CHEMICAL TERRORISM This chemical terrorism case and discussion will focus on Nerve Agent exposure and toxicity.

OBJECTIVES Learn how to perform a rapid assessment of a nerve agent terrorism situation. Recognize characteristic signs and symptoms of nerve agent poisoning.

OBJECTIVES Understand proper decontamination for nerve agent poisoning. Learn medical management of nerve agent exposed victims. Learn specific antidotes for nerve agent poisoning victims.

Scenario Friday, January 31 – 8:47 AM (Rush Hour) An unknown gas is released in the downtown rapid transit station. It is described as a thick mist, and was found in 5 separate stops. Thousands of commuters rapidly fled the stations to the streets. EMS transport is overwhelmed, and several local ED’s are unable to absorb the patients presenting by ambulance, car, taxi, and on foot. Many patients present to offices and local health departments. The following scenario could take place in a major metropolitan or urban setting.

Scenario Friday, January 31 – 10:02 AM One patient that presents to a local health clinic complains of tearing and runny nose. He also has mild shortness of breath. Mild wheeze is noted on exam. Ten other patients at the clinic are asymptomatic, but are very worried. This could be in a outpatient clinic setting or emergency department

Scenario Friday, January 31 – 10:27 AM Public health officials confirm that the gas was Sarin, similar to the toxin used in the subway of Tokyo. Sarin gas was released by a terrorist cult group in a Tokyo, Japan subway system in 1995. Hundreds of people were directly exposed. Thousands of patients quickly overwhelmed the Japanese EMS and hospital systems.

Things to Consider Has your staff been adequately trained about chemical weapons? Does your staff understand basic principles of decontamination? Who should your staff alert? Who will alert your staff in the event of a chemical terrorism event? Now the discussion should be focused back on the target audience to bring this potential toxic scenario closer to home.

Nerve Agents

Characteristics of Nerve Agents Liquids that disseminate in the vapor/aerosolized form Onset is abrupt (seconds to hours) Designed to irritate, incapacitate, injure or kill Predominantly inhalational and dermal threats If death occurs, usually respiratory cause Note that chemical agents such as Sarin and other nerve agents act rapidly, unlike biologic agents which tend to be more gradual and insidious in onset.

Characteristics of Nerve Agents Chemical incidents are obvious shortly after exposure. Biological agents will take days to cause symptoms. ONE patient can contaminate your facility First responders/health care providers are in the line of fire Emphasize the importance of outside decontamination in order to protect the health care team by establishing a dedicated decon unit outside the emergency department.

History of Nerve Agent Weapons Use First used as a weapon during WWI Most recent event - Japanese subway incident in 1995 Aum Shinrikyo cult released Sarin into 5 subway cars in downtown Tokyo 12 deaths, hundreds injured, 5500 sought care – 4,600 self-referred 135 first responders were injured WWI – 22 April 1915, Germans used chlorine in large drums – it would cause lung damage and was readily available. Mt. Fuji - where the cult facilities where located in Japan

Shoko Asahara Shoko Asahara: Leader of the1995 Japanese cult- When approaching him, you are to address him first by kissing his great toe to demonstrate respect.

NERVE AGENTS

General Characteristics Military Tabun (GA), Sarin (GB), Soman (GD), VX Commercial Parathion, Sevin Therapeutic Drugs Antilirium® Prostigmine ® Mestinon ® G agents represent a German scientist – all of these were synthesized by Germany. Military - Tabun (GA) - Colorless to brown; fruity odor Sarin (GB) - Colorless; odorless; easiest to make Soman (GD) - Colorless; fruity, camphor odor *(“NOTION THAT THIS HAS A FRUITY SMELL, BUT I WOULDN’T WANT TO TEST THAT…”) VX - Colorless to straw-colored; odorless; liquid skin hazard; consistency of motor oil Commercial – (Kids are commonly exposed to commercial agents) Parathion - organophosphate insecticide Sevin - carbamate insecticide Therapeutic Drugs Antilirium® Prostigmine ® Mestinon ®

