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Anticholinergic Poisoning, Emergency Medicine

Basics

Description

- Many drugs contain anticholinergic properties: - Mild at therapeutic doses - Life threatening in overdose

- Anticholinergic substances: - Antihistamines - Belladonna alkaloids and synthetic congeners - Antiparkinsonian drugs - Cyclic antidepressants - Antipsychotics (neuroleptics) - Mydriatics - Skeletal muscle relaxants (orphenadrine, cyclobenzaprine) - Antispasmodics - Mushrooms-Amanita muscaria, Amanita pantherina - Plants-deadly nightshade, mandrake, henbane - Jimson weed-smoked or ingested

- GI: - Decreased/absent bowel sounds - Dysphagia - Decreased GI motility - Decreased salivation

- CNS: - Altered mental status - Auditory or visual hallucinations - Coma - Seizures

- Physostigmine (Antilirium): - Reversible acetylcholinesterase inhibitor that crosses the blood-brain barrier - Short-term reversal of both central and peripheral anticholinergic effects - Indicated in the presence of peripheral anticholinergic signs and the following: - Seizures unresponsive to conventional therapy - Uncontrollable agitation

  • Central and peripheral cholinergic blockade
  • Depending on the drug involved, antagonism occurs at muscarinic (most common), nicotinic, or both receptors.
  • Onset of activity: 15-30 min after ingestion
  • Duration of effect: 2-24 hr

Etiology

  • Many drugs contain anticholinergic properties:Mild at therapeutic dosesLife threatening in overdose
  • Anticholinergic substances:AntihistaminesBelladonna alkaloids and synthetic congenersAntiparkinsonian drugsCyclic antidepressantsAntipsychotics (neuroleptics)MydriaticsSkeletal muscle relaxants (orphenadrine, cyclobenzaprine)AntispasmodicsMushrooms-Amanita muscaria, Amanita pantherinaPlants-deadly nightshade, mandrake, henbaneJimson weed-smoked or ingested

Diagnosis

Signs and Symptoms

History

  • Onset and duration of symptoms
  • Type and extent of ingestion/exposure

Physical Exam

  • Classic toxidrome:"Mad as a hatter"-altered mental status"Hot as a hare"-hyperthermia"Red as a beet"-flushed skin"Dry as a bone"-dry skin and mucous membranes"Blind as a bat"-blurred vision secondary to mydriasis
  • General:HyperthermiaAltered mental status
  • Ocular:Unreactive mydriasisInability to accommodate
  • Cardiovascular:Sinus tachycardiaDysrhythmias (rare except in massive ingestions)Hypotension/HTNCardiogenic pulmonary edema
  • Pulmonary:TachypneaRespiratory failure
  • GI:Decreased/absent bowel soundsDysphagiaDecreased GI motilityDecreased salivation
  • Genitourinary (GU):
  • Integument:Decreased sweatingFlushed skinDry skin and mucous membranes
  • CNS:Altered mental statusAuditory or visual hallucinationsComaSeizures

Essential Workup

Diagnosis based on clinical presentation and an accurate history

Diagnosis Tests & Interpretation

Lab

  • Urine toxicologic screen if clinically indicated
  • Electrolytes, BUN, creatinine, and glucose
  • CBC
  • Creatine phosphokinase (CPK) if suspected rhabdomyolysis
  • Urinalysis
  • Acetaminophen and salicylate levels:Detects occult ingestion (e.g., Tylenol PM)

Imaging

ECG:

  • Sinus tachycardia most common
  • QRS prolongation
  • AV blockade
  • Bundle branch block pattern
  • Dysrhythmias

Differential Diagnosis

  • Sympathomimetic intoxication
  • Withdrawal syndrome
  • Acute psychiatric disorders
  • Sepsis
  • Thyroid disorder

Treatment

Pre-Hospital

Transport all pills/pill bottles involved in overdose for identification in ED.

