Organophosphate toxicity: Difference between revisions
No edit summary |
|||
| Line 1: | Line 1: | ||
==Background== | ==Background== | ||
*Irreversibly binds acetylcholinesterase -> cholinergic crisis | *Highly lipid soluble: absorbed via dermal, gastrointestinal or respiratory routes | ||
*Irreversibly binds acetylcholinesterase -> accumulation of acetylcholine at sympathetic and parasympathetic receptors -->cholinergic crisis | |||
**Parasympathetic: SLUDGE | |||
*Used as insecticides (malathion) and chemical warfare (sarin, VX) | *Used as insecticides (malathion) and chemical warfare (sarin, VX) | ||
*Consider in ddx of pt w/ AMS + miotic pupils | *Consider in ddx of pt w/ AMS + miotic pupils | ||
==Clinical Features== | ==Clinical Features== | ||
*SLUDGE(MM) | |||
**'''S'''alivation, '''L'''acrimation, '''U'''rination, '''D'''iarrhea, '''G'''I pain, '''E'''mesis, '''M'''iosis, '''M'''uscle weakness | |||
*Killers B's | |||
**'''B'''radycardia, '''B'''ronchorrhea, '''B'''ronchospasm | |||
==Diagnosis== | ==Diagnosis== | ||
| Line 18: | Line 20: | ||
**Pulmonary edema in severe cases | **Pulmonary edema in severe cases | ||
*ECG | *ECG | ||
**Ventricular | **Ventricular dysrhythmias, torsades, QT prolongation, AV block | ||
==Differential Diagnosis== | ==Differential Diagnosis== | ||
| Line 32: | Line 34: | ||
==See Also== | ==See Also== | ||
[[Toxidromes]] | *[[Toxidromes]] | ||
*[[Atropine]] | |||
== | ==References== | ||
<references/> | |||
[[Category:Tox]] | [[Category:Tox]] | ||
Revision as of 20:05, 24 April 2015
Background
- Highly lipid soluble: absorbed via dermal, gastrointestinal or respiratory routes
- Irreversibly binds acetylcholinesterase -> accumulation of acetylcholine at sympathetic and parasympathetic receptors -->cholinergic crisis
- Parasympathetic: SLUDGE
- Used as insecticides (malathion) and chemical warfare (sarin, VX)
- Consider in ddx of pt w/ AMS + miotic pupils
Clinical Features
- SLUDGE(MM)
- Salivation, Lacrimation, Urination, Diarrhea, GI pain, Emesis, Miosis, Muscle weakness
- Killers B's
- Bradycardia, Bronchorrhea, Bronchospasm
Diagnosis
- CBC
- May show leukocytosis
- Lipase
- LFT
- CXR
- Pulmonary edema in severe cases
- ECG
- Ventricular dysrhythmias, torsades, QT prolongation, AV block
Differential Diagnosis
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
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 only requires decon and 6-8hr obs
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.