Novichok Poisoning

“EMS 2, respond code 2 for sickness.”

You arrive to three people reporting symptoms of shortness of breath, headache, and vomiting. You suspect carbon monoxide exposure and usher everyone out. The fire department and gas company are notified, and the patients are transported.

After your shift you go home. Two days later you start to feel sick—abdominal pain, salivating, tearing eyes. You call your partner, and she feels sick too, with the same complaints.

You call work to let them know you won’t be in. They tell you to stay put—wait for the EMS duty chief to arrive at your house, but do not go outside. You turn on the news—the FBI is holding a press conference in front of the same hospital you transported to, talking about a potential terrorist event.

Composition

Novichok (Russian for newcomer) agents are unique organophosphorus compounds also known as A series or fourth-generation nerve agents (4GAs). They are 10 times more deadly than soman and can be distributed as a fine powder or liquid. They cause convulsions leading to coma or death; victims suffocate as their nervous and respiratory systems shut down.

4GAs were designed to be undetectable and defeat current military PPE. They are safer to handle because they are binary weapons, which use two or more chemical precursors that are either nontoxic or less toxic until mixed together. Their composition differs slightly, with the same phosphorus, oxygen, and nitrogen atoms, but now adding fluorine.

4GAs are persistent: They require a greater amount of atropine to treat, and if not decontaminated, they can remain on the patient and environmental surfaces for days to months. The latent period between dermal exposure and symptom onset may be up to three days. If the patient has been exposed via inhalation, ingestion, or a large dermal exposure, they will have shorter a period until they exhibit signs and symptoms.

The most famous cases using Novichoks are the 2018 poisoning of Russian double agent Sergei Skripal and his daughter Yulia in the U.K. and Russian dissident Alexei Navalny in 2020.

How 4GAs Work

Acetylcholine conducts nerve impulses from the brain to the body. When released by the presynaptic neurons, it crosses the synaptic cleft and activates receptors on the postsynaptic side of the neuroeffector junction, stimulating a muscle or organ. When enough acetylcholine has been released, acetylcholinesterase is then secreted to break it down.

The symptoms of nerve agent poisoning affect both the sympathetic and parasympathetic nervous systems. 4GAs block cholinesterase at the synaptic junction, causing acetylcholine to collect at the synaptic cleft, continuing to stimulate the organs/muscles. Symptoms of this are summarized through the mnemonic DUMBELS.

• Diarrhea/diaphoresis
• Urination—Excessive urination, with incontinence
• Miosis—Pinpoint/nonreactive pupils
• Bronchospasm/bradycardia/bronchorrhea
• Excitation—Stimulation of muscles (tremors/twitching, weakness), seizures
• Lacrimation—Excessive tearing
• Salivation—Excessive saliva

We may see tachycardia if there is stimulation of the nicotinic receptors. Patients may also suffer chemically mediated acute pulmonary edema. Mental status changes can include anxiety, headache, dizziness, CNS depression, loss of coordination, confusion, and slurred speech. We can also see hypothermia and hypoglycemia.

EMS Goals

Maintain scene safety and security. Pay attention to enclosed spaces and multiple patients sick simultaneously at one location—these scenarios should set off alarm bells. You respond to an apartment where multiple people are exhibiting varying degrees of severity of a similar complaint—SOB, increased salivation, muscle tremors, unconsciousness—think 4GA.

The EMS goals in managing an incident include:

• Early recognition of the situation;
• Appropriate PPE;
• Isolation of the scene to prevent further exposure;
• Decontamination of the patient(s) and provision of treatment to reverse the agent’s effects.

Basic Decontamination

Dealing with nerve agents, your priority is decontamination ASAP—if not, recovery becomes unlikely. Decontamination occurs in the warm zone. Those providing treatment/decontamination in the warm zone needs to wear Level B protection. Cold zone teams should wear disposable gowns and chemical-resistant gloves as well. Think hazmat naked: The patient hasn’t been decontaminated until they have all their clothing removed. Keep in mind that these clothes are evidence, so make sure they’re bagged and secured.

Remove as much of the 4GA as possible prior to application of water: brush off powders, blot off liquids. Decontamination of skin and hair is crucial and may provide clinical benefit even when performed hours to days after exposure, although earlier is better.

For decon use tincture of green soap or any dishwashing soap. Nerve agents are also hydrolyzed readily by alkaline solutions, so soap and water or even hypochlorite solutions make good decontamination agents. Do not use hypochlorite solutions in the eyes, as they will cause opacities; open body cavity wounds, as they may lead to adhesions; in airway/open lung injuries, since they destroy the lipid protein layer; and in brain and spinal cord injuries, for the same reason.

Do not scrub patients down; this will cause further penetration of the nerve agent into the skin. Use brushes with soft bristles or sponges. For the eyes concentrated mixtures of 4GAs may require 10–15 minutes of flushing with water/saline.

Patient Care

Airway: The patient is at high risk for respiratory arrest due to bronchospasm and increased secretions; monitoring of oxygen saturation and securing the airway are important. Use an OPA/NPA/ETI as indicated. Have suction available and ready to use.

