Template:Cholinergic Toxicity Treatment: Difference between revisions
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==Antidotes==
==Antidotes==
===[[Atropine]]===
===[[Atropine]]===
*Competitively blocks muscarinic sites (does nothing for nicotinic-related muscle paralysis)
*'''First-line antidote''' — muscarinic antagonist; treats bronchorrhea, bronchospasm, bradycardia, and secretions<ref>Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008;371(9612):597-607. doi:10.1016/S0140-6736(07)61202-1</ref>
*May require massive dosage (hundreds of milligrams)
*'''Does NOT reverse nicotinic symptoms''' (weakness, fasciculations, paralysis)
*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>  
*Starting dose: {{MedicationDose|drug=Atropine|dose=1-2 mg IV (double q5min until atropinization)|route=IV|context=Cholinergic toxicity antidote (muscarinic)|indication={{PAGENAME}}|population=Adult|notes=May need 100+ mg in first 24h; endpoint is drying of secretions}}
*Adult: Initial bolus of 2-6mg IV; titrate by doubling dose q5-30m until tracheobronchial secretions controlled
*Pediatric: {{MedicationDose|drug=Atropine|dose=0.02-0.05 mg/kg IV (min 0.1 mg), double q5min|route=IV|context=Cholinergic toxicity antidote (muscarinic)|indication={{PAGENAME}}|population=Pediatric}}
**Once secretions controlled → start IV gtt 0.02-0.08 mg/kg/hr
*'''Doubling protocol''': If inadequate response after 5 minutes, double the dose (1 → 2 → 4 → 8 → 16 mg...) until atropinization is achieved<ref>Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008;371(9612):597-607. doi:10.1016/S0140-6736(07)61202-1</ref>
**Child: 0.05-0.1mg/kg (at least 0.1mg) IV; repeat bolus q2-30m until tracheobronchial secretions controlled
*Massive doses may be required — total doses of 100+ mg in the first 24 hours have been reported<ref>Eddleston M, Chowdhury FR. Pharmacological treatment of organophosphorus insecticide poisoning: the old and the (possible) new. Br J Clin Pharmacol. 2016;81(3):462-470. doi:10.1111/bcp.12784</ref>
**Once secretions controlled → start IV gtt 0.025 mg/kg/hr
*'''Endpoints of adequate atropinization''' (goal of therapy):
*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>
**Drying of bronchial secretions ('''most important endpoint''')
**Heart rate >80 bpm
**Systolic BP >80 mmHg
*'''Do NOT target''': Fully dilated pupils, absent bowel sounds, or HR >150 — these indicate atropine toxicity<ref>Mitra RL, Mohan S. Anaesthesia and organophosphorus poisoning. World Federation of Societies of Anaesthesiologists. Anaesthesia Tutorial of the Week. 2011.</ref>
*After initial atropinization: Consider atropine infusion (10-20% of loading dose per hour) to maintain effect
*'''Optimize oxygenation before giving atropine''' to reduce risk of dysrhythmias (though in resource-limited settings, do not withhold atropine waiting for oxygen)<ref>Eddleston M, Chowdhury FR. Pharmacological treatment of organophosphorus insecticide poisoning: the old and the (possible) new. Br J Clin Pharmacol. 2016;81(3):462-470. doi:10.1111/bcp.12784</ref>
 


===[[Pralidoxime]]===
===[[Pralidoxime]]===
*AKA 2-PAM
*AKA 2-PAM
*For Organophosphate poisoning only - reactivates AChE by removing phosphate group → oxime-OP complex then excreted by kidneys.
*Oxime that reactivates phosphorylated AChE → primarily reverses '''nicotinic''' symptoms (weakness, fasciculations, respiratory muscle paralysis)<ref>Bhatt MH, Bhatt S. Pralidoxime. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024.</ref>
**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>
*'''Must give atropine BEFORE pralidoxime''' to prevent worsening of muscarinic symptoms
**Pralidoxime can actually bind and inhibit AChE once all AChE enzymes have aged, and can make the toxicity worse
*'''Must be given before aging occurs''' (see [[#Aging and Oxime Window|aging table above]])
**Window to aging depends on the agent, and is a matter of debate, but pralidoxime within 1-2 hours of exposure is the goal
*{{MedicationDose|drug=Pralidoxime|dose=1-2 g IV over 15-30 min, then 8-10 mg/kg/hr infusion (or repeat bolus in 1 hr)|route=IV|context=Cholinergic toxicity (oxime reactivator)|indication={{PAGENAME}}|population=Adult}}
*Dosing<ref name="CDC"></ref>
*Pediatric: {{MedicationDose|drug=Pralidoxime|dose=20-50 mg/kg IV, then 5-10 mg/kg/hr infusion|route=IV|context=Cholinergic toxicity (oxime reactivator)|indication={{PAGENAME}}|population=Pediatric}}
**Adult: 1-2gm IV over 15-30min; repeat in 1 hour if needed '''or''' 50 mg/hr infusion.
*Continue until clinical improvement or patient is off ventilator
**Child: 20-40mg/kg IV over 20min; repeat in 1 hour if needed '''or''' 10-20 mg/kg/hr infusion.
*'''Controversies''':
**Evidence for benefit of pralidoxime is inconsistent; several meta-analyses have not shown clear mortality benefit when added to atropine<ref>Peter JV, Sudarsan TI, Moran JL. Clinical features of organophosphate poisoning: A review of different classification systems and approaches. Indian J Crit Care Med. 2014;18(11):735-745. doi:10.4103/0972-5229.144017</ref>
**However, per AHA 2023 guidelines and expert consensus, oximes should still be given for significant OP poisoning, particularly when fasciculations, weakness, or paralysis are present<ref>Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008;371(9612):597-607. doi:10.1016/S0140-6736(07)61202-1</ref>
**Efficacy depends on timing (before aging), dose, and the specific OP compound involved
*'''Caution''': Administer slowly — rapid IV push can cause hypertensive crisis, cardiac arrest

