II. Types: Chemical Weapon - G Agents
- Characteristics
- Clear, colorless, tasteless liquids that dissolve in water and solvents
- Volatile at Ambient Temperature
- Aeroselize easily
- Degrade quickly
- Agents
- Tabun (GA)
- Sarin (GB)
- Soman (GD)
- GF Nerve Agent
III. Types: Chemical Weapon - V Agents
- Characteristics
- Long-lasting liquids which are easily absorbed via skin
- Rapidly fatal within minutes of inhalation, ingestion or skin exposure
- Agents
- VX Nerve Agent
IV. Types: Chemical Weapon - Fourth Generation
- Novichok Agents (Russian for "Newcomer")
- Organophosphate agents with 5-8 fold toxicity of VX agents
- Low volatility, but highly persistent as liquid on surfaces
- Dermal exposure is most common and effects may be delayed by days
- Inhalation or ingestion may also occur
- Developed in Soviet Union in 1970's and used in politically motivated assassinations
-
Carbamates (EA-3990, EA-4056)
- Non-Organophosphate agents with toxicity 3 fold higher than VX Nerve Agents
V. Types: Non-Chemical Weapons
- Pesticides and Insecticides (Organophosphates)
-
Acetylcholinesterase Inhibitors (accidental Poisoning in children taking an adult's neurologic medication)
- Rivastigmine
- Donezapil
- Tacrine
- Galantamine
VI. History
- Developed in Germany before World War II
- U.S. stockpiles included GB, VX
- Iraq has used Nerve Agents frequently
- Iran-Iraq war
- Kurdish Refugees
- Tokyo subway 1995
- Aum Shinrikyo cult used dilute sarin (GB)
VII. Pathophysiology
- Penetrates skin, eyes, and lungs
- Toxic effects manifest as Cholinergic Toxicity (with Acetylcholine accumulation)
- Results in irreversible phosphorylation and inactivation of Acetylcholinesterase
- Allows Acetylcholine to accumulate in Cholinergic nerve junctions resulting in muscarinic and nicotinic effects
-
Organophosphate esters (Acetylcholinesterase Inhibitors)
- Nerve Agents (e.g. Type G and Type V) are the most toxic of Chemical Warfare Agents
- Similar to Insecticide Organophosphates (e.g. Malathion), but far more potent
- Even single drops of some Nerve Agents are lethal within 15 minutes of exposure
- Nerve Agents (e.g. Type G and Type V) are the most toxic of Chemical Warfare Agents
VIII. Adverse Effects: Lethal doses
- Skin LD50 (from least to most toxic)
- GA, GB: 1000, 1700 mg
- GD, GF: 50, 30 mg
- VX: 10 mg
- Vapor LCt50 (from least to most toxic)
- GA: 400 mg-min/m3
- GB: 100 mg-min/m3
- GD: 70 mg-min/m3
- GF: Unknown
- VX: 50 mg-min/m3
IX. Signs: General
- See Cholinergic Toxicity
- Children - common presentation (initially misdiagnosed in 80% of cases)
- Cholinergic Muscarinic affects
- Cholinergic Nicotinic affects
- Muscle Weakness and hypotonia
- Lethargy
- Tachycardia (contrast with Bradycardia in adults)
- Apnea
- Seizure
- Adults - common presentations
- Cholinergic Muscarinic affects are prominent
- Excessive Salivation and Lacrimation
- Urination and Defecation
- Cholinergic Nicotinic affects are also present
- Muscle Fasciculations and weakness
- Paralysis
- Respiratory arrest
- Altered Mental Status
- Autonomic instability
- Cholinergic Muscarinic affects are prominent
X. Signs: Muscarinic Receptor (Smooth Muscle, glands)
- Increased Glandular secretion ("All faucets on")
- Salivation
- Lacrimation
- Rhinorrhea
- Airway secretions
- Sweating
- Ocular
- Miosis
- Eye Pain
- Dim or Blurred Vision
- Conjunctival injection
- Respiratory
- Bronchoconstriction
- Central Apnea within minutes of severe exposure
- Gastrointestinal
XI. Signs: Nicotinic Receptors (Skeletal Muscle, Ganglia)
- Skeletal Muscle changes
- Initial
- Later
- Weakness
- Flaccid Paralysis
- Ganglionic effects
- Cardiovascular Effects
- Heart Block
- Ventricular Arrhythmia
- Neurologic Effects
- Onset
- Vapor: 1 minute of large exposure
- Skin contact: 1-30 minutes
- Acute
- Loss of consciousness
- Seizures
- Apnea
- Prolonged (4-6 weeks)
- Forgetfulness
- Inability to concentrate fully
- Insomnia
- Bad dreams
- Irritability
- Impaired judgment
- Depression
- No frank confusion or Hallucination
- Onset
XII. Grading: Severity of exposure (used to dose antidote)
