicity.
Diagnosis
1. History of ingestion of antidepressant.
2. Suggestive clinical signs and symptoms.
3. Measurement of blood levels of the drug and arterial blood gases
to detect acidosis and hypoxemia.
4. Physostigmine testAdministration of IV physostigmine in the
obtunded or comatose patient causes arousal inpatient with
antidepressant intoxication. The sensitivity of the test is greater
than 90 percent, the specificity, however, is completely unknown.
Adverse effects due to IV physostigmine are anticholinergic
syndrome, seizures, bradyarrhythmias and asytole. This test in
tricyclic overdoses in both reproducible and sensitive. The results
of test appear to have minimal impact on management and no
beneficial effect on outcome.
Management
Standard conservative life support measures should be employed in
all patients. Emesis should be avoided in symptomatic children
because of danger of aspiration. Emesis is only indicated in
asymptomatic children. Gastric lavage should be done immediately
after ingestion to remove the unabsorbed drugs from stomach. It is
followed by administration of activated charcoal, 50-100 g in
adolescents and
15-30 g in younger children. Activated charcoal 10-20 g may be given
repeatedly every 2-6 hours in symptomatic children. A single dose
of cathartics such as sorbitol, magnesium or sodium sulphate should
be administrated. Unfortunately, no method exists to hasten the
process of metabolism or excretion of tricyclics and tetracyclics. The
large volume of distribution of drug precludes effective use of forced
diuresis, peritoneal dialysis, hemodialysis and charcoal hemoperfusion.
Sodium Bicarbonate
The aim of sodium bicarbonate therapy is to raise sodium
concentration and arterial pH. It also shortens QT interval, narrows
QRS complexes and increases myocardial contractility, thus often
suppress ventricular arrhythmias and reverse hypotension. These
can be achieved by administering 1 to 2 mEq/kg bolus infusion of
sodium bicarbonate until arterial pH is > 7.45 and is followed by
continuous infusion as a solution of 150 mEq/L of 5 percent dextrose
to maintain alkalosis.
Respiratory Depression
Intubation and mechanical ventilation are indicated in the presence
of respiratory depression. Arterial blood gases should be monitored
and supplemental oxygen administered to correct arterial hypoxemia
in-patient not requiring intubation and mechanical ventilation.
Choreoathetosis and Myoclonus

They generally do not require treatment. Rarely myoclonus is so
severe that it may produce rhabdomyolysis. Physostigmine is effective
in controlling both the choreoathetosis and myoclonus but should
be used only to prevent secondary complications. Physostigmine is
given slowly IV as 0.5 mg test dose in children and may be repeated
every 20 minutes to a maximum dose of 20 mg. Atropine should be
readily available to reverse any toxic cholinergic effects that may
result form physostigmine.
Seizures
A single seizure does not require specific treatment but repetitive
continuous seizure activity must be controlled rapidly to avoid
secondary complication particularly systemic acidosis, with resultant
increase in free drug and rhabdomyolysis. IV diazepam is the drug
of choice and controls most of the seizures. The dose of diazepam
is 0.1-0.3 mg/kg to a maximum of 10 mg in children. If seizures are

not controlled with diazepam, phenytoin may be used an alternative
but has disadvantage of long half-life and the potential for causing
hypotension, bradycardia and conduction defects. Barbiturates should
not be used because they may further depress respiration and
exacerbate hypotension.
Status epilepticus is usually refractory to conventional anticonvul-
sants (diazepam, phenytoin,
barbiturates) as well as Key Points
physostigmine. Paralysis with
Diagnosis
pancuronium bromide should be
employed in status epilepticus 1. History of intake
refractory to anticonvulsants. Initial anticholinergic effects
Cardiac arrhythmias
Arrhythmias Lethargy, seizure and coma
Physostigmine test positive
There is a lot of controversy
regarding which antiarrhythmic Management
drugs should be given and in 1. Supportive and symptomatic
what order. The following is 2. Emesis contraindicated
generally accepted modality for 3. Gastric lavageeffective upto 12 hrs
of ingestion
the treatment of arrhythmias.
4. Repeated doses of activated charcoal
Sinus tachycardia generally 5. Arrhythmias
requires no treatment. Sodium Sinus tachycardiano treatment
bicarbonate is administered first Supraventricular tachycardia
to achieve a pH of 7.45-7.55. Alkalinization
Phenytoin is given if electro- Physostigmine
Propranolol
cardiogram shows widened QRS Ventricular tachycardialido-
(more than 0.12 seconds) and caine
prolongation of QT interval. The Conduction disturbances
dose of phenytoin is 15 mg/kg, Isoproterenol, atropine
IV upto a maximum of 1 g and Cardiac pacing
the rate of administration should not exceed more than 0.5 mg/kg/
min. In children with ventricular arrhythmias, the acidosis is corrected
first with sodium bicarbonate or mechanical hyperventilation then
lidocaine is administered at a loading dose of 1 mg/kg/dose and
appropriate maintenance dose thereafter. Bretylium should not be
used in hypotensive patients or in those with fixed cardiac output.
In adolescents, propranolol may be used in a dose of 1.0 mg IV every
2 to 5 minutes until a response is seen. In younger children, the dose
of propranolol is 1 mg/kg IV upto a maximum of 1 mg. Physostigmine
used only rarely, is administered in the dose of 0.5 mg IV over 2
to 3 minutes and repeated 2 to 3 times. Physostigmine and propranolol
are most useful in supraventricular arrhythmias. Second or third

degree A-V block, bradyarrhythmias should be treated with
alkalinization, isoproterenol and cardiac pacing, physostigmine and
phenytion being contraindicated in these setting. Antiarrhythmic
drugs, which are contraindicated in arrhythmias induced by
antidepressants, are quinidine, procainamide and disopyramide.
Hypertension and Hypotension

Hypertension is usually self-limited and requires no treatment. It
usually responds to physostigmine. Hypotension should be initially
managed with cautious crystalloid fluid administration and monitoring
of central venous pressure or pulmonary capillary wedge pressure.
Alkalinization may also be effective. Vasopressor amines are usually
ineffective and increase ventricular irritability. Hypotension
sometimes responds to norepinephrine. Physostigmine may be
effective and should be used if other measures fail. Severe hypotension
may require intra-aortic ballon. Digitalis should be avoided.
All patients with antidepressant overdosage should be closely
monitored for at least 24 hours or until their mental status has
returned to baseline and conduction defects (excluding QTC
prolongation) and arrhythmias are absent. Only completely
asymptomatic children should be discharged after 6 hours.
BIBLIOGRAPHY
1. Aquilonium SM, Hedstrand U. The use of physostigmine as an antidote in
tricyclic antidepressant intoxication. Acta Anesth Scand 1978;22:40-45.
2. Biggs JT, Spiker DG, Petit JM, Ziegler VE. Tricyclic antidepressant overdose:
Incidence of symptoms. JAMA 1977;238:135-38.
3. Crome P, Newman B. Fatal tricyclic antidepressant poisoning. J Roy Soc
Med 1979;72:649-53.
4. Fasoli RA, Glauser FL. Cardiac arrhythmias and ECG abnormalities in
tricyclic antidepressant overdose. Clin Toxicol 1981;18:155-63.
5. Starkey IR, Lawson AA. Poisoning with tricyclic and related antidepressant:
A ten-year review. QJ Med 1980;49:33-49.
17
Carbon Monoxide
Carbon monoxide is a colorless, odorless, tasteless and non-irritating

gas produced by incomplete combustion of carbonaceous material.
It is produced in furnaces, automobile exhaust fumes (3-7 percent),
fires in closed spaces, bukhari burning, vapors of paint removers
containing methylene chloride and after explosive blasts. The burning
of kerosene stove in a closed space may generate considerable amounts
of carbon monoxide. Carbon monoxide poisonings have an increasing
trend in tropical countries and is mostly accidental.
Pathophysiology
The toxic effects of carbon monoxide are the results of tissue hypoxia.
Carbon monoxide reacts with hemoglobin to form carboxyhemoglobin
and reduces oxygen delivery to tissues leading to central hyperventi-
lation and respiratory alkalosis, which further shifts the oxygen-
hemoglobin dissociation curve to the left. Carbon monoxide and
oxygen reacts with the same group in hemoglobin molecule.
Hemoglobin has much higher affinity for carbon monoxide, which
is 200 times greater than oxygen, carboxyhemoglobin thus formed
dissociates very poorly at tissue level causing marked tissue hypoxia.
Hypoxia causes increased capillary premeability resulting in cerebral
edema and raised intracranical pressure.
The half-life of carboxyhemoglobin is 320 minutes, which is
drastically reduced to 80 minutes by 100% oxygen at 1 atmosphere
and to 23 minuts by 100% oxygen at 3 atmospheres. This is the basis
for use of hyperbaric oxygen therapy in treatment of carbon monoxide
poisoning.
The extent to which hemoglobin is saturated with carbon monoxide
is determined by its concentration in inspired air, the duration of
exposure and the activity status of the individual at the time of
exposure. The concentration of carboxyhemoglobin following exposure
to different concentration are shown in Table 17.1.
Carbon Monoxide 181
Table 17.1: Blood concentration of carboxyhemoglobin and its determinants
Blood concentration Concenration of carbon Duration of Activity of status

carboxyhemoglobin monoxide in inspired air exposure
< 10% 0.01%

20% 0.05% 1 hour Light activity
30-80% 0.05% 1 hour Heavy activity
50-80% 0.1% 1 hour
The clinical manifestation depends on carboxyhemoglobin concen-
tration in the blood (Table 17.2).
Table 17.2: Blood concentration of carboxyhemoglobin and clinical manifestation
Carboxyhemoglobin Clinical features

concentration in blood
< 10% Impaired judgement, retarded psychomotor activity

10-20% Mild headache, dyspnea, decreased visual activity
20-40% Irritability, nausea, fatigues, dizziness, tachypnea and
tachycardia, blurring of vision
40-60% Confusion, hallucinations, ataxia, convulsion, coma
70-80% Death results from cardiorespiratory depression
Key Points
The most characteristic sign
of severe poisoning is the cherry Diagnosis
red color of skin and mucous 1. History of carbon monoxide exposure.
membrane. Other clinical mani- 2. Clinical featuresThrobbing head-
festations are excessive sweating, ache, dyspnea, cyanosis, tachycar-
fever, skin lesions like vesicles, dia, diziness, confusion, convulsion
and coma.
bullae which may lead to eschar
3. Estimation of carboxyhemoglobin in
formation, leukocytosis, hepato- the blood.
megaly, bleeding diathesis, Chemical method
albuminuria and glycosuria. Spectroscopycharacteristic
absorption bands at D and E
Chemical Method region.
One ml of patients blood is
Management
diluted with 10 ml of water and
add 1 ml of 5% sodium hydro- 1. Remove the patient from source of
exposure.
xide. Normally the solution turns
2. Administration of 100% of oxygen
yellow. If significant amounts of (hyperbaric).
carboxyhemoglobin are present, 3. Blood transfusion preferably packed
the solution will turn straw red cells.
yellow (< 20% carboxyhemo- 4. 20% mannitol and IV dexamethasone
in presence of cerebral edema.
globin) or will remain pink
(> 20% carboxyhemoglobin).

Kunkels test also indicates presence of carboxyhemoglobin in
blood. In this test a few drops of 3% tannic acid are added to
patients blood diluted 1:10 with distilled water; the appearance of
a crimson red coagulum indicates the presence of COHb.
Spectroscopic Method
This is useful when the blood contains more than 40% carboxy-
hemoglobin. Two absorption bands are seen at D and E, which
persists, on addition of reducing agents in contrast to oxyhemoglobin
bands, which fuse together.
Treatment
The patient should be immediately removed from contaminated
space. Artificial ventilation using bags and mask or by respirator
should be instituted promptly if respiratory distress is apparent.
Oxygen (100%), preferably hyperbaric (2-2.5 atmosphere) should be
administered at once in order to accelerate the release of carbon
monoxide to carboxyhemoglobin. The patient should be kept in
isothermic atmosphere and at complete bed rest to reduce metabolic
rate to a basal level. Blood transfusion, preferably packed cells may
be used, if given within first 30 minutes of exposure but is
contraindicated in the presence of myocardial damage. Intravenous
mannitol (20%) and parenteral dexamethasone may be given if features
of cerebral edema or raised intracranial pressure are present.
BIBLIOGRAPHY
1. Caraval HF, Park DH. Burns in children. Paediatric Burn management.
Chicago YearBook Medical, 1988.
2. Strongin J, Hales CA. Pulmonary disorders in burn patient. In: Philadelphia
WB Saunders 1990;25-45.
3. Menon J, Mathews L. A case of carbon monoxide poisoning. Indian
Pediatr.2004;17:291-92.
4. Raub JA, et al. carbon monoxide poisonig: A public health perspective.
Toxicology 2000;145:1-14.
5. Mehta SR, Niyogi M, Kasthuri AS, et al . Carbon monoxide poisoning. J
Assoc Phys India 2001;49:622-25.
18
Ethylene Glycol
Ethylene glycol is commonly used as an anti-freeze fluid in car radiators

and has a variety of commercial applications. Its ready availability
and sweet taste have made it a popular suicide agent and substitute
of alcohol for poor person. Children are usually accidental victims of
ethylene glycol intoxication. The fatal dose in an adult is approximately
100 ml.
Pathophysiology
Ethylene glycol, itself is nonpoisonous, rather it metabolites produced
in liver and kidneys cause poisoning. It is metabolized by alcohol
dehydrogenase and aldehyde dehydrogenase. Ethylene glycol is first
converted to glycoaldehyde, which is then converted to glycolic, and
oxalic acids. Glycoaldehyde inhibits oxidative phosphorylation, cellular
respiration and glucose metabolism, protein synthesis, DNA replication
and ribosomal RNA synthesis and serotonin metabolism. It also alters
central nervous system amine levels. Glycolic acid is primarily
responsible for development of acidosis. Oxalic acid cause renal
damages and further aggravates acidosis. Oxalic acid also chelates
calcium ions to form insoluble calcium oxalate crystals and may result
in hypocalcemia, renal intratubular obstruction and impairment of
cerebral function consequent to deposition of crystals in the brain.
Lactic acid is produced as the result of formation of NADH, which
prevent flow of carbon through citric acid cycle.
The clinical manifestation of ethylene glycol intoxication are arbitrarily
divided into three stages depending on the time of ingestion. The
severity and progression from one stage to another depends on the
amount of ethylene glycol ingested. Blood concentration 500 mg/liter
or more indicates severe poisoning.
Stage I (30 Min-12 Hours)

In this stage gastrointestinal and neurological features are dominant,
which are the following:
1. Patients appear intoxicated with alcohol but no breath odor of
alcohol
2. Nausea, vomiting, hematemesis
3. convulsion often focal and coma
4. Nystagmus, ophthalmoplegia and papilledema
5. V, VII and VIII cranial nerve palsies
6. Depressed reflexes, myoclonic jerks and occasionally titanic
contractions.
Stage II (12-24 Hours)

This stage is characterized by involvement of cardiorespiratory system
and manifestations are tachypnea, tachycardia, hypertension,
congestive heart failure and features of pulmonary edema.
Stage III (24-72 Hours)

Renal involvement is the predominant in this stage and characterized
by flank pain, renal angle tenderness and features of acute tubular
necrosis.
Treatment
Gastric lavage should be done as early as possible to prevent further
absorption and to confirm diagnosis. Supportive measures to combat
shock, hypocalcemia, metabolic acid and respiratory distress should
be instituted. Thereafter, the key strategy is blocking the generation
of toxic metabolites.
The classical intervention is the administration of ethanol, which
has higher affinity for the binding sites on alcohol dehydrogenase. The
goal is to saturate these binding sites, thereby, preventing the generation
of toxic mebatolites. The dose of ethanol is 50 g orally followed by IV
10-12 g/hour to acheive a blood concentration of 1 g/liter. Therapy
is continued till parent compound is cleared from body.
Fomepizole (4-methylpyrazole), a new most effective drug in
treatment of methylene glycol and methanol intoxication, is a
competitive inhibitor of alcohol dehydrogenase. It is metabolized by
cytochrome P450 mixed function oxidase system and induces its own
metabolism. Fomepizole has several advantages over ethanol. It does
not alter mental status unlike inebration caused by ethanol. Its half-
life is longer than ethanol therefore, dosing is at 12 hours interval
Ethylene Glycol 185
rather than constant infusion. Key Points

