II. Types: G Agents

  1. Characteristics
    1. Clear, colorless, tasteless liquids that dissolve in water and solvents
    2. Volatile at Ambient Temperature
    3. Aeroselize easily
    4. Degrade quickly
  2. Agents
    1. Tabun (GA)
    2. Sarin (GB)
    3. Soman (GD)
    4. GF Nerve Agent

III. Types: V Agents

  1. Characteristics
    1. Long-lasting liquids which are easily absorbed via skin
    2. Rapidly fatal within minutes of inhalation, ingestion or skin exposure
  2. Agents
    1. VX Nerve Agent

IV. Types: Pesticides

  1. Organophosphate
  2. Organophosphate Poisoning Management
  3. Cholinergic Toxicity

V. 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)

VI. Pathophysiology

  1. Penetrates skin, eyes, and lungs
  2. Toxic effects manifest as Cholinergic Toxicity
  3. Organophosphate esters (Acetylcholinesterase inhibitors)
    1. Most toxic of chemical agents
    2. Similar to Insecticide Organophosphates (e.g. Malathion), but far more potent
    3. Even single drops of some Nerve Agents are lethal within 15 minutes of exposure

VII. Adverse Effects: 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

VIII. Signs: General

  1. See Cholinergic Toxicity
  2. Children - common presentation (initially misdiagnosed in 80% of cases)
    1. Cholinergic Muscarinic affects
      1. Miosis
      2. Excessive Salivation
    2. Cholinergic Nicotinic affects
      1. Muscle Weakness and hypotonia
      2. Lethargy
      3. Tachycardia (contrast with Bradycardia in adults)
      4. Apnea
      5. Seizure
  3. Adults - common presentations
    1. Cholinergic Muscarinic affects are prominent
      1. Excessive Salivation and Lacrimation
      2. Urination and Defecation
    2. Cholinergic Nicotinic affects are also present
      1. Muscle fasciculations and weakness
      2. Paralysis
      3. Respiratory arrest
      4. Altered Mental Status
      5. Autonomic instability

IX. 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

X. 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

XI. Grading: 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

XII. Differential Diagnosis

  1. See Cholinergic Toxicity
  2. Children (misdiagnosed initially in 80% of cases)
    1. Head Trauma
    2. Cerebral Aneurysm
    3. Heat Stroke
    4. Diabetic Ketoacidosis
  3. Adults
    1. Syncope
    2. Heat Stroke
    3. Drug Overdose
    4. Alcohol Intoxication
    5. Cyanide
      1. No increased secretions
      2. No Miosis
      3. Cyanosis uncommon

XIII. Labs: 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

XIV. Labs: Diagnosis (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

XV. Management: General

  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

XVI. Management: Antidotes for Military in field (MARK I Kits)

  1. Preparations: Kit contents
    1. Kits contain and autoinjector with both Atropine and 2-PAM (and separate Diazepam)
      1. Three kits are given to each of U.S. military
    2. Atropine
      1. Effects muscarinic receptors more than nicotinic
        1. Decreases secretions and improves respiratory status
      2. MARK I Auto-injectors contain 2 mg Atropine per injector
    3. Pralidoxime chloride (Protopam chloride, 2-PAMCl)
      1. MARK I Auto-injectors contain 600 mg of 2-PAM per injector
    4. Diazepam (also contained in kit, but is not in autoinjector)
      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. Mark I auto-injectors may be used in children >2 years old and >12 kg
    2. Mild to moderate vapor or liquid Nerve Agent Exposure
      1. Mark I kit (Atropine and 2-PAMCl): 1-2 doses
    3. Severe vapor or liquid Nerve Agent Exposure
      1. Mark I kit: 3 doses
      2. Diazepam (Valium)

XVII. Management: Triage (Field)

  1. See Personal Protection Equipment
  2. See Contaminated Casualty Management
  3. See Decontamination
  4. See Decontamination in Children
  5. 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
  6. Minimal Management Indications
    1. Patient walking, talking with normal Vital Signs
    2. More reassuring if exposure to vapor Nerve Agent
  7. Delayed Management Indications
    1. Severe exposure post-stabilization