- Vapor Exposure (Effect in seconds, Peaks in minutes)
- Low Exposure
- High Exposure
- Liquid Exposure
- Small amount (delayed effects up to 18 hours)
- Localized sweating
- Fasciculations
- Moderate amount (delayed effects up to 18 hours)
- Gastrointestinal effects
- Large amount (Effects within 30 minutes)
- Small amount (delayed effects up to 18 hours)
XIII. Differential Diagnosis
- See Cholinergic Toxicity
- Children (misdiagnosed initially in 80% of cases)
- Adults
XIV. Labs: General
- See Poisoning
-
Troponin
- Reflects myocardial injury
-
Lactic Acid
- Decreased
XV. Labs: Detection
- Odor
- Fish or fruit
- Detection kits
- M256A1: GB, VX (unknown threshold for GF, GA, GD)
- M272: GA, GB, GD, VX
- MINICAMS: GB, GD, VX
- ICAD: GA, GB, GD
- M18A2: GB, VX
- M21: GA, GB, GD
- M90: GA, GB, GD, GF, VX
- M93A1 Fox: GB, GD, VX
- ACAMS: GB, VX
- Bubbler: GB, VX
- CAM: GA, GB, GD, GF, VX
- DAAMS: GB, VX
XVI. Labs: Diagnosis (Obtain prior to therapy if possible)
- Plasma Pseudocholinesterase Level (easiest to measure)
- Decreased after exposure
- Erythrocyte Cholinesterase activity (best reflects clinical activity)
- Severe Nerve Agent Exposure results in <30% baseline
- Return to exposure risk when level >75% baseline
XVII. Management: General
- Medical providers wear full protective gear and mask
- Level C Personal Protection Equipment
- Risk of patient off-gassing
-
Decontamination
- Vapor
- Remove all clothing (risk of trapped vapor)
- Liquid
- Hypochlorite
- M291
- M258A1
- Blot skin with cloth to remove any visible product
- Wash with soap and copious water irrigation of all contacted areas
- Vapor
XVIII. Management: Antidotes for Military in field (MARK I Kits)
- Preparations: Kit contents
- Kits contain and autoinjector with both Atropine and 2-PAM (and separate Diazepam)
- Three kits are given to each of U.S. military
- Atropine
- Effects Muscarinic Receptors more than nicotinic
- Decreases secretions and improves respiratory status
- MARK I Auto-injectors contain 2 mg Atropine per injector
- Effects Muscarinic Receptors more than nicotinic
- Pralidoxime chloride (Protopam chloride, 2-PAMCl)
- MARK I Auto-injectors contain 600 mg of 2-PAM per injector
- Diazepam (also contained in kit, but is not in autoinjector)
- Raises Seizure threshold
- Useful if Status Epilepticus ensues
- Administer if 3 MARK I Kits are given at same time
- Kits contain and autoinjector with both Atropine and 2-PAM (and separate Diazepam)
- Protocol (based on severity rated above)
XIX. Management: Triage (Field)
- See Personal Protection Equipment
- See Contaminated Casualty Management
- See Decontamination
- See Decontamination in Children
- Immediate Management Indications (Antidotes)
- Severe Nerve Agent casualty if circulation intact
- Unconscious, convulsing, post-ictal or flaccid
- Difficult breathing or apnea
- Intact breathing and mentation with severe symptoms
- Minimal Management Indications
- Patient walking, talking with normal Vital Signs and no Miosis
- More reassuring if exposure to vapor Nerve Agent
- Delayed Management Indications
- Severe exposure post-stabilization
XX. Management: Emergency Department
- See Poisoning
- See Personal Protection Equipment
- See Contaminated Casualty Management
- See Decontamination
- See Decontamination in Children
- Supportive Care
- ABC Management
- Observe for Cardiac Arrhythmia
- Ingestions
- Immediate Activated Charcoal may be given in awake, alert patients able to swallow
- Do not induce Vomiting
- Mechanical Ventilation
- Do NOT use Succinylcholine (metabolized by Acetylcholinesterase)
- Results in prolonged effects
- Use Rocuronium instead
- Usually required for 30 minutes to 3 hours
- Airway resistance high (50-70 cm of water)
- Improves after Atropine
- Do NOT use Succinylcholine (metabolized by Acetylcholinesterase)
- Antidotes in the emergency department (see field kits above)
- Atropine (Preservative-free) for bronchorrhea, bronchospasm, Bradycardia (muscarinic effects)
- Goal: Drying of secretions (will not reverse neuromuscular effects, Muscle Weakness or Respiratory Failure)