Breathing: Provide high-concentration oxygen via a nonrebreather facemask. Be prepared to ventilate with a BVM. Patients exposed to nerve agents go into respiratory arrest because of increased airway resistance, respiratory muscle paralysis, and loss of central respiratory drive.

Circulation: Treat for shock. Keep the patient supine if they can tolerate it. Maintain body temperature without making the patient too hot or cold—too hot, their pores open; too cold increases the metabolic rate, and both of these will increase the rate of absorption. Start a large-bore IV line of normal saline and maintain the patient’s BP.

Administer atropine every 3–5 minutes at 2 mg either via an IM autoinjector or IV push until the symptoms resolve. After the first 2 mgs of atropine, the patient has received the complete vagolytic dose, so don’t become concerned with increasing the patient’s heart rate. Administer atropine until the signs and symptoms of DUMBELS stop. The more acetylcholine that accumulates, the more you need to reverse the effects. Atropine acts to block the effect of the accumulated acetylcholine.

Novichoks bond to acetylcholinesterase, and if this bond is allowed to age, it may become permanent. Depending on the agent, the half-time aging can be from 2 minutes to 15 hours. Pralidoxime chloride breaks the bond between the 4GA and the acetylcholinesterase. When this happens acetylcholinesterase is reactivated, breaking down acetylcholine. It must be given early and simultaneously with atropine.

Administer pralidoxime chloride via autoinjector at 600 mg. If you do not have an autoinjector, administer a dose of 1–2 grams in 100 ml of normal saline over 15–30 minutes. This can be repeated in an hour if muscle weakness is not relieved.

Remember that when administering pralidoxime chloride with atropine, you may have a synergistic effect. This is expected and should not cause alarm.

Seizure activity has been a prominent feature of 4GA toxicity in animal studies. Multiple casualties who are seizing and having airway issues will strain local resources at the point of care. Treat all seizures first with oxygen because hypoxia is not uncommon with nerve agents.

Administer anticonvulsants in severe cases of exposure to 4GAs even in the absence of seizure activity because of the positive synergism of anticonvulsants with atropine and pralodoxime chloride. With seizure activity, continue until it resolves. Administer anticonvulsants in the following dosages: midazolam, 0.15 mg/kg IM; lorazepam, 4 mg IM or 0.1 mg/kg IN; or diazepam, 0.2-0.5 mg/kg IM. Diazepam is also available via an autoinjector, Convulsant Antidote for Nerve Agent (CANA), at 10 mg/IM.

If the patient suffered an ingestion, inducing vomiting will increase damage to the esophagus and stomach. It also increases the chance of pulmonary aspiration. Instead give a slurry of activated charcoal, 50–60 grams, to the patient who is awake and has a gag reflex. Pass a nasogastric tube if possible prior to administration.

Monitor and reassess the patient’s vital signs; they are at increased risk of airway/breathing problems and because of slowing of the heart rate. If the patient is experiencing severe pain in the eyes, administer atropine eyedrops.

Finally, notify area receiving hospitals of the incident and what substances are involved. Patients may self-extricate as they did during the Tokyo subway attack. Providing advanced notification will allow the proper resources to be activated to prevent contamination of the emergency department.

Summary

Stay safe! Certain scenes and scenarios invite a greater degree of caution. Wear your protective gear (Level B for decon), make sure the patient is hazmat naked prior to decontamination, and decon, decon, decon. Maintain the patient’s airway using oral/nasal airways; intubate if indicated. Give high-flow oxygen either by nonrebreather oxygen mask or, if intubated, with a bag-valve mask. Treat for shock by maintaining the patient’s body temperature, keeping them supine if they will tolerate it, and gaining IV access. Administer oxygen, atropine, pralidoxime chloride, and diazepam. Notify the ED and transport rapidly. Remember: Get your patient and get out.

Numbers to Call

CHEMTREC

• Continental U.S.: 800-424-9300
• Beyond continental U.S.: 703-527-3887 (may be called collect)

National Pesticide Information Center: 800-858-7378

Poison Control (toll-free nationwide): 800-222-1222

Resources

Agency for Toxic Substances and Disease Registry. Medical Management Guidelines for Nerve Agents: Tabun (GA); Sarin (GB); Soman (GD); and VX; wwwn.cdc.gov/TSP/MMG/MMGDetails.aspx?mmgid=523&toxid=93.

Cornell Cooperative Extension, Pesticide Management Education Program, http://pmep.cce.cornell.edu/.

National Association of State EMS Officials. National Model EMS Clinical Guidelines, Version 2.0, https://nasemso.org/wp-content/uploads/National-Model-EMS-Clinical-Guidelines-2017-Distribution-Version-05Oct2017.pdf.

Organisation for the Prohibition of Chemical Weapons. Chemical Weapons Convention, www.opcw.org/chemical-weapons-convention.

Daniel R. Gerard, MS, RN, NRP, is EMS coordinator for Alameda, Calif. He is a recognized expert in EMS system delivery and design, EMS/health-service integration, and service delivery models for out-of-hospital care.