General Characteristics Effects of vapor - immediate Wide range of symptoms - Affects sensitive organs of the face and respiratory system - Over-stimulation of the central nervous system *because of the immediacy of effects – rapid pretreatment issue

Normal Nerve Function ACh When a nerve impulse reaches the synapse, ACh is released from the nerve ending and diffuses across the synaptic cleft to combine with receptor sites on the next nerve, and the electrical message continues. NOTE: Emphasize that the effect of unwanted electrical message propagation depends on the receiving end organ. A gland will continue to secrete, a muscle will continue to contract, a nerve will continue to generate additional electrical impulses.

Normal Nerve Function AChE ACh To stop further stimulation of the nerve, ACh is rapidly broken down by acetylcholinesterase (AChE), producing choline, acetic acid, and the regenerated enzyme. Thus, a “check and balance” system prevents the accumulation of ACh and the resultant over-stimulation of nerves, muscles, and glands. ACh NOTE: This slide is an artist’s depiction of AChE metabolism of the neurotransmitter. The actual location of AChE is on the post-synaptic membrane, not in the synaptic cleft. Consider re-emphasizing that inhibition of the AChE allows accumulated ACh to continue stimulating muscle contraction, gland secretion, and nerve propagation of unwanted impulses. This mechanism relates directly to the signs and symptoms resulting from nerve agent exposure, and relating this process of effects to patients with apparently bizarre and varied symptoms could be extremely important in making a correct diagnosis in the aftermath of a terrorist attack.

Nerve Agent Action AChE GB ACh HOW NERVE AGENTS WORK The term “nerve agents” refers to chemicals that produce biological effects by inhibiting the enzyme AChE, thus allowing the neurotransmitter ACh to accumulate. Included among the “nerve agents” are some drugs (such as physostigmine and pyridostigmine) and some insecticides (Sevin®, malathion, and related insecticides). These compounds cause the same biological effects as the nerve agents developed for military use, but the latter are more than a hundred-fold more potent. As a result of inhibition of AChE, the neurotransmitter ACh accumulates to over-stimulate the organs it normally stimulates in the portion of the nervous system. This causes hyperactivity in these organs. These are all innervated by the cholinergic portion of the nervous system and have muscarinic receptors, nicotinic receptors, or a combination (central nervous system and cardiovascular system). ACh GB

Signs and Symptoms Muscarinic Effects SLUGBAM: Salivation Lacrimation Urination GI distress (Nausea, Vomiting, Diarrhea) Bronchorrhea (Bradycardia, Bronchospasm) Abdominal cramps Miosis Mention in Tokyo, majority of victims had only eye-tearing and miosis – important for pre-hospital to recognize. *affects to the GI tract “just like a bad burrito multiplied over and over”

How Bad Is This Stuff? VX – LD50 Example of how little you need: Agent on penny is VX – it has an LD50 much lower than any other agent requiring very little to be extremely devastating IF A DROP THE SIZE OF THE DROP ON THE PENNY WERE PUT ON THE SKIN OF 100 PEOPLE, 50 OF THOSE PEOPLE WOULD DIE FROM THE AGENT’S EFFECTS, THE REMAINDER WOULD SUFFER LESSER SIGNS AND SYMPTOMS…. VX – LD50

Signs and Symptoms Nicotinic Effects System Effect Skeletal muscles Twitching Weakness Flaccidity Cardiovascular HR Blood Pressure CNS LOC, Seizures Nicontic receptors are a mixture of autonomic effects In Frederick Sidel’s lab (a biochemical expert) a technician pipetted a minute amount of sarin into his mouth and after rinsing for 15 minutes the tech. seized. *“Is anybody here in the military?” “Remember the muscle fatigue after doing 100 push-ups everyday? This would be the same feeling.”

