Today, we will be talking about organophosphate toxicity!
Introduction
Organophosphate poisonings occur in agricultural heavy communities. Each year, millions of individuals suffer from organophosphate poisoning, and hundreds of thousands succumb to its adverse effects.
Agricultural workers can encounter organophosphates through various routes, including inhalation, ingestion, injection, or skin absorption.
Furthermore, organophosphate poisonings can exist as nerve agents created for chemical warfare.
Depending on the dose and duration of exposure, sufficient amounts of organophosphates can trigger acute toxicity symptoms.
Mechanism of Action
Organophosphates inhibit acetylcholinesterase, causing acetylcholine buildup and overstimulation of nicotinic and muscarinic receptors, resulting in a cholinergic toxidrome. Sympathetic stimulation occurs, but the parasympathetic response dominates.
Organophosphates irreversibly bind to acetylcholinesterase, permanently inhibiting its activity through "aging." Aging forms covalent bonds between the agent and acetylcholinesterase and can take minutes to days, depending on the organophosphate. Once aging occurs, it takes weeks to synthesize enough acetylcholinesterase to alleviate symptoms.
Clinical Presentation (based on receptor effects)
· Nicotinic
o Mydriasis
o Tachycardia
o Weakness
o Hypertension
o Fasciculations
o Seizures
· Muscarinic – parasympathetic findings
o Acute poisoning (within 8 to 24 hours from exposure)
§ SLUDGE – Salivation, Lacrimation, Urination, Defecation, GI pain/cramping, Emesis
§ Killer Bs – Bradycardia, Bronchorrhea, Bronchospasm
o Intermediate syndrome
§ Occurs within 1 to 5 days after exposure in 40% of individuals
§ Characteristics
· Neck flexor muscle paralysis
· Proximal extremity muscle weakness
· Respiratory muscle weakness
o Can lead to respiratory failure
Diagnosis
The diagnosis of organophosphate poisoning is primarily clinical, relying on a thorough patient history, physical examination findings consistent with a cholinergic toxidrome, detection of a garlic-like or hydrocarbon odor on the patient, or the presence of neuromuscular dysfunction as described earlier.
Two assays can be used to confirm the diagnosis of organophosphate poisoning. Low cholinesterase activity levels are indicative of organophosphate poisoning. However, these assays are send-out tests with turnaround times that make them unlikely to influence emergency department management or treatment decisions.
Management
Prompt intervention is crucial when suspecting acute organophosphate poisoning. Laboratory testing, though valuable, may delay treatment and potentially worsen the patient's condition. The primary objective is to act quickly to prevent aging, alleviate respiratory distress caused by dry secretions, and avert potential cardiopulmonary collapse. Airway management should not be postponed. Intensive care unit (ICU) admission is often necessary
Decontamination and Appropriate Personal Protective Equipment (PPE)
To prevent ongoing exposure to the patient and emergency department (ED) staff, it is essential to follow proper decontamination procedures. In cases of dermal exposure, remove the patient's clothing and wash them thoroughly with soap and water. Dispose of contaminated clothing appropriately and wear PPE to prevent personal exposure.
Organophosphates have a tendency to adsorb onto leather goods such as shoes or belts. Therefore, these items should be discarded along with other hazardous waste and not returned to the patient.
Airway Management
Due to the high risk of respiratory failure, which is the most common cause of death in organophosphate poisoning, early airway management should be considered. This may be necessary due to a combination of hypoxemia, hypercarbia, and neuromuscular weakness resulting from uncontrolled bronchorrhea and bronchospasm.
Mainstay Pharmacologic Therapy
Atropine Sulfate
Atropine sulfate is a competitive antagonist of acetylcholine at muscarinic receptors. It is the primary antidote for organophosphate poisoning and works by blocking the effects of acetylcholine, the neurotransmitter that is overstimulated by organophosphates.
Dose
Adults: 1-2 mg IV (0.02-0.1 mg/kg pediatrics)
Double dose every 5 minutes
Titrate up to endpoint of therapy, which may require very large doses
Target Endpoint of Therapy
Administration
Once the goal is achieved, begin an infusion at 10-20% of the dose required to control secretions in mg/h.
Continue therapy until clinically resolved.
Pralidoxime (2-PAM)
Pralidoxime (2-PAM) is an oxime that reactivates inhibited acetylcholinesterase that has not undergone the aging process. It is another antidote for organophosphate poisoning and works by reversing the effects of organophosphates on the enzyme acetylcholinesterase.
Dosing
Loading dose: 30 mg/kg (max 2 g) IV in 100 mL 0.9% sodium chloride over 15-30 minutes
Maintenance infusion: 8 mg/kg/h (max 650 mg) IV
Alternate regimen: 1-2 g IV loading dose, then repeat in 1 hour, then continue 1-2 g IV q10-12h
Alternate regimen: 600 mg (15 mg/kg pediatric) IM, then repeat q15min for a total 1,800 mg
Administration
REFERENCE
Tintinalli, J. E. (2019). Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th Edition. McGraw-Hill Education. Section 15: Toxicology: 1301-1303.
Eddleston M, Chowdhury FR. Pharmacological treatment of organophosphorus insecticide poisoning: the old and the (possible) new. Br J Clin Pharmacol. 2016;81(3):462-470. doi:10.1111/bcp.12784
Cook Matt, Frey Aaron. Pesticides and Cholinergics. In: Mattu A and Swadron S, ed. CorePendium. Burbank, CA: CorePendium, LLC. https://www.emrap.org/corependium/chapter/recdvP3Xjhrp9vbC8/Pesticides-and-Cholinergics. Updated September 14, 2020. Accessed December 14, 2020.
