Organophosphate Poisoning

Introduction

• Organophosphates are potent chemical compounds composed of carbon and phosphorous acid derivatives.^1,2 They are commonly found in insecticides, herbicides, chemical warfare weapons, and certain medications.^1-3
• Excess exposure to organophosphates can lead to poisoning and toxic systemic symptoms.^1,2

Epidemiology and Sources of Exposure

• Organophosphate insecticides were developed in the mid-1800s and have been employed in agricultural production worldwide since the 1940s.^1,3
• In the United States, there are 37 different insecticides classified as organophosphates.^1,3
• Implementing strict chemical regulations and developing carbamate insecticides have led to a decrease in the incidence of organophosphate poisoning.¹
• The 2022 Annual Report of the National Poison Data System (NPDS) from America’s Poison Center found pesticides to be the 11th most frequently involved substance in human exposures.⁴
• Most cases of organophosphate poisoning in developing countries result from intentional ingestion of pesticides for self-harm.¹
• Sarin, VX, and Novichok are specific organophosphates that have been utilized as neurotoxic weapons.^1,2
• Organophosphates can be found in medicines, such as for the treatment of glaucoma (echothiophate) and myasthenia gravis (pyridostigmine, physostigmine).²

Pathophysiology

• Organophosphates are readily absorbed through the gastrointestinal tract, lungs, and skin.²
  They bind to and inhibit acetylcholinesterase, an enzyme responsible for the hydrolysis of acetylcholine to choline and acetic acid.²
• Inhibition of acetylcholinesterase results in the accumulation of acetylcholine, a neurotransmitter responsible for activating postsynaptic receptors and propagation of action potentials.¹
• Excess acetylcholine can lead to overstimulation of cholinergic receptors, of which there are nicotinic and muscarinic subtypes, resulting in a variety of toxic symptoms.¹ The parasympathetic nervous system is greatly affected as it is heavily regulated by nicotinic and muscarinic cholinergic receptors.²
• The onset and duration of organophosphate poisoning depends on the agents’ rate of enzyme inhibition, route of absorption, lipophilicity, and other characteristics.² Oral and respiratory routes of organophosphate absorption generally display rates of around 3 hours, while the dermal route may take up to 12 hours.² Delayed onset and prolonged symptoms are seen in lipophilic organophosphates as they are stored in adipose tissues.²

Clinical Presentation

• The toxic effects of organophosphates are the result of cholinergic excess in the parasympathetic nervous system, neuromuscular junction, and central nervous system.²
• Muscarinic signs of organophosphate poisoning include:
  • SLUDGE/BBB: Salivation, lacrimation, urination, defecation, gastric emesis, bronchorrhea, bronchospasm, bradycardia
  • DUMBELS: Defecation, urination, miosis, bronchorrhea/bronchospasm/bradycardia, emesis, lacrimation, salivation.²
• Organophosphate poisoning may present with transient tachycardia and mydriasis as sympathetic ganglia also contain nicotinic receptors.²
• Excess acetylcholine at the neuromuscular junction is responsible for nicotinic symptoms, including fasciculations, muscle weakness, and paralysis.²
• Symptoms of central respiratory depression, lethargy, seizures, and coma can be traced to the presence of cholinergic receptors in the brain.²
• Other acute symptoms of organophosphate poisoning may include anxiety, confusion, emotional lability, hallucinations, memory loss, and insomnia.¹
• Most fatal cases of organophosphate poisoning are due to respiratory failure as the result of bronchoconstriction, bronchorrhea, weakness of respiratory muscles, and central respiratory depression.^1,2

Diagnosis

• Diagnosis of organophosphate poisoning primarily relies on clinical signs and a history of possible exposure.² Miosis, diaphoresis, and respiratory distress are the most prevalent symptoms of organophosphate poisoning.¹ A peculiar garlic or petroleum odor emitted by certain organophosphates may assist in diagnosing poisoning.^1,2
• Measuring red blood cell acetylcholinesterase concentration is a powerful diagnostic tool, although it may not be readily available in many facilities.^1,2
• To further help in the diagnosis of organophosphate poisoning, a trial of 1 mg atropine in adults (or 0.01 to 0.02 mg/kg in children) may be administered.²
• The presence of improved symptoms following administration of atropine supports the diagnosis of organophosphate poisoning, but its absence does not exclude it.^1,2

Management

• Before assessing and treating a patient with suspected organophosphate poisoning, healthcare personnel should ensure the use of appropriate personal protective equipment to avoid contamination with the agent.^1,2
• If the patient is not in acute distress, decontamination of the patient should follow, including disposal of the patient’s clothes and repeated skin washes with soap and water.¹
• Patients should receive an intravenous catheter, cardiac monitoring, pulse oximetry, and respiratory support with 100 percent oxygen and intubation if necessary.^1,2
• If intubation is necessary, succinylcholine should be avoided as it cannot be metabolized in the setting of organophosphate poisoning and will lead to prolonged paralysis.^1,2
• Patients with suspected organophosphate poisoning should receive isotonic crystalloids for volume resuscitation.²
• The primary treatment for organophosphate poisoning is atropine, an antimuscarinic medication that competes with acetylcholine at muscarinic receptors.^1,2 Atropine should be administered intravenously at an initial dose of 2 to 5 mg for adults and 0.05 mg/kg for children.^1,2
• The dose of atropine should be doubled every 3 to 5 minutes until there is an absence of bronchoconstriction and respiratory secretions have decreased.¹ Additional signs of proper atropine administration include dry skin, dry mucosa, decreased bowel sounds, mydriasis, and tachycardia.¹
• After improvement with atropine by bolus, 10 to 20 percent of the cumulative bolus dose should be administered as an intravenous continuous infusion per hour.² The infusion rate of atropine is changed as needed to maintain proper response and slowly tapered until recovery.²
• An epinephrine infusion may be started on patients whose heart rate remains below 80 beats per minute or who remain hypotensive with a normal heart rate despite receiving high doses of atropine.²
• Another effective treatment used in organophosphate poisoning is an antidote, pralidoxime, which reactivates acetylcholinesterase and improves both muscarinic and nicotinic symptoms.^1,2 When using pralidoxime, it is important to note that it must be administered after administration of atropine to avoid worsening symptoms.^1,2
• Pralidoxime should be administered as an intravenous bolus at 30 mg/kg in adults and 25 to 50 mg/kg in children, followed by a continuous infusion at a rate of at least 8 mg/kg/h in adults and 10 to 20 mg/kg/h in children.^1,2 Pralidoxime should be administered over 30 minutes, as fast administration could lead to cardiac arrest.^1,2
• Serial measurements of red blood cell acetylcholinesterase concentrations can aid in the assessment of treatment efficacy.²
• If patients present with seizures, benzodiazepines should be administered.^1,2
• If patients present within 1 hour of organophosphate ingestion, 1 g/kg of activated charcoal may be administered.²

Prognosis

• Global mortality rates caused by organophosphate insecticides range from 2 to 25 percent.¹
• The Peradeniya Organophosphorus Poisoning scale assesses the clinical severity and prognosis of organophosphate poisoning by considering miosis, fasciculations, respiration, bradycardia, level of consciousness, and seizures.¹
• Higher Peradeniya Organophosphorus Poisoning scale scores are associated with increased mortality, need for ventilatory support, and atropine dosages.¹
• The Glasgow Coma Score can also be used to assess prognosis, where a score less than 13 is associated with poor outcomes.²