Pediatric Organophosphates Toxicity

Updated: Sep 07, 2015
  • Author: William Freudenthal, MD; Chief Editor: Timothy E Corden, MD  more...
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Overview

Background

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 clinical syndrome in adults often does not occur in young children. [1, 2, 3, 4]

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]

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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.

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Epidemiology

Frequency

United States

In 2013, the American Association of Poison Control Centers' National Poison Data System reported 2354 single exposures to organophosphate insecticides alone, with two deaths, along with 578 single exposures to organophosphate insecticides in combination with other insecticides, none of which were fatal. Of all those exposures, 715 occurred in children younger than 6 years. [6] Many more exposures probably occur, but patients with minor symptoms often do not seek medical care.

International

Worldwide, pesticide poisonings cause an estimated 20,000 deaths and cause more than one million serious poisonings annually.

Mortality/Morbidity

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.

Race-, Sex-, and Age-related Demographics

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.

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