Latest revision as of 01:08, 21 March 2026

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

  • First-line antidote — muscarinic antagonist; treats bronchorrhea, bronchospasm, bradycardia, and secretions[1]
  • Does NOT reverse nicotinic symptoms (weakness, fasciculations, paralysis)
  • Starting dose: Atropine 1-2 mg IV (double q5min until atropinization) IV — May need 100+ mg in first 24h; endpoint is drying of secretions
  • Pediatric: Atropine 0.02-0.05 mg/kg IV (min 0.1 mg), double q5min IV
  • Doubling protocol: If inadequate response after 5 minutes, double the dose (1 → 2 → 4 → 8 → 16 mg...) until atropinization is achieved[2]
  • Massive doses may be required — total doses of 100+ mg in the first 24 hours have been reported[3]
  • Endpoints of adequate atropinization (goal of therapy):
    • Drying of bronchial secretions (most important endpoint)
    • Heart rate >80 bpm
    • Systolic BP >80 mmHg
  • Do NOT target: Fully dilated pupils, absent bowel sounds, or HR >150 — these indicate atropine toxicity[4]
  • After initial atropinization: Consider atropine infusion (10-20% of loading dose per hour) to maintain effect
  • Optimize oxygenation before giving atropine to reduce risk of dysrhythmias (though in resource-limited settings, do not withhold atropine waiting for oxygen)[5]


Pralidoxime

  • AKA 2-PAM
  • Oxime that reactivates phosphorylated AChE → primarily reverses nicotinic symptoms (weakness, fasciculations, respiratory muscle paralysis)[6]
  • Must give atropine BEFORE pralidoxime to prevent worsening of muscarinic symptoms
  • Must be given before aging occurs (see aging table above)
  • Pralidoxime 1-2 g IV over 15-30 min, then 8-10 mg/kg/hr infusion (or repeat bolus in 1 hr) IV
  • Pediatric: Pralidoxime 20-50 mg/kg IV, then 5-10 mg/kg/hr infusion IV
  • Continue until clinical improvement or patient is off ventilator
  • Controversies:
    • Evidence for benefit of pralidoxime is inconsistent; several meta-analyses have not shown clear mortality benefit when added to atropine[7]
    • However, per AHA 2023 guidelines and expert consensus, oximes should still be given for significant OP poisoning, particularly when fasciculations, weakness, or paralysis are present[8]
    • Efficacy depends on timing (before aging), dose, and the specific OP compound involved
  • Caution: Administer slowly — rapid IV push can cause hypertensive crisis, cardiac arrest
  1. ↑ Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008;371(9612):597-607. doi:10.1016/S0140-6736(07)61202-1
  2. ↑ Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008;371(9612):597-607. doi:10.1016/S0140-6736(07)61202-1
  3. ↑ Eddleston M, Chowdhury FR. Pharmacological treatment of organophosphorus insecticide poisoning: the old and the (possible) new. Br J Clin Pharmacol. 2016;81(3):462-470. doi:10.1111/bcp.12784
  4. ↑ Mitra RL, Mohan S. Anaesthesia and organophosphorus poisoning. World Federation of Societies of Anaesthesiologists. Anaesthesia Tutorial of the Week. 2011.
  5. ↑ Eddleston M, Chowdhury FR. Pharmacological treatment of organophosphorus insecticide poisoning: the old and the (possible) new. Br J Clin Pharmacol. 2016;81(3):462-470. doi:10.1111/bcp.12784
  6. ↑ Bhatt MH, Bhatt S. Pralidoxime. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024.
  7. ↑ Peter JV, Sudarsan TI, Moran JL. Clinical features of organophosphate poisoning: A review of different classification systems and approaches. Indian J Crit Care Med. 2014;18(11):735-745. doi:10.4103/0972-5229.144017
  8. ↑ Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008;371(9612):597-607. doi:10.1016/S0140-6736(07)61202-1
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