Op poisoning

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organophosphate poisoning management atropine pralidoxime

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Organophosphate (OP) Poisoning

Overview

Organophosphates (OPs) are a class of insecticides (and chemical warfare agents) that work by irreversibly inhibiting acetylcholinesterase (AChE). This enzyme normally breaks down acetylcholine (ACh) at synapses; its inhibition causes ACh to accumulate throughout the nervous system. More than 150,000 pesticide poisoning deaths occur globally each year, with OP insecticides accounting for the majority of mortality.

Common OP compounds include: parathion, malathion, diazinon, chlorpyrifos, acephate, coumaphos. Highly potent agents like parathion are used in agriculture; nerve agents (sarin, VX, Novichok) are weaponized derivatives.

Mechanism of Toxicity

OPs inhibit both acetylcholinesterase (at synapses and red blood cells) and pseudocholinesterase (butyrylcholinesterase, in plasma). The result is ACh excess at:

Site	Receptor	Effect
Postganglionic parasympathetic	Muscarinic	SLUDGE symptoms (see below)
Autonomic ganglia	Nicotinic	Tachycardia, hypertension
Neuromuscular junction	Nicotinic	Fasciculations, paralysis
CNS	Both	Seizures, coma

OPs are lipid-soluble and are absorbed through dermal, GI, and respiratory routes. They can deposit in fat, causing delayed or prolonged toxicity. Some OPs have active metabolites that produce delayed toxicity.

Clinical Features

1. Acute Cholinergic Phase (hours)

The classic toxidrome is remembered as SLUDGE / DUMBELS:

SLUDGE:

Salivation
Lacrimation
Urinary incontinence
Diarrhea / Defecation
GI cramps
Emesis

DUMBELS (Killer Bs):

Diarrhea / Diaphoresis
Urination
Miosis
(Killer) Bs: Bradycardia, Bronchorrhea, Bronchospasm
Emesis
Lacrimation
Salivation

Nicotinic effects (from NMJ and ganglionic stimulation):

Muscle fasciculations, tremors
Weakness progressing to paralysis
Tachycardia and tachydysrhythmias (can co-exist with bradycardia)
Diaphoresis

CNS effects:

Anxiety, restlessness, seizures
Altered consciousness, coma

Respiratory failure is the most common cause of death - caused by bronchospasm + bronchorrhea + respiratory muscle paralysis combined.

Pulmonary edema can also occur (via inflammatory mediators and increased vascular permeability) - must be distinguished from bronchorrhea.

Most symptomatic patients present within 8 hours; nearly all within 24 hours of acute exposure.

2. Intermediate Syndrome (24-96 hours after acute phase)

Described by Senanayake and Karalliedde. Occurs after the cholinergic phase resolves:

Weakness/paralysis of proximal limb muscles, neck flexors, motor cranial nerves, and respiratory muscles
Respiratory paralysis may be fatal
Lasts 2-3 weeks then subsides
Does NOT respond to atropine or pralidoxime

3. Delayed Neurotoxicity (2-5 weeks post-exposure)

Organophosphate-induced delayed neuropathy (OPIDN)
Distal symmetrical sensorimotor (predominantly motor) polyneuropathy
Progresses to muscle atrophy
Classic agent: triorthocresyl phosphate (TOCP)
Recovery variable; TOCP survivors may later develop corticospinal tract signs
Does not respond to atropine

Diagnosis

Clinical diagnosis based on history of exposure + cholinergic toxidrome
RBC acetylcholinesterase activity - the gold standard; depressed confirms OP exposure (reflects CNS enzyme activity)
Plasma pseudocholinesterase - quicker and easier to measure but less specific (reduced by other conditions like liver disease, malnutrition)
Note: normal cholinesterase levels do NOT rule out toxicity, especially in early or mild exposures

Management

Decontamination

Remove and destroy contaminated clothing
Thorough skin flushing with water (dermal absorption is significant)
Rescuers must wear PPE (level C: full-face air purifier mask) to avoid secondary contamination
Gastric lavage within 1 hour of ingestion if airway is protected (controversial)

Airway

Early intubation in severe cases - avoid succinylcholine (pseudocholinesterase is inhibited, leading to prolonged paralysis); prefer rocuronium

Antidote Therapy

1. Atropine

Competitive antagonist at muscarinic receptors - controls secretions and bronchospasm
Endpoint: drying of secretions, not pupil dilation or heart rate
Dosing: Start 2-4 mg IV in adults (0.05 mg/kg in children); double dose every 5-10 minutes until secretions dry
Massive doses may be required (hundreds of mg in severe cases)
Does NOT reverse nicotinic effects (muscle weakness/paralysis)

2. Pralidoxime (2-PAM, oxime)

Regenerates AChE by displacing OP from the enzyme before "aging" (irreversible binding) occurs
Must be given early before aging is complete (aging speed varies by agent; sarin ages in minutes, others in hours)
Adult dose: 1-2 g IV over 15-30 min, then 200-500 mg/hr infusion
Effective at both muscarinic and nicotinic sites - reverses muscle weakness unlike atropine
Note: Evidence for pralidoxime in mortality reduction remains debated in some trials, but it is standard of care

3. Benzodiazepines

First-line for OP-induced seizures
Diazepam preferred in many protocols; lorazepam or midazolam also effective

No Role for Enhanced Elimination

Hemodialysis and other extracorporeal techniques have no role in OP poisoning (Rosen's Emergency Medicine)

Summary Table

Feature	Detail
Mechanism	AChE inhibition → ACh excess
Route of exposure	Dermal, GI, inhalation
Key muscarinic signs	SLUDGE/DUMBELS, bradycardia, bronchorrhea
Key nicotinic signs	Fasciculations, weakness, tachycardia
Cause of death	Respiratory failure
Antidote 1	Atropine (muscarinic block)
Antidote 2	Pralidoxime/2-PAM (AChE reactivation)
Seizures	Benzodiazepines
Intermediate syndrome	24-96h; no antidote
Delayed neuropathy (OPIDN)	2-5 weeks; no antidote

Sources: Tintinalli's Emergency Medicine, 9th Ed., p. 1342-1343; Rosen's Emergency Medicine, 9th Ed., p. 3029; Adams & Victor's Principles of Neurology, 12th Ed., p. 1343

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