Organophosphate and carbamate insecticides inactivate the enzyme acetylcholinesterase producing a cholinergic crisis, with the immediate threat to life being respiratory failure.
The diagnosis of organophosphate or carbamate poisoning is clinical, with the history of exposure being key; the combination of miosis and increased salivation is relatively specific.
Immediate administration of adequate doses of atropine can be life-saving.
Pralidoxime is an adjunctive antidote for organophosphate but not for carbamate poisoning.
Historically, the commonest scenario for organophosphate and carbamate exposure in young children involved home aerosol insecticide spray products. Morbidity associated with such exposures was negligible because they contained low concentrations of active ingredients. Organophosphates and carbamates have been replaced by other active compounds in most of these products. However, high-concentration organophosphate and carbamate insecticides intended for outdoor agricultural use are available, with the active ingredients typically dissolved in hydrocarbon solvents. They are meant to be diluted prior to use. Exposure to these concentrated insecticides is responsible for most cases of significant organophosphate and carbamate poisonings.
Organophosphates and carbamates inhibit acetylcholinesterase, the enzyme that inactivates acetylcholine. The resultant accumulation of this neurotransmitter produces ongoing cholinergic stimulation.1 Muscarinic cholinergic receptors are found in secretory glands and smooth muscle, while nicotinic receptors are found in skeletal muscle and autonomic ganglia. There are also central cholinergic receptors in the brain.
Organophosphate and carbamates inhibit acetylcholinesterase by occupying and binding to the acetylcholine receptor site. Organophosphates bind much more avidly than carbamates. In addition, the bond between organophosphates and the acetylcholine receptor over time becomes irreversible; the carbamate bond will reverse spontaneously. Thus organophosphate poisoning is typically more severe than its carbamate counterpart because functional enzyme activity impairment can be prolonged. Despite this, some carbamates such as aldicarb and carbaryl can be highly toxic.2
Carbamate toxicity is primarily restricted to muscarinic effects. Carbamates are much less likely than organophosphates to cause central nervous system (CNS) toxicity since they do not penetrate the blood–brain barrier well. Nicotinic manifestations are also uncommon. However, children with severe carbamate poisoning can develop mental status depression and occasionally seizures.
The largest clinical series of organophosphate and carbamate poisoning in infants and children was published in 1988.3 The initial signs and symptoms of cholinergic toxicity are often muscarinic. “DUMBELS” (Table 132-1) is a helpful mnemonic. Nicotinic effects of excess acetylcholine at the neuromuscular junction include muscle spasm and fasciculations, followed by weakness or paralysis as the muscle fatigues. CNS effects of organophosphate exposure range from agitation and delirium to seizures and coma.
TABLE 132-1DUMBELS: A Mnemonic for Muscarinic Effects of Cholinergic Stimulation