Usual Adult Dose for Organophosphate Poisoning

Intravenous dosing (preferred route of administration):
Initial dose: 1 to 2 g, preferably as an IV infusion in 100 mL of normal saline, over 15 to 30 minutes; if an infusion is not practical or if pulmonary edema is present, the dose should be given slowly (over at least 5 minutes) by IV injection as a 50 mg/mL solution in Sterile Water for Injection (e.g., 1000 mg in 20 mL)

Second dose: 1 to 2 g may be indicated after about 1 hour if muscle weakness has not been relieved

Additional doses may be given every 10 to 12 hours if muscle weakness persists.

Intramuscular dosing (based on severity of symptoms):
MILD SYMPTOMS:
Initial dose: 600 mg IM; recommend waiting 15 minutes for pralidoxime to take effect
Second dose: 600 mg IM if mild symptoms persist after 15 minutes
Third dose: 600 mg IM (cumulative dose of 1800 mg) if mild symptoms persist after an additional 15 minutes

If severe symptoms develop at any time after the first dose, 2 additional 600 mg IM doses in rapid succession should be administered for a total cumulative dose of 1800 mg.

SEVERE SYMPTOMS: Three 600 mg IM doses in rapid succession should be administered for a total cumulative dose of 1800 mg.

PERSISTENT SYMPTOMS: If symptoms persist after administration of the complete 1800 mg regimen, the series may be repeated starting about 1 hour after the administration of the last injection.

Comments:

• The principle indications for use of this drug are muscle weakness and respiratory depression; in severe poisoning, respiratory depression may be due to muscle weakness.
• Treatment should include general supportive care, atropine, and decontamination also.
• Treatment is most effective if initiated immediately after poisoning.
• Little is accomplished if this drug is given more than 36 hours after termination of exposure to the poison.
• When poison is ingested, take into account the likelihood of continuing absorption from the lower bowel as this constitutes new exposure and fatal relapses have occurred after initial improvement; additional doses may be needed every 3 to 8 hours in this situation.
• Keep the patient under observation for at least 48 to 72 hours.
• If dermal exposure occurred, remove clothing and wash skin and hair thoroughly with sodium bicarbonate or alcohol as soon as possible.
• Provide supportive care, including airway management, respiratory and cardiovascular support, correction of metabolic abnormalities, and seizure control as needed for severe poisoning.
• Give atropine as soon as possible after hypoxemia has improved; do not give atropine if significant hypoxia is present because of the risk of atropine induced ventricular fibrillation.
• Administer atropine intravenously at doses of 2 to 4 mg, repeated at 5 to 10 minute intervals until full atropinization (secretions are inhibited) or signs of atropine toxicity appear (delirium, hyperthermia, muscle twitching).
• Maintain some degree of atropinization for at least 48 hours and until any depressed blood cholinesterase activity is reversed.
• Avoid use of morphine, theophylline, aminophylline, reserpine, and phenothiazine-type tranquilizers in organophosphate poisoning patients.
• Use succinylcholine with caution as prolonged paralysis has been reported in combination with anticholinesterases.
• Administer this drug after the effects of atropine become apparent.

Use(s): Antidote for poisoning due to pesticides and chemicals (e.g. nerve agents) of the organophosphate class that have anticholinesterase activity

Usual Adult Dose for Nerve Agent Poisoning

Intravenous dosing (preferred route of administration):
Initial dose: 1 to 2 g, preferably as an IV infusion in 100 mL of normal saline, over 15 to 30 minutes; if an infusion is not practical or if pulmonary edema is present, the dose should be given slowly (over at least 5 minutes) by IV injection as a 50 mg/mL solution in Sterile Water for Injection (e.g., 1000 mg in 20 mL)

Second dose: 1 to 2 g may be indicated after about 1 hour if muscle weakness has not been relieved

Additional doses may be given every 10 to 12 hours if muscle weakness persists.

