Nerve Agents: Recognition and Treatment Ventura County Emergency Medical Services

Chemical Warfare Agents Chemical Agents –Chemicals used in military operations to kill, injure, or incapacitate Incapacitating vs. Lethal Local vs. Systemic Effects

Nerve Agent Terrorist Attacks Matsumoto: –280 injured –7 dead Tokyo –12 dead –Approximately 1,000 hospitalized –5,500 sought medical care –132 first responders injured

Scenario # 1 A chemical is released in a movie theater at 7 PM. Fire and EMS respond to the scene. One patient is dead, Two patients are unconscious but still breathing. Five patients are weak and complaining of eye pain, but are still ambulatory. Others begin running from the scene.

Scenario # 1 (cont.) Two EMTs from the first-in unit arrive first, and while bag-mask ventilating two of the seriously injured victims, become weak, short of breath, with dim vision and eye pain.

Scenario # 1 (cont.) What actions should be taken immediately? Who should be contacted? What options are available for: –Protecting the EMS responders? –Treatment for the victim? –Stabilization and transport?

Nerve Agents Most toxic chemical agents: are liquids, not “gas” GB (Sarin): vapor or liquid hazard; non-persistent VX: liquid hazard; persistent Penetrate skin, eyes, lungs Loss of consciousness, seizures, apnea, death Diagnosis made clinically, confirmed by laboratory test

Nerve Agents Organophosphates Insecticides are easily obtained and commonly used in the community Like insecticides: –Malathion –Diazinon –Chlorpyrifos

Normal Nerve Function ACh

Normal Nerve Function ACh

Normal Nerve Function ACh AChE

How Nerve Agents Work AChE ACh GB

Hyperstimulation of organs of cholinergic nervous system –Muscarinic Smooth muscles Glands –Nicotinic Skeletal muscles Ganglions Effects of Nerve Agents

Effects of Nerve Agents - Muscarinic Sites Increased secretions –Saliva –Tears –Runny nose (rhinorrhea) –Secretions in airways –Secretions in gastrointestinal tract –Sweating

Effects of Nerve Agents - Muscarinic Sites Smooth Muscle Contraction: –Eyes: Small pupils -> dim vision –Airways: Narrowing -> shortness of breath –Intestine: Hyperactivity -> nausea, vomiting, diarrhea

Pupil Response

Nicotinic Sites Skeletal muscles –Fasciculations –Twitching –Weakness –Flaccid paralysis Ganglion –Tachycardia –Hypertension Pinpoint pupils + muscle twitching = Nerve Agent exposure

Central Nervous System Effects Acute Loss of consciousness Convulsions Apnea Prolonged (4 to 6 weeks) Psychological effect

Inhalation Ingestion Direct contact Routes of Exposure

Vapor Exposure Vapor effects occur within seconds, peak within minutes Low exposure –Miosis [constricted pupils] (dim vision, eye pain) –Runny nose (rhinorrhea) –Shortness of breath High exposure –Immediate loss of consciousness, seizures, apnea, flaccid paralysis

Absorption through skin: All agents can be absorbed VX persists longer GB evaporates quickly, but still threat Scrape or cut in skin allows immediate entry Entry also through eyes Direct Contact

Small amount –Localized sweating –Fasciculations Moderate amount (<LD 50 ) –Gastrointestinal effects Large amount (LD 50 ) –Sudden loss of consciousness –Seizures –Apnea

Skin Exposure - Time Course Onset time: minutes to several hours The larger the exposure the shorter the onset time After large exposure, effects within minutes After asymptomatic period, first effect may be loss of consciousness Onset time may be as long as 18 hrs after exposure; in such cases effects usually not lethal

Access to bloodstream via digestive system Effects similar to inhalation, but at greater doses Ingestion

Signs and symptoms could also be due to: Epilepsy Gastroenteritis Exposure to agricultural insecticides (organophosphates and carbanates) Heat illnesses Emphysema Stroke Head trauma Drug overdose Other Possible Causes of Symptoms

Treatment Self-protection Decontamination

Treatment Airway/ventilation Antidotes –Atropine –Pralidoxime (2-PAM) –Midazolam

Atropine Given IV, IM, ET Antagonizes muscarinic effects –Dries secretions; relaxes smooth muscles Does not affect miosis, fasciculations, muscle strength (nicotinic) May cause cardiac arrhythmias IV in hypoxic patient (v-fib)

Atropine Starting dose - 2 mg Maximum cumulative dose - 20 mg Side effects in normal people –Dilated pupils –Blurred vision –Tachycardia –Decreased sweating

