Practice Essentials
Organophosphates and carbamates are the most frequently used insecticides worldwide. These compounds cause 80% of the reported toxic exposures to insecticides. Organophosphates produce a clinical syndrome that can be effectively treated if recognized early. The typically described muscarinic clinical syndrome in adults often does not occur in young children, who instead are more likely to present with altered levels of consciousness (see Presentation). [1, 2, 3, 4] Severe exposures require expeditious anticholinergic therapy (see Treatment and Medication).
Background
Organophosphates were first discovered more than 150 years ago; however, their widespread use began in Germany in the 1920s, when these compounds were first synthesized as insecticides and chemical warfare agents. Interest in the effects of these compounds on humans has increased in recent years due to their potential use as weapons of mass destruction. [5]
Pathophysiology
Organophosphates form an initially reversible bond with the enzyme cholinesterase. The organophosphate-cholinesterase bond can spontaneously degrade, reactivating the enzyme, or can undergo a process called aging. The process of aging results in irreversible enzyme inactivation.
Cholinesterase is found in two forms: an RBC form, which is known as true cholinesterase, and a plasma form, which is known as pseudocholinesterase. Cholinesterases rapidly hydrolyze the neurotransmitter acetylcholine into inactive fragments. Acetylcholine is found in sympathetic and parasympathetic ganglia and in the terminal nerve endings of postganglionic parasympathetic nerves at the motor endplates of nerves in the skeletal muscle. Inactivation of the enzyme allows acetylcholine to accumulate at the synapse, leading to overstimulation and disruption of nerve impulses. Skeletal-muscle depolarization and fasciculations occur secondary to nicotinic stimulation at the motor endplate.
Muscarinic effects occur at the postganglionic parasympathetic synapses, causing smooth-muscle contractions in various organs including the GI tract, bladder, and secretory glands. Conduction can be delayed in the sinus and atrioventricular (AV) nodes. Dysrhythmias are frequently reported; these typically include bradycardia, though tachycardia can also occur.
Acetylcholine receptors are widely dispersed throughout the CNS. The activation of these receptors causes a wide range of effects, including CNS stimulation, seizures, confusion, ataxia, coma, and respiratory or cardiovascular depression.
Organophosphates are generally highly lipid soluble and are well absorbed from the skin, mucous membranes, conjunctiva, GI system, and respiratory system.
Epidemiology
The American Association of Poison Control Centers' (AAPCC's) National Poison Data System reported 1496 single exposures to organophosphate insecticides alone in 2020; 406 of those were in children younger than 6 years, 65 in children 6 to 12 years, and 59 in teenagers. These resulted in 14 major outcomes but no deaths. In addition, the AAPCC reported 435 single exposures to organophosphate insecticides in combination with other insecticides (mostly non-carbamate), none of which were fatal. Of the exposures to combined insecticides, 59 occurred in children younger than 6 years and 27 in older pediatric patients. [6] Many more exposures probably occur, but patients with minor symptoms often do not seek medical care.
Worldwide, pesticide poisonings cause an estimated 20,000 deaths and more than one million serious poisonings annually. [7] No known racial differences in mortality or morbidity are reported. No differences in clinical effects between the sexes are known.
Children are at a significantly increased risk worldwide, particularly in Africa and other developing regions, where the widespread availability and use of organophosphates and the lack of regulation and safety packaging are high risk factors for exposure. Childhood deaths and reported poisonings in the United States have declined over the last few decades, partly because of educational efforts and improved regulation and packaging.
Prognosis
The prognosis for patients treated early is excellent; most patients fully recover in 7-10 days. Patients with toxicity untreated for more than 24 hours may have a prolonged and severe course with lasting neurologic complications. [8]
Intermediate syndrome can develop 24-96 hours after exposure. [9, 10] A combination of presynaptic and postsynaptic impairment of neuromuscular transmission probably causes the syndrome. Features of intermediate syndrome as as follows:
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The syndrome tends to occur in patients with prolonged exposure before treatment.
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The syndrome is characterized by weakness in the motor cranial nerves, proximal limb muscles, neck flexors, and respiratory muscles.
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A delayed peripheral neuropathy may develop days to weeks after the exposure.
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Patients may also have persistent CNS effects, weakness, lethargy, fatigue, and memory impairment. [11]
Shahar et al reported extrapyramidal parkinsonism as a complication of acute organophosphate poisoning. [12, 13] Symptoms developed 5 days after exposure and completely resolved after treatment with amantadine.
Most morbidity and mortality results from anoxic injury due to respiratory failure. Clinical effects range from mild flulike symptoms with low-level exposures to life-threatening respiratory failure with larger exposures.
