Template:Cholinergic Toxicity Treatment: Difference between revisions

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*Aggressive airway management is of utmost importance.
*Aggressive airway management is of utmost importance.
**Intubation often needed due to significant  respiratory secretions / bronchospasm.
**Intubation often needed due to significant  respiratory secretions / bronchospasm.
**Use nondepolarizing agent ([[Rocuronium]] or [[Vecuronium]]).
**Use nondepolarizing agent ([[Rocuronium]] or [[Vecuronium]])
**Succinylcholine is absolutely contraindicated
*[[Benzodiazepines]] for seizures


===Antidotes===
===Antidotes===
*'''[[Atropine]]'''
*Dosing with atropine and pralidoxime are time dependent and provides ability to reverse symptoms while awaiting agent metabolism
**Competitively blocks muscarinic sites (does nothing for nicotinic-related muscle paralysis)
*For exposure to nerve agents, manufactured IM autoinjectors are available for rapid administration:
**May require massive dosage (hundreds of milligrams)
**Mark 1
**Dosing<ref name="CDC">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). [http://www.atsdr.cdc.gov/csem/cholinesterase/docs/cholinesterase.pdf PDF] Accessed 06/21/15</ref>  
***Contains 2 separate cartridges: atropine 2 mg + 2-PAM 600 mg
***Adult: Initial bolus of 2-6mg IV; titrate by doubling dose q5-30m until tracheobronchial secretions controlled
***Being phased out with newer kits
****Once secretions controlled → start IV gtt 0.02-0.08 mg/kg/hr
**DuoDote
***Child: 0.05-0.1mg/kg (at least 0.1mg) IV; repeat bolus q2-30m until tracheobronchial secretions controlled
***Single autoinjector containing both medications
****Once secretions controlled → start IV gtt 0.025 mg/kg/hr
***Same doses as Mark 1: atropine 2 mg + 2-PAM 600 mg
*'''[[Pralidoxime]]'''
 
**For Organophosphate poisoning only - reactivates AChE by removing phosphate group → oxime-OP complex then excreted by kidneys.
==Antidotes==
***This must be done before "aging" occurs - conformational change that makes OP bond to AChE irreversible.
===[[Atropine]]===
**Dosing<ref name="CDC" />
*Competitively blocks muscarinic sites (does nothing for nicotinic-related muscle paralysis)
***Adult: 1-2gm IV over 15-30min; repeat in 1 hour if needed '''or''' 50 mg/hr infusion.
*May require massive dosage (hundreds of milligrams)
***Child: 20-40mg/kg IV over 20min; repeat in 1 hour if needed '''or''' 10-20 mg/kg/hr infusion.
*Dosing<ref name="CDC">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). [http://www.atsdr.cdc.gov/csem/cholinesterase/docs/cholinesterase.pdf PDF] Accessed 06/21/15</ref>  
*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<ref>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</ref>
 
===[[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<ref>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.</ref>
**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<ref name="CDC"></ref>
**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.

Latest revision as of 19:05, 1 February 2021

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

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.
  1. ↑ 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
  2. ↑ 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
  3. ↑ 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.
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