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Definitions

General approach to
toxicology

Toxicology
Complex subdivision which deals
with toxic substances: detection,
properties, effects and regulation
of toxic substances, including
poisons.
So what is a poison?

2010

Poison

What is Toxicology?

What is a poison?

1. Primarily a multidisciplinary science that


is based on other sciences including:

Any substance which cause a harmful effect


when administered either by accident or by
design to a living organism

Pharmacology
Pathology (disease/death)
Chemistry
Epidemiology

Poisoning is quantitative concept

Hazard potential for harm


Risk probability of producing Harm

Any chemical at some specific dose and time is


harmless, while the same chemical at other
doses and time is toxic

2. Applied Science
Enhancement of the quality of life
Protection of environment
To learn about life processes (i.e uncoupling
agents)

Management of a Poisoning
More simply

Dose makes the poison


It is the primary determinant of
Toxicity

Immediate measures are called for in


every case of poisoning regardless of
cause.

1. Support Vital Functions

2. ID drug poisoning as the problem

3. Reduce the amount of drug in the body

Support vital life functions (ABCs)

General Treatment of a
Comatose Patient

Airway endotracheal tube if needed, watch for


fluid accumulation in airway (i.e.. Aspiration of
vomit)

Breathing Supplemental Oxygen, bag valve

Circulation Monitor ECG, watch for arrhythmias,

mask (BVM) and respirator.

There are several general antidotes


that are used in the treatment of
comatose patients upon presentation
at the hospital.

cardiac arrest and shock

Vasogenic Shock faulty vasomotor tone, increase


capillary permeability.
Cardiogenic Shock inadequate cardiac output can be
due to cardiac dilation (barbituate
(barbituate,, Ca channel
blocker)

Supportive Drug Therapy


Treat all patients who come into the
hospital in a coma with glucose,
thiamine and naloxone.
naloxone.

Immediate Stabilization

Airway with cervical spine control

Breathing

Circulation

Intubate
Intubate
100% O2 , ventilate to normal PCO2

Use drugs to treat emergent


conditions, ie:
ie:

Seizures anticonvulsants (valium)


Cardiac Dysrhythmias antianti-arrhythmias
(lidocaine,
lidocaine, digoxin)
Severe Agitation anxiolytics (benzo)
benzo)

Coma Cocktail

Dextrose
Oxygen
Naloxone
Thiamine

Insert new IVs


Draw bloods with IV start
Bolus 11-2L NS
Cardiac monitor

Some toxicologic emergencies require specific


interventions during the primary survey (eg
(eg..
cyanide)

Dextrose

Rationale: Hypoglycemia common cause of LOC


Case series - hypoglycemia found in 29/349
consecutive calls to EMS for altered mental status

D50W 50cc IV or D25W 22-4cc/kg in peds


DDx hypoglycemia
Tox insulin, oral hypoglycemics,
hypoglycemics, EtOH,
EtOH, salicylates
NonNon-tox sepsis, hyperthermia, hepatic failure,
myxedema

Cautions diabetic or hyperosmolar pts, cerebral


infarct

Thiamine

CoCo-factor for pyruvate dehydrogenase, and ketoglutarate dehydrogenase


Decreased levels in:
chronic liver dz,
dz, folate deficiency, malabsorption,
malabsorption,
malnutrition, EtOH intake

Deficiency - Wernicke
Wernickes encephalopathy
ophthalmoplegia
ataxia
altered mental status

Dose: 100 mg IV
Little evidence to support its use, but safe,
inexpensive, costcost-effective

Antidotes

Naloxone

If after stabilization a toxin is


identified, there may be a specific
antidote
There are approximately 16
antidotes commonly stored in
tertiary care centers in N. America
5% of all poisons have antidotes

Narcan - Pure opioid antagonist used for


reversal of acute intoxication
Diagnostic and therapeutic
0.40.4- 2 mg (max 10mg) IV, IM, SC, ETT or
intralingual
Cautions - Associated with life threatening
complications:
seizures, arrhythmias, cardiac arrest and
precipitation of violence

Antidotes
antidote

poison

antidote

poison

Acetylcysteine

acetaminophen

Ethanol

MeOH,
MeOH, et glycol

Crotalid
Antivenin

Crotalid snake
bite

Flumazenil

BDZ

Atropine

Fomepizole

Cyanide kit

Carbamate or
Glucagon
organophosphate
Octreotide
CCB or hydrogen
Methylene blue
fluoride
Naloxone
cyanide