Monitoring of serum concen-
Diagnosis
tration of ethanol, preparation
and administration and 1. H/O ingestion
calculation of dose are difficult. 2. C/F: nausea, vomiting, oliguria, oph-
thalmoplegia, confusion, coma,
Unlike that of ethanol, the use pulmonary edema
of fomepizole does not require 3. Blood concn > 500 mg/L
an ICU setting and does not
cause hypoglycemia. Management
Half-life of fomepizole is 1. Gastric lavage
approximately 12 hours. Since 2. Supportive measures for shock,
it is dialyzable, its dosing hypocalcemia, acidosis and resp.
frequency should be increased distress
3. Fomepizole: 15 mg/kg/dose followed
during dialysis. It can be given
by 10 mg/kg IV 12 hrly.
either orally or intravenously. 4. Ethanol: 50 gm PO followed by 10-12
The loading dose of fomepizole gm/hr
is 15 mg/kg followed by doses
of 10 mg/kg every 12 hours for four doses and then 15 mg/kg every
12 hours therafter until serum ethylene glycol concentration become
less than 20 mg/dl. All doses are given intravenously over 30 minutes.
Indications of its use are serum concentration more than 20 mg/dl,
increased anion gap, metabolic acidosis and history of ethylene glycol
ingestion. During hemodialysis, dosing frequency should be reduced
to every 4 hours. The chief short coming is its high cost. The adverse
reactions of fomepizole reported are headache, nausea and vertigo.
Ethylene glycol, its metabolites and glycolate may be removed by
either peritoneal or hemodialysis and continued till ethylene glycol is
no longer detectable in blood. Acute tubular necrosis and renal failure
should be managed by judicious administration of fluid, electrolytes,
and hemodialysis.
BIBLIOGRAPHY
1. Harry P, et al. Efficacy of 4- methylpyrazole in ethylene glycol poisoning:
Clinical and toxokinetic aspects. Hum Exp Toxicol. 1994;13:61-64.
2. Harry P, Jobard E, Briand M, et al. Ethylene glycol poisoning in a child
treated with 4-methylpyrazole. Pediatrics 1998;102:31.
3. Peterson CS, Collins AJ, et al. Ethylene glycol poisoning: Pharmacokinetics
during therapy with ethanol and hemodialysis. N Eng J Med 1981;304:21-
23.
4. Weintranb M, et al. 4-methylpyrazole: An antidote for ethylene glycol and
methanol intoxication. Hospital Formularly 1988;23:960-69.
19
Epidemic Dropsy
Epidemic dropsy is an acute non-infectious disease characterized by

pitting edema of extremities, cutaneous erythema and local tenderness.
It is caused by consumption of argemone seed oil which may be
accidently or deliberately present as contaminant in mustard or other
edible oils. The toxic molecules present in argemone seed oil are
benzophenanthridine alkaloids; sanguinarine and its derivatives
dihydrosanguinarine.
Epidemiology
Epidemic dropsy was first reported from Kolkata in 1977. Since then
a number of outbreaks have been reported from Indian Subcontinent
including Fiji and South Africa. In India several outbreaks have occurred
in West Bengal, Orissa, MP, UP, Gujrat, Maharastra, Bihar, Delhi. Last
epidemic occurred in 1998 which involved almost entire country
including neighboring countries like Nepal, Bangladesh and costs
thousands of human lives including children.
Argemone seed oil is derived from plant Argemone mexicana
commonly known as prickly poppy, which grows widely as weed
during wheat and mustard harvesting season in Indian subcontinent.
The seeds of Argemone mexicana resembles mustard seeds and oil is
used as adulterant of mustard oil. The toxic substances are sanguinarine
and dihydrosanguinarine, the former being more toxic. The mode of
intoxication are ingestion and transcutaneous application of oil.
Pathophysiology
The organs involved mainly are cardiac, gastrointestinal tract, eyes
and skin. The followings are the postulated mechanisms for
pathophysiology of epidemic dropsy.
1. Sanguinarine and dihydrosanguinarine enhances glycogen
breakdown in liver and inteferes the oxidation of pyruvic acid,
which accumulates in blood. The increased serum pyruvate causes
Epidemic Dropsy 187
uncoupling of oxidative phosphorylation, vasolidation and

increased capillary permeability thus leads to erythema and edema
of body and extremities and breathlessness as observed in patients
with epidemic dropsy.
2. Sanguinarine inhibits Na+/K+ - ATPase activity of cell membrane
in various organs like brain, heart, liver, intestine and skeletal
muscle. The inhibition leads not only to positive ionotropic effects
on cardiac muscle but also decrease the active transport process
especially that of glucose which is fundamental nutrient of most
cells.
3. It binds to cytochrome P450 and causes its loss in liver. It also
causes reduction of hepatic cytochrome-b5 content, thus acts as
xenobiotic.
4. It also causes generation of highly reactive oxygen-free radicals
that cause peroxidation of lipids and proteins of cell membrane and
depletion of endogenous hepatic glutathione content and gluta-
thione-5 transferase activity. Hepatic microsomal and mitochondrial
membrane damage is also observed, which may be responsible for
impaired hepatic function and elevation of ALT, AST and alkaline
phosphatase seen in patients with epidemic dropsy.
5. It has been found to express mutagenic and carcinogenic effects by
directly binding with DNA template. This process is further
complicated with generation of reactive oxygen-free radicals and
subsequent depletion of endogenous glutathione reserve.
Clinical Features
The onset of disease is insidious with loss of appetite, fever, nausea,
vomiting, pain abdomen, diarrhea and pitting edema over the legs.
Sometimes edema may massive to involve upper limbs and face.
Extremities are warm and erythematous due to vasodilatation.
Pigmentation and darkening of skin and perianal itching have been
observed in most of the patients. Subcutaneous telangiectasia or even
hemangiomata may develop on mucous membrane of cheek, gums,
tongue and nose as fleshy dark red or warty growth (sarcoid). Injury
to sarcoids may lead to ulceration, bleeding and infection.
Cardiovascular manifestations are tachycardia, pericardial effusion,
myocarditis and congestive heart failure. Bilateral pleural effusion
and bronchopneumonia too may aggravate the breathlessness of
patients with epidemic dropsy. Hepatosplenomegaly and ascites have
been observed in more than half of the patients. Neurological features
are tingling and numbness of extremities and calf tenderness. Glaucoma
is most common ophthalmological manifestations. Glaucoma has been
reported in approximately 10 percent patients and is hypersecretory.

Glaucoma probably occurred as a result of excessive release of histamine
and prostaglandins E2. Sachdev et al have observed increased level of
PGE2 and histamine in aqueous humors of dropsy patients. Other
ophthalmological changes are bilateral Roths spot, sub-hyloid
hemorrhage and retinal venous congestion. Acute uveitis may also
occur due to dilatation of capillaries of uveal tract.
Nonspecific: Fever, pallor, perianal itching, tender pitting, edema of
limbs.
Dermatological: Erythema, pigmentation, telangiectasia, heman-
giomata.
CVS: Carditis, congestive heart failure and pericardial effusion.
Pulmonary: Bronchopneuomonia and pleural effusion.
GIT: Nausea, vomiting, diarrhea, pain abdomen and ascites,
hepatosplenomegaly.
Neurological: Numbness and tingling of extremities, calf tenderness.
Ophthalmological: Glaucoma, acute uveitis.
Diagnosis
1. Epidemiological: The occurrence of clinical manifestations in a family
or community simultaneously who have taken same brand of
mustard oil points towards diagnosis of epidemic dropsy.
2. Clinical manifestations as mentioned.
3. Laboratory findings:
A. Supportive
i. Hematologicalanemia
ii. Liver function test ALT, AST, alkaline phosphatase
Serum albumin
2-globulin
iii. CXR: Cardiomegaly
Bronchopneumonia
iv. USG: Free fluid in peritoneal, pleural and
pericardial cavity
v. ECG: Tachycardia and evidence of carditis.
B. Confirmatory tests, i.e. to detect the presence of argemone oil

in a sample of oil.
a. Qualitative tests
1. Nitric acid test: One ml of suspected mustard oil is mixed
with equal volume of concentrated nitric acid. The
development of brown to orange red color indicates
presence of argemone oil.
Epidemic Dropsy 189
2. Cupric acetate test: To 2.5 ml of oil sample, 0.5 ml glacial

acetic acid and 1 ml cupric acetate (10%) solution is added,
mixed properly and incubated in boiling water bath for
15 minutes. The greenish color slowly disappears in
presence of argemone oil.
3. Ferric chloride test: To 2 ml of oil sample, 1 ml concentrated
hydrochloric acid is added, mixed and incubated in boiling
bath for 5 minutes. This is followed by addition of 0.5 ml
of ferric chloride (10%) solution and reincubation in hot
water bath (50-60oC) for 10 minutes. A red precipitate
confirms presence of argemone.
b. Quantitative tests
1. Thin layer chromatography: This is a very sensitive test. A
bright yellow fluorescent spot observed under U/V light
indicates the presence of argemone oil. This method can
detect upto 55 ppm level of sanguinarine in oil.
2. High performance liquid chromatography: This is the most
sensitive test, which can detect sanguinarine in nanogram
range. The method makes use of ethyl silane column with
acidic and basic ion-pairing reagents in mobile phase and
can easily be applied for detection of sanguinarine in
biological fluids also.
Treatment
Since no effective antidote is available against sanguinarine, supporitve
treatments with adequate nutritional support are the principles of
management inpatient of epidemic dropsy. The following are the basic
principles in management:
i. Withdrawal of toxic mustard oil from market immediately.
ii. Complete bed rest as excessive exertion may exacerbate
breathlessness and precipitate congestive heart failure.
iii. Salt restriction.
iv. Nutritional support: Adequate nutritional support either enteral
or parenteral should be given to all patients, judicious IV fluid
administration recommended.
v. Decongestants: Decongestants such as diuretics, i.e. furosemide
and digitalis should be given in patients with congestive heart
failure. In presence of myocarditis, digitalis is contraindicated
as it may precipate various types of arrhythmias.
vi. Appropriate antibiotics may be given in presence of concomittant
infection.
vii. Blood transfusion for severe anemia.
viii. Antipyretics and analgesics may be administered for fever and

tenderness (calf) respectively.
ix. The use of antioxidants including riboflavin, beta-carotene and
alfa-tocopherol have been found to be effective in reducing
argemone oil toxicity.
BIBLIOGRAPHY
1. Cala PM, Norby JG, Tosteson DC. Effect of the plant alkaloid sanguinarine
on cation transport by human red blood cells and lipid bilayer membranes.
J Membr Biol 1982;64:23-31.
2. Gomber S, Bist SS. Resurgence of epidemic dropsy. Indian Pediatr 1997;34:
953.
3. Kumar A, Hussain F, Das M, Khanna SK. An outbreak of epidemic dropsy
in Barabanki district of Uttar Pradesh, India: A limited trial for the scope
of antioxidants in management of symptoms. Biomed Environ Sci 1992;5:251-
56.
4. Sachdev MS, Sood NN, Verma LK, Gupta SK, Jaffeny NF. Pathogenesis of
epidemic dropsy glaucoma. Arch Ophthalmol 1988;106;1221-23.
5. Sood NN, Sachdev MS, Mohan M, Gupta SK, Sachdev HPS. Epidemic dropsy
following transcutaneous absorption of Argemone mexicana oil. Trans R Soc
Trop Med Hyg 1985;79:510-12.
6. Tandon RK, Singh DS, Arora RR, Lal P, Tandon BN. Epidemic dropsy in New
Delhi. Am J Clin Nutr 1975;28:883-87.
20
Mustard Gas
From ancient times, the military advantages of using noxious chemicals

have been recognized. The enemy may be killed or disabled. Even
merely threatened to use chemical warfare agents has a powerful
psychological effect. Mustard gas, a vesicant compounds extensively
used in past, was first used by German on 12 July 1917 during First
World War. Recently in 1984, Iran accused Iraq of using it. The name
mustard was used by soldiers during First World War because of
smell. It is an oily liquid at room temperature. The vapor of this passes
through clothing and penetrates and get absorbed through the skin
producing local and systemic effects. It may be delivered by artillary
shell, rocket and bomb or aircraft spray. It is persistent in air and
ground may remain contaminated for long periods in cold weather.
The exposed drinking water may be contaminated.
Pathogenesis
Mustard gas is an alkylating agent, which is converted in the body
to an active ethylenimonium intermediate compound, which binds to
a range of molecules including protein, enzymes and nucleic acids.
Sulfur mustard is converted in part to a similar sulfonium ion. These
two intermediate compounds bind to guanine residues causing severe
disruption of DNA structure and function. The damage to DNA will
have profound effects on rapidly dividing tissues resulting in bone
marrow depression, hair loss and gastrointestinal effects.
Clinical Features
There is latent period of 2-4 hours after exposure to vapor before
appearance of clinical manifestations. The clinical presentations depend
on the mode of exposure. The exposure to liquid has similar effects
but local vesication will be more marked. Fatalities may result from
bronchopneumonia complicated by severe bone marrow depression.
Clinical presentations in respect to time of exposure are the followings.
Time of exposure Clinical presentations
1. 20-60 minutes Nausea, retching, vomiting and eye-smarting.

2. 2-6 hours Nausea, vomiting, fatigue, headache, swelling of eyes, lacrimation,
blepharospasm, photophobia, rhinorrhea, flushed face and neck,
soreness of throat, tachycardia and tachypnea.
3. 24 hours Generalized increase in severity of above effects. Inflammation of
inner thigh, axillae, genitalia, buttocks followed by onset of blister
formation.
4. 48 hours Conditions generally worsened. Blistering more marked. Bronchitis
with expectoration of mucopus and necrotic slough. Increase in
temperature, pulse and respiration.
Treatment
Since there is no specific therapy, first aid measures are of great
importance. The universal precautions while handling these patients
are to bear adequate protective clothings and have respirator.
First Aid
1. Patients should be removed from source.
2. Severely affected patients should not be allowed to walk.
3. Clothing should be removed and affected areas washed with soap
and water.
4. If eyes are contaminated, eyes should be rinsed out immediately
with isotonic normal saline preferably or water.
Therapeutic Measures
A number of palliative approaches have been recommended. Cysteine
can reduce antitumour effects of alkylating agents probably by
providing alternate binding sites to those of DNA.
Calamine should be applied to areas of erythema and minor
blistering. Recently beclomethasone dipropionate cream has been used
but is unlikely to enhance healing. The areas of deeper burns are
difficult to manage. Standard thermal burn therapy, i.e. silver
sulfadiazine may play a useful role in preventing secondary infection.
Grafting may be required for full thickness burn.
The contaminated eyes should be rinsed with isotonic saline. Topical
prednisolone drop (1%), potassium ascorbate (10%) and sodium citrate
(10%) drop each once per hour until stable epithelium has reformed
are recommended local anesthetic agents such as amethocaine
hydrochloride (0.5%) but not cocaine which may produce corneal
sloughing and mydriatics hyoscine (0.5%) have been suggested. Topical
antibiotics should be used to prevent infection.
Mustard Gas 193
Codeine linctus may be useful for severe and intractable cough.

