Ep 150: Gas Exposure

This episode examines toxic gas exposures—how they present, how to recognize them, and the antidotes that can save lives.

Read more on this topic on AccessMedicine.

Harrison's Principles of Internal Medicine, 22nd Edition

Transcript

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[Ms. Heidhausen] This is Katerina Heidhausen, executive editor of Harrison's Principles of Internal Medicine. Harrison's Podclass is brought to you by McGraw Hill's AccessMedicine, the online medical resource that delivers the latest content from the best minds in medicine. And now, on to the episode. 

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[Dr. Handy] Hi, everyone. Welcome back to Harrison's Podclass. We're your co-hosts. I'm Dr. Cathy Handy. 

[Dr. Wiener] And I'm Dr. Charlie Wiener, and we're joining you from the Johns Hopkins School of Medicine. Welcome to today's episode, which is about an alert in the emergency department. 

[Dr. Handy] Sounds exciting. 

[Dr. Wiener] Cathy, here it goes. You're working in the emergency room of a large metropolitan hospital when you're alerted to a possible terrorist attack. Ten people that were all riding on the same bus are being transported immediately to your hospital. The EMTs report that a passenger boarded the bus, opened up a portable gas tank, and then ran away. Minutes later, the people on the bus reported eye burning and respiratory distress. On arrival to the emergency department, you don appropriate personal protective gear and examine your first patient who's reporting severe GI distress. He's a young man with notable bilateral pinpoint pupils, extensive secretions in the upper and lower airway with hypoxia. Minutes later, the patient vomits, seizes, and becomes apneic. You successfully endotracheal intubate him and place him on mechanical ventilation. 

[Dr. Handy] This is a nightmare scenario. Let's start with some history. The use of chemical warfare agents in modern warfare began in World War I, likely with the blistering agent sulfur mustard. Many mistakenly believe that mass chemical attacks will always be so severe that little can be done except to bury the dead. Thankfully, where we have data, that does not seem totally true. In World War I, even before the advent of modern ICU support, the mortality rate among US forces on the battlefield was under 2%, far lower than the 7% mortality rate from conventional wounds. More recently, among the 5,500 patients who sought medical attention at hospitals after the 1995 Tokyo subway sarin incident, 80% were not actually symptomatic, and only 12 died. It's important to be able to recognize the likely chemical agents in these attacks and be able to respond appropriately. 

[Dr. Wiener] What are the broad categories of chemical warfare agents? 

[Dr. Handy] The three most common are vesicant agents such as sulfur mustard, nerve agents such as sarin, and cyanide. The history of sulfur mustard and how it became our first cancer chemotherapy agent is beautifully articulated in the book, "The Emperor of All Maladies." 

[Dr. Wiener] Of those three, which do you think we're dealing with in today's case? 

[Dr. Handy] I think it's likely a nerve agent. 

[Dr. Wiener] Tell me why. 

[Dr. Handy] The nerve agents are organophosphates and are the most rapid-acting and toxic chemical weapon agents. They work by inhibition of tissue synaptic acetylcholinesterase, creating an acute cholinergic crisis. Death ensues because of respiratory depression and can occur within seconds to minutes. I already mentioned sarin and other nerve agents include VX, VR, and the Novichok agents used in recent assassination attempts. These are highly volatile, so inhalation is a major source of exposure, as in today's case, but others have been manufactured to be less volatile and can be transmitted by skin exposure. 

[Dr. Wiener] How does the cholinergic crisis present clinically? 

[Dr. Handy] Exposure to nerve agent vapor will cause cholinergic symptoms in the order in which the toxin encounters cholinergic synapses. The most exposed synapses on the human are in the papillary muscles. Nerve agent vapor easily crosses the cornea, interacts with these synapses, and produces myosis or pinpoint pupils. Exocrine glands in the nose, the mouth, and the pharynx are next, and cholinergic overload here causes increased secretions, rhinorrhea, excess salivation, and drooling. The toxin then interacts with exocrine glands in the upper airway and that causes bronchorrhea, and with bronchial smooth muscle, causing bronchospasm and hypoxia. 

