(See also General Principles of Poisoning.)
Some organophosphates were developed as nerve agents 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 and carbamates are common causes of poisoning and poison-related deaths worldwide.
Pathophysiology
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
Acute
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 is possible, and organophosphates may cause arrhythmias such as heart block and QTc interval prolongation.
Delayed
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.
Diagnosis
Muscarinic toxidrome with prominent respiratory findings, pinpoint pupils, muscle cramping, and weakness
Sometimes RBC cholinesterase levels
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.
Treatment
Supportive therapy
Decontamination
In-hospital treatment
Supportive therapy is key. Patients should be closely monitored for respiratory failure due to weakness of respiratory muscles.
Decontamination
Benzodiazepines
Out-of-hospital exposure
> 41 kg; 1 mg for children 19 to 41 kg; 0.5 mg for children <chemical attack by nerve agents.
Key Points
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.
