1. Organophosphate Poisoning (with General Poisoned-Patient Framework)

Quick Recap

Toxicology System, Protocol 1/8. Introduces the general poisoned-patient framework (toxidromes, decontamination, enhanced elimination, ICU admission criteria) used throughout this system, then covers organophosphate-specific management in full.

1. General Approach to the Poisoned Patient (Framework for This Entire System)

Key steps (apply to any suspected poisoning before drilling into a specific agent):

1. ABCDE first — oxygen, intubate/ventilate for airway protection or respiratory failure; IV access with crystalloid for hypotension; ECG and routine labs; draw extra tubes of blood for serum drug/toxin levels before treatment alters them; expose the patient and perform a secondary survey
2. Treat potentially reversible causes of altered mental status/coma empirically: rapid glucose check/treatment; thiamine 500mg IV if Wernicke encephalopathy is possible; naloxone 0.4-2.0mg IV/IM or 2.0-4.0mg intranasal if possible opioid toxicity (give BEFORE glucose/thiamine delays further workup)
3. Assess for and treat the specific toxidrome (Section 2) — give specific antidotes when indicated; call the regional Poison Control Center for management advice
4. Block absorption (decontamination, Section 3) when appropriate
5. Enhance elimination (Section 4) when appropriate

2. Clinical Toxidromes — Pattern Recognition Reference

Anticholinergic vs cholinergic are near-opposite presentations (dry vs wet) — use this contrast as a fast bedside discriminator when the ingested agent is unknown.

3. Decontamination

Dermal exposure (organophosphates especially): remove clothing, copiously irrigate/wash skin with mild soap and water.

Ocular exposure (acids/alkalis): copious water irrigation.

Gastric lavage: role is DEBATABLE, only of benefit in the hyperacute phase (<1h); patient must be awake with a preserved gag reflex.

Activated charcoal: 50g as soon as possible, then 50g every 4h while indicated; most effective within 1h of ingestion; co-administration with sorbitol has NOT been shown to increase efficacy. Contraindications: elemental metals (lithium, iron), pesticides, strong acids/alkalis, cyanide, late presentation (>4-6h post-ingestion), unprotected/unsafe airway (aspiration risk is itself high-morbidity/mortality — do NOT give charcoal without a protected airway).

4. Enhanced Elimination

Urine alkalinization may help excretion in salicylate, phenobarbital, chlorpropamide poisoning.

Hemodialysis/hemoperfusion for severe poisoning if the toxin is removable: hemodialysis — methanol, ethylene glycol, boric acid, salicylates, lithium, glutethimide, tricyclic antidepressants; hemoperfusion — theophylline, phenobarbital, phenytoin, carbamazepine, paraquat.

Plasmapheresis has been tried for certain poisons (heavy metals, thyroxine, theophylline).

ECMO has been tried for cardiac/pulmonary support in severe poisoning (amiodarone, beta-blocker, calcium channel blocker, opioid overdose) — salvage option in refractory cardiotoxicity.

5. ICU Admission Criteria for the Poisoned Patient

Respiratory depression (PaCO2 >45); emergency intubation; seizures; cardiac arrhythmia (QT prolongation); QRS duration >0.12s; 2nd/3rd degree AV block; SBP <80; unresponsive to verbal stimuli; GCS <12; need for emergency dialysis/hemoperfusion/ECMO; increasing metabolic acidosis; toxin-induced pulmonary edema; TCA/phenothiazine overdose with anticholinergic signs/QRS or QT prolongation; administration of pralidoxime in organophosphate toxicity; antivenom administration; need for continuous naloxone infusion.

6. Antidote Reference Table

7. Organophosphate Poisoning — Mechanism

Organophosphates irreversibly inhibit acetylcholinesterase -> accumulation of acetylcholine at both muscarinic and nicotinic synapses -> the classic cholinergic toxidrome (SLUDGE) plus nicotinic effects (muscle fasciculations, weakness, tachycardia can occur alongside the muscarinic bradycardia — the net cardiovascular effect is variable). Cholinesterase level can guide diagnosis/severity, though treatment should not be delayed pending results in a compatible clinical picture.

8. Immediate Stabilization (ABCDE)

Airway/Breathing: bronchorrhea and bronchoconstriction are the primary threats to airway/respiratory status — aggressive suctioning and early consideration of intubation for respiratory failure; avoid succinylcholine where possible for RSI given its metabolism depends on plasma cholinesterase, which is already depleted/inhibited in organophosphate poisoning, prolonging paralysis unpredictably.

Circulation: atropine is titrated to DRYING OF SECRETIONS, not to a fixed dose or heart rate — typical approach: 1-3mg IV bolus, DOUBLING the dose every 5 minutes if inadequate response, until bronchorrhea/secretions clear ("atropinization") — doses required can be very large (tens to hundreds of mg over the course of treatment) in severe poisoning; atropine addresses the MUSCARINIC effects only, NOT the nicotinic effects (muscle weakness/fasciculations), which require pralidoxime.

