Clinical Effects
USES: Used for pest control in industrial agriculture, to control ectoparasites on farm and companion animals and humans (head lice), and for home and garden pest control. TOXICOLOGY: Competitively inhibits pseudocholinesterase and acetylcholinesterase, preventing hydrolysis and inactivation of acetylcholine. Acetylcholine accumulates at nerve junctions, causing malfunction of the sympathetic, parasympathetic, and peripheral nervous systems and some of the CNS. Clinical signs of cholinergic excess develop. EPIDEMIOLOGY: Exposure is common, but serious toxicity is unusual in the US. Common source of severe poisoning in developing countries. MILD TO MODERATE POISONING: MUSCARINIC EFFECTS: Can include bradycardia, salivation, lacrimation, diaphoresis, vomiting, diarrhea, urination, and miosis. NICOTINIC EFFECTS: Tachycardia, hypertension, mydriasis, and muscle cramps. SEVERE POISONING: MUSCARINIC EFFECTS: Bronchorrhea, bronchospasm, acute lung injury. NICOTINIC EFFECTS: Muscle fasciculations, weakness, respiratory failure. CENTRAL EFFECTS: CNS depression, agitation, confusion, delirium, coma, seizures. Hypotension, ventricular dysrhythmias, metabolic acidosis, pancreatitis, and hyperglycemia also develop. DELAYED EFFECTS: Intermediate syndrome is characterized by paralysis of respiratory, cranial motor, neck flexor, and proximal limb muscles 1 to 4 days after apparent recovery from cholinergic toxicity, and prior to development of delayed peripheral neuropathy. Manifestations can include inability to lift the neck or sit up, ophthalmoparesis, slow eye movements, facial weakness, difficulty swallowing, limb weakness (primarily proximal), areflexia, respiratory paralysis. Recovery begins 5 to 15 days after onset. Distal sensory-motor polyneuropathy may rarely develop 6 to 21 days following exposure to some organophosphate compounds. Characterized by burning or tingling followed by weakness beginning in the legs which then spreads proximally. In severe cases may result in spasticity or flaccidity. Recovery requires months and may not be complete. CHILDREN: May have different predominant signs and symptoms than adults (more likely CNS depression, stupor, coma, flaccidity, dyspnea, and seizures). Children may also have fewer muscarinic and nicotinic signs of intoxication (ie, secretions, bradycardia, fasciculations and miosis) as compared to adults. INHALATION EXPOSURE: Organophosphate vapors rapidly produce mucous membrane and upper airway irritation and bronchospasm, followed by systemic muscarinic, nicotinic and central effects if exposed to significant concentrations.
Treatment
Support: MANAGEMENT OF MILD TOXICITY: 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. MANAGEMENT OF MODERATE TO SEVERE TOXICITY: Immediate assessment and evaluation. Airway management is likely to be necessary. Simple decontamination (i.e. dermal and gastrointestinal, removal of contaminated clothes). ANTIDOTES: Administer 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.
Decontamination: INGESTION: Activated charcoal, gastric lavage or nasogastric tube aspiration of gastric contents after recent large ingestion if patient intubated or able to protect airway. Ipecac contraindicated. DERMAL: Remove contaminated clothing. Copious soap and water wash. Avoid contamination of personnel. OCULAR: Copious irrigation. UNIVERSAL PRECAUTIONS should be followed by all staff members caring for the patient; nitrile gloves are suggested.
Airway management: 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.
Antidote: There are three primary classes of antidotes: ATROPINE (muscarinic antagonist); OXIMES (pralidoxime in the US, or obidoxime in some other countries) to reverse neuromuscular blockade. Use of oximes is usually indicated for patients with moderate to severe toxicity. BENZODIAZEPINES are indicated for agitation and seizures. PREHOSPITAL TREATMENT: AUTOINJECTORS: 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. MARK 1 (Meridian Medical Technologies, Columbia, MD) is used by the US military and the autoinjector delivers 2 milligrams atropine/0.7 milliliter and 600 milligrams pralidoxime chloride/2 milliliters into two separate devices for intramuscular use.
Atropine: 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 administering 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.