Intramuscular dosing (based on severity of symptoms):
MILD SYMPTOMS:
Initial dose: 600 mg IM; recommend waiting 15 minutes for pralidoxime to take effect
Second dose: 600 mg IM if mild symptoms persist after 15 minutes
Third dose: 600 mg IM (cumulative dose of 1800 mg) if mild symptoms persist after an additional 15 minutes

If severe symptoms develop at any time after the first dose, 2 additional 600 mg IM doses in rapid succession should be administered for a total cumulative dose of 1800 mg.

SEVERE SYMPTOMS: Three 600 mg IM doses in rapid succession should be administered for a total cumulative dose of 1800 mg.

PERSISTENT SYMPTOMS: If symptoms persist after administration of the complete 1800 mg regimen, the series may be repeated starting about 1 hour after the administration of the last injection.

Comments:

• The principle indications for use of this drug are muscle weakness and respiratory depression; in severe poisoning, respiratory depression may be due to muscle weakness.
• Treatment should include general supportive care, atropine, and decontamination also.
• Treatment is most effective if initiated immediately after poisoning.
• Little is accomplished if this drug is given more than 36 hours after termination of exposure to the poison.
• When poison is ingested, take into account the likelihood of continuing absorption from the lower bowel as this constitutes new exposure and fatal relapses have occurred after initial improvement; additional doses may be needed every 3 to 8 hours in this situation.
• Keep the patient under observation for at least 48 to 72 hours.
• If dermal exposure occurred, remove clothing and wash skin and hair thoroughly with sodium bicarbonate or alcohol as soon as possible.
• Provide supportive care, including airway management, respiratory and cardiovascular support, correction of metabolic abnormalities, and seizure control as needed for severe poisoning.
• Give atropine as soon as possible after hypoxemia has improved; do not give atropine if significant hypoxia is present because of the risk of atropine induced ventricular fibrillation.
• Administer atropine intravenously at doses of 2 to 4 mg, repeated at 5 to 10 minute intervals until full atropinization (secretions are inhibited) or signs of atropine toxicity appear (delirium, hyperthermia, muscle twitching).
• Maintain some degree of atropinization for at least 48 hours and until any depressed blood cholinesterase activity is reversed.
• Avoid use of morphine, theophylline, aminophylline, reserpine, and phenothiazine-type tranquilizers in organophosphate poisoning patients.
• Use succinylcholine with caution as prolonged paralysis has been reported in combination with anticholinesterases.
• Administer this drug after the effects of atropine become apparent.

Use(s): Antidote for poisoning due to pesticides and chemicals (e.g. nerve agents) of the organophosphate class that have anticholinesterase activity

Usual Adult Dose for Anticholinesterase Overdose

Initial dose: 1 to 2 g IV slowly
Maintenance dose: Increments of 250 mg IV every 5 minutes as needed to control symptoms

• Solution should be diluted to 10 to 20 mg/mL

Comments:

• The principle indications for use of this drug are muscle weakness and respiratory depression; in severe poisoning, respiratory depression may be due to muscle weakness.

Use(s): Control of overdosage by anticholinesterase drugs such as neostigmine, pyridostigmine, and ambenonium, used in the treatment of myasthenia gravis

Usual Pediatric Dose for Organophosphate Poisoning

16 years and younger:

Intravenous administration (preferred method of administration):
LOADING DOSE FOLLOWED BY CONTINUOUS INFUSION
Loading dose: 20 to 50 mg/kg (maximum 2000 mg/dose) of a 10 to 20 mg/mL solution, intravenously over 15 to 30 minutes

• Follow with a continuous infusion of 10 to 20 mg/kg/hour

INTERMITTENT INFUSION
Initial dose: 20 to 50 mg/kg (maximum 2000 mg/dose) of a 10 to 20 mg/mL solution, intravenously over 15 to 30 minutes

• A second dose of 20 to 50 mg/kg may be indicated after about 1 hour if muscle weakness is not relieved.
• Repeat dosing every 10 to 12 hours as needed
• If the above dose is not practical or pulmonary edema is present, give dose diluted to a 50 mg/mL solution as a slow IV injection over at least 5 minutes
• A second 20 to 50 mg/kg dose may be given after about 1 hour if muscle weakness has not been relieved.
• Additional doses may be given every 10 to 12 hours if muscle weakness persists.