Systemic antimicrobials may be used to combat infection. ARDS may
occur in severe cases and should be managed with mechanical
ventilation.
Bone marrow depression resulting from mustard gas has been
considered irreversible but colony-stimulating factor may be a worth
therapeutic trial. If there is severe aplasia of bone marrow platelet and
granulocyte transfusions should be given at regular interval. Bone
marrow transplantation should be considered. Vomiting may be
controlled by phenothiazine group of drugs. Hemodialysis and
hemoperfusion have been suggested but their efficacy is uncertain.
Corneal ulceration and blindness are long-term ophthalmological
effects. There are increased incidences of bronchitis and lung cancer
in soldiers exposed to sulfur mustard.
BIBLIOGRAPHY
1. Beebe GW. lung cancer in World War I veteram: Possible relation to mustard
gas injury and the 1918 influenza epidemic. Journal of the National Cancer
Institute 1960;25:1231-52.
2. Foster J. Ophthalmic injuries from mustard gas (DES). BMJ 1939;1181-83.
3. Fox M. The genetic toxicity of nitrogen and sulfur mustard. Mutational
Research 1980;75-1051-58.
4. Yamada A. On late injuries following occupational inhalation of mustard gas
with special reference to carcinoma of respiratory tract. Pathologica 1986;
13:131-55.
21
Methanol (Methyl Alcohol)
Methanol is widely used as solvent and to denature alcohol. It is also

found in antifreeze solutions, paints, duplicating fluids, paint removers,
varnishes and shoe polishes. The usual mode of intoxication in children
is accidental ingestion but may also occur as a result of inhalation or
percutaneous absorption. The fatal dose is 10-30 ml. Methylated spirit
consists of 5 percent methyl alcohol and 95 percent ethyl alcohol.
Pathophysiology
In human methanol is metabolized by alcohol dehydrogenase and
catalase enzyme systems to formaldehyde and formic acid which
inhibits mitochondrial respiration, thus cause metabolic acidosis. It also
depresses hepatic NAD+; NADH ratio, hence inhibits gluconeogenesis
from lactate and further increases the tendency of acidosis. Visual
toxicity of methanol is either due to formation of formaldehyde in
retina or interruption of axoplasmic flow in optic nerve as a result of
inhibition of cytochrome oxidase activity by formate ions.
Methanol causes mild and transient inebriation and drowsiness. After
8-36 hours, nausea, vomiting, abdominal pain, headache, dizziness and
coma may occur. The blurring of vision and diminished visual activity
may occur. The presence of dilated pupil, non-reactive to light suggests
permanent blindness. Blood methanol concentration greater than 500
mg/liter indicate severe intoxication and are associated with metabolic
acidosis, hyperglycemia and raised serum amylase. The mortality
increases with the severity and duration of metabolic acidosis. Morbidity
related to methanol poisoning includes permanent blindness, rigidity,
hypokinesis and parkinsonian-like signs due to development of optic
neuropathy and putamenial necrosis respectively.
Treatment
Gastric lavage should be done in patients who present less than one
hour after ingestion. Thereafter, the principles of methanol poisoning
are the following:
A. Correction of metabolic acidosis by IV sodium bicarbonate in a dose
of 1-2 ml/kg slowly.
Methanol (Methyl Alcohol) 195
B. Inhibition of methanol oxidation: Key Points

fomepizole and ethanol. Diagnosis
C. Removal of circulating methanol 1. H/O ingestion
and its toxic metabolites. 2. Vomiting, hematemesis, drowsiness,
Fomepizole (4-methyl pyrazole) dizziness, blurring of vision, dilated
is a competitive inhibitor of alcohol and fixed pupil, coma
3. Blood concn > 500 mg/L
dehydrogenase and is metabolized 4. Metabolic acidosis, hyperglycemia,
by the cytochrome P450. Thus it serum amylase
prevents the generation of toxic Management
metabolites. Half-life is approxi- 1. Gastric lavage
mately 12 hours. Because it is dialyz- 2. Correct acidosis with IV sod. bicar-
able, its dosing frequency should be bonate
3. Fomepizole: 15 mg/kg/dose followed
increased during dialysis. It can be by 10 mg/kg IV 12 hrly.
given either by mouth or intra- 4. Ethanol: 50 gm PO followed by
venously. The loading dose is 15 10-12 gm/hr
5. Peritoneal/hemodialysis
mg/kg, followed by doses of 10 mg/
kg every 12 hours for four doses and then 15 mg/kg every 12 hours
thereafter, until serum methanol concentration become less than 20 mg/
dl. All doses are given intravenously over 30 minutes. During
hemodialysis dosing frequency should be reduced to every 4 hours. The
chief shortening is its high cost. Adverse reactions associated with
fomepizole are headache, nausea and vertigo.
Since ethanol inhibits methanol oxidation when taken together or
given earlier, it is also effective in methanol intoxication. However, in
absence of plasma methanol, ethanol may not of benefit and exacerbate
acidosis. The loading dose is 50 g orally followed by IV 10-12 gm/hour
to achieve blood concentration of approximately 1 g/liter. Plasma
ethanol and methanol concentrations should be monitored continuously
and infusion of ethanol should be continued until methanol is
undetectable in blood, when peritoneal dialysis is being employed,
ethanol may be added to dialysate fluid (1-2 g/liter).
Dialysis is an effective method of removal of methanol and its
metabolites. The indications of dialysis are, ingestion of methanol more
than 30 g, metabolic acidosis, mental, visual or fundoscopic abnormalities
and blood methanol concentration greater than 500 mg/liter.
Hemodialysis is three times more effective than peritoneal dialysis.
Folinic acid, 30 mg IV 6 hourly, may protect against ocular toxicity
by accelerating formate metabolism.
BIBLIOGRAPHY
1. Anon. Methanol poisoning Lancet 1983;i:910-2.
2. Burns MJ, et al. Treatment of methanol poisoning with intravenous 4-methyl
pyrazole. Ann Emerg Med 1997;30:829-32.
3. Fisher DM, Diaz JE. Pediatric methanol poisoning treated with fomepizole
(Antizol). J Toxicol Clin Toxicol 1998;36:512.
4. Mc Coy HG, et al. Severe methanol poisoning. Application of a pharmacoki-
netic model for ethanol therapy and hemodialysis. Am J Med 1979;67:804-07.
22
Oleander Poisoning
Oleander commonly known as kernels, evergreen shurb is distributed

throuhghout world inluding India, Nepal, Srilanka and China along
road side and in garden. The two common members are common
(Nerium oleander) and yellow (Thevetia peruviana) oleander. Both
members have long pointed leaves with prominent rib, clusters of dull
orange, white, pink, red and yellow flowers that appears in summer
followed by fleshy globular black fruit. The Greek, Roman and Hindus
considered oleander to be seriously toxic. Though all parts of plants
are poisonous, fruits and seeds caused most toxic effects. The ingestion
of one leaf is considered potentially lethal, the larger amounts may
cause serious toxicity.
The preparations of oleander have been used as rodenticides and
insecticides as well as remedies for indigestion, malaria and skin
diseases including leprosy. The Chinese used oleander extract for
treatment of mental disorders. The most common folk use is as an
abortifacient. In childern, the poisoning is usually due to accidental
ingestion of parts of plant due to their natural curiosity but may be
of suicidal intention in adolescents. In Srilanka and Nepal oleander
is one of the common poison used for suicides in adolescents.
Fatal dose: One leaf or one seed.
Fatal period: 6 days.
Pathophysiology
The common oleander contains at least five cardiac glycosides, i.e
oleandrin, digitoxigenin, nerrin, folinerin and rosangenin, whereas
toxic extracts of yellow oleander include thevetin A and B, thevotoxin,
peruvoside, ruvoside and nerrifolin. These glycosides have some
structural simillarity to digitoxin and exert digitoxin-like effects by
inhibiting Na+-K+ ATPase enzyme system. Alkaloids also activate Na+
channels producing prolonged depolarizatron and impaired
repolarization of excitable membrane. The resulting toxic syndromes
Oleander Poisoning 197
resemble digitalis poisoning with hyperkalemia, conduction

distrubances and ventricular arrhythmias. Oleandrin is also locally
irritant to gastrointestional tract and leads to mucosal erythema, nausea,
vomiting and diarrhea. After absorption from GI tract, glycosides are
more concentrated in heart than blood.
Clinical Features
The clinical manifestations of oleander poisining closely resembles
digitoxin/digoxin poisoning with predominantly gastrointestinal and
cardiac symptoms. Nausea, vomiting, diarrhea and mucosal erythema
develop within hour following ingestion. In addition, perioral
paresthesias, dizziness, progressive skeletal muscle weakness and
excessive salivation have been reported in early phase. Cardiac
manifestations are characteristics of poisoning and include hypotension,
sinus bradycardia, supraventricular tachyarrhythmias, torsade de
pointes and conduction disturbances such as variable A-V block and
complete heart block. Some patients may develop ventricular
tachycardia and ventricular fibrillation. Hypotension may be due to
cardiotoxicity and persistent vomiting and diarrhea. The common
metabolic derangements as hyperkalemia, hypokalemia and
hypomagnesemia.
Diagnosis
1. H/O ingestion
3. Characteristic ECG changes
4. Radioimmunoassay: Digoxin radioimmunoassy in patients with
poisoing confirms the presence of cardiac glyosides, which show
some cross-reactivity with digoxin.
Management
The casual contact by children usually does not result in serious
morbidity. If children have inges-
ted even less than one leaf or Key Points
flower, children should be
observed at home after emesis i. Emesis with syrup of ipecac
ii. Gastric lavage
with syrup of ipecac. Any sympo-
iii. Activated charcoal
matic patient or petients who iv. HypotensionIV fluid and vaso-
have ingested more than one leaf pressor
or seed should be admitted in v. Atropine-0.02-0.05 mg/kgIV
hospital. Emesis and gastric vi. Temporary pacemaker
lavage should be done as early as vii. Anti-digoxin Fab fragment IV
possible followed by administration of activated charcoal. Activated

charcoal is not routinely recommended since there is no evidence that
this improves clinical outcome, however, multiple doses of activated
charcoal can reduce plasma levels of digoxin and other glycosides by
decreasing absorption and later by interrupting enterohepatic
circulation.
The close cardiac monitoring should be done in all patients.
Hypotension usually responds to IV fluid and vasopressor agents.
Sinus bradycardia should be treated with IV atropine (0.02-0.05 mg/
kg/dose). Ventricular arrhythmias are often refractory to cardioversion
or lidocaine. Bretylium, procainamide, amiodarone and flecainide are
also not effective. The arrhythmias usually resolve within 24 hours,
however, in some patients may persist for 3-6 days. Temporary
pacemakers are required in majority of patients. Indications of
temporary pacemakere are complete heart block, mobitz type-II second
degree block, sinus bradycardia with heart rate less than 40/min, sinus
arrest or block with sinus pauses longer than 2 sec and ST-segment
depression greater than 2 mm at point greater than 80 ms from j-point.
Recently anti-digoxin Fab fragment has been recommended for
treatment of oleander poisoning. It reverses rapidlly and safely oleander
induced arrhythmias, restores sinus rythm and rapidly corrects
bradycardia and hyperkalemia. Cardiac responses usually occur within
one hour, i.e. complete heart block improved to 1st degree block 1 hour
after therapy and regular sinus rythm by 2 hours. Serum K+
concentration decreases significantly by 2 hours in patient receiving
anti-digoxin Fab. The dose of anti-digoxin Fab is 400 to 800 mg and
administered by intravenous infusion over 20 minutes in 200 ml saline.
Patients should be closely monitored during administration for signs
suggestive of anaphylactic reactions such as itching, urticarial rashes,
bronchospasm and angioedema of lips. Patients who develop
anaphylactic reactions should be managed with IV epinephrine,
hydrocortisone and chlorpheniramine.
BIBLIOGRAPHY
1. Eddleston M, Ariaratnam NA, et al. Epidemic of self poisoning with seeds
of yellow oliander tree in nothern Srilanka. Trop Med Int Heath 1999;4:266-
73.
2. Edleston M, Rajapaske S, et al. Anti-digoxin Fab fragments in cardiotoxicity
induced by ingestion of yellow oleander: A randomized control trial. The
LANCET 2000;355:967-72.
3. Misra A. Poisoning from Thevetia nerifolia (yellow oleander). Postgrad Med
J 1990;66:492.
4. Osterloh J, Harold S, Pond S. Oleander interference in digoxin radioimmuno-
assay in a fatal ingestion. JAMA 1982;247:1596-7.
5. Shumaik GM, et al. Oleander poisoning: Treatment with digoxin-specific Fab
antibody fragment. Ann Emerg Med 1988;17:732-5.
23
Miscellaneous
DAPSONE POISONING
Dapsone, a sulfonamide derivative has been used commonly in
treatment of leprosy, dermatitis herpetiformis, sometimes in malaria,
maduromycosis and more recently in the prophylactic treatment of
Pneumocystis carinii pneumonia with human immunodeficiency virues.
Accidental dapsone poisoning is a pediatric emergency in pre-school
children. On ingestion, dapsone is well-absorbed from gastrointestinal
tract with peak level in plasma after two to six hours. It can be detected
in tissue upto 3 weeks after ingestion. The half-life normally varies
from 9-45 hours (mean 30 hours) but in toxic doses may be prolonged
to two to four days.
Pathophysiology
Iron normally exists as iron porphyrin complex in heme portion of the
hemoglobin molecules. Dapsone causes oxidation of iron from ferrous
to ferric state reulting in formation of methemoglobin. The clinical
presentation varies and depends on methemoglobin concentrations in
the blood. Normal methemoglobin content is less than 2 percent of
the total hemoglobin in pre-term babies and less than 2.2 and
1.5 percent in term and one year old babies respectively. Methemoglobin
is incapable of binding oxygen and increases the affinity of unaltered
hemoglobin for oxygen, shifting the oxygen dissociation curves to the
left, thus further impairing oxygen delivery.
Clinical Presentation
The clinical presentation of dapsone poisoning depends upon the
concentration of methemoglobin in the blood (Table 23.1).
Management
1. Gastric lavage should be done immediately to take out remaining
tablets from the stomach. Gastric lavage is followed by adminis-
tration of activated charcoal orally for gut decontamination.
Table 23.1: Clinical features of dapsone poisoning is determined

by methemoglobin level (%) in blood
Methemoglobin Clinical features

(% in blood)
15 Cyanosis, particularly acrocyanosis

20 Cyanosis, mild fatigue
30-40 Cyanosis, weakness, tachycardia, nausea
> 40 In addition to all above, restlessness, confusion, coma, death
2. Administration of 100 percent Key Points

oxygen by mask.
Diagnosis
3. Reducing agents such as
methylene blue and ascorbic 1. History
acid are effective antidotes for 2. Clinical features: acrocyanosis or
severe cyanosis, weakness, tachy-
dapsone poisoning. When cardia, confusion and coma depend-
given intravenously they ing on methemoglobin concentration.
improve the oxygen delivery
to tissues. Methylene blue Management
when given intravenously in 1. Gastric lavage
severe methemoglobinemia is 2. Activated charcoal
rapidly reduced to leuko- 3. 100 percent oxygen by mask
methylene blue in the presence 4. Antidote:
of NADPH and methemo- i. One percent methylene blue
1-2 mg/kg slows IV injection.
globin reductase. Leukomethy- ii. Ascorbic acid, 200-500 mg IV
lene blue reduces methemo- injection.
globin to hemoglobin. 5. Exchange transfusion in severe
Dose: One percent aqueous refractory cases.
solution of methylene blue, 1-
2 mg/kg as a slow IV injection over 5 minutes. The dose may be
repeated after 4-6 hours. In less severe cases, ascorbic acid 200-500
mg can be given intravenously.
4. Exchange transfusion may be done in cases not responding to
methylene blue.
DIGITALIS
The incidence and severity of digitalis toxicity have decline substantially
in past two decades due to fast development of alternative drugs for
treatment of supraventricular arrhythmias, increased understanding
of digoxin pharmacokinetics and recognition of important interactions.
Digitalis poisoning occurs most frequently due to over dosage
during chronic maintenance therapy, accidental ingestion and rarely
due to ingestion of crude digitalis from the dried leaf of the foxglove
Miscellaneous 201
plant Digitalis purpurea. Digitalis acts by inhibiting the enzyme sodium-

potassium ATPase, leading to increase intracellular Na+ and Ca++ and
decreased K+. Digoxin is slowly absorbed and distributed and the
serum levels may not correlate with pharmacologic effects for upto
8 hours following a therapeutic dose.
Digoxin is 25 to 30 percent protein bound in plasma and has a large
volume of distribution of 5 to 6 L/kg of body weight. It is localized
in skeletal muscle, liver and heart. Elimination is primarily by
the kidney (85%) in unchanged form and the remainder is metabo-
lized by the liver. The half-life ranges between 36 to 45 hours. The
mean therapeutic concentration ranges from 0.6 to 2.5 nmol
(0.5-2.0 mg/ml).
Clinical Features of Toxicity