- Repeat doses until Shortness of Breath and Wheezing resolve and excess secretions reduce
- Adult: 1-2 mg slow IV push (up to 2-5 mg IV) every 15 minutes as needed
- May be given as often as every 3-5 minutes, doubling dose
- Most effective for pulmonary symptoms in adults
- Very high doses (e.g. 40 mg) may be needed
- Child <12 years: 0.015 to 0.05 mg/kg slow IV push (up to 0.1 mg/kg) every 15 minutes as needed
- May be given as often as every 3-5 minutes, doubling dose
- Most effective for CNS symptoms in children
- Taper dose, and discontinue by 24 hours
- Atropine may be continued as drip at 0.5 to 2.4 mg/kg/h
- Indicated for persistent symptoms (up to 48 hours may be needed in severe cases)
- Goal: Drying of secretions (will not reverse neuromuscular effects, Muscle Weakness or Respiratory Failure)
- Pralidoxime chloride (2-PAMCl)
- Indicated with Atropine in Nerve Agent and non-carbamate Organophosphate exposures
- 2-PAMCl is not needed in carbamate InsecticidePoisoning (reversible)
- Goal: Reverse muscle Fasciculations, Muscle Weakness to Flaccid Paralysis and coma (nicotinic effects)
- 2-PAMCl cleaves agent-Acetylcholinesterase bond, freeing the Acetylcholinesterase for activity
- Only administer in combination with Atropine
- Without Atropine, 2-PAMCl alone may inhibit Acetylcholinesterase
- Most effective if given within minutes (to maximum of hours) of exposure
- Nerve Agents irreversibly bind Acetylcholinesterase over time ("aging")
- May have effect at 24-48 hours
- Liberally administer doses even with mild effects (Neurotoxins may have delayed effect)
- Treatment may need to be continued longer (esp. fat soluble compounds)
- May continue as infusion (e.g. in adults, 500 mg/h IV)
- Adult
- Dose: 2 g IM or 1 to 2 g IV (in 100 ml saline as infusion)
- May repeat in 30-60 minutes (if Muscle Weakness not improved), then every 6-8 hours as needed
- Child
- IV: 25 to 50 mg/kg up to 1 to 2 g in 200 ml D5W or NS IV over 15-30 min OR
- IM: 50 mg/kg up to 2 g IM
- May repeat in 30-60 minutes (if Muscle Weakness not improved), then every 6-8 hours as needed
- Indicated with Atropine in Nerve Agent and non-carbamate Organophosphate exposures
- Atropine (Preservative-free) for bronchorrhea, bronchospasm, Bradycardia (muscarinic effects)
- Other specific agents
- Diazepam (Valium) for Seizures
- May use other Benzodiazepines (e.g. Midazolam, Lorazepam)
- Non-Benzodiazepine anticonvulsants are not effective for Cholinergic crisis
- Adult: 5-10 mg IV push q5-10 minutes up to 30 mg
- Child >5 years: 0.2 to 0.5 mg/kg q5 minutes to 10 mg
- Child <5 years: 0.2 to 0.5 mg/kg q5 minutes to 5 mg
- Furosemide (Lasix) for pulmonary congestion has been used
- Maximize Atropine prior to Furosemide use
- Dose: 40 to 160 mg IV prn pulmonary congestion
- Diazepam (Valium) for Seizures
- Disposition
- Symptomatic Exposure
- Observe >8 hours for respiratory decompensation
- Asymptomatic Exposure
- Observe for 4 to 6 hours and may discharge if continues to be asymptomatic
- Symptomatic Exposure
XXI. Management: Return to work recommendations
XXII. Prevention
- Protective gear
- Chemical protective mask with Activated Charcoal
- Charcoal in chemical protective over-garment
- Butyl Rubber in chemical protective gloves and boots
- Antidotal Enhancement ("Pretreatment")
- Pyridostigmine Bromide 30 mg PO q8h before exposure
- Research topics
XXIII. Complications: Long-term
- Neurotoxicity symptoms may be delayed 1 to 3 weeks after exposure (rare)
- Neuropsychiatric changes may persist weeks to months
- Polyneuropathy
- Cognitive changes associated with prolonged Seizures
XXIV. Resources
- Nerve Agents (Wikipedia)
XXV. References
- (2016) CALS Manual, 14th ed, p. I-135-7
- Seeyave (2015) Crit Dec Emerg Med 29(5): 13-21
- Tagliaferro (2023) Crit Dec Emerg Med 37(1): 21-9
- Tomaszewski (2020) Crit Dec Emerg Med 34(10): 24
- Koh (2017) Crit Dec Emerg Med 31(5): 24
- Medical Response to Chemical Warfare and Terrorism
- US Army Medical Research Institute Chemical Defense
- Video-Teleconference: 4/20/00 to 4/22/99
- Video-Teleconference: 12/5/00 to 12/7/00
- Text: 3rd Edition, December 1998