Malathion

CAS RN:121-75-5

Treatment Overview

0.4.2 ORAL EXPOSURE
  • A) MANAGEMENT OF MILD TOXICITY
    • 1) A patient who is either asymptomatic or presents with mild clinical symptoms (i.e. normal vitals, pulse oximetry and an acetylcholinesterase greater than 80% of lower reference range), and remains stable for 12 hours can be discharged. Obtain appropriate psychiatric evaluation if an intentional exposure.
  • B) MANAGEMENT OF MODERATE TO SEVERE TOXICITY
    • 1) Immediate assessment and evaluation. Airway management is likely to be necessary. Simple decontamination (i.e. skin and gastrointestinal, removal of contaminated clothes). Administer antidotes: atropine for muscarinic manifestations (e.g. salivation, diarrhea, bronchorrhea), pralidoxime for nicotinic manifestations (e.g. weakness, fasciculations). Treat seizures with benzodiazepines. Admit to intensive care with continuous monitoring, titration of antidotes, ventilation, and inotropes as needed. Consult a medical toxicologist and/or poison center.
  • C) DECONTAMINATION
    • 1) PREHOSPITAL: Activated charcoal is contraindicated because of possible respiratory depression and seizures and risk of aspiration. Remove contaminated clothing, wash skin with soap and water. Universal precautions and nitrile gloves to protect personnel.
    • 2) HOSPITAL: Activated charcoal for large ingestions. Consider nasogastric tube for aspiration of gastric contents, or gastric lavage for recent large ingestions, if patient is intubated or able to protect airway.
    • 3) DERMAL: Remove contaminated clothing. Wash skin thoroughly with soap and water. Universal precautions and nitrile gloves to protect staff from contamination. Systemic toxicity can result from dermal exposure.
    • 4) OCULAR: Copious eye irrigation.
  • D) AIRWAY MANAGEMENT
    • 1) Immediately assess airway and respiratory function. Administer oxygen. Suction secretions. Endotracheal intubation may be necessary because of respiratory muscle weakness or bronchorrhea. Avoid succinylcholine for rapid sequence intubation as prolonged paralysis may result. Monitoring pulmonary function (FVC, FEV1, NIF) may help anticipate need for intubation.
  • E) ANTIDOTES
    • 1) Atropine is used to antagonize muscarinic effects. Oximes (pralidoxime in the US, or obidoxime in some other countries) are used to reverse neuromuscular blockade. Use of oximes is usually indicated for patients with moderate to severe toxicity.
      • a) AUTOINJECTORS: PREHOSPITAL TREATMENT: DuoDote
  • (R) (Meridian Medical Technologies, Columbia, MD) is a dual chambered device that delivers 2.1 mg atropine and 600 mg pralidoxime in a single needle for intramuscular use. It is intended for use in a civilian/community setting, and is administered by EMS personnel who have been trained to recognize and treat nerve agent or insecticide intoxication. ATNAA (Antidote Treatment Nerve Agent Autoinjector, Meridian Medical Technologies, Columbia, Maryland) is currently used by the US military and provides atropine injection and pralidoxime chloride injection in a single needle. Each self-contained unit dispenses 2.1 mg of atropine in 0.7 mL and 600 mg of pralidoxime chloride in 2 mL via intramuscular injection. The safety and efficacy of ATNAA or DuoDote
  • (R) has not been established in children. These autoinjectors contain benzyl alcohol as a preservative. The AtroPen
  • (R) autoinjector (atropine sulfate; Meridian Medical Technologies, Inc, Columbia, MD) delivers a dose of atropine in a self-contained unit. Since the AtroPen
  • (R) comes in different strengths, certain dose units have been approved for use in children. If pralidoxime is required, pralidoxime prefilled autoinjector delivers 600 mg IM (adult dosing). The safety and efficacy of pralidoxime auto-injector for use in nerve agent poisoning have not been established in pediatric patients.
    • b) ATROPINE
  • 1) Atropine is used to treat muscarinic effects (e.g. salivation, lacrimation, defecation, urination, bronchorrhea). ADULT: 1 to 3 mg IV; CHILD: 0.02 mg/kg IV. If inadequate response in 3 to 5 minutes, double the dose. Continue doubling the dose and administer it IV every 3 to 5 minutes as needed to dry pulmonary secretions. Once secretions are dried, maintain with an infusion of 10% to 20% of the loading dose every hour. Monitor frequently for evidence of cholinergic effects or atropine toxicity (e.g. delirium, hyperthermia, ileus) and titrate dose accordingly. Large doses (hundreds of milligrams) are sometimes required. Atropinization may be required for hours to days depending on severity.
    • c) PRALIDOXIME