MeOH

Deferoxamine

Iron

Ca gluconate
or Ca chloride

AACT/EAPCCT Position statement on


gastrointestinal decontamination
Clinical Toxicology 1997; 35(7), 695695-762

Ipecac
Gastric Lavage
Whole bowel irrigation
Single dose activated charcoal
Cathartics

Sulfonylureas
methemoglobin
opioids
anticholinergic

Digoxine
immune Fab

Digoxin,
Digoxin, digitoxin Pralidoxime
Pyridoxine

organophosphate

Dimercaprol
(BAL)

Arsenic, mercury, Sodium


bicarbonate
lead

TCA, cocaine,
salicylates

isoniazid

Ipecac

Gastrointestinal Decontamination

Physostigmine

-blocker, CCB

Emetic both peripherally and central acting


>90% effective
Dose: 30cc PO >5yrs, 15cc 11-5yrs, 10cc 66-12 mo
Indications
None
consider in the out of hospital toxic ingestion

Contraindications
Unprotected or anticipated unprotected airway
Hydrocarbons, caustics
Debilitated patients

Complications
Diarrhea, lethargy/drowsiness, prolonged vomiting

Gastric Lavage

3636-40 Fr NG, sequential instillation and removal


of small volumes of isotonic fluid

Whole bowel irrigation

PEG via NG at 11-2 L/h (500cc/h in peds)


peds)
until effluent clear

Indications
Potentially toxic ingestion of SR or EC
prep
Ingested packets of illicit drug (stuffers,
packers)
Substances not adsorbed by AC
Iron ingestions

Activated Charcoal

1g/kg PO or NG
Indications
Within 1 hour of ingestion
Nearly all suspected toxic ingestions except
May be considered more than 1 hour after ingestion but
insufficient data to support or exclude use

Contraindications
Unprotected airway
When AC therapy may increase risk and severity of
aspiration
GI tract not anatomically intact (Boerhaaves
)
(Boerhaaves)

Cathartics

Sorbitol,
Sorbitol, Mg citrate, Phosphosoda
May be an argument for adding to
initial dose of multiple dose activated
charcoal
No studies have demonstrated a
benefit in clinical outcome with
cathartics

Complications
Aspiration, emesis, corneal abrasion

Enhancing elimination

Multiple dose activated charcoal


Alkalinization
Hemodialysis
Hemoperfusion
Hemofiltration
Molecular Absorbent Recirculating
System (MARS)

Multiple Dose Activated Charcoal

Consider only if lifelife-threatening amount


of:

Carbamazepine
Phenobarbital
Dapsone
Quinine
Theophylline

May also increase elimination of :

amitriptyline,
amitriptyline, propoxyphene,
propoxyphene, digitoxin,
digitoxin,
digoxin,
digoxin, disopyramide,
disopyramide, nadolol,
nadolol,
phenylbutazone,
phenylbutazone, phenytoin,
phenytoin, piroxicam,
piroxicam, sotalol

Alkalinization

Enhances elimination of weak bases


by ion trapping
Useful for:

Hemodialysis

Blood passed across membrane with


countercurrent dialysate flow
Toxins removed by diffusion

Salicylates, phenobarbital,
phenobarbital,
chlorpropamide,
chlorpropamide, methotrexate,
methotrexate,
myoglobin

NaHCO3 1-2 mEq/kg


mEq/kg IV Q3Q3-4H
Aim for Urine pH 77-8
Must replace K

Substances amenable to
hemodialysis or hemperfusion

Hemoperfusion

Blood passed through cartridge


containing AC
Toxins removed by adsorption

LET ME SAV P

Lithium
Ethylene glycol
Theophylline

MEthanol
MEthanol

Properties required:
Low Vd <1L/kg
Low endogenous clearance <4cc/min/kg
Adsorbable to AC

Molecular Absorbent
Recirculating System
(MARS)

Salicylates
Atenolol
Valproic acid
Potassium, paraquat

The MARS principle

Albumin Dialysis

Summary

Airway with cervical spine control


Breathing
Circulation
Drugs (coma cocktail),
Decontamination
Elimination
Find an antidote
General management

Disposition of Tox Patient

Unstable patient
Potentially lethal overdose
Cardiotoxic overdose

Prolonged Observation (12 - 24


hours) or Admission
Overdose with delayed onset or
sustained release preparation

ED Observation 4 6 hours
Mild symptoms, low lethality OD
Asymptomatic, unknown OD

Hospital Admission
Moderately symptomatic patient with
low fatality potential

Disposition of Tox Patient

ICU Admission

TAKE HOME MESSAGE

Supportive care is the most


important measure in most serious
overdoses
When in doubt observe in the ED
When faced with an unfamiliar or
serious toxic exposure call a Poison
Control Centre or consult with a
toxicologist