Atropine Atropine - How much to give? –Until secretions are drying or dry –Until ventilation is “easy” If conscious, and victim is comfortable –Don’t rely on heart rate/pupil size

Atropine Overdose If excessive atropine is administered: Signs of atropinization will become even more severe and patient may also develop –blurring of vision –delirium –urinary retention When signs and symptoms of atropinization develop, no more atropine should be injected until atropinization subsides

Pralidoxime Chloride (2-PAM) Remove nerve agent from AChE in absence of aging (2-PAM “crowbar”) Does not reverse muscarinic effects on glands and smooth muscles Helps at nicotinic sites

2-PAM may cause: –blurred vision –diplopia –impaired accommodation –headache –nausea 2-PAM Adverse Reactions These are relatively mild when compared to effects of nerve agents – dizziness – drowsiness – tachycardia – hyperventilation – hypertension

Midazolam Decreases seizure activity Reduces seizure-induced brain injury Must observe carefully for respiratory depression

Autoinjectors

Auto-Injectors Simple, compact injection systems Permit rapid injection of required antidotes Prevent needle from being subject to cross-contamination Enable rapid and accurate administration even if care giver or patient is in protective clothing

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Directions for Use 1. Remove safety cap Yellow on atropine Yellow on atropine Gray on 2-PAM Gray on 2-PAM Mark I kit clip holds the safety caps Mark I kit clip holds the safety caps – May not notice if using Mark I kits Do not touch colored end of injector after removing cap - injector will inject Do not touch colored end of injector after removing cap - injector will inject into fingers or hand

Directions for Use 2. Hold injector - either like a pen or in fist. 3. Place colored end (Green on atropine, black on 2-PAM) on thickest part of thigh and press hard until injector functions. Pressure automatically activates the spring, inserts the needle into the muscle and injects the medicationPressure automatically activates the spring, inserts the needle into the muscle and injects the medication

4. After auto-injector has been activated, empty container should be disposed of properly It cannot be refilled nor can the protruding needle be retracted It should be disposed of in a “sharps” container 5. Note dosage on triage tag or write on chest or forehead of patient AI 18© Directions for Use

Potential Exposure No signs or symptoms –Reassure –Segregate in cold zone –Observe –Arrange transport to ED by bus or vans

Mild Exposure Miosis, rhinorrhea - observation only –IV or IM atropine will not reverse miosis Localized fasciculations and sweating –Exclusion (Hot) Zone: No immediate treatment –Contamination Reduction (Warm) Zone: One MARK I (2 mg atropine/600 mg 2-PAM) OR Atropine 2 mg IV/IM –Peds (Age < 12) –0.02 mg/kg (min 0.1 mg) IV/IM 2-PAM 600 mg IM (Adult only)

Moderate Exposure Miosis, rhinorrhea, SOB, wheezing, secretions, muscle weakness, GI effects –Exclusion (Hot) Zone: No immediate treatment –Contamination Reduction (Warm) Zone: One to two MARK I kits (repeat every 5-10 min) OR Atropine 2-4 mg IV/IM (repeat every 5-10 min) –Peds (< 12) mg/kg (min 0.1 mg) IV/IM 2-PAM mg IM (Adult only)

Severe Exposure Unconscious, seizing, flaccid, apnea Exclusion (Hot) Zone: –3 MARK I kits IM as soon as possible Contamination Reduction (Warm) Zone: –3 MARK I kits IM as soon as possible OR –Atropine 2-6 mg IV/IM Peds (<12) mg/kg (min 0.1 mg) IV/IM –2PAM mg IM (Adult only)

Severe Exposure (cont.) –For seizures: Midazolam IM –Adult: 5 mg –Peds (<12) : 0.1 mg/kg

VC EMS Policy Nerve Agent 1. “Exclusion Zone" or “Hot Zone”: The innermost of three circles around a hazardous materials site. Special protection is required for all personnel within. 2. "Contamination Reduction Zone (CRZ)" or “Warm Zone”: Site of decontamination and between Exclusion (Hot) and Support (Cold) Zones. Requires a lesser degree of protection equipment. 3. Mark 1 Kits contain two auto-injectors, one containing 2 mg atropine and one containing 600 mg pralidoxime (2PAM). 4. Nerve agent poisoning can be very toxic. Large amounts of atropine may need to be utilized (in the 100’s of mg’s). If the patient is initially symptomatic and no response is seen to the initial doses of medication, continue giving until a response is achieved. 5. Adult = age >= 12. Peds = age <12.