The clinical features are divided into two categories, extracardiac and
cardiac.
Extracardiac
These are anorexia, nausea, vomiting, abdominal pain, fatigue, malaise,
dizziness, confusion, delirium and occasionally hallucinations, blurred
vision, photophobia, scotomata and disturbed color perception (yellow
vision).
Cardiac
Cardiac manifestations include sinus arrhythmias, sinus bracycardia
and all degrees of A-V block. Premature ventricular contractions,
bigeminy, ventricular tachycardia and fibrillation also occur. The
combination of supraventricular tachyarrhythmias and A-V block is
highly suggestive of digitalis toxicity. Clinical toxicity occurs with
digoxin levels in excess of 3.8 to 6.4 nmol/L (3-5 ng/ml) and levels
as high as 64 to 77 nmol/L have been seen in a overdose.
ECG Manifestations
i. Depression of ST segment with inverse check mark configuration.
ii. Flattening or inversion of T-wave.
iii. Shortening of Q-T interval.
iv. Extrasystoles, bigeminal rhythm either unifocal or multifocal,
multifocal ventricular tachycardia, ventricular fibrillation, first
degree heart block (common) second and third degree heart
block.
Treatment of Digitalis Toxicity Key Points

1. Stop the administration of Diagnosis
digitalis and gastric lavage
1. History of drug ingestion
should be done, if digoxin is 2. Clinical features
ingested within one hour. i. Nausea, vomiting, abdominal pain
2. Gastrointestinal deconta- ii. Cardiac arrhythmias
mination should be done as 3. ECG
i. Inverse checkmark ST segment
soon as possible. Since emesis
ii. Prolonged P-R interval
and gastric intubation may iii. Shortened Q-T interval
cause vagal stimulation, which iv. Flat or inverted T
may worsen existing conduc- v. Various arrhythmic patterns.
tion disturbances, activated
charcoal is preferred for Management
decontamination which 1. Stop further administration.
reduces absorption and also 2. Activated charcoal for GI decontami-
enhance elimination. nation.
3. Potassium, magnesium and calcium
3. Potassium, magnesium and
abnormalities should be corrected.
calcium abnormalities should 4. Treatment of arrhythmias
be corrected. Potassium is 1st and 2nd degree heart block
contraindicated, if higher i. Atropine
degree of A-V block is present. ii. Isoproterenol
4. Electrical pacing may be neces- iii. Cardiac pacing, if refractory
ventricullar arrhythmias
sary when sinus bradycardia i. Lidocaine
and second and third degree ii. Magnesium sulfate
heart block result in hypo- iii. Phenytoin.
tension and fail to respond to 5. Digoxin-specific Fab fragment anti-
atropine and isoproterenol. body for refractory potentially life-
threatening arrhythmias.
5. Magnesium sulfate as well as
phenytoin (1 mg/kg over 5
min to a maximum of 10 mg/kg IV) and lidocaine (1-mg bolus
followed by 0.03 g/kg/min) may be useful in treatment of
ventricular arrhythmias induced by digitalis.
6. Digoxin-specific antibody fragments (Fab) prepared from IgG
produced in sheep has been available commercially since 1986
(Digibind, Ovine). Antibody therapy is quite valuable because of
risk of life with severe toxicity and limited clinical benefit from
conventional treatment. The antibody fragments rapidly bind
intravascular and interstial digoxin. Their low molecular weight
(50-kDa) permits rapid diffusion into interestitial space, where
binding of free digoxin sets up a concentration gradient leading
to egress of tissue stores of glycoside. An initial clinical response
can usually be expected within 20-40 minutes and complete reversal
Miscellaneous 203
of toxicity within about 4 hours. If the renal function is normal, the

digoxin bound to Fab is excreted with a half-life of approx. 16
hours.
Fab antibody fragments lack complement fixing activity. They
are not susceptible to immune degradation and neither are they
immunogenic. Though allergic reactions have been reported in less
than 1 percent of patient treated with Fab.
The dose of Fab is based on body weight and plasma digoxin
concentration from patients toxic from excessive or overdose therapy.
Ths usual dose is 6-8 mg/kg intravenously with isotonic saline
over 30-60 minutes as bolus. Forty mg of digoxin-specific Fab can
neutralize approx. 0.6 mg of digoxin.
The calculation of the amount of polyclonal antidigoxin
I. Estimation of total body digoxin burden (mg)
Total drug in body (mg) Average oral bioavailability
Amount ingested
A. following acute digoxin = of tablet/elixir formulation
(mg)
ingestion (0.8 for digoxin)
or
Knon or suspected Volume of
Serum concentration Weight
B. toxicity during = distribution
(ng/ml or g/L in kg
therapy 5.6 liters/kg
II. Calculation of Fab fragment dose
Molecular mass
Total digoxin content
of Fab fragment
Dose of (mg)
(50,000 daltons)
A. Fab fragment =
Molecular mass of digoxin
(mg)
(781daltons)
or
Estimated total body load of

Dose of Digibind digoxin (mg)
=
(number of vials) Binding capacity
B. (0.6 mg digoxin bound
1 vial of Digibind)
For reversal of digitoxin toxicity, substitute 1.0 for oral

bioavailability and 0.56 liter/kg for volume of distribution in formula
above. Fab antibody fragments to be administered is based on dose
of Fab that is steichiometrically equivalent to the total body burden
of digoxin.
7. Forced diuresis, hemoperfusion and hemodialysis have very little
role to play in the management of digitalis toxicity.
NAPHTHALENE
Naphthalene occurs as large, lustrous, crystalline plate with
characteristic odor. It is insoluble in water but dissolves freely in ether,
chloroform, alcohol and oils. It is used as deodorant in lavatories, as
pesticide in mothballs and in the dye industry. Poisoning with
naphthalene in children is usually accidental either from ingestion of
mothballs or inhalation from bedclothes heavily dusted with powder.
As it is very soluble in oil, baby oils may act as a solvent promoting
absorption through skin and may result in accidental poisoning. Toxicity
following exposure to diapers and blankets stored in naphthalene has
also been reported in infants.
Pathophysiology
The toxic metabolite of naphthalene is alphanaphthol, which causes
hemolysis with subsequent blockage of renal tubules and hepatic
necrosis. Hemolysis occurs only in those with hereditary deficiency
of glucose-6-phosphate dehydrogenase in the red cells.
Fatal dose: The fatal dose of ingested naphthalene is about 2 g.
Fatal period: Death may occur in a few hours of delayed upto two
or three days. Children are most susceptible, in whom absorption
occurs rapidly.
Clinical Features
An acute hemolytic anemia is the commonest toxicity produced by
naphthalene. Other serious effects are acute nephritis, optic neuritis
and jaundice. When ingested, it causes gastric irritation with nausea,
vomiting and abdominal pain. Other clinical manifestations include,
burning sensation in urethra, pain in loin and suprapubic region,
strangury and passage of dark brown or black urine containing
hemoglobin and albumin. Severe toxicity may result in hepatic and
renal damage, fever, convulsions, cyanosis, profuse perspiration, coma
and death.
When it is inhaled, it causes headache, malaise, nausea, vomiting,
conjunctivitis, mental confusion, visual disturbances and dermatitis.
The usual sequence of acute toxicity in neonate is an acute hemolytic
reaction with anemia and jaundice, terminating kernicterus.
Investigations
1. Peripheral blood smear shows fragmented red cells and anisocytosis.
2. Hemoglobinuria and albuminuria.
3. Methemoglobinemia.
Miscellaneous 205
Treatment Key Points

If the poisoning has occurred due Diagnosis
to ingestion of mothballs, emesis
1. H/O exposure to naphthalene
should be induced with ipecac 2. Clinical features: Nausea, vomiting,
syrup, provided the ingestion was abdominal pain, jaundice, optic
within two hours. Stomach should neuritis, cyanosis, convulsion and
be washed out with warm water coma.
or saline. Bowels should be 3. Lab findings:
Fragmented RBC and anisocyto-
cleared with cathartics like mag- sis in peripheral smear.
nesium sulfate and activated Hemoglobinuria, proteinuria
charcoal. As naphthalene is fat Methemoglobinemia.
soluble, milk and fatty foods
should be avoided for 2-3 hours. Management
IV fluids with sodium bicarbonate Emesis with syrup of ipecac (if
should be administered in presented within 2 hours).
suitable doses to maintain an Stomach wash with warm normal
alkaline urine to prevent the saline.
Activated charcoal/cathartics.
precipitation of acid hematin Avoid milk/fatty foods.
crystals in renal tubule. Close IV fluids and blood transfusion.
monitoring for hemolysis must be Hydrocortisone IM/IV for prevention
continued for at least a week after of hemolysis.
exposure. Severe hemolysis may IV methylene blue for methemo-
globinemia.
require blood transfusions.
Diet-rich in carbohydrate, protein and
Hydrocortisone is helpful in vitamins and low in fat.
limiting naphthalene hemolysis.
In cases with extensive liver damage, a diet high in carbohydrate,
moderately high in protein and low in fat content should be given
along with vitamin supplements. In children presenting with cyanosis
and hypoxia due to methemoglobinemia or methemoglobin level
exceeding 30 percent methylene blue, should be administered.
MUSHROOMS
Although there are many species of mushrooms, most of the poisoning
is due to Amanita phalloides, Amanita muscaria, Amanita bresa and Galerina
venenata. Fatalities are known to follow even, if a small quantity of
poisonous mushroom is consumed. Among all mushrooms, A. phalloides
is the worst offender. Mushrooms are common food items and
poisoning is usually accidental when the identity of a poisonous species
is missed.
A. phalloides contains heat labile cyclopeptide cytotoxin, which
rapidly binds to tissues. The principal toxin is alpha-amantin, which
binds to and inhibits RNA polymerase responsible for mRNA synthesis.
Key Points
Diagnosis
1. History
2. Clinical features:
i. Parasympathomimetic effects with A. muscaria poisoning.
ii. Severe abdominal pain, bloody vomiting, cardiovascular collapse,
convulsion coma. Late-tender hepatomegaly and jaundice, oliguria
and anuria.
Management
1. Gastric lavage
2. According to type of species ingested:
A. muscaria A. phalloides
i. Atropine repeated every i. Treatment of hypoglycemia
30 minutes
ii. Supportive measures ii. T/t of convulsion
iii. General supportive measures
iv. Thioctic acid and cytochrome
v. T/t of renal failure
3. Hemodialysis and hemoperfusion.
Severe cell damage and fatty degeneration may occur in liver, kidneys,
striated muscle and brain.
Ingestion of A. phalloides is followed by a latent period of 6 to 20
hours. Manifestations of cytotoxicity may occur suddenly and consist
of nausea, severe abdominal pain, hematemesis, diarrhea and
cardiovascular collapse. Headache, mental confusion, coma or
convulsions are common. Tender hepatomegaly, jaundice, hypogly-
cemia, dehydration and oliguria or anuria frequently appear on the
first or second day after ingestion. The patient may die from acute
hepatic necrosis within four days. Approximately half the cases of A.
phalloides have a fatal outcome in 5 to 8 days.
Ingestion of A. muscaria which contains parasympathomimetic
alkaloid muscarine, presents with features of parasympathomimetic
stimulation such as lacrimation, salivation, nausea, vomiting, diarrhea,
abdominal pain, bronchorrhea, wheezing, dyspnea, bradycardia and
hypotension. Muscular tremors, confusion, excitement and delirium
are common in severe poisoning. Ingestion of other poisonous
mushrooms may cause gastrointestinal symptoms, visual disturbances,
ataxia, disorientation, convulsions, coma, fever, hemolysis and
methemoglobinemia.
Treatment of mushroom poisoning depends upon the species
ingested. If parasympathomimetic manifestations are prominent
atropine is given IM and repeated every 30 minutes until symptoms
Miscellaneous 207
are controlled. Poisoning by cytotoxic mushrooms like A. phalloides is

managed mainly symptomatically. Fluid and electrolyte balance must
be maintained. Hypoglycemia should be avoided by giving large
carbohydrate diet or IV dextrose solution. Excitement, convulsions,
pain, hypotension and fever may need symptomatic therapy. Early
intensive hemoperfusion or hemodialysis can remove alpha-amanitin
from body. Both thioctic acid and cytochrome have been recommended
as antidote for A. phalloides poisoning but convincing data regarding
their efficacy is lacking. Penicillin is also recommended in treatment
of A. phalloides poisoning.
ALUMINIUM PHOSPHIDE (CELPHOS)

The ongoing green revolution in India particularly in eastern, northern
and central parts and available potent pesticides in the market have
significantly altered the pattern of poisoning because of easy availability
and lowcost. Aluminium phosphide is used in almost all houses of
rural and urban areas as a major grain preservatives and fumigative
agent which protects grain against pests. Aluminium phosphide is
commonly known as celphos, quick phos, alphos and phostoxin. It is
available as sealed metal tubes containing 10 pellets each of 3 grams.
In adult, 1/6th of one pellet, i.e. 0.5 g of aluminium phosphide is fatal.
In children the exact fatal dose has not been evaluated till date. In
children, aluminium phosphide poisoning has become one of the most
important causes of death due to poisoning. The poisoning is most
commonly due to accidental ingestion of tablet available in home but
may be suicidal in adolescents.
Its toxic effects in human being are due to liberation of toxic
phosphine gas (PH3) when it comes in contact with moisture of grains
and hydrochloric acid of stomach.
AlP + 3HCl AlCl3 + PH3

AlP + 3H2O Al (OH) 2 + PH3
Properties of Phosphine
Phosphine has a molecular weight of 34.00 and is colorless gas with
odor of carbide or decaying fish. The odor threshold this pesticide is
0.02 ppm. The density and melting point are 1.214 and 133oC
respectively. The solubility in water is 0.26 volume at 20oC. It is
spontaneously flammable. Phosphine in air reacts with hydroxyl
radical (OH) and is removed by it, with half-life of 5-24 hours. The
nontoxic residues left in grains after fumigation are phosphite ad
hypophosphite of aluminium. WHO/FAO recommended permissible
levels of 0.1 mg/kg of phosphine for cereals, which do not cause any
ill effects in humans on consumption. Phosphine is rapidly absored
throughout the gastrointestinal tract and after ingestion and lungs
after inhalation and excreted unchanged through it.
Pathophysiology
On ingestion when aluminium phosphide comes in contact with
moisture or gastric acid, it readily liberates phosphine gas, which is
locally irritant and gets quickly absorbed in the blood. In body
phosphine interrupts the terminal stages of mitochondrial electron
transport system by non-competitive inhibition of cytochrome oxidase.
Later on some workers have found inhibition of catalase and stimulation
of superoxide dismutase activity resulting in increased production of
oxygen-free radicals and superoxide. These oxygen-free radicals lead
to lipid peroxidation and change in fluidity of cell membrane and
ultimately cells drop out. This process is reversible and full recovery
occurs in patient who survive without any residual effect.
Pathology
The organs commonly affected are heart, liver, and lungs. Rarely
kidneys and adrenals may be affected. Pathologicals changes in different
organs are the followings:
Lungs
Congestion, edema, desquamated epithelium with thickened alveoli
and lymphocytic infiltration around bronchioles.
Heart
Toxic myocarditis with congestion, edema, areas of focal necrosis and
fragmented fibers with leukocytic infiltration.
Liver
Congestion, edema, areas of centrizonal necrosis and mild to moderate
fatty change.
Kidneys
In addition congestion, edema, necrosis, degenerative and regene-
rative changes in some tubules with dystrophic calcification in some
points.
Miscellaneous 209
Adrenals
Congestion, hemorrhagic necrosis and areas of lipid depletion.
Clinical Features
The clinical presentation depends on the mode of intoxications, i.e.
ingestional or inhalation but symptomatology is more or less same
with slight variation.
Inhalation Intoxication
The occupational threshold of phosphide is 0.3 ppm in air and higher
concentration is known to cause symptoms. Mild inhalational exposure
produces mucous membrane irritation, acute respiratory distress,
headache, dizziness and tightness in chest, fatigue and gastrointestinal
disturbances. Moderate intoxication produces ataxia, numbness,
paresthesia tremors, diplopia and weakness of muscles, incoordination,
paralysis and jaundice. Severe intoxication produces multiple organ
failure with involvement of heart, lungs, kidneys and liver. At
concentration of 270-300 ppm it is dangerous and at 400 ppm, it kills
the individual within half an hour.
Ingestional Intoxication
It could be mild, moderate or severe depending on the dose of
aluminium phosphide consumed.
Mild Toxicity
It occurs either due to ingestion of large dose of partially exposed
compound or small dose of fresh compound. Systemic manifestations
are less florid and include hypotension with nausea, vomiting,
abdominal cramps and headache. ECG changes and metabolic acidosis
occur in 10-20 percent of cases. Silver nitrate paper test is usually
negative and mortality is quite low.
Moderate to Severe Toxicity