Initial Stabilization/Therapy

  • Airway, breathing, and circulation (ABCs):Airway control essentialAdminister supplemental oxygen.IV accessCardiac monitor and pulse oximetry
  • Naloxone, thiamine, D50 (or Accu-Chek) if altered mental status

Ed Treatment/Procedures

  • Supportive care:IV rehydration with 0.9% NSStandard aggressive cooling measures for hyperthermiaUse benzodiazepines for treatment of agitation:Avoid phenothiazines owing to anticholinergic effects.Treat seizures with benzodiazepines and barbiturates.Dysrhythmias:Use standard antidysrhythmics.Avoid class Ia antidysrhythmic owing to the quinidine-like effect of many anticholinergic drugs.Sodium bicarbonate boluses may reverse the quinidine-like effects.
  • Decontamination:Administer activated charcoal for oral ingestions if within 1 hr.Ocular lavage for eyedrop exposure
  • Physostigmine (Antilirium):Reversible acetylcholinesterase inhibitor that crosses the blood-brain barrierShort-term reversal of both central and peripheral anticholinergic effectsIndicated in the presence of peripheral anticholinergic signs and the following:Seizures unresponsive to conventional therapyUncontrollable agitationUse with caution if prolonged QRS is present on ECG owing to risk of dysrhythmias (especially asystole), seizures, and cholinergic crises:Place on cardiac monitor.Observe for cholinergic symptoms.Contraindications:Cyclic antidepressant overdose (potentiates toxicity)Cardiovascular diseaseAsthma/bronchospasmIntestinal obstructionHeart blockPeripheral vascular diseaseBladder obstruction

Medication

  • Activated charcoal: 1 g/kg PO
  • Dextrose: 50-100 mL D50 (peds: 2 mL/kg of D25 over 1 min) IV; repeat if necessary
  • Diazepam: 5-10 mg (peds: 0.2-0.5 mg/kg) IV every 10-15 min
  • Dopamine: 2-20 μg/kg/min IV with titration to effect
  • Lorazepam: 2-4 mg (peds: 0.03-0.05 mg/kg) IV every 10-15 min
  • Physostigmine: 0.5-2.0 mg (peds: 0.02 mg/kg) IV over 5 min; repeat if necessary in 30-60 min
  • Phenobarbital: 10-20 mg/kg IV (loading dose); monitor for respiratory depression
  • Thiamine (vitamin B1): 100 mg (peds: 50 mg) IV or IM

First Line

Lorazepam or Diazepam

Second Line

Physostigmine (use with caution and consult with medical toxicologist)

Follow-Up

Disposition

Admission Criteria

  • ICU admission for moderate to severe anticholinergic symptoms (agitation control, temperature control, and observation for seizures or dysrhythmias)
  • Any patient receiving physostigmine

Discharge Criteria

Mild and improving symptoms of anticholinergic toxicity after 6-8 hr of ED observation

Issues for Referral

  • Substance abuse referral for patients with recreational anticholinergic abuse
  • Patients with unintentional (accidental) poisoning require poison prevention counseling.
  • Patients with intentional (e.g., suicide) poisoning require psychiatric evaluation.

Followup Recommendations

Appropriate psychiatric referral for intentional ingestions

Pearls and Pitfalls

  • Aggressively treat hyperthermia.
  • Antipyretic medications are not effective in toxic hyperthermia.
  • Use physostigmine cautiously and consult with medical toxicologist when available.

Additional Reading

  • Burns MJ, Linden CH, Graudins A, et al. A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning. Ann Emerg Med. 2000;35:374-381.
  • Ceha LJ, Presperin C, Young E, et al. Anticholinergic toxicity from nightshade berry poisoning responsive to physostigmine. J Emerg Med. 1997;15:65-69.
  • Delaney KA. Anticholinergics and antihistamines (H1 antagonists). In: Ford MD, Delaney KA, Ling LJ, et al., eds. Clinical Toxicology. Philadelphia, PA: WB Saunders; 2001;472-477.
  • Hidalgo HA, Mowers RM. Anticholinergic drug abuse. Ann Pharmacother. 1990;24:40.
  • Patel RJ, Saylor T, Williams SR, et al. Prevalence of autonomic signs and symptoms in antimuscarinic drug poisonings. J Emerg Med. 2004;26(1):89-94.
  • Reilly KM, Chan L, Mehta NJ, et al. Systemic toxicity from ocular homatropine. Acad Emerg Med. 1996;3:868-871.

Codes

ICD9

971.1 Poisoning by parasympatholytics (anticholinergics and antimuscarinics) and spasmolytics

ICD10

T44.3X1A Poisoning by oth parasympath and spasmolytics, acc, init

SNOMED

  • 216593002 Accidental poisoning by anticholinergics (disorder)
  • 296393006 Anticholinergic drug overdose (disorder)