[Dr. Wiener] Our patient has all of these symptoms. Does it end there? 

[Dr. Handy] No, the vapor easily enters the bloodstream via the lungs and can affect the GI tract, which would cause abdominal cramping and pain, can cause nausea, vomiting, and diarrhea. Because there are cholinergic synapses on both the vagal and the sympathetic inputs to the heart, one cannot predict how heart rate and blood pressure will change once intoxication has occurred. In the brain, since the cholinergic system is so widely distributed, bloodborne nerve agents may cause rapid loss of consciousness, seizures, and central apnea, leading to death within minutes. 

[Dr. Wiener] Wow, this sounds a lot like our patient. Is there any good news? 

[Dr. Handy] Yes. The time from exposure to the development of full-blown cholinergic crisis after nerve agent vapor inhalation can be minutes or even seconds. Yet, there is no depot effect. Since nerve agents have a short circulating half-life, if the patient is supported and ideally treated with antidotes, improvement should be rapid without any subsequent deterioration. I should also point out that we've been discussing a vapor or inhaled exposure. Liquid exposure to nerve agents results in slower speeds on the order of minutes to hours, and less acute eye and respiratory manifestations as the agent enters the bloodstream via the skin. 

[Dr. Wiener] Okay, well, that finally gets us to our question which asks, which of the following should be immediately administered to this patient as an antidote? The options are A. atropine; B. lamotrigine; C. phenytoin; D. sodium nitrite; or E. sodium thiosulfate. 

[Dr. Handy] The antidote that must be given as quickly as possible to counteract an organophosphate nerve agent is atropine, so the answer is A. The other agent that is also used with atropine is pralidoxime. 

[Dr. Wiener] What about the others? 

[Dr. Handy] Options B. and C. are both anticonvulsants, but importantly, the seizures due to nerve agents do not respond to phenytoin or lamotrigine. You must give a benzodiazepine such as midazolam to treat the seizures. 

[Dr. Wiener] That's important because our patient is seizing. What about the last two sodium compounds? 

[Dr. Handy] Sodium nitrate and sodium thiosulfate are the antidotes to cyanide poisoning. Cyanide is also an agent that's been developed for chemical warfare. Hydrogen cyanide and cyanogen chloride, the major forms of cyanide, are either true gases or liquids very close to their boiling points at standard room temperature. It's an effective weapon in an indoor space such as a train station or a sports arena. Cyanide smells like bitter almonds, but 50% of people lack the ability to smell it. 

[Dr. Wiener] And it's lethal due to its effect on mitochondrial electron transport, causing cellular asphyxia and organ failure, right? 

[Dr. Handy] That's right, after inhalation of a high concentration of cyanide, the patient develops hyperpnea within seconds, followed closely by convulsions and status epilepticus. Respiratory activity stops two to three minutes later, and cardiac activity ceases several minutes after that. Exposure, especially via inhalation, to a large challenge of cyanide can cause death within as little as eight minutes. The classic appearance of a patient with cyanide toxicity has a cherry red appearance because their venous blood remains oxygenated. 

[Dr. Wiener] The teaching points today are that frontline clinical personnel need to be aware of the threat of chemical warfare agents, both on an individual and population level. Fortunately, rapid institution of treatment can mitigate many of the effects of the most common chemical threats. Atropine is the treatment of choice for nerve agents that typically present with a cholinergic crisis. 

[Dr. Handy] You can find this question and other questions like it in Harrison's Self-Review, and you can read more about this topic in the Harrison's chapter on chemical terrorism. Visit the show notes for links to helpful resources, including related chapters and review questions from Harrison's, available exclusively on AccessMedicine. If you enjoyed this episode, please leave us a review, so we can reach more listeners just like you. Thanks so much for listening. 

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