The systemic features are predominant and mentioned in Table 23.2.
Shock in Aluminium Phosphide Poisoning

Shock is a cardinal manifestation. Its exact pathogenesis is still unknown
but most probably of cardiogenic nature. Arrhythmias, conduction
disturbances, myocarditis and raised serum CPK (MB) support it to
be cardiogenic. On other hand low CVP and low or normal pulmonary
capillary wedge pressure indicate toward hypovolemic shock.
Table 23.2: Systemic manifestations of aluminium phosphide poisoning
GI tract: Nausea, vomiting, burning epigastrium, diarrhea, excessive thirst and

dryness of mouth.
CVS: Hypotension or shock, brady or tachycardia, arrhythmias, myocardial
ischemia, conduction defects, myocarditis, pericarditis and CHF.
Respiratory: Cough, dyspnea, crackles, type I and type II respiratory failure.
Hepatobilliary: Jaundice, tender hepatomegaly, raised transaminases, acute hepatic
failure.
Renal: Oliguric and nonoliguric acute renal failure.
CNS: Anxiety, apprehension, unusual cry and restlessness. Terminally convulsions,
stupor and coma.
Others: Bleeding diathesis and muscle wasting.
Pseudo-shock syndrome, i.e. maintenance of adequate urine output

and consciousness despite unrecoverable blood pressure is present
during early stage of poisoning. Later on, circulation to internal organs
decreased then oliguria sets in and syndrome of multiple organ failure
developed. This stage is due to high levels of circulating angiotensins
leading to splanchnic vasoconstriction and make the shock irreversible.
Adult Respiratory Distress Syndrome (ARDS)

It is a known complication and occurs earlier after inhalation of
phosphine than ingestion. Most of the patient develops it within
6-12 hours of shock. The clinical features include unexplained breath-
lessness with diffuse crepitations and ronchi despite normal CVP.
Blood analysis initially revealed hypoxemia and hypocarbia with low
bicarbonate levels but later on hypercapnia and cyanosis. Radiograph
of chest showed hilar to perihilar lung congestion without cardiac
enlargement.
Diagnosis
i.History of ingestion of fresh tablets.
ii.Decaying fish or garglic odor of breath.
iii.Clinical features.
iv. Sudden onset cardiac arrhythmias.
v. Metabolic acidosis.
vi. Positive qualitative silver nitrate paper test with gastric fluid
or breath.
This test depends on the property of phosphine to react with silver
nitrate of paper turning it black. Its sensitivity is 100 percent with
gastric fluid and 50 percent with breath, whereas specificity is also
Miscellaneous 211
high but paper sometimes gets blackened with presence of H2S in air
as impurity. The chemical equation is as follows:
PH3+8AgNO3 8Ag+H3PO4+8HNO3
To 5 ml of gastric aspirate, add 15 ml of water in a flask which is
heated to 55-60oC and keep silver nitrate impregnated paper (0.1N)
on the mouth of flask. Remove paper after 20 minutes and make it
dry. The test paper turns black after sometimes.
In breath test, impregnated filter paper issued as mask covering
mouth and nose of patient and patient is asked to breath in and out
through this paper for 20 minutes. The paper turns black if test is
positive. Once this test is positive, it remained positive on second and
third day in most patients due to slow release of phosphine.
Laboratory and Other Investigation Parameters

i. Hemogramnormal
ii. Serum electrolytesK, or N or Mg, Ca
iii. Blood and creatinine if ARF
iv. Albuminuria and hematuria
v. ABGMetabolic acidosis
vi. LFT Bil, ALT, AST
vii. Serum cholinesterase activitylow
viii. Hypoglycemia, occassionally
ix. CPKMB
x. Plasma renin activity
xi. ECG: Evidence of ischemia, arrhythmias and conduction
disturbances.
xii. ECHO:
Wall motion abnormality
Generalized hypokinesia of left ventricle and interventricular
septum
Ejection fraction below 50 percent
Fractional shortening below 50 percent
Pericardial effusion in about 30 percent.
Management
The children with aluminium phosphide poisoning usually come in
emergency in a sate of shock on receiving the patient, first ensure
patency of the airways and administer oxygen. Then next step is to
establish an intravenous line and combat the shock with crystalloids
and vasopressor amines such as dopamine or dobutamine.
After initial stabilization the Key Points

following should be done:
Diagnosis
1. Gastric lavage with 1:1000
solution of potassium per- 1. History of ingestion
2. Positive silver nitrate test of gastric
manganate or 2 percent
aspirate
sodium bicarbonate or 3. ECGDecreased amplitude of T-
freshly prepared lime to wave
remove and oxidize the Elevation of ST segment
remaining poison. Prolongation of Q-T interval
2. Activated charcoal orally Arrhythmias or ectopic beats
4. ECHO:
followed by a cathartic to Ejection fraction below 50 percent
increase phosphine excre- Fractional shortening below 50
tion. percent
3. Administer 2-4 ml/kg 5. Biochemical hypoglycemia
weight of 50 percent glu- AST and ALT
cose intravenously to Mg, Ca, K and Na.
combat hypoglycemia and
1-2 ml/kg of 10 percent Management
calcium gluconate intra- 1. Gastric lavage with 1:1000 solution
venously under electro- of KMnO4 or 2 percent NaHCO3
cardiographic monitoring 2. 2-4 ml/kg of 50 percent glucose IV
for hypoglycemia
for hypocalcemia. 3. 1-2 ml/kg of 10 percent calcium
4. H 2 -receptor antagonist, gluconate for hypocalcemia
ranitidine and oral antacids 4. IV Magnesium sulphate (1%) solu-
may be used. tion100 mg/kg/dose at interval of
5. Adequate hydration to 4-6 hours
5. Mechanical ventilation for ARDS.
maintain a satisfactory
urine output is recommended for enhanced elimination of
phosphine. IV diuretics may be used if blood pressure is normal.
Hemodialysis is effective in patients with uremia.
6. Other supportive measures include oxygen, treatment of shock
with fluids and low dose dopamine, IV hydrocortisone,
correction of acidosis with sodium bicarbonate and assisted
ventilation.
7. IV Magnesium sulfateThe mainstay in treatment of aluminium
phosphide poisoning is magnesium, although challenged by
many workers. Magnesium being an antioxidant is required to
quench the free radicals. Since free radicals are elevated as
evidenced by higher level of lipid peroxides and decreased
level of vitamin C and B, carotene in plasma. Magnesium
is administered IV as magnesium sulfate 1 percent solution
in a dose of 100 mg/kg/dose at an interval of 2 to 6 hours
Miscellaneous 213
depending the severity of illness and clinical improvement for

a period of 4-5 days.
8. If the patient has developed pulmonary edema, it should be
managed with 100 percent oxygen, IV frusemide and
aminophylline.
9. ARDS is very common in children with aluminium phosphide
poisoning because of direct damage of alveolar cells by
phosphine gas. Children with ARDS must be managed effectively
with mechanical ventilation, corticosteroids and suitable
antibiotics.
Recently xanthinol nicotinate has been reported to increase the
survival rate of rats subjected to aluminium phosphide poisoning in
two different trials. Increased survival is probably due to favorable
actions on cardiac output, coronary blood flow and peripheral resistance
in the presence of shock. Xanthinol nicotinate is under trial on human
being and may emerge in future as the most promising drug for
management of aluminium phosphate intoxication.
Preventive Measures
1. Keep pesticides away from reach of children and family members.
2. Do not fumigate the grains when temperature is below 5oC.
3. Adequate washing after handling.
4. Children should not sleep in room fumigated.
5. Always open the container in air.
6. Do not inhale dust or fumes of fumigated grains.
[Note: The optimum temperature for fumigation is 15-20oC and
humidity 63.7%].
The state agencies should restrict the open sales of this pesticide.
The tablets should not give to children or adolescent. The future of
children and adolescents is bleak with free sale of pesticide. The death
due to consumption of pesticide is effortless and more or less peaceful.
The pesticide is consumed by young generation under emotional
upset or frustation due to any reason. Considering high mortality
nothing other than banning of pesticide can solve this problem,
otherwise this tragedy will be worst than Bhopal gas tragedy.
COWDUNG POWDER POISONING

Cowdung powder is locally called as Sani powder in Tamil Nadu
and used basically to smear the floor mixed with water on festive
occasion in rural areas. It is available in two colors, i.e. green and
yellow. It is freely available at home and consumed by children
accidentally. The clinical features of cowdung powder poisoning are

due to heavy metals namely copper (in green powder).
Clinical Features
Clinical features start 15 to 30 minutes after ingestion and include
metallic taste, increased salivation, burning in stomach, excessive thirst,
nausea, vomiting, acid eructation, diarrhea rarely mixed with blood,
hematuria, oliguria and acute renal failure. Centrilobular necrosis of
liver is common resulting in jaundice. The features of billiary stasis
may occur. The neurological features include nonspecific muscle
cramps, spasms, convulsions, focal deficit, coma and death.
Investigations
1. Renal function: blood urea and creatinine
2. LFT: ALT, AST, bilirubin
3. CBC: TLC
4. CXR: Infiltrations in both lung fields.
Management
Since emesis is a feature of all case, there is no need to induce vomiting
but gastric lavage with 1% ferrocyanide solution is very useful. This
forms insoluble cupric ferrocyanide complexes. Various adsorbents
like milk, egg white and demulcents can also be used. Benzodiazepines/
morphine is very effective for sedation and neurological findings and
to allay anxiety. Diuretics may be helpful in prerenal states. Specific
antidote, i.e. calcium EDTA either oral/IV, BAL or d-penicillamine are
effective in severe cases. Some authors have reported that steroids
may be of used in hepatic and neurological derangements.
BIBLIOGRAPHY
1. Antaman EM, Wenger TL, Butler VP, et al. Treatment of 150 cases of life-
threatening digitalis intoxication with digoxin-specific Fab antibody
fragments, circulation 1990;81:1744.
2. Avasthi R, Sharma R. Aluminium phosphate poisoning and magnesium
sulfate therapy. JAPI 1994;42:670.
3. Behrman RE, Kliegman RM, Arvin AM. Poisoning. In: Nelson Textbook of
Pediatrics, 15th edn. WB Saunders Company 2:2002-30.
4. Benjamin DR. Mushrooms poisoning in infant and children. Clin Toxicol
1992;30:13.
5. Cook TJL. Dapsone poisoning. Med J Aust 1970;1:1158-9.
6. Gupta MS, Malik A. Combined toxicity due to alcohol and aluminium
phosphide. JAPI 1995;43:74.
Miscellaneous 215
7. Gupta MS, Singh H, Gupta BK, Malik A. Acute myocardial injury in aluminium
phosphide poisoning. JAPI 1995;43:58.
8. Kabra SG, Narayanan R. Aluminium phosphide worse than Bhopal. Lancet
1988;1:1333.
9. Khan MA, Singh SD, Agrawal AK. Acute sulfone poisoning. Indian Pediatr
1981;18:199-200.
10. Kumar A, Anatomy TJ, Junen KM, et al: Exchange transfusion for dapsone
poisoning. Indian Ped 1988;25:789-800.
11. Mitchell DH. Amanita mushroom poisoning. Ann Rev Med 1998;31:51.
12. Nair PM, Philip E. Accidental dapsone poisoning in children. Ann Trop
Pediatr 1984;4:241-2.
13. Nayak US, Gandhi DJ, et al. Acute dapsone poisoning. Indian Ped 1989;26,
730-1.
14. Sehvartsman S, Marcondes E. Accidental poisoning by sulfones in childhood,
presentation of 12 cases. Trop Dis Bull 1964;61:162-3.
15. Seigel E, Wason S. Mothball toxicity. Pediatr clin N Am 1986;33:369-74.
16. Sharma A. Oral aluminium phosphide poisoning in Indian children. J Trop
Med Hyg 1992;92:221-2.
17. Singh B, Gupta S, Minocha SK, Aggarwal NM. Hypoglycemia in aluminum
phosphide poisoning. JAPI 1994;42:663.
18. Singh RB. Aluminium phosphide poisoning. JAPI 1994;42:84.
19. Subramanyam V, Subbiah B. Methemoglobinemia following dapsone
ingestion. Indian Ped 1981;18:142-3.
20. Valaes T, Psyros AD, Phadrum F. Acute hemolysis due to naphthalene
inhalation. J Pediatr 1963;63:904-15.
21. Winkler JV, Kuling K, Rumack BH. Mothball differentiation. Naphthalene
from paradichlorobenzene. Ann Emer Med 1985;15:30-2.
24
Theophylline
Theophylline (aminophylline) is used widely as a bronchodilator in

treatment of bronchial asthma, emphysema, and chronic obstructive
pulmonary disease. It is available in several different chemical forms
(salts) as a white, odorless powder as well as free state. It is classified
structurally as a methylxanthine. Sustained release preparations are
used more commonly than the regular-release products. Theophylline
poisoning in young children is unusual. Children younger than 4
years of age appear to be at high risk of developing serious toxicity
than older children.
Pathophysiology
Theophylline is rapidly and completely absorbed after oral ingestion.
It is present in blood as protein bound (40%; primarily to albumin)
and enters the cerebrospinal fluid and breast milk and crosses the
placenta. The volume of distribution is 0.4-0.6 L/kg. Theophylline
undergoes hepatic metabolism through the P450 system. It is then
excreted in urine, with 90 percent having undergone metabolism and
10 percent remaining unchanged (50% unchanged in neonates).
However, conditions such as extreme of age, hypothyroidism, body
temperature (>102F), liver disease, congestive heart failure, acute
illness, sepsis, and shock may reduce clearance. In healthy children,
the serum half-life is usually 4-10 hours. The peak serum level occurs
within 2 hours after liquid ingestion, 4 hours after nonsustained-
release tablet or capsule ingestion, and 4-12 hours after ingestion of
a sustained-release tablet or capsule.
Theophylline acts to induce smooth muscle relaxation, resulting in
bronchodilation and causes diuresis and stimulation of central nervous
system and myocardium. The exact means by which bronchodilation
occurs are still uncertain. The bronchodilatory effects are due to its
inhibition on two isoenzymes of phosphodiesterase, i.e. PDE III and
PDE IV. Theophylline also acts to suppress the airway response to
Theophylline 217
irritant stimuli. Other actions that are induced or promoted by

theophylline include promoting diaphragmatic contractility, muco-
ciliary clearance, and a decrease in pulmonary artery pressure. The
serum therapeutic range is 10-20 mcg/ml (unbound theophylline range
is 6-12 mcg/ml). A level greater than 20 mcg/ml is considered toxic.
However, any side effect (including toxic effects) can occur at levels
less than 20 mcg/ml.
An acute overdose occurs with accidental ingestion of a single
large dose. These patients usually present with gastrointestinal
symptoms and cardiovascular manifestations. Seizure risk is not as
great as in a chronic overdose unless the theophylline serum concen-
tration is greater than 100 mcg/ml. A chronic overdose occurs in
people who have ingested repeated doses over time that are greater
than their ability to clear the medication. This can be due to patient
error in taking the medication, an excessive prescribed dose, or some
mitigating factor that has altered the patients clearance rate. These
patients are more likely to have seizures, and these neurological events
often occur at lower theophylline concentrations than in acute overdose
(> 30 mcg/ml).
Nausea, vomiting, diarrhea, abdominal pain/cramping are common
initial features. Cardiovascular manifestations occur later but fatal for
children and include hypotension, arrhythmias (e.g. sinus tachycardia,
premature ventricular complexes, atrial fibrillation, atrial flutter,
supraventricular tachycardia, ventricular tachycardia, ventricular
fibrillation). Other clinical features include headache, restlessness,
tremors, disorientation, hallucinations, insomnia, and seizures.
Metabolic changes associated with theophylline toxicity include
hypokalemia, hyperglycemia, hypercalcemia, rhabdomyolysis, and
acidosis.
Diagnosis
1. H/O of theophylline ingestion.
2. Clinical manifestations.
3. Theophylline levels in bloodconcentration greater than 50 mcg/
ml in acute overdose, greater than 40 mcg/ml in chronic overdose
and concentration greater than 40 mcg/ml in patients younger
than 6 months indicate toxicity.
4. Electrolytes and glucose levelshypokalemia, hyperglycemia, or
hypercalcemia.
5. Serum creatine kinasefor evidence of rhabdomyolysis.
6. Arterial blood gasesto monitor for acid-base disturbances.

