DESCRIPTION

The organophosphate insecticides include chemicals of organophosphorus structure used as pesticides in both domestic and industrial settings.

FORMS AND USES

The organophosphates are found in agricultural and large-scale landscape maintenance settings; some low-toxicity forms are found as components in home gardening products. They are also used in many industrial processes. They are classified by their relative toxicity:

• Low-toxicity (LD₅₀ >1,000 mg/kg) products include bromophos (Nexagan), etrimfos (Ekamet), iodofenphos (Nuvanol N), malathion (Cythion), phoxim (Baythion), propylthiopyrophosphate (Aspon), temephos (Abate, Abathion), and tetrachlorvinphos (Gardona, Rabon).
• Moderate-toxicity (LD₅₀ 50-1,000 mg/kg) products include acephate (Orthene), bensulide (Betasan), chlorpyrophos (Lorsban, Dursban), crotoxyphos (Ciodrin), cythioate (Proban), DEF (De-Green, E-Z-off D), demeton-S-methyl (Metasystox), diazinon (Spectracide, Basudin), di-chlorovos (DDVP, Vapona), dimethoate (Cygon), dioxathion (Delnav), edifenphos (EDDP), ethion (Nialate), ethoprop (Mocap), fenitrothion (Accothion), fenthion (Baytex, Entex), formothion (Anthio), IPB (Kitazin), leptophos (Phosvel), merphos (Folex), methyl trithion, naled (Dibrom), phencapton, phosalone (Zofos), phosmet (Imidan, Prolate), pirimiphos-ethyl (Fernex), profenophos (Curacron, Ploycron, Selecron), propetamphos (Safrotin), pyrazophos (Afugan, Curamil), quinalphos (Bayrusil), sulprofos (Bolstar), thiometon (Ekatin), triazophos (Hostathion), tribufon (Butonate), and trichlorofon (Tugon, Dylox, Dipterex).
• Highly toxic (LD₅₀ <50 mg/kg) organophosphate products include bomyl (Swat), carbophenothion (Trithion), chlormephos (Dotan), chlorthiophos (Celathion), chlorfenvinfos (Birlane), coumaphos (Co-ral), cyanofenphos (Surecide), dementon (Systox), dialifor (Torak), dicrotophos (Bidrin), disulfoton (Disyston), EPN, famphur (Warbex, Bo-ana), fenamiphos (Nemacur), fenophosphon (Agritox), isofenphos (Amaze, Oftanol), diisopropyl fluorophosphate, mephosfolan (Cytrolane), methamidophos (Monitor), methidathion (Supracide), mevinphos (Phosdrin), monocrotophos (Azodrin), ethyl-parathion, phorate (Thimet), phosfolan (Cyolane), phosphamidon (Dimecron), prothoate (Fac), sulfotep (Bladafum), terbufos (Counter), and tetraethyl pyophosphate (TEPP, Bladan, Tetron).

TOXIC DOSE

Toxicity varies by potency. Several swallows are needed to produce toxicity from low-potency compounds, whereas only a few milliliters may be needed for high-toxicity compounds.

PATHOPHYSIOLOGY

• Organophosphate insecticides reversibly bind to the enzyme acetylcholinesterase, inhibiting its activity and resulting in excessive stimulation of the acetylcholine receptor.
• The binding then "matures" and the inhibition becomes irreversible over a period of hours.
• Toxicity may manifest as nicotinic effects (muscle weakness, fasciculation, hypertension, tachycardia) or muscarinic effects (diaphoresis, vomiting, diarrhea).

EPIDEMIOLOGY

• Poisoning is common.
• Toxic effects are typically mild to moderate.
• Death is rare and usually occurs before health care is provided.

CAUSES

• Toxic ingestion or dermal exposure is usually accidental.
• Child abuse or neglect must be considered if the patient is less than 1 year of age; suicide attempt if the child is older than 6 years.

RISK FACTORS

Patients with congenital low levels of acetylcholinesterase are at increased risk of toxicity from any given exposure.

DRUG AND DISEASE INTERACTIONS

• Organophosphates prolong the activity of neurologic blocking agents.
• Gentamicin and other antibiotics may prolong organophosphate toxicity.

PREGNANCY AND LACTATION

Numerous animal studies indicate teratogenic effects of various organophosphate compounds. However, some have no effect; therefore, each agent should be addressed individually.

