The pictured autoinjector is a MARK-1 kit containing 2 mg of atropine and 600 mg of pralidoxime. This kit has historically been issued to US service members for treating nerve agent toxicity from agents such as soman, sarin, tabun, and VX, all of which are organophosphates and cause a cholinergic toxidrome. The MARK-1 autoinjector kit has been replaced by the Nerve Agent Antidote Kit (NAAK), or DuoDote™, which contains both atropine and pralidoxime in one single injection [1, 2].
What are nerve agents? [1-3]
Nerve agents inhibit acetylcholinesterase (AChE) and lead to a cholinergic crisis.
They were first developed in the 1950s by the Nazis and were used in chemical warfare in the Iran-Iraq War in the 1980s, by the Japanese Aum Shinrikyo cult in Tokyo, and in Syria in the 2010’s.
The early “G series” agents such as soman, sarin, and tabun exist mostly in a vapor form.
Newer “V series” agents such as VX, VR, and Novichok are less volatile and exist in liquid or powder form. They have been used in Europe recently for assassinations .
What are the symptoms of nerve agent poisoning? [1, 5]
Muscarinic symptoms (Common acronyms SLUDGE or DUMBBELLS)
Salivation, emesis, diarrhea, and lacrimation
Bradycardia, bronchospasm, and bronchorrhea are usually the cause of death.
Fasciculations -> muscle weakness -> paralysis
The onset and progression of symptoms differ based on route of exposure and concentration however is typically rapid within seconds to minutes. Because of rapid progression, typical symptoms of industrial organophosphate poisoning may not be seen. Death may occur within minutes of exposure without rapid treatment.
Notably with Novichok, symptom onset can be delayed for days .
What is the treatment for nerve agent toxicity? [1, 3, 5]
Decontamination with removal of contaminated clothing and washing with soap and water.
Atropine is given to counteract the muscarinic effects of cholinergic crisis, most importantly the bronchorrhea and bronchospasm.
Give 1-3 mg IV every 5 minutes until breathing improves and secretions decrease.
Total average dose for severe cases is 20-30 mg.
Pralidoxime acts as an antidote, preventing the nerve agent from permanently binding to AChE.
Pralidoxime must be given minutes to hours after nerve agent exposure because the AChE-nerve agent complex “ages”. The time to aging is unique for each nerve agent.
Give 600 mg IM every 5 min prehospital or 1-2 g loading dose IV in hospital with optional repeat bolus after 1 hour or continuous infusion.
Use benzodiazepines such as diazepam or midazolam for seizures.
Provide supportive care.
The patient will likely require intubation. Note that succinylcholine is contraindicated as it is metabolized by plasma pseudocholinesterase.
Even with rapid treatment, the mortality rate is high. Patients who survive initial exposure may require prolonged ventilator support and suffer numerous neurologic long-term sequelae.
Bedside Pearls for Nerve Agent Poisoning
Nerve agents such as sarin, soman, VX, and Novichok inhibit acetylcholinesterase and cause a cholinergic toxidrome similar to organophosphate pesticide poisoning.
Symptom onset is typically rapid and death is possible within minutes of exposure without prompt treatment, although it may be delayed with Novichok.
Decontamination is essential to prevent further exposure to patients and health care providers.
Treat with atropine, pralidoxime, benzodiazepines, and supportive care.