7. CT scanif seizures occur.
8. Electrocardiogram for arrhythmias.
Treatment
The basic principles of poison management should be applied with
theophylline toxicity and include stabilization of airways, restoration
of circulation, removal of drugs from body and treatment of associated
complications. Gastric lavage must be done with normal saline if
patients report within 4 hours of ingestion. At the end of gastric
lavage, administer activated charcoal every 2 hours until the serum
theophylline level has fallen to less than 20-25 mcg/ml. It adsorbs
100-1000 mg of drug per g of charcoal. For maximum effect, administer
it within 30 minutes after ingestion of poison. Patients with repeated
vomiting may require metoclopramide, domperidone, or ondansetron.
Avoid ipecac because it does not reduce absorption.
Consider other methods of removal if emesis, seizure, or cardiac
arrhythmia is intractable and cannot be adequately controlled. Charcoal
hemoperfusion is indicated in: (1) patients with intractable seizures
with duration longer than 30 minutes or seizures at intervals of less
than 20 minutes, (2) patients with persistent hypotension unresponsive
to treatment with fluids and pressure support, or (3) patients with
uncontrollable arrhythmias. Charcoal hemoperfusion directs blood
from an arterial source through a charcoal cartridge and then returns
it to the patient. This is better than hemodialysis for removal of highly
protein-bound substances. Hemoperfusion can increase clearance
6-fold. The end point of treatment is serum theophylline level less than
60 mcg/ml in acute overdoses and
Key Points less than 40 mcg/ml in chronic
Diagnosis overdoses with the resolution of
symptoms. Adverse effects include
1. H/O ingestion
thrombocytopenia, hypoglycemia,
2. C/F: nausea, vomiting, abd. pain,
headache, restlessness, cardiac hemorrhage, infection, and hemo-
arrhythmias, tremor, coma lysis. Peritoneal dialysis is ineffec-
3. Serum level > 20 mcg/ml tive. Hemodialysis is indicated if
charcoal hemoperfusion is not
Management
available or is contraindicated or
1. Gastric lavage with normal saline multiple-dose oral activated
2. Activated charcoal
3. Diazepam/lorazepam for seizure
charcoal is not effective secondary
4. Charcoal hemoperfusion if coma to emesis.
5. Hemodialysis definitive T/T Seizures are common in
6. T/T of arrhythmias patients with theophylline toxicity
Theophylline 219
and are difficult to control. Administer benzodiazepines; diazepam

(0.2-0.3 mg/kg), lorazepam (0.05-0.1 mg/kg, max: 4 mg) or midazolam
(0.2 mg/kg) and may be repeated if required. If seizure activity
continued or lasts longer than 15 minutes, administer phenobarbital
10 mg/kg IV. With repetitive seizure activity, load with phenobarbital
20 mg/kg IV over 30-60 minutes than maintain on 5 mg/kg/day. High
morbidity and mortality rates occur with theophylline-induced
seizures. Arrhythmias resolve spontaneously in most of the patients
with theophylline clearance. If the patient is hemodynamically
compromised, treat each arrhythmia appropriately. The goals of
pharmacotherapy are to reduce morbidity, prevent complications, and
decrease toxic levels of theophylline.
ICU care is indicated in children with hemodynamic instability,
life-threatening arrhythmias, seizures, respiratory failure, severe
acidosis, renal or other organ failure, or coma.
BIBLIOGRAPHY
1. Civetta J, Taylor R, Kirby RP, (Eds). Critical Care Critical care. 3rd edn.
Philadelphia, Pa: Lippincott-Raven; 1997.
2. Dawson AH, Whyte IM. The assessment and treatment of theophylline
poisoning. Med J Aust 1989;151(11-12):689-93.
3. Ellenhorn MJ. Ellenhorns Medical Toxicology, Diagnosis, and Treatment of
Human Poisoning, 2nd edn. Baltimore, Md: Williams and Wilkins; 1997.
4. Grenvik A, Shoemaker WC, Ayres SM, et al. Textbook of Critical Care, 3rd
edn. Philadelphia, Pa: WB Saunders Company; 1995.
5. Shechter P, Berkenstat H, Segal E. Theophylline intoxication: Clinical features
and pharmacokinetics during treatment with charcoal hemoperfusion. J Med
Sci 1996;32(9):766-70.
25
Calcium
Channel Blocker
Calcium channel blocker agents currently are among the most widely
prescribed drugs. The widespread use and easy availability of calcium
channel blocker for treatment of hypertension, arrhythmias, congenital
heart malformations and congestive heart failure has led to an increase
in the number and severity of these drug ingestions by children either
accidentally in pre-school children/toddlers or intentional in
adolescents. Calcium channel blocker ingestions show a bimodal
distribution in the pediatric age. Infants often accidentally ingest tablets
that they mistake for food or candy. During the adolescent years,
teenagers ingest calcium channel blocker agents as a suicide gesture.
Generic preparations include amlodipine, bepridil, diltiazem, felodipine,
isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, and
verapamil. Each preparation has its own pharmacological properties
and exhibits a slightly different effect and duration of action.
Pathophysiology
Calcium channel blockers are absorbed early in the GI system and are
significantly bound to plasma proteins in blood. The liver predomi-
nantly metabolizes it; thus its metabolism is unaltered by impaired
renal function. Calcium channel blockers bind to the L-subtype, voltage-
sensitive, slow calcium channels found in cell membranes and decreases
the flow of calcium into the cell, which leads to an inhibition of the
phase 0 depolarization in cardiac pacemaker cells and to the phase
2 plateau of Purkinje cells, cardiac myocytes and vascular smooth
muscle cells. Thus it causes life-threatening bradyarrhythmias,
hypotension and GI hypomotility. Some calcium channel blocker agents
also demonstrate weak cross-reactivity with fast sodium channels,
partially blocking these voltage-gated ion pores, which are responsible
for rapid membrane depolarization. Different calcium channel blockers
Calcium Channel Blocker 221
work by slightly different mechanisms. Nifedipine probably plugs

the slow calcium channel, whereas drugs such as diltiazem and
verapamil interact with the calcium channel after it has been
depolarized to its inactivated recovery state. Each calcium channel
blocker displays a certain degree of tissue specificity, but they have
common properties.
Ascertain whether patient had ingested a sustained-release
preparation. Ask the patients family members what medications they
are taking? Finally, try to determine the time between ingestion and
presentation to the emergency because this interval provides an
indication of how long the calcium channel blockers have had to be
absorbed in the patients digestive system. If a suicide attempt is
suspected, determine whether other medications or alcohol were co-
ingested.
Patients may be either asymptomatic or in altered mental state at the
time of presentation in emergency. Patients may have syncopal attacks,
drowsiness, confusion, seizure, dizziness, headache, tremor and coma
due to decreased cerebral perfusion. The life-threatening clinical
manifestations of overdose is various types of bradyarrhythmias, which
is caused by inhibition of pacemaker cells and A-V dissociation or
A-V block and hypotension. Hypotension is mainly due to
vasodilatation and impaired cardiac contractility. It also affects other
organs. Pulmonary manifestations include pulmonary edema,
cardiogenic or noncardiogenic and may require cautious fluid
resuscitation and early ventilatory support. Other features are chest
pain, diaphoresis, flushing, palpitations, weakness, peripheral edema,
dyspnea and cough. Patients may have nausea, ileus and constipation
due to inhibition of GI motility. Bowel sounds are either absent or
markedly diminished. Bowel perforation has also been reported.
On physical examination patients may have bradycardia or reflex
tachycardia secondary to hypotension and focal neurological deficits.
Examination of abdomen reveals enlarged and tender liver due to
venous congestion and stretching of the hepatic capsule. Hepatojugular
reflux also may be present. Listen for normal bowel sounds because
it may cause enteric dysmotility. Bowel perforation has also been
reported. Peritoneal signs of rebound and guarding are ominous
findings in perforation.
1. Complete blood count: Increased WBC count.
2. Biochemical: Hypocalcemia, hyperglycemia, hypokalemia and a
decreased serum bicarbonate level secondary to acidosis.
3. Arterial blood gas: In the patient with significant toxicity, ABG can
be used to determine acid-base status and respiratory function.
4. Serum drug level of ingested medication if possible but not helpful
in management.
5. Urine toxicology: To look for evidence of co-ingestion.
6. Chest radiograph for evidence of pulmonary edema.
7. Electrocardiogram: ECG may reveal bradycardia; tachycardia; first,
second or third degree A-V block; any type of bundle-branch block;
nonspecific ST segment changes; inverted P-wave; low amplitude
T-waves; sinus arrest and asystole.
Treatment
Patients with calcium channel blockers toxicity should be treated
preferably in a well-equipped emergency facility or an intensive care
setting. Basic supportive care is the first and possibly most important
mode of management. Blood pressure can be augmented with isotonic
sodium chloride solution or Ringer lactate solution. Both are efficient
volume expanders and should be given in 20 ml/kg boluses, which
may be repeated if the patient remains hypotensive. If this does not
raise the blood pressure to the desired level, positive inotropes can
be added. If hypotension persists, administer oxygen with a nasal
cannula. Correction of acid-base disturbances and electrolyte
abnormalities also is important to optimize cardiac function.
Gut decontamination may be considered because it delays gastric
emptying. Perform gastric lavage with a large-bore tube. The use of
a wide-diameter tube is necessary because sustained-release tablets
are larger and more resistant to breakdown. A smaller tube decreases
lavage effectiveness. If the child has ingested a large number of tablets,
especially sustained-release tablets, consider whole bowel irrigation
with polyethylene glycol or a cathartic, such as sorbitol. Under these
circumstances, the pills may aggregate to form bezoars and can be
absorbed continuously for long periods. Administer polyethylene glycol
at a rate of 0.5 L/h for 4-6 hours or until rectal effluent becomes clear.
Administer activated charcoal in a dose of 1 g/kg initially and repeated
every 4 hours at half the initial dose. Because gastric emptying may
be delayed, administer activated charcoal even if the patient presents
long time after the ingestion. Ipecac syrup always is contraindicated.
The added vagal tone of emesis also can worsen cardiovascular status.
An antiemetic can be administered to prevent vomiting secondary to
ingestion of drug.
Calcium administered IV theoretically creates a large enough
concentration gradient to partially overcome the channel blockade,
driving calcium into the cells. Calcium usually is administered IV as

calcium gluconate or calcium chloride; either form is acceptable to
manage CCB overdose if an equal amount of ionized calcium is
administered. Administer a calcium bolus if the patient is symptomatic
at presentation. High-dose IV push calcium can be repeated, or a slow
calcium drip can be implemented if the response to the initial bolus
begins to diminish.
4-aminopyridine or its more potent form 3,4-diaminopyridine is
effective in severe toxicity to increase calcium entry into the cell. Their
exact mechanism is not known but may promote calcium entry
indirectly by blocking voltage-sensitive potassium channels. Although
these medications have reversed verapamil toxicity in experimental
animals, their value and safety in human has not been established.
Positive inotropic agents, e.g. dopamine, epinephrine, norepineph-
rine stimulate myocardial contractility and cause vasoconstriction by
activating adrenergic receptors on the cell membrane. These receptors
then activate adenyl cyclase to produce the second messenger cAMP.
This intracellular intermediary causes calcium to enter the cell and
causes its release from the endoplasmic reticulum. Calcium then effects
conformational changes to cellular machinery and initiates smooth
and cardiac muscle contractions. Other agents that raise intracellular
cAMP levels indirectly cause an increased cellular response by
promoting calcium entry into the cell. High-dose vasopressor therapy
is an effective modality of therapy in children with bradycardia and
hypotension.
High-dose insulin is the most recently proposed remedy for calcium
channel blocker toxicity. Insulin has an intrinsic positive inotropic
effect. Insulin appears to promote calcium entry into the cells through
an unknown mechanism. Because it inhibits insulin production or
release and also decreases the hearts ability to use free fatty acids,
it seems that exogenous insulin administration would improve the
clinical picture. Although therapeutic efficiency of high-dose insulin
has been proven effective in animal models, no human trial has been
completed. It is always important to monitor serum potassium and
glucose levels closely when administering high doses of insulin. First
give a loading dose of glucose (0.5 g/kg) followed by an infusion at
0.5 g/kg/hr after glucose bolus an insulin bolus of 0.1 to 0.2 IU/kg
is given followed by an infusion of 0.1 to 0.2 IU/kg/hr while monitoring
blood glucose concentration. Glucagon is thought to have its own
receptor that is separate from adrenergic receptors and is believed to
increase cAMP production and has been found be effective in treatment
of myocardial toxicity. It is administered as drip in 5% dextrose water
to avoid administering large doses of propylene glycol.
A transvenous pacemaker/ Key Points

transthoracic cutaneous pacemaker
is ideal in patients with sympto- Clinical Features
matic bradycardia. Pacing may CVS: Bradyarrhythmias, hypotension
decrease the need for vasopressors. Pulmonary: Pulmonary edema
Cardiac pacing is required for 12-48 CNS: Disorientation, seizures, coma
GI: Ileus, perforation
hours. Consider temporary place-
ment of an intra-aortic balloon Treatment
pump for hypotension that is
refractory to all other medical and 1. Support airway, ventilation and
oxygenation
surgical treatments. Cardiopulmo- 2. T/t of bradyarrhythmias
nary bypass can be a last resort to 3. Cardiac pacing, temporary
support the blood pressure long 4. Calcium chloride/gluconate
enough for the body to clear the 5. High-dose vasopressors
ingested toxin. 6. Insulin-dextrose infusion
7. Mechanical ventilation
Hemodialysis or charcoal hemo-
perfusion indicated in patients with severe toxicity, patients condition
is worsening or if the ingestion is known to be very large. Although
calcium channel blockers are highly protein bound, hemodialysis or
charcoal hemoperfusion may be used as a last resort in severely toxic
patients who have no other hope.
Prognosis
The prognosis depends upon amount and formulation of drug ingested,
co-ingestions, patients age, time elapsed before treatment begins,
underlying disease states, specific treatments, initial rhythm, use of
a pacemaker and time before it is placed.
Bibliography
1. Adams BD, Browne WT. Amlodipine overdose causes prolonged calcium
channel blocker toxicity. Am J Emerg Med 1998;16(5):527-8.
2. Howarth DM, Dawson AH, Smith AJ, et al. Calcium channel blocking drug
overdose: An Australian series. Hum Exp Toxicol 1994;13(3):161-6.
3. Humbert VH Jr, Munn NJ, Hawkins RF. Noncardiogenic pulmonary edema
complicating massive diltiazem overdose. Chest 1991;99(1):258-9.
4. Mahr NC, Valdes A, Lamas G. Use of glucagon for acute intravenous diltiazem
toxicity. Am J Cardiol 1997;79(11):1570-1.
5. Passal DB, Crespin FH Jr. Verapamil poisoning in an infant. Pediatrics
1984;73(4):543-5.
6. Plewa MC, Martin TG, Menegazzi JJ, et al. Hemodynamic effects of 3,4-
diaminopyridine in a swine model of verapamil toxicity. Ann Emerg Med
1994;23(3):499-507.
7. Proano L, Chiang WK, Wang RY. Calcium channel blocker overdose. Am J
Emerg Med 1995;13(4):444-50.
8. Wax PM. Intestinal infarction due to nifedipine overdose. J Toxicol Clin

