Chapter 131: Organophosphates and Carbamates

• Organophosphate and carbamate insecticides inactivate the enzyme acetylcholinesterase resulting in a cholinergic crisis with the immediate threat to life being respiratory failure.

• The diagnosis is clinical with the history of exposure being key; the combination of miosis and increased salivation is relatively specific.

• Immediate administration of very large doses of atropine is 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 aerosol spray products available to the consumer for insect control in the home. This produced negligible morbidity because of low concentrations of active ingredients. Organophosphates and carbamates have been replaced by other active compounds in most of these products. However, organophosphate and carbamate insecticides intended for outdoor use and in particular for agricultural use are available in high concentrations typically dissolved in hydrocarbon solvents. They are diluted prior to use. Exposures to these concentrated insecticides are responsible for most 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 exocrine glands and smooth muscle while their nicotinic counterparts are found in skeletal muscle and autonomic ganglia. There are also central cholinergic receptors in the brain.

These compounds inhibit acetylcholinesterase by occupying the acetylcholine binding site. The attachment by organophosphates is much more robust than for carbamates; the latter is often spontaneously reversible. Thus, organophosphate poisoning is usually more severe than its carbamate counterpart. In carbamate poisoning, functional enzyme activity is often largely restored within 8 hours, with red blood cell cholinesterase completely restored within 48 hours. 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 CNS effects 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 131-1) 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. Central nervous system effects of organophosphate exposure range from agitation and delirium to seizures and coma.

Because of the different types of cholinergic receptors, vital signs at presentation can vary. The patient may be bradycardic because of the parasympathetic cardiac effect, or tachycardic because of hypoxia or nicotinic action on sympathetic ganglia including the adrenal gland.⁴ Likewise, the patient may be hypotensive or hypertensive. Presenting symptoms may be affected by the route of exposure. External dermal contamination by organophosphates or carbamates can initially cause localized sweating and fasciculations. Inhalation exposure can present with predominant respiratory manifestations. Ingestion can cause early vomiting, diarrhea, and abdominal distress.

Although there is the potential for toxic effects upon virtually all tissues and organs, significant morbidity and mortality is a consequence of respiratory system toxicity. The muscarinic bronchospasm and bronchorrhea along with the nicotinic paralysis of chest wall muscles lead to respiratory insufficiency and failure. Hydrocarbons are commonly used as solvents for these insecticides. An additional potential insult upon the respiratory system is a concomitant chemical aspiration pneumonitis.

Organophosphate-induced delayed neuropathy (OIDN) has been described with an onset 1–3 weeks after the acute phase. This often starts with leg cramping, followed by weakness and diminished deep tendon reflexes in the lower extremities. OIDN is predominantly a distal motor polyneuropathy; cranial nerves and the muscles of respiration are usually spared.⁵ An “intermediate syndrome” has also been reported, starting 1–3 days after acute toxicity, with weakness of neck flexors, proximal limb and respiratory muscles, and muscles innervated by cranial nerves. Respiratory failure can occur. This syndrome has not been described in children.

History, suggestive clinical signs and symptoms, and a high index of suspicion are the keys to making the diagnosis of organophosphate and carbamate poisoning. The combination of miosis and increased salivation is relatively specific. The diagnosis is clinical.

Cholinesterase in plasma and red blood cells can be measured and values below normal are consistent with organophosphate and carbamate poisoning. Many hospital laboratories do not perform these tests and must send them to an outside facility. Although a decreased plasma cholinesterase supports the diagnosis, the actual value itself does not seem to have prognostic significance.⁶ Red blood cell cholinesterase—although more difficult to measure—more closely reflects enzyme activity in the central and peripheral nervous systems, and more accurately parallels clinical severity.

Other laboratory tests can be obtained if clinically indicated. Pulse oximetry helps evaluate oxygenation status. A chest radiograph may show aspiration pneumonitis, which is especially likely if the organophosphate preparation included a hydrocarbon vehicle. Noncardiogenic pulmonary edema may also be seen.

Adequate external decontamination is important to prevent continued exposure. All clothing and jewelry should be removed and placed in sealed plastic bags. Contaminated skin should be irrigated with copious amounts of water, or gently washed with soap and water. Vigorous scrubbing should be avoided since it might actually increase systemic uptake.

To prevent secondary contamination, all members of the medical team who are directly treating or decontaminating the patient should wear adequate protective gear. Simple surgical masks and gowns do not provide sufficient protection. Butyl rubber gloves and aprons are more effective. If the patient is vomiting, gastric contents may contain the organophosphate agent and be a source of secondary contamination.

Neither gastric lavage nor activated charcoal has any demonstrated benefit in the setting of organophosphate ingestion. Either intervention would be expected to increase the risk of pulmonary aspiration.

As for any seriously ill patient the primary goal is support of airway, breathing, and circulation. This is accomplished by routine interventions and by the timely administration of sufficient antidote.

The goal is to treat respiratory insufficiency, which is the primary threat. The antidote is atropine sulfate, which reverses the muscarinic bronchospasm and bronchorrhea. The initial dose is 0.02 mg/kg intravenously. In severe cases, this dose should be doubled every 5 minutes until pulmonary secretions dry up, bronchospasm resolves, and the child can be oxygenated and ventilated.⁷ Tachycardia is not a contraindication to the administration of atropine. There is no maximum dose of atropine. Frequently, surprisingly large amounts are required.

Pralidoxime chloride should be given to treat moderate-to-severe cholinergic toxicity from organophosphates or an unknown agent. The dose is 25–50 mg/kg IV over 30 minutes. Pralidoxime regenerates acetylcholinesterase by removing organophosphate from the enzyme's active site. The dose can be repeated at 6 hours intervals, or a continuous infusion of 10 mg/kg/h can be started after the initial load. Pralidoxime is not indicated in confirmed carbamate exposure because the bond between carbamate and acetylcholinesterase is weak and spontaneously reverses. However, it should be administered in cases of significant cholinergic toxicity where the specific insecticide is not known.

Diazepam is the treatment of choice for seizures. Studies indicate that it may also be beneficial in any patient with evidence of severe central cholinergic toxicity, such as those who are comatose or minimally responsive. If a patient needs to be paralyzed to facilitate endotracheal intubation, succinylcholine should not be used because it is metabolized by plasma cholinesterase. Since this enzyme is inactivated by organophosphates, administration of succinylcholine may result in markedly prolonged paralysis.^8,9

Arrangements should be made for admission to a critical care unit.