Basics
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
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:
- 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):
- 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
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 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)
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)