Pralidoxime: Administer for nicotinic effects (e.g. weakness, fasciculations, respiratory failure), generally given to any patient requiring atropine therapy. ADULT: 2 grams IV loading dose over 20 minutes followed by infusion of 500 to 1000 mg/hr; CHILD: 25 to 50 mg/kg (2 g maximum) loading dose diluted to 5% concentration in NS infuse over 15 to 30 minutes, followed by infusion of 10 to 20 mg/kg/hr. Oximes can usually be stopped 12 hours after atropine is stopped or if butyrylcholinesterase (plasma cholinesterase) is increasing.
Seizure: IV benzodiazepines are indicated for seizures or agitation, diazepam 5 to 10 mg IV, lorazepam 2 to 4 mg IV, repeat as needed.
Hypotensive episode: IV fluids, dopamine, norepinephrine.
Bronchospasm: Inhaled ipratropium or glycopyrrolate may be useful in addition to intravenous atropine.
Drug interaction: Avoid the use of depolarizing neuromuscular blockers (succinylcholine) as prolonged paralysis may develop.
Monitoring of patient: Cardiac monitoring, pulse oximetry, obtain plasma and red cell cholinesterase levels. Monitor clinical exam for evidence of muscarinic (e.g. bronchospasm, bronchorrhea, salivation, lacrimation, defecation, urination, miosis) nicotinic (e.g. muscle weakness or fasciculations, respiratory insufficiency) or CNS (e.g. seizures, coma) manifestations of cholinergic toxicity. Monitor pulmonary function (FVC, FEV1, NIF) in symptomatic patients (may help anticipate need for intubation). Monitor serial ECGs, serum electrolytes and lipase in symptomatic patients.
Patient disposition: 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. 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 (muscarinic, nicotinic or central) should be admitted to an intensive care setting. CONSULT CRITERIA: Consult a medical toxicologist or poison center for assistance with any patient with moderate to severe cholinergic manifestations.
Range Of Toxicity
TOXICITY: Organophosphates are absorbed across the lung, mucous membranes (including gut), and skin. Poisoning depends upon inherent toxicity, dosage, rate of absorption, rate of metabolic breakdown, and prior exposure to other cholinesterase inhibitors.
USES: Used for pest control in industrial agriculture, to control ectoparasites on farm and companion animals and humans (head lice), and for home and garden pest control. TOXICOLOGY: Competitively inhibits pseudocholinesterase and acetylcholinesterase, preventing hydrolysis and inactivation of acetylcholine. Acetylcholine accumulates at nerve junctions, causing malfunction of the sympathetic, parasympathetic, and peripheral nervous systems and some of the CNS. Clinical signs of cholinergic excess develop. EPIDEMIOLOGY: Exposure is common, but serious toxicity is unusual in the US. Common source of severe poisoning in developing countries. MILD TO MODERATE POISONING: MUSCARINIC EFFECTS: Can include bradycardia, salivation, lacrimation, diaphoresis, vomiting, diarrhea, urination, and miosis. NICOTINIC EFFECTS: Tachycardia, hypertension, mydriasis, and muscle cramps. SEVERE POISONING: MUSCARINIC EFFECTS: Bronchorrhea, bronchospasm, acute lung injury. NICOTINIC EFFECTS: Muscle fasciculations, weakness, respiratory failure. CENTRAL EFFECTS: CNS depression, agitation, confusion, delirium, coma, seizures. Hypotension, ventricular dysrhythmias, metabolic acidosis, pancreatitis, and hyperglycemia also develop. DELAYED EFFECTS: Intermediate syndrome is characterized by paralysis of respiratory, cranial motor, neck flexor, and proximal limb muscles 1 to 4 days after apparent recovery from cholinergic toxicity, and prior to development of delayed peripheral neuropathy. Manifestations can include inability to lift the neck or sit up, ophthalmoparesis, slow eye movements, facial weakness, difficulty swallowing, limb weakness (primarily proximal), areflexia, respiratory paralysis. Recovery begins 5 to 15 days after onset. Distal sensory-motor polyneuropathy may rarely develop 6 to 21 days following exposure to some organophosphate compounds. Characterized by burning or tingling followed by weakness beginning in the legs which then spreads proximally. In severe cases may result in spasticity or flaccidity. Recovery requires months and may not be complete. CHILDREN: May have different predominant signs and symptoms than adults (more likely CNS depression, stupor, coma, flaccidity, dyspnea, and seizures). Children may also have fewer muscarinic and nicotinic signs of intoxication (ie, secretions, bradycardia, fasciculations and miosis) as compared to adults. INHALATION EXPOSURE: Organophosphate vapors rapidly produce mucous membrane and upper airway irritation and bronchospasm, followed by systemic muscarinic, nicotinic and central effects if exposed to significant concentrations.