Toxicol 1995;33(6):725-8.
9. Wells TG, Graham CJ, Moss MM, Kearns GL. Nifedipine poisoning in a child.
Pediatrics 1990;86(1):91-4.
10. Wolf LR, Spadafora MP, Otten EJ. Use of amrinone and glucagon in a case
of calcium channel blocker overdose. Ann Emerg Med 1993;22(7):1225-8.
11. Yuan TH, Kerns WP II, Tomaszewski CA, et al. Insulin-glucose as adjunctive
therapy for severe calcium channel antagonist poisoning. J Toxicol Clin
Toxicol 1999;37(4):463-74.
26
Benzodiazepines
Benzodiazepine has become a popular in the treatment of various

medical disorders such as insomnia, anxiolytic, anticonvulsant, muscle
relaxant, preanesthetic medication, treatment of alcohol withdrawal
syndrome and along with analgesic. It is one of the common drugs
of abuse. Benzodiazepine overdoses (usually combined with alcohol)
are commonly observed in emergency. Benzodiazepine overdose in
itself is remarkably safe. The overdose is usually accidental in children
but may be of intentional in adolescents. Numerous studies have
demonstrated that most patients with benzodiazepine overdose can
be managed in the emergency. When combined with other sedatives
(most frequently alcohol), patients can present with profoundly
depressed levels of consciousness.
Pathophysiology
Ingested benzodiazepines are rapidly absorbed from gastrointestinal
tract. In the serum, more than 70 percent of the drug is protein bound.
The unbound fraction crosses the blood-brain barrier and interacts
with neuronal benzodiazepine receptors in the central nervous system.
In the central nervous system, benzodiazepines exert their clinical
effect by enhancing the activity of the inhibitory neurotransmitter
GABA. The stimulation of GABA receptors, located on postsynaptic
neurons, cause an influx of negatively charged chloride ions into the
neuron and cause hyperpolarization of the cell membrane and therefore
inhibit depolarization. The duration of the clinical effect is proportional
to the drug concentration in the central nervous system. Benzodiaze-
pines that quickly diffuse from central nervous system has a relatively
short duration of action yet may have a long half-life. The clinical
effects of GABA release and binding of the GABA receptor include
sleep induction and excitement inhibition.
Benzodiazepines 227
Clinical Features
Key Points
The main effect of benzodiazepine Diagnosis
is on central nervous system and
1. H/O ingestion
clinical features include depres- 2. C/F: ataxia, drowsiness, slurred
sion, blurred vision, dizziness, speech, coma and respiratory
confusion, drowsiness, anxiety, failure
agitation, and unresponsiveness 3. Serum/urine benzodiazepines
or coma. On examination patients
may have decreased respiratory Management
rate, hypotension, slurred speech, 1. Gastric lavage
ataxia, hallucination, altered 2. Activated charcoal
sensorium, coma and decreased 3. Flumazenil: 0.002-0.02 mg/kg IV
(max: 5 mg)
oxygen saturation. There is a risk 4. Mechanical ventilation if respiratory
of pulmonary aspiration, respi- failure
ratory failure, anoxic brain
damage, rhabdomyolysis and death.
1. CBC count: To exclude sepsis.
2. Electrolytes: Sodium, calcium, magnesium, and phosphate levels.
3. Urea and creatinine: To rule out renal dysfunction.
4. Blood glucose: Hyperglycemia or hypoglycemia.
5. Myoglobin: To exclude rhabdomyolysis.
6. Toxicologic screen: Benzodiazepines can be easily identified in
routine urine toxicologic screens.
7. CT scanning or MRI: Patient with significant decreased level of
consciousness.
8. ECG: Useful in any unstable patients with coexisting electrolyte
abnormalities or co-ingested other agents.
Treatment
The most important aspect of the management of benzodiazepine
overdoses is good supportive care. The airway must be controlled in
any patient with significantly decreased level of consciousness or
respiratory insufficiency. Supplementary oxygen may be all that is
needed if patients are alert and gag reflex is present. Endotracheal
intubation is needed if patients cannot maintain airways and breathing
on their own. Monitor all patients preferably in ICU. Significant
cardiovascular instability may warrant central venous access in order
to provide medications, fluids, and invasive monitoring.
Activated charcoal is beneficial if administered within 2-4 hours of
ingestion and if the risk of aspiration is minimal. The repeat doses may
be used, especially with ingestion of sustained-release agents.

Dangerous fluid and electrolyte abnormalities have been reported.
Dialysis is not useful because of its large volume of distribution and
high level of protein binding.
Flumazenil, a competitive antagonist of the GABA receptor, is a
specific antidote for benzodiazepine overdoses. However, use of
flumazenil is associated with significant adverse effects, such as seizures
or status epilepticus and acute benzodiazepine withdrawal syndrome.
Flumazenil also causes a decrease in the seizure threshold by blocking
the binding of GABA. Flumazenil use in overdoses with co-ingestion
of substances that tend to induce seizures (e.g. Tricyclic antidepressants)
may actually precipitate seizure activity. Flumazenil should not be
used routinely or as part of a coma cocktail. It is selective competitive
antagonist of the GABA receptor and the only available specific antidote
for benzodiazepines. The dose flumazenil is 0.002-0.02 mg/kg IV over
1 min and may be repeated if required. If overdosed patient has not
responded after 5 mins of receiving a cumulative dose of 5 mg, the
cause of sedation is probably not benzodiazepines. The goals of
pharmacotherapy are to reduce absorption of the drug, prevent
complications, and reduce morbidity.
Bibliography
1. Buckley NA, Dawson AH, Whyte IM. Relative toxicity of benzodiazepines
in overdose. BMJ 1995;310:219-21.
2. Farrell SE, Roberts JR. Benzodiazepines. In: Clinical Management of Poisoning
and Overdose. WB Saunders Co 1998;609-28.
3. Spivey WH, Roberts JR, Derlet RW. A clinical trial of escalating doses of
flumazenil for reversal of suspected benzodiazepine overdose in the
emergency department. Ann Emerg Med 1993;22(12):1813-21.
4. Weinbroum AA, Flaishon R, Sorkine P, et al. A risk-benefit assessment of
flumazenil in the management of benzodiazepine overdose. Drug Safe 1997;
17(3):181-96.
27
Fluoride Toxicity
Fluoride is found in many common household products, including

toothpaste, dietary supplements, cleaning agents, and insecticides
and rodenticides. Fluoride toxicity most commonly occurs following
accidental ingestion in children or intentional overdose in adolescents
of fluoride-containing products.
Pathophysiology
Fluoride ingestion initially acts locally on the intestinal mucosa. It can
transform into hydrofluoric acid in the stomach, which leads to GI
irritation or corrosive effects. Following ingestion, the GI tract is the
earliest and most commonly affected organ system. After absorption
from GIT, fluoride binds to serum calcium ions and may lead to
hypocalcemia. Fluoride has also direct cytotoxic effects and interferes
with enzyme systems, i.e. enzyme of oxidative phosphorylation,
glycolysis, coagulation, and neurotransmission (by binding calcium).
Fluoride also inhibits Na+/K+ -ATPase and may lead to hyperkalemia
by extracellular release of potassium. By inhibiting acetylcholinesterase,
it may be partly responsible for excessive salivation, vomiting, and
diarrhea. Seizures may result from both hypomagnesemia and
hypocalcemia. Severe fluoride toxicity will result in multiorgan failure.
Central vasomotor depression and cardiotoxicity also may occur. Death
usually results from respiratory paralysis, arrhythmia, or cardiac failure.
The fatal dose in children is 16 mg/kg or 500 mg.
The most common manifestations are gastrointestinal and include
excessive salivation, nausea, vomiting, diarrhea, abdominal pain and
dysphagia. Neurological effects are headache, tremors, muscular spasm,
tetanic contractions, hyperactive reflexes, seizures and muscle
weakness. Patients may develop various types of arrhythmia, shock
and cardiac arrest.
Laboratory Finding
Key Points
1. Electrolyte changes: Hyper-
Diagnosis
kalemia, hypocalcemia, hypo-
1. H/O ingestion
magnesemia 2. Excessive salivation, abd. pain,
2. Hypoglycemia tremor, muscular spasm, seizure,
3. ECG changes: Peaked T-waves, shock, arrhythmias and cardiac
widened QRS, bradycardia, A- arrest
V block and prolonged QTc 3. Serum/urine fluoride level
4. Serum and urine fluoride levels Management
if facilities exist. 1. Gastric lavage with milk
2. Activated charcoal
Treatment 3. Diazepam/lorazepam for seizure
4. Correct hypoglycemia
Children with history of fluoride 5. Ca-gluconate: 50-100 mg/kg IV
ingestion in emergency, airway 6. Hemodialysis
and breathing should be checked
first than establish IV line. Gastric lavage is done immediately because
of potential severity of this ingestion. Lavage should be done with milk
or a solution containing calcium or magnesium hydroxide (e.g. milk
of magnesia). Some recommend lavage with 1-5 percent calcium
chloride or gluconate solution to bind fluoride in the stomach. Gastric
aspiration and lavage are most effective when done within 1 hour of
ingestion. Some amount of milk, calcium carbonate or aluminum and
magnesium-based antacids should be left in stomach to bind fluoride.
Activated charcoal is still recommended for those with intentional
overdose when another substance overdose is suspected. Patients,
who developed seizures, check for blood glucose and calcium and
correct it immediately. Hypoglycemia should be corrected with 10%
dextrose in dose of 2-5 ml/kg intravenously.
Calcium gluconate or chloride is administered to correct hypo-
calcemia that may result from fluoride poisoning. Calcium chloride
provides 3 times more calcium than calcium gluconate on an equal-
volume basis and is preferred. 20-25 mg/kg IV push of calcium chloride
under cardiac monitoring and may be repeated as necessary; may
need massive doses with severe poisoning.
Correct electrolyte abnormalities, especially hyperkalemia
hypocalcemia and hypomagnesemia. Hemodialysis may be for critically
ill patients that are refractory to all other forms of treatment. Cardiac
arrhythmias are difficult to treat because they do not respond to
lidocaine, cardioversion or defibrillation.
Fluoride Toxicity 231
BIBLIOGRAPHY
1. Augenstein WL, Spoerke DG, Kulig KW, et al. Fluoride ingestion in children:
A review of 87 cases. Pediatrics 1991;88(5):907-12.
2. Eichler HG, Lenz K, Fuhrmann M, Hruby K. Accidental ingestion of NaF
tablets by childrenreport of a poison control center and one case. Int J Clin
Pharmacol Ther Toxicol 1982;20(7):334-8.
3. Gessner BD, Beller M, Middaugh JP, Whitford GM. Acute fluoride poisoning
from a public water system. N Engl J Med 1994;330(2):95-9.
4. Klasaer AE, Scalzo AJ, Blume C, et al. Marked hypocalcemia and ventricular
fibrillation in two pediatric patients exposed to a fluoride-containing wheel
cleaner. Ann Emerg Med 1996;28(6):713-8.
5. McIvor M. Acute Fluoride Toxicity. Drug Safety 1990;5:79-85.
28
Radioactive Hazards
Radioactive hazards in the form of various ionizing and non-ionizing

waves are of particular importance in pediatrics since deleterious
biological effects of radiation are most serious in growing tissues. The
pediatric population today is likely to have great risk of exposure to
ionizing radiation due to increasing usage of atomic energy. Most
acute and intermittent excessive exposures occur during medical
diagnosis and therapy, nuclear weapon detonation, radiation devices
and nuclear reactor accidents. Low-dose radiation exposure is from
natural sources, of which radon, radionuclide in the earth and
radioactive elements in the body are the major sources. In the first half
of this century, thorium dioxide (Thorotrast) was employed as a contrast
medium throughout the world and incidences of hepatic tumors,
leukemia or aplastic anemia were reported in many exposed persons.
Many other different types of cancers due to radioactive exposure
have been reported in survivors of atomic bomb fall out in Hiroshima
and Nagasaki and in victims of Chernobyl reactor accident.
Plutonium (239Pu), Cesium (132Cs), 144Ce, and strontium are major
radioactive products of nuclear fall-out. Uranium, radium, thorium
and cobalt are other radioactive elements having toxic potential. Radon
an alpha particle emitting gas is derived from naturally occurring
uranium deposits in the earth.
Pathophysiology
Deleterious biological effects are mainly determined by the dose of
radiation, charge and energy of radiation. Intracellular molecules
coming in the path of waves of radiation become ionized. They alter
biochemical processes within the cell temporarily or permanently,
which eventually lead to cell death or genetic mutation. Structural
alteration of DNA, and chromosome may lead to damage to the
genetic apparatus of nucleus. Low-energy radiation causes DNA
damage by single strand breaks and base alteration, whereas high-
Radioactive Hazards 233
energy radiation produces double strand breaks and complex base

alteration. Rapidly proliferating cells like bone marrow, lymphoid
tissues, intestinal epithelium and cells of reproductive organs are most
susceptible. The fetus is also highly sensitive and suffers radiation
injuries when pregnant females are subject to radiation. Large doses
of radiation produces direct cell death due to membrane or cytoplasmic
structural damage.
Clinical manifestations depend manily on the dose and duration of
radiation. Acute or early effects may occur within first few minutes
or upto about 2 months. Acute radiation syndromes are due to cell
death, impairment of cell function, inflammation, infection and
hemorrhage. These effects are divided into four classical clinical stages.
First stage or stage of prodrome consists of anorexia, nausea, vomiting,
diarrhea, increased salivation, abdominal cramp and fever. It
commences within minutes and lasts for hours to 1-2 days. If radiation
dose is high, there may be apathy, lethargy and prostration followed
by convulsions, and ataxia. Hypotension, arrhythmia and shock may
also occur and ultimately death may ensue.
In those who recover, prodrome is followed by second stage of a few
days to few weeks duration and it is usually asymptomatic. The third
stage usually begins during the second to fifth weeks following exposure
with abrupt onset of moderate to severe gastrointestinal disturbances
and features of bone marrow depression. It includes hematemesis,
melena, persistent diarrhea, dehydration, and shock. Hematological
manifestations due to bone marrow depression are characterized by
lymphopenia, leukopenia, thrombocytopenia and anemia, leading to
pharyngeal ulcerations, cutaneous petechiae, generalized bleeding
and secondary infections, usually death occurs in this stage but if
patient survives, he may go to the recovery stage which may take
weeks to months.
Delayed effects of radiation include, reduced life span, alopecia,
general cachexia, hypertension and cataract and most significantly an
increased incidence of many different types of cancers. Children under
age of 10 years are more prone to develop cancers and have shorter
latent periods. Leukemia is most important and the earliest one. Others
include multiple myeloma, thyroid cancer, lymphoma, bone tumors,
cancers of gastrointestinal tract and urinary tract. However, radiation
carcinogenesis in atomic bomb survivors is still unknown. Some
important late effects of atomic bomb survivors are still unknown.
Some important late effects of common radionuclide exposure are as
follows:
1. Thorium dioxideAngiosarcoma of liver, renal cell carcinoma, bile

