Anticholinergic toxicityMANAGEMENT

TOXICOLOGIC PRESENTATIONS · 12 SECTIONS

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343 items

☷ Legend

01Approach to the Critical Patient/attcp30

Immediate priorities

›Stabilization

›If airway compromise or refractory agitation, intubation with post-intubation sedation

›If intubating, avoid succinylcholine if concern for rhabdomyolysis or hyperkalaemia

›Post-intubation sedation with benzodiazepine or propofol based on hemodynamics

›If hyperthermia, aggressive external cooling

›If core temperature ≥ 40 C, treat as heat stroke physiology

›If shivering limits cooling, sedation escalation

›If seizures, benzodiazepine first line

›If refractory, levetiracetam or phenobarbital per status epilepticus pathway

›If hypotension, isotonic crystalloid bolus

›If persistent hypotension, norepinephrine infusion

Toxidrome recognition

›Anticholinergic toxidrome pattern

›Delirium with agitation or hallucinations

›Mydriasis with poor accommodation

›Dry hot flushed skin with anhidrosis

›Tachycardia

›Ileus with decreased bowel sounds

›Urinary retention

Monitoring and environment

›Monitoring set

›Continuous cardiac monitoring

›Frequent temperature checks including core temperature if hyperthermia suspected

›Capnography if sedated or intubated

›Point-of-care glucose early in altered mental status

Key decision points

›Antidote candidacy

›Physostigmine only for severe anticholinergic delirium with suspected pure antimuscarinic toxicity

›If QRS widening or concern for sodium channel blockade coingestion, avoid physostigmine

›If seizure risk high or mixed toxidrome, prioritize supportive care and sedation

›Decontamination threshold

›If large recent ingestion and airway protected, activated charcoal consideration