Treatment
Support: MANAGEMENT OF MILD TOXICITY: 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. MANAGEMENT OF MODERATE TO SEVERE TOXICITY: Immediate assessment and evaluation. Airway management is likely to be necessary. Simple decontamination (i.e. dermal and gastrointestinal, removal of contaminated clothes). ANTIDOTES: Administer 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.
Decontamination: INGESTION: Activated charcoal, gastric lavage or nasogastric tube aspiration of gastric contents after recent large ingestion if patient intubated or able to protect airway. Ipecac contraindicated. DERMAL: Remove contaminated clothing. Copious soap and water wash. Avoid contamination of personnel. OCULAR: Copious irrigation. UNIVERSAL PRECAUTIONS should be followed by all staff members caring for the patient; nitrile gloves are suggested.
Airway management: 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.
Antidote: There are three primary classes of antidotes: ATROPINE (muscarinic antagonist); OXIMES (pralidoxime in the US, or obidoxime in some other countries) to reverse neuromuscular blockade. Use of oximes is usually indicated for patients with moderate to severe toxicity. BENZODIAZEPINES are indicated for agitation and seizures. PREHOSPITAL TREATMENT: AUTOINJECTORS: 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. MARK 1 (Meridian Medical Technologies, Columbia, MD) is used by the US military and the autoinjector delivers 2 milligrams atropine/0.7 milliliter and 600 milligrams pralidoxime chloride/2 milliliters into two separate devices for intramuscular use.
Atropine: 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 administering 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.
Pralidoxime: Administer for nicotinic effects (e.g. weakness, fasciculations, respiratory failure), generally given to any patient requiring atropine therapy. ADULT: 2 grams IV loading dose over 20 minutes followed by infusion of 500 to 1000 mg/hr; CHILD: 25 to 50 mg/kg (2 g maximum) loading dose diluted to 5% concentration in NS infuse over 15 to 30 minutes, followed by infusion of 10 to 20 mg/kg/hr. Oximes can usually be stopped 12 hours after atropine is stopped or if butyrylcholinesterase (plasma cholinesterase) is increasing.
Seizure: IV benzodiazepines are indicated for seizures or agitation, diazepam 5 to 10 mg IV, lorazepam 2 to 4 mg IV, repeat as needed.
Hypotensive episode: IV fluids, dopamine, norepinephrine.
Bronchospasm: Inhaled ipratropium or glycopyrrolate may be useful in addition to intravenous atropine.
Drug interaction: Avoid the use of depolarizing neuromuscular blockers (succinylcholine) as prolonged paralysis may develop.
Monitoring of patient: Cardiac monitoring, pulse oximetry, obtain plasma and red cell cholinesterase levels. Monitor clinical exam for evidence of muscarinic (e.g. bronchospasm, bronchorrhea, salivation, lacrimation, defecation, urination, miosis) nicotinic (e.g. muscle weakness or fasciculations, respiratory insufficiency) or CNS (e.g. seizures, coma) manifestations of cholinergic toxicity. Monitor pulmonary function (FVC, FEV1, NIF) in symptomatic patients (may help anticipate need for intubation). Monitor serial ECGs, serum electrolytes and lipase in symptomatic patients.
Patient disposition: 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. 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 (muscarinic, nicotinic or central) should be admitted to an intensive care setting. CONSULT CRITERIA: Consult a medical toxicologist or poison center for assistance with any patient with moderate to severe cholinergic manifestations.
Range Of Toxicity
TOXICITY: Organophosphates are absorbed across the lung, mucous membranes (including gut), and skin. Poisoning depends upon inherent toxicity, dosage, rate of absorption, rate of metabolic breakdown, and prior exposure to other cholinesterase inhibitors.
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