WORKPLACE STANDARDS

Malathion

ACGIH. TLV TWA is 10 mg/m³.

Parathion

• ACGIH. TLV TWA is 0.1 mg/m³.
• OSHA. PEL TWA is 0.1 mg/m³.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• TOXIC DOSE
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES
• RISK FACTORS
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION
• WORKPLACE STANDARDS
  • Malathion
  • Parathion

DIFFERENTIAL DIAGNOSIS

• Other toxic causes of acute onset of acetylcholine effects include carbamates, nicotine, carbachol, methacholine, arecoline, bethanechol, pilocarpine, and some mushrooms, among others.
• Nontoxic causes include myasthenia gravis and Eaton-Lambert syndrome, among others.

SIGNS AND SYMPTOMS

Muscarinic effects are manifested by the DUMBELS syndrome (diaphoresis and diarrhea; urination; miosis; bradycardia, bronchospasm, and bronchorrhea; emesis and excess of lacrimation; and salivation and seizures) and usually occur soon after exposure.

Vital Signs

Bradycardia, hypotension, and hypothermia may occur.

HEENT

Miosis, blurred vision, rhinorrhea, salivation, and lacrimation are common.

Dermatologic

Profuse diaphoresis is common.

Cardiovascular

• Hypotension and bradycardia may occur.
• Cardiac depression and cardiovascular collapse may occur.
• Atrial fibrillation, atrioventricular blocks, and asystole may occur.

Pulmonary

Bronchospasm and bronchorrhea are common, leading to pulmonary edema in severe cases.

Gastrointestinal

Nausea, vomiting, abdominal pain, and diarrhea are common; fecal incontinence may occur.

Renal

Urinary incontinence occurs, especially in severe cases.

Musculoskeletal

Fasciculation, weakness, paralysis, and respiratory failure may occur.

Neurologic

Confusion, seizures, and coma may occur.

PROCEDURES AND LABORATORY TESTS

Essential Tests

Red blood cell cholinesterase level correlates roughly with effects; first sample should be drawn before treatment (plasma cholinesterase can be used if red blood cell cholinesterase is unavailable).

• Latent Poisoning. No clinical manifestations are present; cholinesterase levels are 50% to 90% of baseline.
• Mild Poisoning. Patient is ambulatory, and may experience nausea, vomiting, fatigue, headache, dizziness, sweating and salivation, tightness in chest, and abdominal cramps or diarrhea; cholinesterase activity is 20% to 50% of baseline.
• Moderate Poisoning. Patient cannot walk and experiences generalized weakness, difficulty speaking, fasciculation, and miosis; cholinesterase activity is 10% to 20% of baseline.
• Severe Poisoning. Patient is unconscious, with miosis, fasciculation, flaccid paralysis, increased secretions, moist rales, and cyanosis; cholinesterase activity is less than 10% of baseline.

Recommended Tests

• Serum electrolytes, glucose, BUN, calcium, magnesium, phosphate, and creatinine should be assayed to detect other causes of dysrhythmia, weakness, or kidney injury.
• ECG and continuous cardiac monitoring should be performed to assess potential causes of hypotension and bradycardia.
• Serum acetaminophen and aspirin levels should be measured in an overdose setting to detect occult ingestion.
• Arterial blood gases should be measured if acidosis or hypoxia develop.
• Comprehensive urine drug screen should be done if source of intoxication is unknown (abused drugs may contain contaminants).
• CT, lumbar puncture, cultures, and other tests as indicated should be performed in patients with altered mental status of unknown etiology.
• Negative inspiratory force should be followed to assess ventilatory capacity.
• Chest radiographs can assist evaluation of pulmonary edema.
• Patients with delayed polyneuropathy may demonstrate denervation on electromyography.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Dermatologic
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Renal
  • Musculoskeletal
  • Neurologic
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests

• Treatment should focus on decontamination, airway management, and administration of atropine and pralidoxime.
• Dose and time of exposure should be determined for all substances involved.

DIRECTING PATIENT COURSE

The health-care provider should call the poison control center when:

• Breathing difficulty, hypotension, or other severe effects are present.
• Toxic effects are not consistent with organophosphate poisoning.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

The patient should be referred to a health-care facility when:

• Attempted suicide or homicide is possible.
• Patient or caregiver seems unreliable.
• Any toxic effects develop.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

Admission Considerations

Inpatient management is warranted if the patient develops toxic effects that require treatment.

