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tox.anticholinergic-toxidrome.core.v1PRODUCTION
tox.anticholinergic-toxidrome.core.v1

Anticholinergic toxidrome

toxicologyacuteadultpediatricgeriatric
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12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Recognize the antimuscarinic toxidrome and immediately stratify pure-antimuscarinic vs Na-channel co-toxic (TCA/diphenhydramine) — that split governs physostigmine eligibility [ACMT physostigmine guidance 2018]

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Toxidrome recognized; Na-channel co-tox risk flagged

Patient inputs (14)

Pediatric exploratory plant/OTC antihistamine ingestion; geriatric polypharmacy anticholinergic burden delirium [2024 crit-care tox review]

Weight-based benzodiazepine, physostigmine and sodium bicarbonate dosing

Diphenhydramine & TCA carry Na-channel blockade (QRS) co-toxicity that contraindicates physostigmine; antipsychotics add QT/hyperthermia risk [ACMT physostigmine guidance 2018]

Sustained-release/anticholinergic ileus delays peak and prolongs Datura course; physostigmine short half-life vs persistent toxin [Burns 2000]

TCA / Na-channel agents / sympathomimetics / serotonergics change the pivot (physostigmine, bicarbonate, antidote) [2024 crit-care tox review]

Urinary retention (needs catheter — agitation source) and ileus (delays decontamination, prolongs absorption)

MANDATORY — wide QRS (>100 ms) / terminal R in aVR = Na-channel blockade → sodium bicarbonate AND a hard contraindication to physostigmine; QT for antipsychotic co-tox

Mandatory co-ingestion screen in any intentional overdose [2024 crit-care tox review]

Anhidrotic hyperthermia is the dominant mortality driver — drives active cooling + ICU [Burns 2000]

Sinus tachycardia is the cardinal peripheral sign; distinguishes from cholinergic bradycardia

Hypertension early; hypotension with TCA Na-channel co-tox signals decompensation

Agitated delirium with mumbling/picking + central + peripheral signs is the physostigmine indication; severity drives sedation

Mydriasis/cycloplegia + dry flushed anhidrotic skin separate antimuscarinic from sympathomimetic (diaphoretic) and cholinergic (miosis/wet)

Rhabdomyolysis from agitation/restraint + hyperthermia → AKI risk

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (6)

6 need judgement
  • informationallife_threateninganhidrotic_hyperthermia
    Core temperature >39°C with anhidrotic skin in an antimuscarinic toxidrome [Burns 2000]
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningwide_qrs_na_channel_cotox
    QRS >100 ms, terminal R in aVR, or known TCA/diphenhydramine co-ingestion (Na-channel blockade) [2024 crit-care tox review]
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningseizure_in_antimuscarinic_toxicity
    Seizure (single or status) in antimuscarinic toxicity — diphenhydramine notably proconvulsant [2024 crit-care tox review]
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresevere_agitation_with_rhabdomyolysis_risk
    Severe agitation/combativeness with rising CK or hyperthermia (rhabdomyolysis risk) [Burns 2000]
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverephysostigmine_eligible_refractory_delirium
    Refractory pure antimuscarinic delirium (central + peripheral signs) with NORMAL QRS and no TCA/Na-channel co-tox, no asthma, no obstruction, no AV block [ACMT physostigmine guidance 2018]
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveredatura_jimsonweed_protracted_course
    Confirmed/suspected Datura, jimsonweed, or belladonna exposure — delayed onset and days-long delirium [2025 crit-care tox review]
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

Run this disease's risk and dosing calculators inline.

RISK_STRATIFICATIONrequiredDrives risk stratification
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Recommended regimen