duct carcinoma and leukemia.
2. RadiumOsteosarcoma, chondroblastoma, sarcoma, leukemia,
mastoid and colon cancers.
3. RadonLung cancers.
4. IodineHypothyroidism, thyroid adenoma, thyroid cancers.
5. Phosphorus (32P)Skin burns, ultimately causing scars, leukemia.
The fetus is highly susceptible to radiation, and manifestations of
in utero exposure during first trimester include small head size of child,
mental retardation, leukemia and thyroid diseases.
The effects due to atomic bomb detonation are mostly due to blast,
thermal burns and acute radiation syndrome. Death occurs usually
due to thermal burns.
Ingestion of radioactive substances produce similar effects but
generalized weakness, progressive anemia and necrosis of jaw are
more marked.
Management
Treatment of acute radiation syndrome is largely symptomatic.
Investigations must be done to estimate dose of radiation exposure
as early as possible by dosimeter, exposure history and severity of
clinical symptoms and hematological abnormalities. Patient with
surface contamination from radioactive metals should be evacuated
and decontaminated. If exposure is less than 2 Gy, it requires no
treatment but close observation for hematological abnormalities for
few days must be done. If exposure is in range of 2-6 Gy, it requires
vigorous supportive therapy with intravenous fluid, correction of
electrolyte imbalance, broad-spectrum antibiotic coverage, adminis-
tration of antifungal and antiviral agenst. If bleeding is marked, platelet
transfusion should be done.
If exposure is high and blood count indicates severe pancytopenia
bone marrow transplantation should be done within first 3-5 days of
exposure. Concomitant administration of genetically cloned hemo-
poietic growth factor may be carried out.
Chelation therapy for radioactive metals is under trial. DTPA
(Diethylenetriaminopenta acetic acid) has been tried in cases of Pu
poisoning and has proved to be of limited success.
Prevention
Pediatrician should limit as much as possible the exposure of children
to the emanations of radioisotopes. Nuclear medicine and diagnostic
procedures should be used only when indicated absolutely. Great care
Radioactive Hazards 235
must be exercised in radioactive endemic areas. Children exposed to

fall out in contaminated areas should be treated prophylactically with
130 mg/day of potassium iodide for 10 days in order to prevent the
accumulation of radioiodine in thyroid. Also consumption of food
products from contaminated areas especially milk and vegetables
should be avoided.
BIBLIOGRAPHY
1. Committee on biological effects of ionizing radiations: Health effects of
exposure to low levels of ionizing radiation. Washington DC, National
Academy Press, 1990.
2. Mettler FA, Upton AC. Medical effects of ionizing radiation. Health Phy 1990;
59:57.
3. Neel JV, Schull WJ. The Children of Atomic Bomb Survivors: A Genetic
Study. Washington DC, National Academy Press, 9191
Index
A Chronic lead poisoning 56

abdominal 57
Accidental poisoning 1 developmental 57
Acetaminophen 138 encephalopathy 56
Acute iron intoxication 46 hematological 57
gastrointestinal stage 46 neuromuscular 57
stage of apparent recovery 46 renal 57
stage of circulatory failure 47 lab investigation 62
stage of gastric scarring 47 Classification of barbiturate based on
stage of hepatic necrosis 47 duration of action 146
Adult respiratory distress syndrome 210 intermediate acting 146
Aluminium phosphide (celphos) 207 long acting 146
Aluminium toxicity 76 short acting 146
Animal poisoning 82 ultra-short acting 146
Antidotes 25 Classification of insecticides 109
chemical antidotes 26 inorganic chemical insecticides 109
physical antidotes 25 organic chemical insecticides 110
physiological or pharmacological Classification of phenothiazines and
antidotes 26 related neuroleptics 169
Anti-venom reactions 104 butyrophenones 170
Arsenic poisoning 67 dibenzoxazepines 170
Atropine sulphate 118 dihydroindolones 170
phenothiazines 169
B aliphatic 169
piperazine 169
Barbiturate poisoning 146 piperidine 169
Bee and wasp sting 105 thioxanthenes 170
Benzodiazepines 226 Clinical feature of acute mercury
Blood concentration of carboxyhemoglobin poisoning 62
and clinical manifestation 181 Clinical features and acute arsenic
poisoning 68
cardiovascular 69
C
dermatological 69
Calcium channel blocker 220 gastrointestinal 68
clinical manifestation 221 hematological 69
laboratory investigations 221 neurological 69
pathophysiology 220 ophthalmological 69
prognosis 224 renal 69
treatment 222 respiratory 69
Carbamates 120 Clinical features of acute barbiturate
Carbon monoxide 180 intoxication 147
Caterpillar 107 mild poisoning 147
Caustic potash and soda 41 moderate poisoning 147
Central antimuscarinic effects 157 severe poisoning 147
Chikitsasthana 1 Clinical features of lead poisoning 54
Childhood poisoning 1 abdominal syndrome 55
Cholinesterase regeneration compounds acute lead poisoning 54
118 chronic intoxication 54
developmental dysfunction 55 Clinical manifestations of snake bite 96

encephalopathy 55 atractaspididae (natal black snakes,
hematological manifestations 56 address) 96
neuromuscular effects and peripheral colubridage (boomslang, bird
neuropathy 55 snakes) 96
renal manifestations 56 elapidae (cobras, krait, mambas,
Clinical features of phenothiazines and coral snakes)
related neurolepticus 171 hydrophiidae (sea snake) 98
allergic and idiosyncratic 172 venom ophthalmia 97
autonomic nervous system 171 viperidae (pit vipers, Russels viper,
cardiovascular 171 rattle snakes) 98
central nervous system 171 Cocaine 159
ECG 172 Complications associated with dialysis
24
extrapyramidal symptoms 171
metabolic 24
eye 172
acid-base imbalance 24
gastrointestinal 172
hypoproteinemia 24
pulmonary 171
water and electrolyte imbalance 24
skin 172
technique related 24
Clinical features of toxicity 201
arrhythmias 24
cardiac 201
leakage or infiltration of dialysate
extracardiac 201 with hydrothorax 24
Clinical manifestation of aluminium perforation of bowel or blood
toxicity 77 vessel 24
Clinical manifestation of chronic arsenic peritonitis 24
poisoning 70 pneumonia 24
Clinical manifestation of ethylene glycol pulmonary edema 24
183 Complications of opioid abuse 165
stage I (30 min-12 hours) 184 cardiovascular 165
stage II (12-24 hours) 184 central nervous system 165
stage III (24-72 hours) 184 dermatological 166
Clinical manifestation of organophos- endocrinal 166
phate poisoning 114 eye 166
Clinical manifestations of acute mercury gastrointestinal 166
poisoning 62 genitourinary 166
Clinical manifestations of acute infections 166
phosphorus poisoning 73 musculoskeletal 166
latent phase 73 pulmonary 166
primary phase 73 Composition of fluid 135
secondary phase 74 Contraindications to anti-venom therapy
Clinical manifestations of carbon 104
history of atopic disorders 104
monoxide 181
sensitive of equine anti-serum 104
chemical method 181
Corrosive poisons 33
spectroscopic method 182
Corrosives 33
Clinical manifestations of iron poisoning alkalies 33
47 ammonium hydroxide 33
Clinical manifestations of opioids 163 potassium hydroxide 33
adulterants 164 sodium hydroxide 33
central nervous system (CNS) 163 mineral acids 33
opioid overdose 165 hydrochloric acids 33
opioid withdrawal 165 nitric acids 33
opioid withdrawal in newborn 165 sulfuric acids 33
smooth muscle of various system 164 organic acids 33
Clinical manifestations of scorpion sting acetic acid 33
84 carbolic acid (phenol) 33
Index 239
oxalic acids 33 gastrointestinal 132

salicylic acid 33 laboratory investigations 134
vegetable acids 33 metabolic disturbances 134
hydrocyanic acid 33 renal 133
Cowdung powder pisoning 213 respiratory 132
Cyclic antidepressant 174 vision and hearing 133
Fluoride toxicity 229
Fluorides 128
D
Forced diuresis 22
Dapsone poisoning 199 forced acid diuresis 23
Datura 156 forced alkaline diuresis 22
DDT (Dichloro-Diphenyl Trichloroethane)
122 G
Diagnosis of barbiturate poisoning 148
investigations 148 Gammexane 125
mild intoxication 148
severe intoxication 148 H
Diagnosis of mineral acids 35
analysis of vomitus or stool 35 Hemofiltration 25
clinical features 35 Hemoperfusion 25
endoscopy 35 Hydrocarbon 150
history of ingestion 35 Hydrocyanic acid and its salts 39
Differentiating features between arsenic Hypertension and hypotension in cyclic
poisoning and cholera 70 antidepressants 179
Digitalis 200
I
E
Indications of anti-venom 102
ECG manifestations 201
local manifestations 103
Effectiveness and duration of therapy 51
systemic manifestations 102
Effects of corrosives 34 Ingestional intoxication 209
delayed effects 34
Inhalation intoxication 209
early effects 34
Insecticide based on the potential of
late effects 34 toxicity 110
Endrin 124
comparatively harmless 110
clinical manifestations 124
highly toxic 110
treatment 124 mildly toxic 110
Epidemic dropsy 186
virtually harmless 110
Epidemiology of epidemic dropsy 186
Insecticide poisoning 109
Ethylene glycol 183 Investigations of aluminium toxicity 78
bone biopsy from iliac crest 78
F deferoxamine infusion test 78
Factors affecting severity of snake bite 96 peripheral smear 78
age 96 radiographs 78
location of bite 96 serum aluminium level 78
post snake bite activity 96 Iodine 75
secondary injection 96
size of snake 96 K
Features of salicylate poisoning 132 Kalpasthana 1
cardiovascular 133
Kerosene oil poisoning 152
CNS 133
coagulation system 134
complications of salicylate intoxication
L
134 Lead poisoning 53
fluid and electrolyte disturbances 134 Lizard bite 107
M pure agonist 162

pure antagonist 163
Management of acetaminophen 141 Organophosphorus poisoning 111
assessment 141 Organosphosphates 112
general measures 141 action on CNS 113
specific measures 142 muscarine-like effect 112
Management of airways 117 nicotine-like effect 112
Management of cyclic antidepressant 176
Management of hypothermia 15
Management of opioid overdose 167
P
general management 167 Pathogenesis of mustard gas 191
specific management 167 Pathological changes in iron poisoning 45
Management of opioid withdrawal 167 Pathology of lead poisoning 64
Management of pain 16 Pathophysiology of acetaminophen 138
Management of pulmonary edema 15 Pathophysiology of aluminium toxicity
Management of scorpion sting 88 77
local management 88 Pathophysiology of arsenic poisoning 68
prevention 91 Pathophysiology of cocaine 159
systemic management 89 Pathophysiology of datura 156
Management of seizure 118 Pathophysiology of DDT 122
Management of stress ulcers 15 Pathophysiology of hydrocarbon
Mercury poisoning 61 poisoning 150
Metals and non-metals 43 Pathophysiology of hydrocyanic acid 39
Methanol (methyl alcohol) 194 Pathophysiology of lead poisoning 53
clinical manifestations 194 Pathophysiology of mineral acid 34
pathophysiology 194 Pathophysiology of phenol 37
treatment 195 Peripheral antimuscarinic effects 157
Mild toxicity 209 Petroleum and derivatives 154
Mineral acid 34 Phenol (carbolic acid) 37
Moderate to severe toxicity 209 Phenothiazines and related neuroleptics
Morphology of snakes 92 169
absorption of venom 94 Phosphorus poisoning 72
fangs 93 Poison 1
pathophysiology 94 Poison management 8
poison gland 93 Principles of poisoning management 8
venom 93 correction of acid-base disturbances
Mushrooms 205 11
Mustard gas 191 metabolic acidosis 11
respiratory acidosis 12
N respiratory alkalosis 13
fluid management in hypotension 10
Naphthalene 204 initial resuscitation stabilization 8
Nausea and vomiting 16 management of cardiac arrhythmia 13
Neurological manisfestation of scorpion management of convulsion 13
sting 85 H 2-receptor antagonists 16
autonomic nervous system 85 management of hypotension or
centrtal nervous system 85 hemodynamic support 9
Nicotine 126 symptomatic and supportive
management 9
O Problems resulting from iron toxicity 47
Prognosis of acetaminophen 144
Oleander poisoning 196 Properties of phosphine 207
Opioids 162 Pyrethrins 121
classification of opioids 162 Pyrethroid 128
mixed agonistantagonist 162 clinical manifestations 129
Index 241
diagnosis 129 T
pathophysiology 129
treatment 129 Theophylline 216
Toxicology 1
Treatment of datura poisoning 157
R antidote 158
Radioactive hazards 232 gastrointestinal decontamination 158
Reconstitution of anti-venom 103 supportive care 158
Removal of unabsorbed poison from GI Treatment of digitalis toxicity 202
tract 17 Treatment of hydrocyanic acids and its
adsorption 19 salts 40
catharsis 20 Treatment of iron poisoning 48
dilution 17 decontamination (removal of
emesis 17 unabsorbed iron) 49
gastric lavage 18 definitive therapy 50
Rhabdomyolysis 16 indications of chelation therapy 50
Rotenone 122 Treatment of mineral acids 36
Routes and dosage of desferrioxamine 50 esophageal dilatation 36
surgery 36
Treatment of mustard gas 192
S first aid 192
Salicylate poisoning 131 therapeutic measures 192
Scorpion sting 82 Treatment of phenol 38
Signs and symptoms of poisoning 5 Treatment of snake bite 101
face and scalp 6 first aid 101
gastrointestinal tract 6 immediate management 101
cardiovascular symptoms 7 specific therapy 102
nervous system 6
respiratory symptoms 7 U
skin and mucous membrane 6 Universal antidote 27
Snake bite 91 action 27
Sodium bicarbonate 177 ingredient 27
Sodium fluoroacetate 126 proportion 27
clinical manifestations 126 Uttarasthana 1
management 126
Solvent sniffing 154
Specific treatment of lead poisoning 59 W
Spider bites 106 Whole bowel irrigation 21
Supportive therapy 51
Supportive treatment of lead poisoning
58
Z
Symptoms and signs of poisoning 3 Zinc phosphide 125
Systemic manifestations of aluminium clinical features 125
phosphide poisoning 210 treatment 125

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Poisoning

Utpal Kant Singh MD PhD FRCP (Lond) FCCP FIAP

First Edition : 1998

Children are by nature exploratory, and therefore they are liable to

Poisonings form an inescapable part of pediatric practice. It is not

The reported incidence of childhood poisonings in India varies from

Children are the principal victims of poisoning/intoxications by

Utpal Kant Singh

Toxicology is the scientific study of poison, their detection, action and

Utpal Kant Singh

I can never express myself adequately about the inspirations,

Toxicology is the branch of medical science which deals with the

While supportive therapy is being initiated to maintain physiologic

A. Stimulant poisoning B. Depressant poisoning

flushed skin, hyperthermia, cramps, diarrhea, involuntary

The chest may show features of pulmonary edema (carbon

GENERAL SIGNS AND SYMPTOMS OF POISONING

Signs and Symptoms

Face and Scalp

Skin and Mucous Membrane

4. Coma Salicylates, mushrooms, cholinesterase

Poison management involves domestic intervention as well as hospital

Initial Resuscitation Stabilization

Airway, Breathing, Circulation

d. Respiratory stimulants like Nikethamide and Doxapram are

Symptomatic and Supportive Management

Management of Hypotension or Hemodynamic Support

Fluid Management in Hypotension

Repeat isotonic crystalloid Continue fluid,

Assess cardiac status (CXR, ECG)

CVP <10 mmHg CVP >10 mmHg CVP>15 mmHg

iv. Inotropic agents

Correction of Acid-base Disturbances

ABG in different situations

Acid-base disturbances pH PCO2 HCO3

Metabolic acidosis: It is defined as reduction in HCO3 that reflects either

The acidosis must be corrected with parenteral bicarbonate when

Normally half of this calculated deficit should be given over 6

Respiratory alkalosis: It is characterized by a decrease in PCO2 due to

Management of Cardiac Arrhythmia

i. Direct effect of the poison on CNS

ii. IV Furosemide0.5-1.0 mg/kg IV alone or with 20 percent

Management of Pulmonary Edema

Management of Stress Ulcers

Nausea and Vomiting

Removal of Unabsorbed Poison

Removal of unabsorbed poison is an essential step which aims to

Removal of Unabsorbed Poison from GI Tract

Prevention of absorption of poison from the GI tract along with the

Mechanical stimulation Gastric lavage

Apomorphine acts rapidly by stimulating CTZ causing emesis within

vi. 50 ml of water is pushed inside the stomach and this process

Whole Bowel Irrigation

Removal from Skin, Eyes, Other Body Cavities

Hastenting the Elimination of Absorbed Poisons

a. Forced Alkaline Diuresis

b. Forced Acid Diuresis

Indications for dialysis

the function of a major metabolic or excretory organ for that

Toxins/Drugs where Dialysis is Employed

Complications Associated with Dialysis

Contraindications for Peritoneal Dialysis

a. Demulscents: They prevent absorption by forming a coating on

3. Physiological or Pharmacological Antidotes