- 1 Background
- 2 Clinical Features
- 3 Differential Diagnosis
- 4 Evaluation
- 5 Management
- 6 Antidotes
- 7 Disposition
- 8 See Also
- 9 References
- Organophosphate nerve agent has been used as chemical weapon
- Colorless, odorless, low volatility, and high lipophilicity
- LD50 of 0.04mg/kg (10 mg). Death can occur within 15 minutes after absorption
- Blocks acetylcholinesterase enzyme causing excess accumulation of acetylcholine at the neurojunction and cholinergic poisoning
- Highly lipid soluble: absorbed via dermal, gastrointestinal or respiratory routes
- Binds acetylcholinesterase → accumulation of acetylcholine at receptor sites → cholinergic crisis
- Used as insecticides (malathion) and chemical warfare (sarin, VX)
- Over 100 regularly used organophosphate compounds today.
- Symptoms caused by acetylcholine buildup in CNS and PNS.
- CNS symptoms = headache, confusion, coma, vertigo
- Muscarinic Receptors
- SLUDGE(M) = Salivation, Lacrimation, Urination, Diarrhea, GI pain, Emesis, Miosis
- Nicotinic Receptors (NMJ)
- Muscle weakness, fasciculations, paralysis
- Common causes of death in organophosphate toxicity
- Killers B's = Bradycardia, Bronchorrhea, Bronchospasm
- Syndrome that occurs 24-96 hours after acute cholinergic crisis.
- Proximal muscle weakness, cranial nerve palsies
- Can last for days - weeks
- May require mechanical ventilation
- Neuromuscular weakness
- Upper motor neuron:
- Lower motor neuron:
- Spinal and bulbar muscular atrophy (Kennedy's syndrome)
- Spinal cord disease:
- Peripheral nerve disease:
- NMJ disease:
- Muscle disease:
- Non-neuromuscular weakness
- Can't miss diagnoses:
- Emergent Diagnoses:
- Other causes of weakness and paralysis
- Acute intermittent porphyria (ascending weakness)
- Blister chemical agents (Vesicants)
- Pulmonary chemical agents
- Incendiary agents
- Cyanide chemical weapon agents
- Nerve Agents
- Inferior MI (involving RCA)
- Sick Sinus Syndrome
- May show leukocytosis
- Comprehensive Metabolic Panel
- Pulmonary edema in severe cases
- Ventricular dysrhythmias, torsades, QT prolongation, AV block
- Clinical diagnosis
- Blood tests such as RBC and plasma pseudocholinesterase levels are available, but little clinical utility
- Providers should wear appropriate PPE during decontamination.
- Neoprene or nitrile gloves and gown (latex and vinyl are ineffective)
- Dispose of all clothes in biohazard container
- Wash patient with soap and water
- IVF, O2, Monitor
- Aggressive airway management is of utmost importance.
- Dosing with atropine and pralidoxime are time dependent and provides ability to reverse symptoms while awaiting agent metabolism
- For exposure to nerve agents, manufactured IM autoinjectors are available for rapid administration:
- Mark 1
- Contains 2 separate cartridges: atropine 2 mg + 2-PAM 600 mg
- Being phased out with newer kits
- Single autoinjector containing both medications
- Same doses as Mark 1: atropine 2 mg + 2-PAM 600 mg
- Mark 1
- Competitively blocks muscarinic sites (does nothing for nicotinic-related muscle paralysis)
- May require massive dosage (hundreds of milligrams)
- Adult: Initial bolus of 2-6mg IV; titrate by doubling dose q5-30m until tracheobronchial secretions controlled
- Once secretions controlled → start IV gtt 0.02-0.08 mg/kg/hr
- Child: 0.05-0.1mg/kg (at least 0.1mg) IV; repeat bolus q2-30m until tracheobronchial secretions controlled
- Once secretions controlled → start IV gtt 0.025 mg/kg/hr
- AKA 2-PAM
- For Organophosphate poisoning only - reactivates AChE by removing phosphate group → oxime-OP complex then excreted by kidneys.
- This must be done before "aging" occurs - conformational change that makes OP bond to AChE irreversible.
- Adult: 1-2gm IV over 15-30min; repeat in 1 hour if needed or 50 mg/hr infusion.
- Child: 20-40mg/kg IV over 20min; repeat in 1 hour if needed or 10-20 mg/kg/hr infusion.
- Minimal exposure + asymptomatic at least 12 hours after exposure can likely be discharged.
- Admit all symptomatic patients!
- If evidence of deliberate self harm, place on hold and consult psychiatry
- Agency for Toxic Substances and Disease Registry, Case Studies in Environmental Medicine, Cholinesterase Inhibitors: Including Pesticides and Chemical Warfare Nerve Agents. Centers for Disease Control (CDC). PDF Accessed 06/21/15