Anticholinergic — benzodiazepine sedation → active cooling → physostigmine (pure antimuscarinic, ECG-gated) → sodium bicarbonate if QRS wide → supportive (2024 crit-care tox review; ACMT physostigmine guidance 2018)
axis: anticholinergic_supportive_and_physostigmine_ladderstep 1 - Step 1 — Benzodiazepine sedation (FIRST-LINE for agitation & seizure)
Selected step "Step 1 — Benzodiazepine sedation (FIRST-LINE for agitation & seizure)" — Any agitation, delirium, hyperadrenergic features, or seizure
  • lorazepam
    first line
    benzodiazepine
    2 mg IV, repeat/titrate q5–10 min to calm-but-rousable • IV • titrated PRN
    triggers: agitation, delirium, seizure, hyperthermia_with_agitation
    First-line: controls agitation/seizure, reduces heat generation and rhabdo risk; titratable; preferred over antipsychotics which worsen antimuscarinic burden, QT and thermoregulation [Burns 2000]
    rxcui 6470
  • diazepam
    first line
    benzodiazepine
    5–10 mg IV, repeat q5–10 min • IV • titrated PRN
    triggers: seizure, severe_agitation, lorazepam_unavailable
    Rapid-onset alternative for seizure/severe agitation [2024 crit-care tox review]
    rxcui 3322
  • midazolam
    add on
    benzodiazepine
    0.05–0.1 mg/kg IV bolus, then infusion if continuous sedation needed • IV • bolus then infusion
    triggers: continuous_sedation_required, no_IV_access_use_IM
    Infusion option for refractory agitation requiring deep continuous sedation in ICU
    rxcui 6960

ed playbook — drug actions (5)

  1. 1. lorazepam (or diazepam)
    Lorazepam 2 mg IV (or diazepam 5–10 mg IV), titrate q5–10 min • IV • titrated PRN
    trigger: Agitation, delirium, or seizure
    First-line control; reduces heat generation/rhabdo [Burns 2000]
  2. 2. isotonic crystalloid
    IV bolus then maintenance • IV • bolus + continuous
    trigger: Hyperthermia / hypotension / rhabdo risk
    Volume support + AKI prevention
  3. 3. physostigmine
    1–2 mg IV slow over ≥5 min, atropine at bedside, continuous ECG • IV • single; redose for recrudescence
    trigger: Pure antimuscarinic delirium, central+peripheral, NORMAL QRS, no TCA/Na-channel co-tox/asthma/obstruction/AV block
    Diagnostic + therapeutic for pure antimuscarinic delirium [Burns 2000]
  4. 4. sodium bicarbonate
    1–2 mEq/kg IV bolus, repeat for QRS narrowing • IV • bolus then infusion
    trigger: QRS >100 ms / terminal R in aVR / TCA / diphenhydramine co-tox
    Reverses Na-channel blockade; OVERRIDES physostigmine [2024 crit-care tox review]
  5. 5. activated charcoal
    1 g/kg PO/NG (~50 g adult) • PO/NG • single
    trigger: Early presentation (window extended by ileus) + airway protected
    GI decontamination when airway protected and no obstruction

Auto-drafted A&P note

ed

Subjective

- Possible entry pathways: Agitated/hyperactive delirium (mumbling, picking at air, hallucinations) + dry flushed skin [ACMT physostigmine guidance 2018]; Reported ingestion of diphenhydramine / TCA / antipsychotic / atropine / scopolamine / dicyclomine / oxybutynin / cyclobenzaprine [2024 crit-care tox review]; Jimsonweed / Datura / belladonna plant or seed-tea exposure (prolonged course) [2025 crit-care tox review].

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Anticholinergic toxidrome** (tox.anticholinergic-toxidrome.core.v1).
Phenotype framing: Distinguish from sympathomimetic toxidrome (DIAPHORETIC/wet skin — sweat is the pivot), serotonin syndrome / NMS (clonus/rigidity), sepsis/meningoencephalitis, hyperthyroid storm, alcohol/sedative withdrawal, primary psychiatric delirium, heat stroke; peripheral antimuscarinic signs (dry skin, mydriasis, ileus, retention, tachycardia) distinguish from other delirium causes [Burns 2000]
Scope: Recognize the antimuscarinic toxidrome and immediately stratify pure-antimuscarinic vs Na-channel co-toxic (TCA/diphenhydramine) — that split governs physostigmine eligibility [ACMT physostigmine guidance 2018]

No severity triggers fired against current inputs.