  • 1) Treat moderate to severe poisoning (fasciculations, muscle weakness, respiratory depression, coma, seizures) with pralidoxime in addition to atropine; most effective if given within 48 hours. Administer for 24 hours after cholinergic manifestations have resolved. May require prolonged administration. ADULT DOSE: A loading dose of 30 mg/kg (maximum: 2 grams) over 30 minutes followed by a maintenance infusion of 8 to 10 mg/kg/hr (up to 650 mg/hr). ALTERNATE ADULT DOSE: 1 to 2 grams diluted in 100 mL of 0.9% sodium chloride infused over 15 to 30 minutes. Repeat initial bolus dose in 1 hour and then every 3 to 8 hours if muscle weakness or fasciculations persist (continuous infusion preferred). In patients with serious cholinergic intoxication, a continuous infusion of 500 mg/hr should be considered. Intravenous dosing is preferred; however, intramuscular administration may be considered. A continuous infusion of pralidoxime is generally preferred to intermittent bolus dosing to maintain a target concentration with less variation. CHILD DOSE: A loading dose of 20 to 40 mg/kg (maximum: 2 grams/dose) infused over 30 to 60 minutes in 0.9% sodium chloride. Repeat initial bolus dose in 1 hour and then every 3 to 8 hours if muscle weakness or fasciculations persist (continuous infusion preferred). ALTERNATE CHILD DOSE: 25 to 50 mg/kg (up to a maximum dose of 2 g), followed via continuous infusion of 10 to 20 mg/kg/hr. In patients with serious cholinergic intoxication, a continuous infusion of 10 to 20 mg/kg/hr up to 500 mg/hr should be considered.
F) SEIZURES
  • 1) IV benzodiazepines are indicated for seizures or agitation, diazepam 5 to 10 mg IV, lorazepam 2 to 4 mg IV; repeat as needed.
G) HYPOTENSIVE EPISODE
  • 1) IV fluids, dopamine, norepinephrine.
H) BRONCHOSPASM
  • 1) Inhaled ipratropium or glycopyrrolate may be useful in addition to intravenous atropine.
I) PATIENT DISPOSITION
  • 1) HOME CRITERIA: Patients with unintentional trivial exposures who are asymptomatic can be observed in the home or in the workplace.
  • 2) OBSERVATION CRITERIA: Patients with deliberate or significant exposure and those who are symptomatic should be sent to a health care facility for evaluation, treatment and observation for 6 to 12 hours. Onset of toxicity is variable; most patients will develop symptoms within 6 hours. Patients that remain asymptomatic 12 hours after an ingestion or a dermal exposure are unlikely to develop severe toxicity. However, highly lipophilic agents (like fenthion) can produce initially subtle effects followed by progressive weakness including respiratory failure. Cholinesterase activity should be determined to confirm the degree of exposure.
  • 3) ADMISSION CRITERIA: All intentional ingestions should be initially managed as a severe exposure. Determine cholinesterase activity to assess if a significant exposure occurred. Patients who develop signs or symptoms of cholinergic toxicity (e.g. muscarinic, nicotinic OR central) should be admitted to an intensive care setting.
  • 4) CONSULT CRITERIA: Consult a medical toxicologist and/or poison center for assistance with any patient with moderate to severe cholinergic manifestations.
J) PITFALLS
  • 1) Inadequate initial atropinization. Patients with severe toxicity require rapid administration of large doses, titrate to the endpoint or drying pulmonary secretions.
  • 2) Monitor respiratory function closely, pulmonary function testing may provide early clues to the development of respiratory failure.
  • 3) Some component of dermal exposure occurs with most significant overdoses, inadequate decontamination may worsen toxicity.
  • 4) Patients should be monitored closely for 48 hours after discontinuation of atropine and pralidoxime for evidence of recurrent toxicity or intermediate syndrome.
K) TOXICOKINETICS
  • 1) Well absorbed across the lung, mucous membranes (including gut), and skin; significant toxicity has been reported after all these routes of exposure.
  • 2) Most patients who develop severe toxicity have signs and symptoms within 6 hours of exposure, onset of toxicity is rarely more than 12 hours after exposure. Highly lipophilic organophosphates (e.g. fenthion) may produce subtle early toxicity that can progress to severe weakness/respiratory failure over many hours.
  • 3) Recurrence of toxicity after apparent improvement has been described.
  • 4) Some organophosphates undergo "ageing", a process by which the bond of the organophosphate to acetylcholinesterase becomes stronger, and cannot be reversed readily by oximes. Early oxime administration may prevent aging and shorten clinical manifestations of toxicity.
L) PREDISPOSING CONDITIONS
  • 1) Patients with chronic occupational exposure to organophosphates may have chronically depressed cholinesterase activity and may develop severe toxicity after smaller acute exposures.
  • 2) Dermal absorption is enhanced in young children due to larger surface area to volume ratio and more permeable skin.
M) DIFFERENTIAL DIAGNOSIS
  • 1) Gastroenteritis, food poisoning, asthma, myasthenic crisis, cholinergic excess from medications.
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