eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Toxicology

Toxicity, Organophosphates

Author: William Freudenthal, MD, Staff Physician, Department of Emergency Medicine, St. Vincent Hospital Indianapolis, IN
Coauthor(s): Mark Ralston, MD, Department of Pediatric Emergency Medicine, Clinical Assistant Professor, Mary Bridge Children's Hospital, Tacoma WA
Contributor Information and Disclosures

Updated: Jan 23, 2008

Introduction

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

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.²

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 2 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.

Frequency

United States

In 2004, 102,754 exposures were reported. In children younger than 6 years, 52,174 exposures were reported; however, no deaths were reported in this age group. 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.
• 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.

Race

No known racial differences in mortality or morbidity are reported.

Sex

No differences in clinical effects between the sexes are known.

Age

• In 2004, more than 50% of the insecticide exposures in the United States occurred in children younger than 6 years.
• 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.

Clinical

History

• Most symptoms appear within 12-24 hours of exposure.
• Exposure can occur by means of ingestion, dermal exposure, or inhalation.
• Children often ingest home pesticides they find in unmarked or poorly stored containers.
• Children can also be exposed when playing in areas recently treated with organophosphate compounds.
• A history of possible exposure combined with physical signs and symptoms consistent with exposure often lead to diagnosis.
• Many organophosphates can irritate the skin and mucous membranes. Some have a characteristic odor, such as a garliclike smell.

Physical

Physical findings vary according to the route of exposure, the age of patient, and the specific chemical.

• Muscarinic findings may include the following:³
  • Diaphoresis and diarrhea, urination, miosis, bradycardia, bronchorrhea, bronchospasm, emesis, lacrimation and salivation (DUMBELS)
  • Wheezing and/or bronchoconstriction
  • Pulmonary edema
  • Increased pulmonary and oropharyngeal secretions
  • Sweating
  • Bradycardia
  • Abdominal cramping and intestinal hypermotility
  • Miosis
• Nicotinic findings may include the following:
  • Muscle fasciculations (twitching)
  • Fatigue
  • Paralysis
  • Respiratory muscle weakness
  • Diminished respiratory effort
  • Tachycardia
  • Hypertension
• CNS findings may include the following:
  • Anxiety
  • Restlessness
  • Confusion
  • Headache
  • Slurred speech
  • Ataxia
  • Seizures
  • Coma
  • Central respiratory paralysis
  • Altered level of consciousness and/or hypotonia
• Predominant symptoms and signs vary according to the age of the affected person. Children, particularly young children, present with altered levels of consciousness rather than the classic DUMBELS signs that are most commonly observed in adults.
  • Zwiener and Ginsburg (1988) retrospectively examined 37 patients aged 1 month to 11 years who had been exposed to insecticides.⁴ The most common signs were miosis, excessive salivation, muscle weakness, and lethargy. Approximately 49% of these children presented with tachycardia.
  • Lifshitz et al (1999) retrospectively examined 36 children aged 2-8 years who were exposed to organophosphates or carbamates in Israel.⁵ The authors observed a decreased level of consciousness, including coma, stupor, and hypotonicity in all children.
  • Lima and Reis (1995) reported carbamate poisoning in Rio de Janeiro.⁶ Symptoms included salivation, lacrimation, urination, defecation, GI distress, and emesis (SLUDGE) and were more commonly observed in adults than in children.
  • Sofer et al (1989) retrospectively examined 25 patients aged 3 months to 7 years with carbamate or organophosphate poisoning in Israel.⁷ The most common presenting symptoms were CNS depression, stupor, coma, and flaccidity. The classic SLUDGE symptoms were more likely to be absent in these children.

Causes

Exposure to organophosphates through the skin, mucous membranes, conjunctiva, GI tract, or respiratory systems is the cause of organophosphate toxicity.

Other diagnostic considerations include the following:

• Toxicity due to various poisons, such as carbamates, phosgene, paraquat,⁸ and nerve agents, can cause symptoms similar to those of organophosphates.
• In young children, suspect organophosphate poisoning if they have any illness that depresses the level of consciousness.

• Search for CME/CE on This Topic »

• Toxicity, Organophosphate (Emergency Medicine)
• Toxicity, Lidocaine (Emergency Medicine)
• Organophosphates (Neurology)
• Toxicity, Mercury (Emergency Medicine)

• Serotonin Toxicity, ECG Abnormalities Seen With Escitalopram Overdose
• Dietary Supplement May Protect Against Acetaminophen-Induced Liver Toxicity
• "Substantial" Toxicity With Peginterferon Use: FDA Staff

• Depression and Pesticide Exposures Among Private Pesticide Applicators Enrolled in the Agricultural Health Study
• Tenofovir-associated Renal and Bone Toxicity
• EGFR-Targeted Therapies in Lung Cancer: Predictors of Response and Toxicity