Plan

Regimen axis: **Anticholinergic — benzodiazepine sedation → active cooling → physostigmine (pure antimuscarinic, ECG-gated) → sodium bicarbonate if QRS wide → supportive (2024 crit-care tox review; ACMT physostigmine guidance 2018)** — step "Step 1 — Benzodiazepine sedation (FIRST-LINE for agitation & seizure)".
1. lorazepam 2 mg IV, repeat/titrate q5–10 min to calm-but-rousable IV titrated PRN (benzodiazepine, first line) — First-line: controls agitation/seizure, reduces heat generation and rhabdo risk; titratable; preferred over antipsychotics which worsen antimuscarinic burden, QT and thermoregulation [Burns 2000]
2. diazepam 5–10 mg IV, repeat q5–10 min IV titrated PRN (benzodiazepine, first line) — Rapid-onset alternative for seizure/severe agitation [2024 crit-care tox review]
3. midazolam 0.05–0.1 mg/kg IV bolus, then infusion if continuous sedation needed IV bolus then infusion (benzodiazepine, add on) — Infusion option for refractory agitation requiring deep continuous sedation in ICU

Setting playbook (ed) — Recognize the toxidrome, get a MANDATORY ECG to screen Na-channel co-tox, sedate with benzodiazepines, cool aggressively, adjudicate physostigmine eligibility, decontaminate and disposition (2024 crit-care tox review)
4. lorazepam (or diazepam) Lorazepam 2 mg IV (or diazepam 5–10 mg IV), titrate q5–10 min IV titrated PRN — Agitation, delirium, or seizure (First-line control; reduces heat generation/rhabdo [Burns 2000])
5. isotonic crystalloid IV bolus then maintenance IV bolus + continuous — Hyperthermia / hypotension / rhabdo risk (Volume support + AKI prevention)
6. physostigmine 1–2 mg IV slow over ≥5 min, atropine at bedside, continuous ECG IV single; redose for recrudescence — Pure antimuscarinic delirium, central+peripheral, NORMAL QRS, no TCA/Na-channel co-tox/asthma/obstruction/AV block (Diagnostic + therapeutic for pure antimuscarinic delirium [Burns 2000])
7. sodium bicarbonate 1–2 mEq/kg IV bolus, repeat for QRS narrowing IV bolus then infusion — QRS >100 ms / terminal R in aVR / TCA / diphenhydramine co-tox (Reverses Na-channel blockade; OVERRIDES physostigmine [2024 crit-care tox review])
8. activated charcoal 1 g/kg PO/NG (~50 g adult) PO/NG single — Early presentation (window extended by ileus) + airway protected (GI decontamination when airway protected and no obstruction)

Non-pharmacologic actions:
- Active external cooling (evaporative + ice packs + cooling blanket + cold IV fluids) for anhidrotic hyperthermia (Burns 2000)
- Indwelling urinary catheter for retention (treat a missed agitation source) (2024 crit-care tox review)
- Continuous cardiac monitor + serial ECG (2024 crit-care tox review)
- AVOID antipsychotics (worsen antimuscarinic burden, hyperthermia, QT) (2024 crit-care tox review)
- AVOID physical-restraint-only without sedation (rhabdo/hyperthermia) (Burns 2000)
- Medical toxicology / regional poison centre consult (2024 crit-care tox review)

AVOID / contraindication checks:
- Physostigmine_contraindicated_if_TCA_or_wide_QRS_or_Na_channel_cotox (ACMT physostigmine guidance 2018)
- Physostigmine_contraindicated_in_reactive_airway_disease_asthma (ACMT physostigmine guidance 2018)
- Physostigmine_contraindicated_in_bowel_or_bladder_obstruction (ACMT physostigmine guidance 2018)
- Physostigmine_contraindicated_in_AV_block_or_bradydysrhythmia (ACMT physostigmine guidance 2018)
- Physostigmine_slow_IV_over_5min_with_atropine_at_bedside_continuous_ECG (Burns 2000)
- Avoid_antipsychotics_worsen_antimuscarinic_hyperthermia_QT (2024 crit care tox review)
- Avoid_physical_restraint_only_without_sedation_rhabdo_hyperthermia (Burns 2000)
- Sodium_bicarbonate_overrides_physostigmine_when_QRS_wide (2024 crit care tox review)

Monitoring

Regimen monitoring:
- continuous telemetry and serial ECG QRS QT (2024 crit-care tox review)
- core temperature q15 30min during active cooling (Burns 2000)
- RASS or agitation score hourly (Burns 2000)
- recrudescence watch after physostigmine short half life (ACMT physostigmine guidance 2018)
- CK and renal for rhabdomyolysis (2024 crit-care tox review)
- bladder scan and hourly UOP (2024 crit-care tox review)
- post bicarbonate QRS narrowing serial ABG for target pH (2024 crit-care tox review)