Intramuscular dosing (based on severity of symptoms):
Weight under 40 kg: 15 mg/kg per single dose; 45 mg/kg total (3 injection) dose
Weight 40 kg and above: 600 mg per single dose; 1800 mg total (3 injection) dose

MILD SYMPTOMS: Give weight appropriate dose (see above) intramuscularly; allow 15 minutes for drug to take effect

• If symptoms persist after 15 minutes, give a second dose; allow 15 minutes for drug to take effect.
• If mild symptoms persist, a third dose may be given.
• If severe symptoms develop any time after the first dose, administer two additional doses intramuscularly in rapid succession.

SEVERE SYMPTOMS: Administer three weight appropriate doses intramuscularly in rapid succession.

PERSISTENT SYMPTOMS:

• If symptoms persist after the complete regimen, the series may be repeated about 1 hour after administration of the last injection

Comments:

• The principle indications for use of this drug are muscle weakness and respiratory depression; in severe poisoning, respiratory depression may be due to muscle weakness.
• Treatment should include general supportive care, atropine, and decontamination also.
• Treatment is most effective if initiated immediately after poisoning.
• Little is accomplished if this drug is given more than 36 hours after termination of exposure to the poison.
• When poison is ingested, take into account the likelihood of continuing absorption from the lower bowel as this constitutes new exposure and fatal relapses have occurred after initial improvement; additional doses may be needed every 3 to 8 hours in this situation.
• Keep the patient under observation for at least 48 to 72 hours.
• If dermal exposure occurred, remove clothing and wash skin and hair thoroughly with sodium bicarbonate or alcohol as soon as possible.
• Provide supportive care, including airway management, respiratory and cardiovascular support, correction of metabolic abnormalities, and seizure control as needed for severe poisoning.
• Give atropine as soon as possible after hypoxemia has improved; do not give atropine if significant hypoxia is present because of the risk of atropine induced ventricular fibrillation.
• Administer atropine intravenously until full atropinization (secretions are inhibited) or signs of atropine toxicity appear (delirium, hyperthermia, muscle twitching).
• Maintain some degree of atropinization for at least 48 hours and until any depressed blood cholinesterase activity is reversed.
• Avoid use of morphine, theophylline, aminophylline, reserpine, and phenothiazine-type tranquilizers in organophosphate poisoning patients.
• Use succinylcholine with caution as prolonged paralysis has been reported in combination with anticholinesterases.
• Administer this drug after the effects of atropine become apparent.

Use(s): Antidote for poisoning due to pesticides and chemicals (e.g. nerve agents) of the organophosphate class that have anticholinesterase activity

Usual Pediatric Dose for Nerve Agent Poisoning

16 years and younger:

Intravenous administration (preferred method of administration):
LOADING DOSE FOLLOWED BY CONTINUOUS INFUSION
Loading dose: 20 to 50 mg/kg (maximum 2000 mg/dose) of a 10 to 20 mg/mL solution, intravenously over 15 to 30 minutes

• Follow with a continuous infusion of 10 to 20 mg/kg/hour

INTERMITTENT INFUSION
Initial dose: 20 to 50 mg/kg (maximum 2000 mg/dose) of a 10 to 20 mg/mL solution, intravenously over 15 to 30 minutes

• A second dose of 20 to 50 mg/kg may be indicated after about 1 hour if muscle weakness is not relieved.
• Repeat dosing every 10 to 12 hours as needed
• If the above dose is not practical or pulmonary edema is present, give dose diluted to a 50 mg/mL solution as a slow IV injection over at least 5 minutes
• A second 20 to 50 mg/kg dose may be given after about 1 hour if muscle weakness has not been relieved.
• Additional doses may be given every 10 to 12 hours if muscle weakness persists.

Intramuscular dosing (based on severity of symptoms):
Weight under 40 kg: 15 mg/kg per single dose; 45 mg/kg total (3 injection) dose
Weight 40 kg and above: 600 mg per single dose; 1800 mg total (3 injection) dose

MILD SYMPTOMS: Give weight appropriate dose (see above) intramuscularly; allow 15 minutes for drug to take effect

• If symptoms persist after 15 minutes, give a second dose; allow 15 minutes for drug to take effect.
• If mild symptoms persist, a third dose may be given.
• If severe symptoms develop any time after the first dose, administer two additional doses intramuscularly in rapid succession.