Signs and Symptoms Dermal Exposure Effects Very small drop Sweating Local twitch Small drop Nausea Vomiting Diarrhea Drop LOC Convulsions Apnea Flaccid paralysis

Signs and Symptoms Vapor Exposure Effects Small amount Miosis SLUGBAM SOB Chest tightness Large amount LOC Convulsions Paralysis Death

Signs and Symptoms Effect on pupil at x number of days 3 6 13 20 Miosis can occur within minutes following nerve agent exposure. This patient has been treated with atropine and can no longer be followed clinically for eye findings to gauge the endpoint of treatment. 41 62

Diagnosis Clinical picture is key Erythrocyte acetylcholinesterase activity level - Amount of inhibition does not correlate with symptoms Various electronic and “paper” detectors are available - for HAZMAT use Mention electronic detectors are expensive

GENERAL PATIENT MANAGEMENT

A bit of comic relief: This slide emphasizes the need for proper decontamination suits.

General Management PPE (mask, gloves and protective suit) Decontamination Don’t let your setting become contaminated ABC’s Communicate with public health officials Poison Control Center (800 222-1222) Antidotes where appropriate APPLIES TO ALL CHEMICAL AGENTS DISCUSSED PPE – proper protective equipment

Prehospital Management Soap and Water Hypochlorite Solution 0.5% for skin 6 oz calcium hypochlorite in 5 gallons water 5.0% for equipment 48 oz calcium hypochlorite in 5 gallons water

Treatment Adult atropine dose: “enough” Give atropine regardless of heart rate Pediatric Considerations 0.01mg/kg Atropine used until endpoint achieved (resolution of secretions) Up to 100 mg of atropine has been required in severely intoxicated patients following organophosphate poisoning. Picture – Atropine compound

Antidote Atropine 2-PAMCl (Pralidoxime) AChE 2-PAMCl Nerve Agent Atropine - Blocks the effects of neurotransmitter 2-PAMCl (Pralidoxime) - Removes nerve agent from the enzyme Military Autoinjector MARK I Atropine will treat SLUGBAM symptoms (smooth muscles) – doesn’t hurt to inject 2-PAMCl will treat muscular and neurologic symptoms – does hurt to inject AGING: after a certain amount of time, can’t stop; for example, epoxy glue (for a period of time you can separate, but it will eventually bond) Sarin (5 hours) and Soman (2 minutes)“ages” quickly, the bond is irreversible – on site treatment gets maximal benefit. MarkI:2 mg of atropine in 0.7 ml diluent 600 mg of 2-PAMCl in 2 ml diluent

“Aging” Name Synonym Aging T1/2 Sarin GB ~5 hours Soman GD ~2 min Tabun GA >40 hours VX None AGING: after a certain amount of time the effects become irreversible; for example, epoxy glue (for a period of time you can separate, but it will eventually bond) Sarin (5 hours) and Soman (2 minutes)“ages” quickly, the bond is irreversible – on site treatment gets maximal benefit.

Nerve Agent Questions 3 multiple choice questions to be answered following the case presentation and discussion.

Question #1 What was the public health lesson learned from the 1995 Sarin terrorists attack in the subway system of Tokyo, Japan? This bioterrorist attack could only occur in a large city with an enclosed underground subway system. The walking wounded and hysterical patients often overload the medical system Religious cults should be placed under strict federal surveillance Ample supplies of the antidotes are readily available The correct answer is: b. The walking wounded and hysterical patients often overload the medical system

Question #2 In the acute phase of poisoning, one of the consistent findings that differentiates Sarin poisoning from hysteria is: Cholinesterase enzyme blood levels Garlic smell on victims Pinpoint pupils Tachycardia The correct answer is: c. Pinpoint pupils

Question #3 Based on past experience, which of the hospital supplies/equipment below is most likely to run out after a mass casualty exposure to Sarin gas? Ventilators Personal Protective Equipment Hemodialysis machines Atropine The correct answer is: d. Atropine

This completes the current presentation. End presentation and distribute activity survey.