Setting (ed) monitoring:
- Continuous telemetry; repeat ECG after bicarbonate and serially (2024 crit-care tox review)
- Core temperature q15–30 min during cooling (Burns 2000)
- Agitation/RASS + GCS hourly (Burns 2000)
- Watch for physostigmine recrudescence (short half-life) (ACMT physostigmine guidance 2018)
- CK + renal function for rhabdomyolysis (2024 crit-care tox review)

Follow-up plan: Psychiatry safety plan if intentional; medication reconciliation / deprescribe anticholinergic burden (geriatric); poison-prevention + plant-identification education; renal follow-up if rhabdo-AKI; counsel that Datura/jimsonweed delirium can persist days [2025 crit-care tox review]
- Close-out criterion: Safety plan + med reconciliation + return precautions documented

Monitoring phase: Continuous telemetry + ECG (re-check QRS/QT), q15–30 min core temp during cooling, mental status / agitation (RASS) hourly, CK + renal for rhabdo, recurrent toxicity after physostigmine wears off (short half-life — may need redose), bladder/UOP, post-bicarbonate QRS narrowing [Burns 2000]

Disposition

Current setting: ed — Recognize the toxidrome, get a MANDATORY ECG to screen Na-channel co-tox, sedate with benzodiazepines, cool aggressively, adjudicate physostigmine eligibility, decontaminate and disposition (2024 crit-care tox review)

Disposition criteria:
- Discharge/observe after several hours if asymptomatic, normal serial ECG, normothermic, no co-ingestant, psych cleared if intentional (2024 crit-care tox review)
- Admit ward/monitored: persistent mild delirium, slow toxidrome resolution, no ICU criteria (2024 crit-care tox review)
- Admit ICU: hyperthermia, wide QRS/Na-channel co-tox, seizure, continuous sedation, physostigmine given, Datura/jimsonweed protracted course (2025 crit-care tox review)

Escalation triggers (move to higher acuity):
- Core temp >39°C / refractory hyperthermia → ICU + paralysis-assisted cooling (Burns 2000)
- Wide QRS / ventricular dysrhythmia / TCA co-tox → ICU + bicarbonate pathway (2024 crit-care tox review)
- Status epilepticus → ICU + airway (2024 crit-care tox review)
- Severe agitation needing continuous sedation, or physostigmine given → ICU/monitored bed (ACMT physostigmine guidance 2018)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Core temperature >39°C with anhidrotic skin in an antimuscarinic toxidrome [Burns 2000]
- [LIFE_THREATENING] QRS >100 ms, terminal R in aVR, or known TCA/diphenhydramine co-ingestion (Na-channel blockade) [2024 crit-care tox review]
- [LIFE_THREATENING] Seizure (single or status) in antimuscarinic toxicity — diphenhydramine notably proconvulsant [2024 crit-care tox review]

Citations

- 2024-2025 critical-care toxicology reviews; ACMT physostigmine guidance; Burns 2000 physostigmine-vs-benzodiazepine for anticholinergic poisoning [PMID:10999558](https://pubmed.ncbi.nlm.nih.gov/10999558/)
- Cited evidence (PMID 12552175) [PMID:12552175](https://pubmed.ncbi.nlm.nih.gov/12552175/)
- Cited evidence (PMID 27322738) [PMID:27322738](https://pubmed.ncbi.nlm.nih.gov/27322738/)
- Cited evidence (PMID 30580804) [PMID:30580804](https://pubmed.ncbi.nlm.nih.gov/30580804/)
- Cited evidence (PMID 33084394) [PMID:33084394](https://pubmed.ncbi.nlm.nih.gov/33084394/)

Last reconciled with current guidelines: 2026-05-16.
References
  • 2024-2025 critical-care toxicology reviews; ACMT physostigmine guidance; Burns 2000 physostigmine-vs-benzodiazepine for anticholinergic poisoning — PMID:10999558
  • Cited evidence (PMID 12552175) — PMID:12552175
  • Cited evidence (PMID 27322738) — PMID:27322738
  • Cited evidence (PMID 30580804) — PMID:30580804
  • Cited evidence (PMID 33084394) — PMID:33084394