XVIII. Management: Emergency Department

  1. See Personal Protection Equipment
  2. See Contaminated Casualty Management
  3. See Decontamination
  4. See Decontamination in Children
  5. Antidotes in the emergency department (see field kits above)
    1. Atropine (Preservative-free) for pulmonary, muscarinic and CNS symptoms
      1. Goal: Drying of secretions (will not reverse neuromuscular effects, Muscle Weakness or respiratory failure)
      2. Adult: 1-2 mg slow IV push (up to 2-5 mg IV) every 15 minutes as needed
        1. May be given as often as every 3-5 minutes
        2. Most effective for pulmonary symptoms in adults
      3. Child <12 years: 0.015 to 0.05 mg/kg slow IV push (up to 0.1 mg/kg) every 15 minutes as needed
        1. May be given as often as every 3-5 minutes
        2. Most effective for CNS symptoms in children
      4. Taper dose, and discontinue by 24 hours
      5. Atropine may be continued as drip at 0.5 to 2.4 mg/kg/h
        1. Indicated for persistent symptoms (up to 48 hours may be needed in severe cases)
    2. Pralidoxime chloride (2-PAMCl)
      1. Goal: Reverse fasciculations and coma
      2. Most effective if given within minutes (to maximum of hours) of exposure
        1. May have effect at 24-48 hours
        2. Treatment may need to be continued longer (esp. fat soluble compounds)
          1. May continue as infusion (e.g. in adults, 500 mg/h IV)
      3. Adult: 1 g IV or 2 g IM
        1. May repeat in 30-60 minutes, then every 6-8 hours as needed
      4. Child
        1. IV: 25 mg/kg up to 1 g in 200 ml D5W or NS IV over 15 min OR
        2. IM: 50 mg/kg up to 2 g IM
        3. May repeat in 30-60 minutes, then every 6-8 hours as needed
  6. Other specific agents
    1. Diazepam (Valium) for Seizures (other anticonvulsants are not effective)
      1. Adult: 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
    2. Furosemide (Lasix) for pulmonary congestion has been used
      1. Maximize Atropine prior to Furosemide use
      2. Dose: 40 to 160 mg IV prn pulmonary congestion
  7. Supportive Care
    1. ABC Management
    2. Observe for cardiac arrhythmia
    3. Ingestions
      1. Immediate Activated Charcoal may be given in awake, alert patients able to swallow
      2. Do not induce Vomiting
    4. Mechanical Ventilation
      1. Usually required for 30 minutes to 3 hours
      2. Airway resistance high (50-70 cm of water)
        1. Improves after Atropine

XIX. Management: 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

XX. 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

XXI. Complications: Long-term

  1. Neuropsychiatric changes may persist weeks to months
  2. Polyneuropathy
  3. Cognitive changes associated with prolonged Seizures

XXII. References

  1. (2016) CALS Manual, 14th ed, p. I-135-7
  2. Seeyave (2015) Crit Dec Emerg Med 29(5): 13-21
  3. 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

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Ontology: Sarin (C0036233)

Definition (MSH) An organophosphorus ester compound that produces potent and irreversible inhibition of cholinesterase. It is toxic to the nervous system and is a chemical warfare agent.
Concepts Hazardous or Poisonous Substance (T131) , Organophosphorus Compound (T115)
MSH D012524
SnomedCT 70846008
English Sarin, Phosphonofluoridic acid, methyl-, 1-methylethyl ester, Phosphonofluoridate, o-Isopropylmethyl, o Isopropylmethyl Phosphonofluoridate, o-Isopropylmethyl Phosphonofluoridate, Phosphonofluoridate, ortho-Isopropylmethyl, ortho Isopropylmethyl Phosphonofluoridate, ortho-Isopropylmethyl Phosphonofluoridate, Sarin [Chemical/Ingredient], sarin, Isopropyl methylphosphonofluoridate, Nerve agent GB, Sarin (substance)
Swedish Sarin
Czech sarin
Finnish Sariini
Russian ZARIN, ЗАРИН
Japanese サリン
Spanish Sarín, sarina (sustancia), sarina
Polish Sarin
French Sarin
German Sarin, Methylfluorphosphonsäureisopropylester
Italian Sarin
Portuguese Sarina

Ontology: Soman (C0037643)

Definition (MSH) An organophosphorus compound that inhibits cholinesterase. It causes seizures and has been used as a chemical warfare agent.
Concepts Pharmacologic Substance (T121) , Hazardous or Poisonous Substance (T131) , Organophosphorus Compound (T115)
MSH D012999
SnomedCT 363650003
English Methylphosphonofluoridate, Pinacolyl, Pinacolyl Methylphosphonofluoridate, Soman, Phosphonofluoridic acid, methyl-, 1,2,2-trimethylpropyl ester, Soman - nerve agent, Soman [Chemical/Ingredient], soman, Nerve agent GD, Soman - nerve agent (substance)
Swedish Soman
Czech soman
Finnish Somaani
Russian ZOMAN, ЗОМАН
Japanese ソマン
Polish Soman
Spanish soman - agente nervioso (sustancia), soman - agente nervioso, Soman
French Soman
German Soman
Italian Soman
Portuguese Soman

Ontology: tabun (C0075762)

Concepts Hazardous or Poisonous Substance (T131) , Organophosphorus Compound (T115)
MSH C009374
SnomedCT 363648006
English dimethylphosphoramidocyanidic acid, ethyl ester, N,N-dimethylamido-O-ethyl cyanophosphate, tabun, Tabun - nerve agent, Nerve agent GA, O-ethyl dimethylamidophosphorylcyanide, Tabun - nerve agent (substance), Tabun
Spanish tabun - agente nervioso (sustancia), tabun - agente nervioso

Ontology: Nerve agent (C1113670)

Concepts Hazardous or Poisonous Substance (T131)
SnomedCT 363647001
English Nerve agent - chemical warfare agent, agent nerve, agents nerve, nerve agent, Nerve agent - chemical warfare agent (substance), Nerve agent
Spanish agente neurotóxico (sustancia), agente neurotóxico, guerra química, agente neurotóxico