DESCRIPTION

• 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 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

[Outline]

• DESCRIPTION
• ETIOLOGY

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:
  • Hyperthermia
  • Altered mental status
• Ocular:
  • Unreactive mydriasis
  • Inability to accommodate
• Cardiovascular:
  • Sinus tachycardia
  • Dysrhythmias (rare except in massive ingestions)
  • Hypotension/HTN
  • Cardiogenic pulmonary edema
• Pulmonary:
  • Tachypnea
  • Respiratory failure
• GI:
  • Decreased/absent bowel sounds
  • Dysphagia
  • Decreased GI motility
  • Decreased salivation
• Genitourinary (GU):
  • Urinary retention
• Integument:
  • Decreased sweating
  • Flushed skin
  • Dry skin and mucous membranes
• CNS:
  • Altered mental status
  • Auditory or visual hallucinations
  • Coma
  • Seizures

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

[Outline]

• SIGNS AND SYMPTOMS
• ESSENTIAL WORKUP
• DIAGNOSIS TESTS & INTERPRETATION
• DIFFERENTIAL DIAGNOSIS

PRE-HOSPITAL

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

INITIAL STABILIZATION/THERAPY

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

ED TREATMENT/PROCEDURES

• Supportive care:
  • IV rehydration with 0.9% NS
  • Standard aggressive cooling measures for hyperthermia
  • Use 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 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
  • Use 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 disease
    • Asthma/bronchospasm
    • Intestinal obstruction
    • Heart block
    • Peripheral vascular disease
    • Bladder 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)

[Outline]

• PRE-HOSPITAL
• INITIAL STABILIZATION/THERAPY
• ED TREATMENT/PROCEDURES
• MEDICATION

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.

FOLLOW-UP RECOMMENDATIONS

Appropriate psychiatric referral for intentional ingestions

[Outline]

• DISPOSITION
• FOLLOW-UP RECOMMENDATIONS

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

ICD9

971.1 Poisoning by parasympatholytics (anticholinergics and antimuscarinics) and spasmolytics

ICD10

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

[Outline]

• ICD9
• ICD10

• 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.

Patrick M. Whiteley