Nerve Agent Exposure

Aka: Nerve Agent Exposure, Nerve Toxin, Organophosphate Poisoning Management, Tabun, Sarin, Soman

1. See Also
   1. Cholinergic Toxicity
   2. Organophosphate
   3. Biological Weapon
   4. Neurotoxin
   5. Pesticide
2. Agents
   1. Tabun (GA)
   2. Sarin (GB)
   3. Soman (GD)
   4. GF Nerve Agent
   5. VX Nerve Agent
3. History
   1. Developed in Germany before World War II
   2. U.S. stockpiles included GB, VX
   3. Iraq has used Nerve Agents frequently
      1. Iran-Iraq war
      2. Kurdish refugees
   4. Tokyo subway 1995
      1. Aum Shinrikyo cult used dilute sarin (GB)
4. Pathophysiology
   1. Penetrates skin, eyes, and lungs
   2. Acetylcholinesterase inhibitors
      1. Most toxic of chemical agents
      2. Similar to insecticides (e.g. Malathion)
5. Toxicity: Lethal doses
   1. Skin LD50 (from least to most toxic)
      1. GA, GB: 1000, 1700 mg
      2. GD, GF: 50, 30 mg
      3. VX: 10 mg
   2. Vapor LCt50 (from least to most toxic)
      1. GA: 400 mg-min/m3
      2. GB: 100 mg-min/m3
      3. GD: 70 mg-min/m3
      4. GF: Unknown
      5. VX: 50 mg-min/m3
6. Signs: Muscarinic receptor (Smooth muscle, glands)
   1. Increased Glandular secretion ("All faucets on")
      1. Salivation
      2. Lacrimation
      3. Rhinorrhea
      4. Airway secretions
      5. Sweating
   2. Ocular
      1. Miosis
      2. Eye Pain
      3. Dim or blurred vision
      4. Conjunctival injection
   3. Respiratory
      1. Bronchoconstriction
      2. Central Apnea within minutes of severe exposure
   4. Gastrointestinal
      1. Nausea and Vomiting (early signs of liquid on skin)
      2. Diarrhea with severe exposure
7. Signs: Nicotinic Receptors (Skeletal muscle, Ganglia)
   1. Skeletal Muscle changes
      1. Initial
         1. Fasciculations
         2. Muscle Twitching
      2. Later
         1. Weakness
         2. Flaccid paralysis
   2. Ganglionic effects
      1. Tachycardia
      2. Hypertension
   3. Cardiovascular Effects
      1. Heart Block
      2. Ventricular arrhythmia
   4. Neurologic Effects
      1. Onset
         1. Vapor: 1 minute of large exposure
         2. Skin contact: 1-30 minutes
      2. Acute
         1. Loss of consciousness
         2. Seizures
         3. Apnea
      3. Prolonged (4-6 weeks)
         1. Forgetfulness
         2. Inability to concentrate fully
         3. Insomnia
         4. Bad dreams
         5. Irritability
         6. Impaired judgment
         7. Depression
         8. No frank confusion or hallucination
8. Severity of exposure (used to dose antidote)
   1. Vapor Exposure (Effect in seconds, Peaks in minutes)
      1. Low Exposure
         1. Miosis
         2. Rhinorrhea
         3. Dyspnea
      2. High Exposure
         1. Altered Level of Consciousness
         2. Seizures
         3. Apnea
         4. Flaccid Paralysis
         5. Death
   2. Liquid Exposure
      1. Small amount (delayed effects up to 18 hours)
         1. Localized sweating
         2. Fasciculations
      2. Moderate amount (delayed effects up to 18 hours)
         1. Gastrointestinal effects
      3. Large amount (Effects within 30 minutes)
         1. Altered Level of Consciousness
         2. Seizures
         3. Apnea
         4. Flaccid paralysis
         5. Death
9. Differential Diagnosis
   1. Cyanide
      1. No increased secretions
      2. No Miosis
      3. Cyanosis uncommon
   2. Syncope
   3. Drug overdose
10. Detection
    1. Odor
       1. Fish or fruit
    2. Detection kits
       1. M256A1: GB, VX (unknown threshold for GF, GA, GD)
       2. M272: GA, GB, GD, VX
       3. MINICAMS: GB, GD, VX
       4. ICAD: GA, GB, GD
       5. M18A2: GB, VX
       6. M21: GA, GB, GD
       7. M90: GA, GB, GD, GF, VX
       8. M93A1 Fox: GB, GD, VX
       9. ACAMS: GB, VX
       10. Bubbler: GB, VX
       11. CAM: GA, GB, GD, GF, VX
       12. DAAMS: GB, VX
11. Labs: Obtain prior to therapy if possible
    1. Plasma Pseudocholinesterase Level
    2. Erythrocyte cholinesterase activity
       1. Severe Nerve Agent Exposure results in <30% baseline
       2. Return to exposure risk when level >75% baseline
