*Thanks to Dr. Clark Owyang for following this “case” with me!
On February 13, Kim Jong-un, son of Kim Jong-il and half-brother of current North Korean leader Kim Jong-un, was poisoned at Kuala Lumpur airport in Malaysia. He died shortly after. Yesterday, the Malaysian police reported that Kim Jong-nam died of exposure to VX gas.
The UK first synthesized VX gas in 1952 in the UK, and then gave it to the U.S. for military development. It is an organic phosphorous compound, and the most potent nerve gas ever developed. The aerosolized dose causing mortality in 50% of humans (LD50) is only 10 mg/minute/m3. Because of its low volatility, it poses a higher risk for dermal exposure than respiratory exposure. Via this dermal route, death generally occurs within several hours.
VX is an acetylcholinesterase inhibitor, meaning that it prevents degradation of acetylcholine bound at the neuromuscular junction. It works at muscarinic, nicotinic, and central receptors. Muscarinic effects include the SLUDGE symptoms we all know: salivation, lacrimation, urination, defecation, GI cramping, and emesis. Nicotinic effects include muscle fasciculations, weakness, and paralysis. Centrally, this agent may cause seizures (prior to the flaccid paralysis caused by nicotinic activation) and respiratory depression.
In an aerosol exposure, the eyes are affected first. Symptoms include miosis (due to direct contact of nerve gas with the eye), blurring of vision, and ciliary spasm that causes eye pain. Next, the patient may experience rhinorrhea, increased airway secretions, and bronchial constrictions.
Self-protection is of the utmost importance. Don your own protective equipment before treating patients. The first treatment step is always decontamination. Clothing exposed to nerve gas may continue to release the toxic agent in fumes. Remove all the patient’s clothing and place it in an airtight receptacle. Next, the patient should be showered. Consider using a solution that releases chlorine, like household bleach or other alkaline substances. These substances hydrolyze and inactivate nerve gas. To make bleach application safe for skin, dilute household bleach in water to make a 1:10 solution. If bleach or an alkaline substance cannot be obtained rapidly, regular soap and water should be used.
Both the muscarinic and nicotinic effects of nerve gas must be addressed. Atropine is an anticholinergic, and should be used to reverse muscarinic symptoms. The standard dose determined by the military is 2mg, but severely poisoned adults should get a first dose of 5-6 mg. Titrate atropine to effect. The endpoint is drying of bronchial secretions. Tachycardia is expected. Do not stop administering atropine to a tachycardic patient who is still experiencing bronchial secretions.
Pralidoxime chloride (pyridine-2-aldoxime, or 2-PAM) reverses the nicotinic (i.e. neuromuscular) effects of nerve gas. It re-activates acetylcholinesterase. If “aging” (i.e. irreversible dealkylation) of the nerve gas-acetylcholinesterase has already occurred, 2-PAM won’t work. VX has an aging half-life of 48 hours.
- Paddock RC, Sang-hun C. Kim Jong-nam was killed by VX nerve agent, Malaysians say. In: The New York Times. 23 February, 2017.
- Hoffman RS, Howland MA, Lewin NA, Nelson L, Goldfrank L. 132: Chemical weapons. In: Goldfrank’s Toxicologic Emergencies. 10th
- Joosen MJ, van den Berg RM, de Jong AL, et al. The impact of skin decontamination on the time window for effective treatment of percutaneous VX exposure. Chem Biol Interact. 2016;20009-2797(16):30030-8.
- Thiermann H, Worek F, Kehe K. Limitations and challenges in treatment of acute chemical warfare agent poisoning. Chem Biol Interact. 2013;206(3):435-43.