›If ileus present, delayed absorption risk with recurrent toxicity

02History/hx38

Exposure and timeline

›Exposure details

›Suspected agent category

›Antihistamines

›Tricyclic antidepressants

›Antipsychotics with antimuscarinic activity

›Antiparkinsonian agents

›Antispasmodics and bladder antimuscarinics

›Plants

›Datura or jimson weed

›Deadly nightshade

›Dose estimate

›Maximum possible ingestion

›Formulation type

›Immediate release

›Extended release

›Time of ingestion

›Last known well time

›Onset and progression of delirium

›Coingestion risk

›Serotonergic agents

›Sympathomimetics

›Sedative hypnotics

›Sodium channel blockers

Clinical vignette

›Typical presentation

›Acute delirium with agitation and visual hallucinations

›Dry mucous membranes and inability to sweat

›Tachycardia with mydriasis

›Urinary retention with suprapubic discomfort

Risk factors and context

›Risk context

›Intentional self-poisoning

›Pediatric exploratory ingestion

›Medication error or polypharmacy

›Elderly with baseline cognitive impairment

›Past history

›Seizure disorder

›Cardiac conduction disease

›Asthma or reactive airway disease

›Glaucoma history

03Physical Exam/exam22

Vital signs and general

›Global assessment

›Hyperthermia with dry skin

›Tachycardia disproportionate to temperature

›Hypertension early with later hypotension if severe

›Altered mental status spectrum

›Agitated delirium

›Somnolence after sedatives

Neurologic and pupils

›Neuro findings

›Mydriasis with sluggish light response

›Disorientation and incoherent speech

›Myoclonus uncommon and suggests alternative diagnosis

›Rigidity and hyperreflexia suggests serotonin syndrome or NMS

Skin, mucosa, GI, GU

›Peripheral findings

›Dry mucous membranes

›Flushed skin

›Anhidrosis

›Decreased bowel sounds

›Bladder distention

PITFALLS

›Diagnostic pitfalls

›Fever with delirium misattributed to infection without toxidrome exam

›Mixed overdose with anticholinergic and sodium channel blockade

›Sedative administration masking delirium while toxicity persists

04Differential Diagnosis/ddx18

Life threats and mimics

›Dangerous alternatives

›Serotonin syndrome ICD-10 T43.205A

›Neuroleptic malignant syndrome ICD-10 G21.0

›Sympathomimetic toxidrome ICD-10 T43.621A

›CNS infection ICD-10 G00.9

›Heat stroke ICD-10 T67.0XXA

›Hypoglycaemia ICD-10 E16.2

›Thyroid storm ICD-10 E05.91

›Toxicologic overlap

›Tricyclic antidepressant poisoning ICD-10 T43.011A

›Anticholinergic delirium with QRS widening

›Diphenhydramine poisoning ICD-10 T45.0X1A

›Anticholinergic delirium with possible seizures and QRS widening at high dose

Bedside differentiators

›Discriminating features

›Dry skin and urinary retention supports anticholinergic syndrome

›Diaphoresis and hyperreflexia supports serotonin syndrome

›Lead pipe rigidity supports NMS

›Severe hypertension with diaphoresis supports sympathomimetic toxicity

05Laboratory Tests/lt22

Core labs

›Baseline assessment

›Electrolytes and renal function

›Potassium for arrhythmia and rhabdomyolysis risk

›Creatinine for AKI from dehydration or rhabdomyolysis

›Venous blood gas

›Acidaemia suggesting seizures or hypoperfusion

›Hypercapnia after sedation

›Creatine kinase

›Rhabdomyolysis risk in agitation or hyperthermia

›Lactate

›Seizure or shock marker

Targeted tests

›Directed testing

›Acetaminophen level for intentional ingestion screening

›Salicylate level when history unclear

›Pregnancy test in patients with uterus of childbearing potential

›Urinalysis

›Myoglobinuria in rhabdomyolysis

›Infection alternative if febrile with unclear toxidrome

Interpretation and pitfalls

›Limitations

›Urine drug screens poor sensitivity for many anticholinergic agents

›Serum antihistamine levels rarely available and not management changing

›Normal labs do not exclude severe delirium requiring antidote or sedation

06Diagnostic Tests/dt30

Scoring Systems

›Structured assessment tools

›Anticholinergic burden tools for medication review

›Anticholinergic Cognitive Burden scale for chronic exposure risk

›Anticholinergic Risk Scale for polypharmacy risk

›Agitation severity tools

›RASS for sedation targets in ICU or post-intubation care

›CIWA-Ar not appropriate for primary anticholinergic delirium

MRI

›Neuroimaging escalation

›MRI brain consideration

›Persistent focal deficits after delirium resolves

›Prolonged altered mental status not explained by toxidrome

›Practical limitations

›Unstable or agitated patients typically not candidates

›Sedation requirement risk in toxidrome

›Time-critical imaging

›CT head consideration

›Trauma concern from agitation or falls

›New focal neurologic deficit

›Anticoagulation with altered mental status

›Abdominal imaging consideration

›Severe abdominal distension with concern for obstruction or urinary retention complication

Ultrasound

›Point-of-care ultrasound

›Bladder ultrasound

›Urinary retention confirmation

›Post-void residual monitoring after catheterization

›Cardiac ultrasound

›Alternative shock causes if hypotensive

›Volume status support in dehydration

›Lung ultrasound

›Aspiration risk assessment after emesis or sedation

07Disposition/dispo21

Level of care

›Admission criteria

›Persistent delirium requiring repeated sedation

›Hyperthermia or rhabdomyolysis

›Seizures

›ECG abnormalities

›QRS widening

›QT prolongation with dysrhythmia risk

›Recurrent symptoms after initial improvement

›ICU criteria

›Intubation

›Vasopressor requirement

›Severe hyperthermia

›Status epilepticus

Observation and discharge

›Discharge criteria

›Normal mental status for a sustained period after last sedative or antidote dose