12. Management
    1. Medical providers wear full protective gear and mask
       1. Level C Personal Protection Equipment
       2. Risk of patient off-gassing
    2. Decontamination
       1. Vapor
          1. Remove all clothing (risk of trapped vapor)
       2. Liquid
          1. Hypochlorite
          2. M291
          3. M258A1
          4. Copious water irrigation of all contacted areas
13. Management: Supportive Care
    1. ABC Management
    2. Mechanical Ventilation
       1. Usually required for 30 minutes to 3 hours
       2. Airway resistance high (50-70 cm of water)
          1. Improves after Atropine
14. Management: Emergency Department
    1. Atropine (Preservative-free) for pulmonary symptoms
       1. Adults: 2-5 mg IV q15 minutes prn pulmonary symptoms
       2. Child <12 years: 0.05 to 0.1 mg/kg q15 minutes prn
       3. Taper dose, and discontinue by 24 hours
    2. Pralidoxime chloride (2-PAMCl)
    3. Furosemide (Lasix) for pulmonary congestion
       1. Maximize Atropine prior to Furosemide use
       2. Dose: 40 to 160 mg IV prn pulmonary congestion
    4. Diazepam (Valium) for Seizures
       1. Adults: 5-10 mg IV push q5-10 minutes up to 30 mg
       2. Child >5 years: 0.2 to 0.5 mg/kg q5 minutes to 10 mg
       3. Child <5 years: 0.2 to 0.5 mg/kg q5 minutes to 5 mg
15. Management: Antidotes for Military (MARK I Kits)
    1. Preparations
       1. Atropine
          1. Effects muscarinic receptors more than nicotinic
             1. Decreases secretions and improves respiratory
          2. MARK I Auto-injectors contain 2 mg each
             1. 3 kits are given to each of U.S. military
       2. Pralidoxime chloride (Protopam chloride, 2-PAMCl)
       3. Diazepam
          1. Raises Seizure threshold
          2. Useful if Status Epilepticus ensues
          3. Administer if 3 MARK I Kits are given at same time
    2. Protocol (based on severity rated above)
       1. Mild to moderate vapor or liquid Nerve Agent Exposure
          1. Mark I kit (Atropine and 2-PAMCl): 1-2 doses
       2. Severe vapor or liquid Nerve Agent Exposure
          1. Mark I kit: 3 doses
          2. Diazepam (Valium)
16. Triage
    1. Immediate Management Indications (Antidotes)
       1. Severe nerve agent casualty if circulation intact
       2. Unconscious, convulsing, post-ictal or flaccid
       3. Difficult breathing or apnea
       4. Intact breathing and mentation with severe symptoms
    2. Minimal Management Indications
       1. Patient walking, talking with normal vital signs
       2. More reassuring if exposure to vapor nerve agent
    3. Delayed Management Indications
       1. Severe exposure post-stabilization
17. Return to work recommendations
    1. Nerve agent LD50 decreases for a second exposure
    2. Return when cholinesterase activity >75% baseline
       1. Severe exposure results in <30% activity
       2. Severe exposure requires >45 days for recovery
       3. Mild to moderate exposure is less reliably predicted
    3. Medically observe severe exposures for >1 week
18. Prevention
    1. Protective gear
       1. Chemical protective mask with Activated Charcoal
       2. Charcoal in chemical protective over-garment
       3. Butyl rubber in chemical protective gloves and boots
    2. Antidotal Enhancement ("Pretreatment")
       1. Pyridostigmine Bromide 30 mg PO q8h before exposure
    3. Research topics
       1. Seizure protection
          1. More reliable alternatives to Valium (e.g. Versed)
          2. Neuro-protective agents
       2. Nerve agent antidotes
          1. Circulating bio-scavengers for nerve agent
19. Complications: Long-term
    1. Neuropsychiatric changes may persist weeks to months
    2. Polyneuropathy
    3. Cognitive changes associated with prolonged Seizures
20. References
    1. Medical Response to Chemical Warfare and Terrorism
       1. US Army Medical Research Institute Chemical Defense
       2. Video-Teleconference: 4/20/00 to 4/22/99
       3. Video-Teleconference: 12/5/00 to 12/7/00
       4. Text: 3rd Edition, December 1998