(See also General Principles of Poisoning General Principles of Poisoning Poisoning is contact with a substance that results in toxicity. Symptoms vary, but certain common syndromes may suggest particular classes of poisons. Diagnosis is primarily clinical, but for... read more .)
Organophosphates and carbamates, although different structurally, both inhibit cholinesterase activity. Some are used medically to reverse neuromuscular blockade (eg, neostigmine, pyridostigmine, edrophonium) or to treat glaucoma (echothiopate), myasthenia gravis (pyridostigmine), and Alzheimer disease (tacrine and donepezil).
Some organophosphates were developed as nerve agents Nerve Chemical-Warfare Agents Nerve agents are chemical-warfare agents that act directly at nerve synapses, typically increasing the activity of acetylcholine. Other chemical agents were used in combat before World War II... read more for use in warfare. One, sarin, has been used by terrorists. Organophosphates and carbamates are commonly used as insecticides (see table Symptoms fn Treatment of Specific Poisons ). Those most often implicated in human poisoning include
Carbamates: Aldicarb and methomyl
Organophosphates: Chlorpyrifos, diazinon, dursban, fenthion, malathion, and parathion
Organophosphates and carbamates are common causes of poisoning and poison-related deaths worldwide.
Organophosphates and carbamates are absorbed through the gastrointestinal tract, lungs, and skin. They inhibit plasma and red blood cell (RBC) cholinesterase, preventing breakdown of acetylcholine, which then accumulates in synapses. Carbamates are cleared spontaneously within about 48 hours after exposure. Organophosphates, however, can irreversibly bind to cholinesterase.
Symptoms and Signs
Organophosphates and carbamates cause cholinergic symptoms due to activation of both major cholinergic receptors, which are characterized as muscarinic and nicotinic:
Muscarinic cholinergic symptoms: Salivation, lacrimation, urination, defecation, vomiting, pinpoint pupils (miosis), bronchorrhea and wheezing, bradycardia
Nicotinic cholinergic symptoms: Mydriasis, tachycardia, weakness and fasciculations, sweating, abdominal pain
Of these manifestations, muscle fasciculations and weakness are typical. Respiratory findings include rhonchi, wheezing, and hypoxia, which may be severe. Most patients have bradycardia and, if poisoning is severe, hypotension. Central nervous system toxicity is common, sometimes with seizures and excitability and often with lethargy and coma. Pancreatitis Overview of Pancreatitis Pancreatitis is classified as either acute or chronic. Acute pancreatitis is inflammation that resolves both clinically and histologically. Chronic pancreatitis is characterized by histologic... read more is possible, and organophosphates may cause arrhythmias Overview of Arrhythmias The normal heart beats in a regular, coordinated way because electrical impulses generated and spread by myocytes with unique electrical properties trigger a sequence of organized myocardial... read more such as heart block and QTc interval prolongation.
Weakness, particularly of proximal, cranial, and respiratory muscles, may develop 1 to 3 days after exposure to organophosphates or rarely carbamates despite treatment (the intermediate syndrome); these symptoms resolve in 2 to 3 weeks. A few organophosphates (eg, chlorpyrifos, triorthocresyl phosphate) may cause an axonal neuropathy that begins 1 to 3 weeks after exposure. The mechanism may be independent of RBC cholinesterase levels, and the risk is independent of the severity of poisoning. Long-term, persistent sequelae of organophosphate poisoning may include cognitive deficits or parkinsonism Secondary and Atypical Parkinsonism Secondary parkinsonism refers to a group of disorders that have features similar to those of Parkinson disease but have a different etiology. Atypical parkinsonism refers to a group of neurodegenerative... read more .
Muscarinic toxidrome with prominent respiratory findings, pinpoint pupils, muscle cramping, and weakness
Sometimes RBC cholinesterase levels
The diagnosis is usually based on the characteristic muscarinic toxidrome in patients with neuromuscular and respiratory findings, particularly in patients at risk. If findings are equivocal, reversal or abatement of muscarinic symptoms after 1 mg of atropine (0.01 to 0.02 mg/kg in children) supports the diagnosis. The specific toxin should be identified if possible. Many organophosphates have characteristic garlic-like or petroleum odors.
RBC cholinesterase activity, which can be measured by some laboratories, indicates the severity of poisoning. If it can be measured rapidly, values can be used to monitor the effectiveness of treatment; however, patient response is the primary marker of effectiveness.
Atropine for respiratory manifestations
Pralidoxime for neuromuscular manifestations
Supportive therapy is key. Patients should be closely monitored for respiratory failure due to weakness of respiratory muscles.
Atropine is given in amounts sufficient to relieve bronchospasm and bronchorrhea rather than to normalize pupil size or heart rate. Initial dosage is 2 to 5 mg IV (0.05 mg/kg in children); the dose can be doubled every 3 to 5 minutes as needed. Grams of atropine may be necessary for severely poisoned patients.
Decontamination is pursued as soon as possible after stabilization. Caregivers should avoid self-contamination while providing care. For topical exposure, clothes are removed, and the body surface is flushed thoroughly. For ingestion within 1 hour of presentation, activated charcoal can be used. Gastric emptying is usually avoided. If done, the trachea is intubated beforehand to prevent aspiration.
Pralidoxime (2-PAM) is given after atropine to relieve neuromuscular symptoms. 2-PAM (1 to 2 g in adults; 20 to 40 mg/kg in children) is given over 15 to 30 minutes IV after exposure to an organophosphate or carbamate because, frequently, whether the poison is an organophosphate or carbamate is unknown at the time of treatment. An infusion can be used after the bolus (8 mg/kg/h in adults; 10 to 20 mg/kg/h in children).
Benzodiazepines are used for seizures. Prophylactic diazepam may help prevent neurocognitive sequelae after moderate to severe organophosphate poisoning.
People exposed to these toxins away from a hospital can give themselves low doses of atropine using commercially prepared autoinjectors (2 mg for adults and for children > 41 kg; 1 mg for children 19 to 41 kg; 0.5 mg for children < 19 kg). Autoinjection of 10 mg diazepam has been recommended for people exposed to a chemical attack by nerve agents Nerve Chemical-Warfare Agents Nerve agents are chemical-warfare agents that act directly at nerve synapses, typically increasing the activity of acetylcholine. Other chemical agents were used in combat before World War II... read more .
Organophosphates have been used in insecticides, medical treatments, and chemical weapons.
Suspect toxicity if patients have a muscarinic cholinergic toxidrome with prominent respiratory and neuromuscular findings.
Confirm the diagnosis by the response to atropine and sometimes RBC cholinesterase levels.
Treat supportively by giving atropine to relieve bronchospasm and bronchorrhea and by giving 2-PAM to relieve neuromuscular symptoms.