Organophosphate toxicity
(Redirected from VX)
Background
- Organophosphates found in:
- Pesticides (e.g. malathion, diazinon)
- Chemical weapons (e.g. Sarin, nerve agents has been used as chemical weapon)
- medications (e.g. neostigmine, edrophonium
- Highly lipid soluble: absorbed via dermal, gastrointestinal or respiratory routes
- Colorless, odorless, low volatility, and high lipophilicity
- These compounds act as Acetylcholinesterase inhibitors
- Block acetylcholinesterase, resulting in excess accumulation of acetylcholine at the neuromuscular junction and cholinergic toxicity
- LD50 of 0.04mg/kg (10 mg). Death can occur within 15 minutes after absorption
Autonomic Nervous System Receptors and Their Effects
- Parasympathetic - ACh is transm
- Muscarinic
- receptors in heart, eye, lung, GI, skin and sweat glands
- Bradycardia
- Miosis
- Bronchorrhea / Bronchospasm
- Hyperperistalsis (SLUDGE)
- Sweating
- Vasodilation
- Nicotinic
- receptors in both sympathetic and parasympathetic nervous systems
- fasciculations, flaccid paralysis
- ?Mild bradycardia, hypotension
- Muscarinic
- Sympathetic
- Alpha effects (vessels, eye, skin)
- Mydriasis, hypertension, sweating
- Beta effects (heart, lungs)
- Tachycardia, bronchodilation
- Alpha effects (vessels, eye, skin)
Clinical Features
- Symptoms caused by acetylcholine buildup in CNS and PNS.
- CNS symptoms = headache, confusion, vertigo, seizures, coma
- Muscarinic Receptors
- SLUDGE(M) = Salivation, Lacrimation, Urination, Diarrhea, GI pain, Emesis, Miosis
- DUMBELLS = Diarrhea, diaphoresis, Urination, Miosis, Bradycardia, Bronchorrea, Emesis, Lacrimation, Lethargic, Salivation
- Nicotinic Receptors (NMJ)
- MTWThF (days of week) = Mydriasis/Muscle cramps, Tachycardia, Weakness, Twitching, Hypertension/Hyperglycemia, Fasciculations, Seizures, Somnolent
- Common causes of death in organophosphate toxicity
- Killers B's = Bradycardia, Bronchorrhea, Bronchospasm
Intermediate Syndrome
- 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
Differential Diagnosis
SLUDGE Syndrome
- Carbamate toxicity
- Mushroom toxicity, especially:
- Organophosphate toxicity
- Nerve agent
- Nicotine toxicity (look alike)
- Acetylcholinesterase inhibitor overdose (e.g in myasthenia gravis or post anesthesia reversal)
Weakness
- Neuromuscular weakness
- Upper motor neuron:
- CVA
- Hemorrhagic stroke
- Multiple sclerosis
- Amyotrophic Lateral Sclerosis (ALS) (upper and lower motor neuron)
- Lower motor neuron:
- Spinal and bulbar muscular atrophy (Kennedy's syndrome)
- Spinal cord disease:
- Infection (Epidural abscess)
- Infarction/ischemia
- Trauma (Spinal Cord Syndromes)
- Inflammation (Transverse Myelitis)
- Degenerative (Spinal muscular atrophy)
- Tumor
- Peripheral nerve disease:
- Neuromuscular junction disease:
- Muscle disease:
- Rhabdomyolysis
- Dermatomyositis
- Polymyositis
- Alcoholic myopathy
- Upper motor neuron:
- Non-neuromuscular weakness
- Can't miss diagnoses:
- ACS
- Arrhythmia/Syncope
- Severe infection/Sepsis
- Hypoglycemia
- Periodic paralysis (electrolyte disturbance, K, Mg, Ca)
- Respiratory failure
- Emergent Diagnoses:
- Symptomatic Anemia
- Severe dehydration
- Hypothyroidism
- Polypharmacy
- Malignancy
- Aortic disease - occlusion, stenosis, dissection
- Other causes of weakness and paralysis
- Acute intermittent porphyria (ascending weakness)
- Can't miss diagnoses:
Chemical weapons
- Blister chemical agents (Vesicants)
- Lewisite (L)
- Sulfur mustard (H)
- Phosgene oxime (CX)
- Pulmonary chemical agents (Choking agents)
- Incendiary agents
- Cyanide chemical weapon agents (Blood agents)
- Prussic acid (AKA hydrogen cyanide, hydrocyanic acid, or formonitrile)
- Nerve Agents (organophosphates)
- Acetylcholinesterase inhibitors
- Household and commercial pesticides (diazinon and parathion)
- G-series (sarin, tabun, soman)
- V-series (VX)
- Lacrimating or riot-control agents
- Pepper spray
- Chloroacetophenone
- CS
Symptomatic bradycardia
- Cardiac
- Inferior MI (involving RCA)
- Sick sinus syndrome
- Neurocardiogenic/reflex-mediated
- Increased ICP
- Vasovagal reflex
- Hypersensitive carotid sinus syndrome
- Intra-abdominal hemorrhage (i.e. ruptured ectopic)
- Metabolic/endocrine/environmental
- Hyperkalemia
- Hypothermia (Osborn waves on ECG)
- Hypothyroidism
- Hypoglycemia (neonates)
- Toxicologic
- Infectious/Postinfectious
- Other
Evaluation
Work-up
- CBC
- May show leukocytosis
- Comprehensive Metabolic Panel
- CXR
- Pulmonary edema in severe cases
- ECG
Diagnosis
- Clinical diagnosis
- Blood tests such as RBC and plasma pseudocholinesterase levels are available, but little clinical utility
Management
Decontamination
- 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
Supportive Care
- IVF, O2, Monitor
- Aggressive airway management is of utmost importance.
- Intubation often needed due to significant respiratory secretions / bronchospasm.
- Use nondepolarizing agent (Rocuronium or Vecuronium)
- Succinylcholine is absolutely contraindicated
- Benzodiazepines for seizures
Antidotes
- 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
- DuoDote
- Single autoinjector containing both medications
- Same doses as Mark 1: atropine 2 mg + 2-PAM 600 mg
- Mark 1
Antidotes
Atropine
- Competitively blocks muscarinic sites (does nothing for nicotinic-related muscle paralysis)
- May require massive dosage (hundreds of milligrams)
- Dosing[1]
- 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
- No max dose, doses >400mg have been reported[2]
Pralidoxime
- 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[3]
- Pralidoxime can actually bind and inhibit AChE once all AChE enzymes have aged, and can make the toxicity worse
- Window to aging depends on the agent, and is a matter of debate, but pralidoxime within 1-2 hours of exposure is the goal
- Dosing[1]
- 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.
Disposition
- 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
See Also
References
- ↑ 1.0 1.1 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
- ↑ Hopmann G, Wanke H. Höchstdosierte Atropinbehandlung bei schwerer Alkylphosphatvergiftung [Maximum dose atropin treatment in severe organophosphate poisoning (author's transl)]. Dtsch Med Wochenschr. 1974;99(42):2106-2108. doi:10.1055/s-0028-1108097
- ↑ Eddleston M, Szinicz L, Eyer P, Buckley, N (2002) Oximes in Acute Organophosphate Pesticide Poisoning: a Systematic Review of Clinical Trials. QJM. 95(5): 275–283.