Prepping for nerve agents

Feds, clinical experts offer guidance for hospitals.


The near-deadly nerve agent attacks that rocked England this past spring have provided hospital physicians with yet another reminder that they could one day be sitting on the front lines of chemical warfare, regardless of where they practice.

In August, several federal agencies released a short refresher document for hospitals and emergency responders with diagnosis, treatment, and decontamination protocols, including how to differentiate a nerve agent poisoning from the far more common scenario of an opioid overdose. More detailed guidance was under development.

Image by Getty Images
Image by Getty Images

Meanwhile, emergency physicians and medical toxicologists are striving to educate physicians about how best to prepare for a potential exposure to organophosphates, a category of highly toxic chemicals that includes tabun, sarin, soman, and VX. In 2017, VX was identified as the toxin used in the alleged assassination of the brother of North Korean dictator Kim Jong-Un. More recently, in March 2018, the highly potent nerve agent Novichok nearly took the lives of a former Russian spy and his daughter in Salisbury, England.

While the Novichok agents have garnered many of the recent headlines, Denver medical toxicologist Vikhyat Bebarta, MD, said that it's the more commonly accessible chemical agents that keep him up at night.

Toxic industrial chemicals like chlorine, hydrogen sulfide, and cyanide are easy to make and are already used in manufacturing, said Dr. Bebarta, professor of emergency medicine, medical toxicology, and pharmacology at the University of Colorado in Denver. He coauthored an American College of Medical Toxicology (ACMT) position statement that was published in late 2017 and highlights medication alternatives if supplies of atropine and other life-saving treatments run short after an attack involving multiple people.

“We're not going to have enough,” Dr. Bebarta said. “So what other alternative therapies can providers use outside of the usual drugs?”

The chemical threat is rising, in part because sarin attacks in Syria have “basically democratized chemical weapons' use, and reinstilled the terrorism effect of it,” he explained, noting that his comments are based on risks that are public knowledge rather than any work he's done with the government.

“Some of the biggest concerns are oral consumption,” Dr. Bebarta said. “Getting into our salad bars, getting into our food supplies, getting into our water supplies.”

Rapid detection

In its August refresher for emergency responders and hospitals, federal officials described some of the key symptoms that signal a nerve agent exposure and its signature after-effects of a cholinergic crisis. (Promised additional guidance incorporating lessons from the England attacks had not been released as of press time.)

Nerve agent toxicity results from an excess of acetylcholine, which triggers the crisis. One common mnemonic used is SLUDGE, with many of the symptoms involving the production of excess fluids: Salivation, Lacrimination, Urination, Diarrhea, Gastrointestinal cramps, and Emesis.

Nerve agent-stricken patients may not demonstrate all of these symptoms, federal officials stressed. Another challenge is that a patient with a severe opioid overdose might exhibit similar symptoms; in both scenarios the patient might have difficulty breathing, exhibit very small pupils, and can be unconscious, Dr. Bebarta said. But certain symptoms point to a possible nerve agent exposure, such as very rapid breathing and the shedding of fluids, such as excessive diarrhea, he said.

Fluid production, whether on the lungs, through diarrhea, or by profuse sweating is a clue, agreed Peter R. Chai, MD, an assistant professor of emergency medicine and medical toxicology at Brigham and Women's Hospital in Boston.

He described one experience treating a psychiatric patient who had suffered a chemical exposure after consuming a bottle of malathion in a suicide attempt. The patient was sweating so much “that you could barely put tape on,” recalled Dr. Chai. “The tape that you'll put on their skin will come right off.”

Another diagnostic challenge is that the order in which the symptoms develop might depend on how the individual was exposed to the nerve agent, Dr. Chai said. “So if you ingest it, it might cause you to develop GI symptoms before you develop neurotoxicity,” he said.

The diagnostic stakes are high, as Dr. Chai noted in an article about Novichok agents published online June 29, 2018, by Toxicology Communications. Novichok agents—novichok means “newcomer” in Russian—are reportedly 5 to 10 times more potent than VX, he wrote.

Considering alternatives

To treat exposure to Novichok agents, doctors should immediately start IV atropine, as they would with other organophosphate exposure, administering 2 to 6 mg every 5 to 10 minutes, according to Dr. Chai's article. Doses should be escalated, even if tachycardia results, until the life-threatening symptoms—bronchorrhea, bradycardia, and bronchospasm—resolve.

