Anticholinesterase Poisoning: Rx

Organophosphate compounds are used as commercial insecticides (isulfoton, phorate, dimethoate, ciodrin, dichlorvos, dioxathion, ruelene, carbophenothion, supona, tepp, epn, hetp, parathion, malathion, ronnel, coumaphos, diazinon, trichlorfon, paraoxon, potasan, dimefox, mipafox, schradan, sevin, and dimetonor) in chemical warfare (nerve gases such as tabun and sarin) and are applied as aerosols or dusts. They can be rapidly absorbed through skin and mucous membranes or by inhalation.

Organophosphates are also used in ophthalmology – echothiopate is used to treat glaucoma.

Organophosphate mechanism of toxicity:

• Acetylcholinesterase inhibitors that form a stable irreversible covalent bond to the enzyme.
• Occurs at cholinergic junctions of the nervous system including postganglionic parasympathetic junctions (sites of muscarinic activity), autonomic ganglia and the neuromuscular junctions (sites of nicotinic activity) and certain synapses in the CNS.
• Acetylcholine is the neurohumoral mediator at the cholinergic junctions. Since acetylcholinesterase is the enzyme that degrades acetylcholine following stimulation of a nerve, by inhibiting acetylcholinesterase, organophosphates allows acetylcholine to accumulate and result in initial excessive stimulation followed by depression.

Signs and Symptoms

Muscarinic signs

(SLUDGE) salivation, lacrimation, urination, diaphoresis, gastrointestinal upset, emesis and progressing to bronchospasm, bronchorrhea, blurred vision, bradycardia or tachycardia, hypotension, confusion, and shock.

Nicotinic effects

Skeletal muscle initially exhibits fasciculation (involuntary irregular, violent muscle contractions) followed by the inability to repolarize cell membranes resulting in weakness and paralysis. Severe reactions can lead to ventilatory failure and death (cholinergic crisis).

Treatment

Termination of the exposure including removing all soiled clothing. Gently cleanse with soap and water to hydrolyze organophosphate solutions.

Airway control and adequate oxygenation. Intubation may be necessary in cases of respiratory distress due to laryngospasm, bronchospasm, bronchorrhea, or seizures. Immediate aggressive use of atropine may eliminate the need for intubation. Succinylcholine should be avoided because it is degraded by AChE and may result in prolonged paralysis.

Continuous cardiac monitoring and pulse oximetry should be established; an ECG should be performed. Torsades de Pointes should be treated in the standard manner. The use of intravenous magnesium sulfate has been reported as beneficial for organophosphate toxicity. The mechanism of action may involve acetylcholine antagonism or ventricular membrane stabilization.

Irrigate the eyes of patients who have had ocular exposure using isotonic sodium chloride solution or lactated Ringer’s solution. Morgan lenses can be used for eye irrigation.

Pharmacologic Treatment

• Atropine – The endpoint for atropine is dried pulmonary secretions and adequate oxygenation. Tachycardia and mydriasis must not be used to limit or to stop subsequent doses of atropine. The main concern with OP toxicity is respiratory failure from excessive airway secretions. Start with a 1-2 mg IV bolus, repeat q3-5min prn for desire effects (drying of pulmonary secretions and adequate oxygenation). Consider doubling each subsequent dose for rapid control of patients in severe respiratory distress. An atropine drip titrated to the above endpoints can be initiated until the patient’s condition is stabilized.
• Pralidoxime – Nucleophilic agent that reactivates the phosphorylated AChE by binding to the OP molecule. Used as an antidote to reverse muscle paralysis resulting from OP AChE pesticide poisoning but is not effective once the OP compound has bound AChE irreversibly (aged). Current recommendation is administration within 48 h of OP poisoning. Because it does not significantly relieve depression of respiratory center or decrease muscarinic effects of AChE poisoning, administer atropine concomitantly to block these effects of OP poisoning. Start with 1-2 g (20-40 mg/kg) IV in 100 mL isotonic sodium chloride over 15-30 min; repeat in 1 h if muscle weakness is not relieved; then repeat q3-8h if signs of poisoning recur; other dosing regimens have been used, including continuous drip.

Acetylecholinesterate Poisoning: Treatment

• Remove clothing and wash skin with soap and water
• Airway management (secretions are the main issue), avoid SCh (degraded by AChE)
• Atropine (titrated to dried secretions, not HR) and pralidoxime (reactivates AChE)