ORGANO PHOSPOROUS COMPOUND POISONING

INTRODUCTION
Organo phosphorous compounds are a large group of compounds having the potential to irreversibly inhibit cholinesterase enzymes like Acetyl Cholinesterase & Neuropathy Target Esterase (NTE).

They are not only used as insecticides & pesticides but also as Chemical Warfare Agents, Petroleum Additives & Industrial Plasticizers. Serious human exposure leads to muscarinic (cholinergic) hyper stimulation as well as nicotinic receptor stimulation.

ORGANO - PHOSPHOROUS COMPOUNDS

NERVE AGENTS G Agents: Sarin, Tabun, Soman V Agents: VX, VE Diethyl Compounds: Chlorpyrifos Diazinon Parathion - ethyl Quinalphos Phenthoate Phorate Phosphamidon Profenofos

INSECTICIDES
Dimethyl Compounds: Dichlorvos Fenthion Malathion Methamidophos OTHERS Acephate Dimethoate Ethion Fentrothion Moncrotofos

HISTORY
First synthesized in the early 1800s when Lassaigne reacted alcohol with phosphoric acid. 1854 Philip de Clermont described the synthesis of Tetra Ethyl Pyro Phosphate at a meeting of the French Academy of Sciences. Eighty years later, Lange in Berlin & Schrader, a chemist at Bayer AG, Germany, investigated the use of Organophosphates as insecticides. However the German Military prevented the use of OPs as insecticides & instead developed an arsenal of chemical warfare agents (tabun, sarin, soman). A fourth agent VX was developed a decade later in England. During World War II, in 1941, OPs were reintroduced worldwide as pesticides as were originally intended.

HISTORY
Jamaican Ginger Palsy incident (1930) - to circumvent prohibition laws led to massive OP intoxication. In 1995 - Aum Shinrikyo - a religious sect - used Sarin to poison people on a Tokyo subway. Worldwide mortality rates currently range from 3 25% The compounds most commonly involved are Malathion, Dichlorvos, Trichlorfon. Agricultural pesticides accounted for 12.8% of all cases of poisoning in India.

Risk Factors for Poisoning

Young age
Low Socio economic strata Unemployment Unstable emotional relationships Psychiatric disorders Alcohol abuse

PATHOLOGY
Organophosphate are absorbed through the skin lungs & GI tract and distributed widely in tissues and are slowly eliminated in hepatic metabolism.

The principal effect is inhibition of cholinesterase enzymes, particularly acetyl cholinesterase (AChE). This leads to accumulation of acetylcholine at: 1. Muscarinic receptors- in cholinergic receptor cells 2. Nicotinic receptors in skeletal neuromuscular junctions and autonomic ganglia 3. CNS

MOA of OP Compounds

CLINICAL FEATURES
Acute Cholinergic Crisis Intermediate Syndrome (IMS) OPIDN EPS, CNS DIPPERS FLU

ACUTE CHOLINERGIC CRISIS

Muscarinic Cardiovascular
Bradycardia Hypotension

Nicotinic Cardiovascular
Tachycardia Hypertension

Central receptors
Anxiety Restlessness Ataxia Convulsions Insomnia Dysarthria Tremors Coma Absent reflexes CS respiration Resp. depression Circulatory collapse

Respiratory
Rhinorrhea Bronchorrhea/spasm Cough

Musculoskeletal
Weakness Fasciculations Cramps Paralysis

Gastrointestinal
Increased salivation Nausea/vomiting Abdominal pain Diarrhoea Fecal incontinence

Genitourinary
Urinary incontinence

Ocular
Blurred vision/miosis Increased lacrimation

COPIND & EPS

Chronic OP Induced Neuropsychiatric Disorder (COPIND):
Behavioural changes Impaired vigilance, information processing & memory Depression, anxiety, irritability

EPS:
Resting tremor Rigidity Hypokinesia Dystonia Chorea NOTE: Dose dependent effects: Muscarinic < Nicotinic < CNS Tachycardia / Hypertension s/o severe poisoning

PARALYSIS
Type I: Acute Paralysis due to continued depolarization at the NMJ Type II: IMS develops 24 - 96 hrs after resolution of acute OPP symptoms. Paralysis & resp. distress; weakness of proximal muscle groups, neck & trunk with sparing of distal muscles; cranial nerve palsies. Persists for 4 18 days , may require mech. Ventilation & may be complicated by infections or cardiac arrhythmias. Type III: OPIDN occurs 2-3 weeks after exposure to large doses & is due to inhibition of NTE. Distal muscle weakness with relative sparing of proximal muscle groups, neck muscles & cranial nerves. Recovery may take upto 12 months.

OTHERS
Neuro-ophthalmic manifestations:
o Optic neuropathy o Retinal degeneration

Rarer manifestations:
o GBS o Ototoxicity o Sphincter involvement

MANAGEMENT
DIAGNOSIS: Mainly based on the characteristic clinical features and history of exposure to a known OP compound. INVESTIGATIONS: Estimation of serum or RBC cholinesterase levels & electro diagnostic tests (not routinely used) Clinical features of OP poisoning appear when RBC cholinesterase activity is < 75% of normal & in clinically overt poisoning it is usually < 10% No definite relationship between plasma levels of cholinesterase & severity of symptoms and prognosis

OTHERS:
CXR - EVALUATE PULMONARY OEDEMA ECG - CARDIAC ARRHYTHMIAS ELECTROLYTES UREA

TREATMENT - PRINCIPLES
Airway Breathing Circulation Decontamination Gastric lavage Activated charcoal through ryles tube 4th hourly Atropine & Oxime therapy

TREATMENT
MILD CASES:

No specific treatment
Clearing the Airway

Adequate ventilation - consider oxygenation

Remove soiled clothes Wash contaminated skin, with soap & running water, to prevent further absorption.

PATIENTS WITH SYSTEMIC FEATURES i) ATROPINE:

Initiate as soon as the diagnosis is suspected
ADULTS: 2 mg IV bolus - repeat dose very 5-15 minutes till atropinised CHILDREN: 0.05 mg/kg initially then 0.02-0.05 mg/kg S/O Atropinisation:
Heart rate about 100/min Pupils mid position / dilated Bowel sounds just heard Clear lung fields

Reduces - Bronchorrhoea & Rhinorrhoea & wheezing It is an anti - muscarinic agent.

ii) Add an OXIME: e.g. Pralidoxime Dose Slow IV injection 30mg/kg every 4-6 hours i.e. 1-2gms IV - or infusion 8-10mg/kg/h i.e. 200-400mgs/h MOA - Reactivates phosphorylated acetyl cholinesterase. - Prevents permanent binding of the organophosphate to cholinesterase.
iii) Gastric lavage within an hour followed by activated Charcoal administered via nasogastric tube iv) Remove soiled clothes v) Wash the exposed areas of skin with soap & running water - to prevent dermal absorption vi) Monitor patient 2 hourly in left lateral position. vii) Consider ICU care if in coma or unconscious.