Other drugs will be needed, such as pralidoxime, which serves as a nerve agent antidote, Dr. Chai said. Benzodiazepines like diazepam are used to treat or prevent seizures. But access to sufficient atropine is of particular concern, given that a nerve agent attack will likely afflict multiple people, he said. “The way that you use atropine in these people, you most likely will deplete your hospital's supply on the first one or two patients,” he said.

In its late 2017 position statement, ACMT officials outlined alternative treatment strategies. In some cases, there are substitutions for other drugs, such as lorazepam in place of diazepam to combat seizures. In addition, atropine, diazepam, and pralidoxime could be used up to two years beyond their expiration date, per an FDA memorandum issued in 2016.

Once the atropine has expired, it may no longer be at full strength but can still be administered without risk, Dr. Bebarta said. “What we're saying is that even if you go beyond those dates, its [effectiveness] is still very high,” he said. “And if it does break down, it doesn't break down into any toxic substances.”

Also, other forms of atropine are an option, the ACMT statement notes. Atropine used for ophthalmology treatment is one alternative and can be given sublingually. Another nearby source might be a veterinary hospital, Dr. Chai said.

An insufficient stock of atropine is the issue most likely to affect hospital physicians, Dr. Bebarta said. (He coauthored expert consensus guidelines, published March 2018 in the Annals of Emergency Medicine, detailing how much antidote hospitals should stockpile for a range of scenarios, from nerve agents to snake bites to acetaminophen toxicity.)

When hospital clinicians develop disaster drills, they should create scenarios in which the number of victims outstrips the drug supply, and then challenge clinicians to find alternatives, Dr. Bebarta said. Make sure physicians “do the math,” he suggested. “Do you have atropine for 20 patients?”

Decontamination strategies

Anyone with suspected nerve agent exposure should be rapidly decontaminated regardless of whether symptoms have yet developed, according to federal officials' recent protocol refresher. Patients should be asked to remove their own clothes, if they are able, at minimum down to their underwear, said Robert Chilcott, PhD, professor of toxicology at the University of Hertfordshire in England.

“It can be explained to the casualty that the more clothes they take off, the better the outcome is going to be,” Dr. Chilcott said. “And hopefully we'll get better compliance.”

Dr. Chilcott was involved with a mock mass decontamination exercise in Rhode Island comparing various approaches, the results of which were published online Aug. 23 in Annals of Emergency Medicine. More than 80 volunteers were sprayed with a chemical warfare agent simulant (methyl salicylate, curcumin, and baby oil), which has been shown to closely mimic sulfur mustard or soman, Dr. Chilcott said.

The participants were “exposed” in three areas: the back of the head, the upper chest, and the palm of the right hand. With whole-body fluorescent imaging, the researchers determined that all existing decontamination approaches removed at least 97% of the mixture from the hair and skin, as long as participants complied with instructions.

The first step in the most effective approach to decontamination (which begins with removal of clothing) is described as dry decontamination, Dr. Chilcott said. With tissue paper, paper towels, or some other absorbent material, they can wipe themselves down, starting with their hair, followed by their face and ears, and then exposed areas such as hands and arms, starting over with a new piece of material for each area, Dr. Chilcott said.

The goal of disrobing and dry decontamination, which only works with liquid chemical agents and not powders, is to quickly remove as much of the agent as feasible from the skin's surface before wet decontamination with a shower unit, or a larger area with hoses in the event of many casualties, Dr. Chilcott said. If the attack involves a powder, then wet decontamination is the next step after disrobing, he said.

Since a decontamination shower or area frequently isn't immediately accessible, the disrobing and dry decontamination helps to remove the agent during that delay, when every minute counts, Dr. Chilcott said. Doctors and other emergency responders should calmly and quickly clarify the process and the stakes involved, he said.

“You might say, ‘You've been exposed to a chemical. You need to get your clothes off. If you don't get your clothes off, it's going to go through your clothing and it is going to affect you. Once we've got your clothes off, we're going to run through the dry decontamination stage.’”

There's another inherent advantage of asking patients to disrobe first, Dr. Chilcott added wryly: “If you take people's clothes off, they'll be less inclined to run away.”

Disclaimer: The views expressed in this article belong to the sources alone and do not necessarily reflect the official position of the United States Government, Department of Defense, or Department of the Air Force.