Decontamination: remove all clothing, copiously wash skin with soap and water per Section 3 — protect staff from secondary/dermal exposure during this process (wear appropriate PPE).

Checklist:

9. Pralidoxime (2-PAM)

Mechanism: reactivates acetylcholinesterase by cleaving the organophosphate-enzyme bond — effective only BEFORE "aging" (a time-dependent conformational change in the bound enzyme that renders it permanently inactive and unresponsive to pralidoxime) — give as early as possible; efficacy diminishes significantly the longer treatment is delayed, though it may still have some benefit even after some hours have passed depending on the specific agent.

Typical dosing: 2g IV loading dose over 15-30 minutes, followed by a continuous infusion (or repeat bolus dosing) — continue until clinical improvement (resolution of nicotinic signs/muscle weakness) or per toxicology guidance, since duration is agent- and severity-dependent.

Administration of pralidoxime is itself an ICU admission criterion (Section 5) given the severity of poisoning it implies and the need for close monitoring during treatment.

10. Intermediate Syndrome — A Distinct, Delayed Complication

A syndrome of proximal muscle weakness and respiratory muscle weakness occurring 24-96 HOURS AFTER apparent initial recovery from the acute cholinergic crisis — distinct from both the acute cholinergic phase and delayed peripheral neuropathy, thought to relate to prolonged nicotinic receptor dysfunction/downregulation. Can cause respiratory failure requiring reintubation in a patient who seemed to be recovering — maintain vigilance and a low threshold for reassessment of respiratory status through this window, not just during the initial acute presentation.

11. Investigations

Cholinesterase level (RBC/plasma, supports diagnosis/severity though not treatment-gating), electrolytes, ABG, ECG (arrhythmia surveillance given variable cardiovascular effects), CXR if aspiration/pulmonary edema suspected, consider co-ingestant screening given organophosphate poisoning is frequently intentional (self-harm context) and other agents may be co-ingested.

12. Organ Support

Atropine (muscarinic effects) and pralidoxime (nicotinic effects, enzyme reactivation) as the dual-pathway antidotal therapy; mechanical ventilation for respiratory failure (acute cholinergic crisis or delayed intermediate syndrome); standard ICU supportive care; benzodiazepines for seizures if they occur.

13. Consultation Matrix

14. Monitoring Framework

Continuous cardiac monitoring, serial respiratory status assessment (extending through the intermediate syndrome window, 24-96h post-recovery), atropine dose/secretion response tracking, cholinesterase level trend if being used to guide pralidoxime duration.

15. Complications

Respiratory failure (acute cholinergic crisis and/or delayed intermediate syndrome), arrhythmia, aspiration, seizures, delayed peripheral neuropathy (a separate, later complication distinct from intermediate syndrome). Prevention: early decontamination with staff protection, prompt atropine titration to secretion-drying endpoint, early pralidoxime before enzyme "aging," vigilance for intermediate syndrome through the 24-96h window. Rescue: reintubation for intermediate syndrome, escalating atropine dosing for persistent muscarinic crisis, benzodiazepines for seizures.

16. Escalation & De-escalation

Escalate: persistent bronchorrhea/secretions despite escalating atropine -> continue doubling-dose titration; respiratory decline 24-96h post-recovery -> reassess for intermediate syndrome, prepare for reintubation.

De-escalate: secretions controlled, nicotinic symptoms resolving, cholinesterase recovering -> taper atropine, discontinue pralidoxime per toxicology guidance, extend monitoring through the intermediate syndrome window before final clearance.

17. ICU Discharge Criteria

No ongoing respiratory compromise (including through the intermediate syndrome window), atropine successfully weaned, hemodynamically stable, psychiatric evaluation completed if intentional ingestion, no evidence of delayed neuropathy at time of assessment.

18. Documentation & Medicolegal Checklist

19. Key Guidelines

Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008;371(9612):597-607.

20. Controversies

Optimal pralidoxime dosing/duration and its true clinical benefit remain debated in the toxicology literature — some studies have questioned its efficacy in certain organophosphate poisoning contexts, though early administration remains standard practice given the "aging" mechanism's time-sensitivity. The precise mechanism and optimal monitoring/prevention strategy for intermediate syndrome remains incompletely understood.

21. References

1. Toxicology (general poisoned patient framework, toxidromes, antidotes). Washington Manual of Critical Care, 4th ed, 2025 (Ch. 36).
2. Singh O, et al. General Poisoning Management. ICU Protocols: A Step-wise Approach, 2nd ed. Springer; 2020 (Ch. 14).
3. Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008;371(9612):597-607.
4. Senanayake N, Karalliedde L. Neurotoxic effects of organophosphorus insecticides: an intermediate syndrome. N Engl J Med. 1987;316(13):761-763.

See also: Guillain-Barré Syndrome and Myasthenic Crisis (Neurology System) for the differential of neuromuscular respiratory failure, relevant given intermediate syndrome's overlapping presentation.