DECONTAMINATION

Out of Hospital

• Emesis should not be induced.
• Providers must wear protection to prevent contamination.
• Patient's clothing should be removed and skin washed with soap and water.

In Hospital

• Patient's clothing should be removed and skin washed with soap and water; providers should wear protection to prevent contamination.
• Gastric aspiration should be performed with a nasogastric tube in the case of recent ingestion or a symptomatic patient.
• One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if a symptomatic ingestion has occurred.

ANTIDOTES

Atropine

• Indications. Control of bronchorrhea and other secretions.
• Contraindication. Preexisting atropinization (dry airway, mydriatic pupils, etc.).
• Method of administration
  • Adult initial dose is 2 to 4 mg intravenously; dose (or double the dose) may be repeated every 5 to 10 minutes as needed until pulmonary secretions are controlled.
  • Pediatric initial dose is 0.05 mg/kg intravenously; dose (or double the dose) may be repeated every 5 to 10 minutes as needed until pulmonary secretions are controlled.
  • In severe cases, massive amounts of atropine may be needed over 12 to 24 hours.
• Adverse effects. Anticholinergic symptoms possible with excessive atropine.

Pralidoxime (2-PAM)

• Indications. Patients with nicotinic effects (weakness, fasciculations) or CNS effects should be treated.
• Method of administration
  • Adult dose is 1 to 2 g intravenously over 15 to 30 minutes or as a continuous intravenous infusion at 500 mg/h.
  • Pediatric dose is 25 mg/kg (up to 1 g) intravenously over 15 to 30 minutes, followed by 25 to 50 mg/kg (up to 500 mg) per hour.

ADJUNCTIVE TREATMENT

Hypotension

• Atropine should be used if hypotension is due to bradycardia.
• The patient should receive 10 to 20 ml/kg 0.9% saline intravenously and be placed in the Trendelenburg position.
• Further fluid therapy should be guided by central pressure monitoring.
• A vasopressor may be added if needed.

Seizure

• A patent airway must be assured.
• A benzodiazepine should be administered for initial control.
• If seizures persist or recur, another anticonvulsant such as phenobarbital may be added.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
  • Atropine
  • Pralidoxime (2-PAM)
• ADJUNCTIVE TREATMENT
  • Hypotension
  • Seizure

PATIENT MONITORING

• Continuous cardiac and respiratory monitoring should be performed.
• Following occupational exposure, patient should not be allowed to work with organophosphate or carbamate insecticides until serum cholinesterase levels have returned to 75% of known baseline.
• If baseline levels are not available, patient should not return to work until two serum cholinesterase levels drawn 1 week apart show an increase of less than 5% (plateau level).

EXPECTED COURSE AND PROGNOSIS

• Toxicity develops rapidly and peaks within hours, but may persist for a day or more if patient does not receive antidotal treatment.
• Patients who receive early decontamination and adequate treatment usually recover without sequelae.

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department. Asymptomatic patients may be discharged after decontamination, a 6-hour observation period, and psychiatric evaluation, if needed.
• From the hospital. Patients who have not required atropine for 24 hours may be discharged.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA/INSTRUCTIONS

Failure to adequately protect health-care providers may result in secondary exposures.

Toxic effect of other substances, chiefly nonmedicinal as to source: organophosphate and carbamate.

See Also: SECTION II, Hypotension, Pulmonary Edema, and Seizures chapters; SECTION III, Atropine and Pralidoxime chapters.

RECOMMENDED READING

Aaron CK, Howland MA. Insecticides: organophosphates and carbamates. In: Goldfrank LR, Flomenbaum NE, Lewin NA, et al., eds. Goldfrank's toxicologic emergencies, 6^th ed. Norwalk, CT: Appleton & Lange, 1998.

Willems JL, De Bisschop HC, Verstraete AG, et al. Cholinesterase reactivation in organophosphorus poisoned patients depends on the plasma concentrations of the oxime pralidoxime methylsulphate and of the organophosphate. Arch Toxicol 1993;67:79-84.

Author: Luke Yip

Reviewer: Richard C. Dart