›Stable vital signs without active cooling

›Normal ECG or stable baseline conduction pattern

›Voiding without retention or catheter plan arranged

›Psychiatric and safeguarding

›Intentional ingestion mental health evaluation prior to discharge

›Pediatric ingestion caregiver education and safe storage plan

08Treatment/t92

Supportive care

›Support bundle

›Quiet low-stimulation environment

›1 to 1 observation for safety

›Minimize restraints when possible

›Fluids

›Isotonic crystalloid bolus 10 to 20 mL per kg for dehydration

›Ongoing maintenance based on urine output and temperature

›Temperature control

›External cooling

›Evaporative cooling with mist and fan

›Ice packs to groin and axilla

›If severe hyperthermia, cold IV fluids adjunct

Sedation for agitation and seizures

›Benzodiazepines

›Diazepam IV

›5 to 10 mg slow IV

›Repeat every 5 to 10 minutes as needed

›Escalation to airway support if repeated dosing

›Lorazepam IV

›1 to 2 mg IV

›Repeat every 5 to 10 minutes as needed

›Lower initial dose in elderly or frail

›Midazolam IM

›5 to 10 mg IM for severe agitation without IV access

›Repeat once if inadequate response

›Transition to IV strategy when access obtained

›Refractory agitation

›Ketamine IM or IV pathway if immediate control required

›IM 4 to 5 mg per kg

›Airway readiness due to hypersalivation and laryngospasm risk

›Transition to benzodiazepine infusion if needed

Physostigmine

›Indications and prerequisites

›Severe anticholinergic delirium with clear antimuscarinic toxidrome

›Agitation or delirium preventing evaluation or safe care

›Failure of adequate benzodiazepine strategy

›Prerequisites

›Continuous ECG monitoring

›Resuscitation equipment immediately available

›Atropine immediately available for bradycardia

›Contraindications

›QRS prolongation suggesting sodium channel blockade

›QRS ≥ 100 ms

›Terminal R in aVR pattern suggesting TCA effect

›Suspected tricyclic antidepressant coingestion

›Second or third degree AV block

›Severe asthma with active bronchospasm

›Adult dosing

›Physostigmine IV slow infusion

›0.5 mg IV over 5 to 10 minutes

›Repeat 0.5 mg every 5 to 10 minutes to clinical effect

›Typical total 1 to 2 mg

›Relapse management

›Repeat dose if delirium recurs due to short duration

›Avoid continuous infusion unless toxicology consult

›Pediatric dosing

›Physostigmine IV slow infusion

›0.02 mg per kg IV over 5 to 10 minutes

›Maximum single dose 0.5 mg

›Repeat every 10 to 15 minutes to effect with monitoring

›Adverse effects and responses

›Cholinergic excess

›Bradycardia

›If symptomatic, atropine IV per ACLS bradycardia dosing

›Bronchorrhea

›Airway suction and oxygenation support

›Seizure

›Benzodiazepine treatment

Cardiac toxicity and sodium channel blockade pathway

›If QRS widening or ventricular dysrhythmia

›Sodium bicarbonate IV bolus

›1 to 2 mmol per kg IV

›Repeat bolus until QRS narrows or pH target reached

›Target pH 7.50 to 7.55 on blood gas

›Bicarbonate infusion

›150 mmol sodium bicarbonate in 1 L D5W

›Rate titration to maintain alkalinization target

›Potassium monitoring for hypokalaemia

Decontamination

›Activated charcoal

›Single dose

›1 g per kg orally

›Maximum 50 g

›Only if airway protected and ingestion within expected benefit window

›Pitfalls

›Ileus increases aspiration risk

›Altered mental status requires airway protection

Urinary retention and ileus

›Urinary retention management

›Bladder scan confirmation

›Catheterization if significant retention

›Foley removal plan once delirium resolves

›Avoid antimuscarinic agents that worsen retention

›Ileus management

›Bowel rest if severe distension

›Nasogastric tube if vomiting or aspiration risk

›Electrolyte correction to support motility

09Special Populations/sp25

Pregnancy

›Pregnancy considerations

›Maternal stabilization priority with fetal secondary assessment

›Medication safety

›Benzodiazepines for severe agitation when needed

›Physostigmine use only with toxicology and obstetric consultation

›Fetal monitoring

›Viable gestation fetal heart rate assessment after maternal stabilization

Geriatric

›Older adult considerations

›Higher delirium sensitivity from therapeutic dosing

›Medication reconciliation for anticholinergic burden

›Lower sedation dosing and slower titration

›Higher urinary retention risk

›Early bladder scan strategy

›Post-episode voiding trial planning

›Higher arrhythmia risk

›Lower threshold for prolonged monitoring

Pediatrics

›Pediatric considerations

›Weight based dosing for all sedatives and antidotes

›Common exposures

›Diphenhydramine

›Imidazoline and mixed ingestions

›Plants and household products

›Safeguarding

›Non-accidental poisoning consideration in inconsistent history

›Social work involvement when indicated

10Background/b26

Epidemiology

›Epidemiology

›Common causes

›Antihistamine overdose as frequent exposure source

›Polypharmacy anticholinergic burden in older adults

›High risk settings

›Recreational ingestion of anticholinergic plants

›Intentional self-poisoning with sedating antihistamines

Pathophysiology

›Mechanism

›Muscarinic receptor antagonism

›CNS delirium from central M1 blockade

›Tachycardia from vagal inhibition

›Anhidrosis and hyperthermia from sweat gland blockade

›Urinary retention from detrusor relaxation and sphincter tone increase

›Mixed mechanisms in common agents

›Sodium channel blockade at high dose with diphenhydramine or TCAs

›Seizure risk from central toxicity

Therapeutic Considerations

›Treatment principles

›Supportive care as foundation

›Cooling for hyperthermia

›Sedation for agitation and seizures

›Physostigmine as targeted reversal agent

›Best for pure antimuscarinic delirium with normal ECG

›Short duration with potential relapse requiring repeat dosing

›Avoidance of harms

›Physical restraints increasing hyperthermia and rhabdomyolysis risk

›Antipsychotics potentially worsening hyperthermia and QT prolongation in some patients

11Patient Discharge Instructions/pdi10

copy discharge instructions

›Discharge text

›Diagnosis explained as anticholinergic toxicity from medication or plant exposure

›Avoid all anticholinergic medications unless prescribed and reviewed

›Hydration and rest for 24 to 48 hours

›No driving or risky activities for 24 hours after sedation or delirium

›Return immediately for confusion, hallucinations, severe agitation, seizure, fainting, chest pain, trouble breathing, inability to urinate, persistent vomiting, or fever

›Safe storage of medications and household products out of reach of children

›Follow-up plan

›Primary care or poison centre follow-up within 24 to 72 hours if symptoms recur

›Mental health follow-up if ingestion was intentional

12References/r9

Core sources

›Evidence sources

›StatPearls Anticholinergic Toxicity updated 2023

›Tintinalli Emergency Medicine Manual Anticholinergic Toxicity chapter

›Narrative review of physostigmine adverse effects 2019

›Toxicology practice survey of physostigmine use 2014 and 2015

Decision support and regional protocols

›Practice resources

›Poison centre physostigmine protocols for dosing and monitoring

›Toxicology consultation for mixed overdoses and ECG abnormalities

›Institutional procedural sedation and agitation pathways

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Reviewed by SymptomDx Medical Team · Last reviewed June 16, 2026

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