SEVERE SYMPTOMS: Administer three weight appropriate doses intramuscularly in rapid succession.

PERSISTENT SYMPTOMS:

• If symptoms persist after the complete regimen, the series may be repeated about 1 hour after administration of the last injection

Comments:

• The principle indications for use of this drug are muscle weakness and respiratory depression; in severe poisoning, respiratory depression may be due to muscle weakness.
• Treatment should include general supportive care, atropine, and decontamination also.
• Treatment is most effective if initiated immediately after poisoning.
• Little is accomplished if this drug is given more than 36 hours after termination of exposure to the poison.
• When poison is ingested, take into account the likelihood of continuing absorption from the lower bowel as this constitutes new exposure and fatal relapses have occurred after initial improvement; additional doses may be needed every 3 to 8 hours in this situation.
• Keep the patient under observation for at least 48 to 72 hours.
• If dermal exposure occurred, remove clothing and wash skin and hair thoroughly with sodium bicarbonate or alcohol as soon as possible.
• Provide supportive care, including airway management, respiratory and cardiovascular support, correction of metabolic abnormalities, and seizure control as needed for severe poisoning.
• Give atropine as soon as possible after hypoxemia has improved; do not give atropine if significant hypoxia is present because of the risk of atropine induced ventricular fibrillation.
• Administer atropine intravenously until full atropinization (secretions are inhibited) or signs of atropine toxicity appear (delirium, hyperthermia, muscle twitching).
• Maintain some degree of atropinization for at least 48 hours and until any depressed blood cholinesterase activity is reversed.
• Avoid use of morphine, theophylline, aminophylline, reserpine, and phenothiazine-type tranquilizers in organophosphate poisoning patients.
• Use succinylcholine with caution as prolonged paralysis has been reported in combination with anticholinesterases.
• Administer this drug after the effects of atropine become apparent.

Use(s): Antidote for poisoning due to pesticides and chemicals (e.g. nerve agents) of the organophosphate class that have anticholinesterase activity

Renal Dose Adjustments

Dose adjustment(s) may be required; however, no specific guidelines have been suggested.

Liver Dose Adjustments

Data not available

Precautions

CONTRAINDICATIONS:

• There are no absolute contraindications to use of this drug
• Relative contraindications include hypersensitivity to the drug and other situations where risk clearly outweighs benefit

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Administration should be done slowly, preferably by infusion.
• If intravenous administration is not feasible, use intramuscularly or subcutaneously.

General:

• Signs of nerve agent and insecticide poisoning:

MILD SYMPTOMS:

• Blurred vision and sore eyes
• Teary eyes (this symptom is less reliable in infants and young children)
• Runny nose (this symptom is less reliable in infants and young children)
• Increased salivation such as sudden drooling (this symptom is less reliable in infants and young children)
• Chest tightness or difficulty breathing
• Tremors throughout the body or muscular twitching
• Nausea and vomiting
• Involuntary respiratory secretions

SEVERE SYMPTOMS:

• Strange or confused behavior
• Severe difficulty breathing or respiratory secretions
• Severe muscular twitching and general weakness (infants may become drowsy or unconscious, with muscle floppiness rather than twitching)
• Involuntary urination and defecation (this symptom is less reliable in infants and young children)
• Convulsions
• Unconsciousness

Patient advice:
Administer only after:

• Individual has donned a mask after recognizing a chemical agent hazard in the area.
• Some or all of the below symptoms of nerve agent poisoning are present:
• Unexplained runny nose
• Tightness of chest with difficulty breathing
• Pinpointed pupils of the eye resulting in blurred vision
• Drooling, excessive sweating
• Nausea, vomiting, and abdominal cramps
• Involuntary urination and defecation
• Jerking, twitching, and staggering
• Headache, drowsiness, coma, convulsions
• Stoppage of breathing