Treatment of Adolescent Antimuscarinic (Anticholinergic) Toxidrome

A Randomized Trial Comparing Physostigmine vs Lorazepam for Treatment of Adolescent Antimuscarinic (Anticholinergic) Toxidrome

Overdose of xenobiotics (antihistamines, antipsychotics, or Jimson Weed) with resulting antimuscarinic toxidrome is a common scenario in medical toxicology. The result of antagonism of muscarinic receptors is a constellation of signs and symptoms (toxidrome): mydriasis, decreased sweat, decreased bowel sounds, agitation, delirium, hallucinations, urinary retention, tachycardia, flushed skin and seizures. Two treatment options are physostigmine or benzodiazepines.

Although the antimuscarinic toxidrome occurs commonly, physostigmine has been used sparingly despite evidence of safety and efficacy. To demonstrate the utility and safety of physostigmine, the investigators propose a randomized clinical trial of physostigmine compared to benzodiazepine for antimuscarinic toxicity.

Inclusion Criteria:

• Age >=10 and < 18 years
• Present to the Emergency Department or Intensive Care Unit for an antimuscarinic toxidrome from either a pharmaceutical agent such as antihistamine overdose, or natural toxins or products such as Datura stramonium
• Antimuscarinic toxidrome will be defined with at least one central nervous system agitation effect (agitation, delirium, visual hallucinations, mumbling incomprehensible speech), and at least 2 peripheral nervous system adverse effect (mydriasis, dry mucus membranes, dry axillae, tachycardia, decreased bowel sounds).
• Patients will also be required to have a RASS score of +2 to +4 on initial assessment.

Exclusion Criteria:

• History of seizures or seizure during acute clinical course
• History of asthma or wheezing during clinical course Bradycardia (Heart Rate <60)
• Concomitant use of atropine or choline ester or depolarizing neuromuscular blocker during present illness and hospital course
• Diabetes gangrene, known intestinal obstruction or urogenital tract, vagotonic state
• QRS interval > 120 ms on electrocardiogram
• Known to be pregnant at the time of enrollment
• Known ward of the state