TPR Podcast Episode #14: VX and the Assassination of Kim Jong-Nam

Podcast – The Poison Review

On February 13, 2017 Kim Jong Nam — half-brother to North Korean leader Kim Jong Un — was attacked by two women in Malaysia’s Kuala Lumpur International airport. The attacks smeared some substance on his face. Within 10 or 15 minutes Mr. Kim collapsed in the airport medical clinic and died apparently in the ambulance on way to hospital.

Days later, Malaysian authorities announced that the nerve agent VX was detected in samples taken from Mr. Kim’s face.

Security camera footage from the airport showing the attack on Mr. Kim and its aftermath can be viewed here. In the video, the attack can be seen at 0:29. Shortly after this (0:42,) Mr. Kim can be seen talking with security personnel and describing the attack. He does not seem to be symptomatic or impaired at that point. At 1:08, Mr. Kim is walking to the airport medical clinic. His walk is somewhat stiff-legged but not, to my eyes, ataxic. At 1:14 he enters the clinic, and there are hints he might be having some problems with vision at that point. There is a jump cut, and staff is seen treating him after he collapsed. According to reports, the time from the attack to when Mr. Kim lost consciousness was 10 or 15 minutes. It was reported that his death was “very painful.”

Although some toxicologists questioned whether the circumstances surrounding Mr. Kim’s death really was consistent with VX poisoning, the presenting symptoms seem similar to those described in a previous attack, as reported by Japan Times.

VX is an acetylcholinesterase inhibitor. Acetylcholinesterase is an enzyme that breaks down and deactivates the neurotransmitter acetylcholine. It is the crucial “off switch,” without which the actions of acetylcholine would explode dangerously out of control.

I like to think of nerve agents — which have the same basic mechanism as organophosphate insecticides — in terms of threes. There are three main types of action, and three separate antidotes:

• Muscarinic actions: Muscarinic acetylcholine receptors are found where nerves connect to secretory glands and to smooth (involuntary) muscle. The mnemonic for the muscarinic actions of acetylcholine is SLUGBAM:

Salivation

Lacrimation

Urination

Gastrointestinal emptying (vomiting and diarrhea)

Bronchorrhea and bronchospasm (the “Killer Bs”)

Abdominal distress

Miosis

• Nicotinic Actions – Nicotinic cholinergic receptors are found in the

neuromuscular junction and some ganglia. Nicotinic effects include voluntary muscle fasciculations and hyperactivity, followed eventually by flaccid paralysis.

• Central Actions: Acetylcholine is an important neurotransmitter in the

cerebrum and brainstem. Uncontrolled agonism at these receptors causes loss of consciousness and seizures.

The most important clinical manifestations of nerve agent poisoning — certainly initially – are bronchorrhea and bronchospasm. In fact, these are so important they’re called the “Killer Bs.” When victims of nerve agent exposure die, they suffer a respiratory death. Basically they suffocate, drowning in uncontrolled respiratory tract secretions on top of bronchospasm. In addition, from the nicotinic effects the voluntary muscles of respiration are impaired, as is the central impulse to breath.

Just as there are 3 different effects of the nerve agents, there are 3 antidotes:

• Muscarinic effects: the antidote is the antimuscarinic drug atropine.
• Nicotinic effects: the antidote is pralidoxime (2-PAM)
• Central effects: the antidote is a benzodiazepine (usually diazepam or midazolam.)

Because of severe bronchorrhea and bronchospasm, it might be impossible to ventilate a victim exposed to nerve agent unless antidote is administered first. The most important antidote initially is atropine, given in whatever dose is needed to dry up secretions, relax the bronchial muscles, and allow ventilation and oxygenation.

One vexing question concerns why the attackers of Kim Jong Nam — or bystanders or medical personnel at the airport — were not seriously affected by the nerve agent. There are several possible explanations. The G-type nerve agents — GA (tabun,) GB (sarin,) and GD (soman) — have the consistency of water and vaporize readily. Thus they are a vapor threat and can quickly affect a large number of people in an enclosed space. VX, on the other hand, is viscous and has the consistency of motor oil. It does not vaporize readily and is mainly a danger from direct dermal contact. Apparently the assassins decontaminated their skin by washing immediately after the attack. There has also been speculation that they may have used a binary weapon — two chemicals, each harmless on its own that react to form VX when combined.

This film clip from the History Channel is fairly informative, although some statements such as “There are no confirmed cases of VX being used on people” are clearly outdated:

Key articles about VX and other nerve agents:

The Tokyo Subway Sarin Attack: Disaster Management, Part 1: Community Emergency Response. Okumura T et al. Acad Emerg Med 1998 Jun;5:613-617.

The Tokyo Subway Sarin Attack: Disaster Management, Part 2: Hospital Response. Okumura T et al. Acad Emerg Med 1998 Jun;5:618-624.

The Tokyo Subway Sarin Attack: Lessons Learned. Okumura T et al. Toxicol Appl Pharmacol 2005 Sep 1;207(2 Suppl):471-6

Emergency Management of Chemical Weapons Injuries. Anderson PD. J Pharm Practice 2012;25:61-68.

Nerve Agents. Newmark J. Neurol Clin 2005 May;23:623-41.

Therapy for Nerve Agent Poisoning. Newmark J. Arch Neurol 2004 May;61:648-652.

Clinical Manifestations of Sarin Nerve Gas Exposure. Lee Ec. JAMA 2003 Aug;290:659-62.

Link to: CDC CHEMPACK program

Quizzler

Last episode’s Quizzler was: Name the tox-related, novel way used to put out fires in the Churchill War Rooms in London during World War II.

Answer: Asbestos Blankets

Asbestos blanket in the Churchill War Rooms {Photo by Steve Aks)

This was an unusually difficult Quizzler, and no one submitted a correct answer. Therefore, the prize for this episode’s Quizzler will be increased to a $25 Amazon gift certificate plus choice of a TPR t-shirt or hoodie (large.) The Quizzler is announced at the end of this podcast. Answers should be submitted to [e-mail]. Deadline is midnight (Chicago time), April 14, 2017. The winner will be selected in a random drawing of all correct answers received by the deadline. Good luck!