Treatment of Adolescent Antimuscarinic (Anticholinergic) Toxidrome

University of Colorado, Denver19 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Anticholinergics Toxicity

Interventions

Eligibility

Sex: ALLMin age: 10 YearsMax age: 17 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Comparison of RASS Score Between Physostigmine and Lorazepam: Before Bolus

Determine the effectiveness of physostigmine as compared with lorazepam for control of antimuscarinic agitation. Richmond Agitation Sedation Scores (RASS) will be compared throughout treatment protocol. The Richmond Agitation-Sedation Scale (RASS) measures sedation and agitation. Possible scores range from -5 (unarousable) to 0 (alert \& calm) to +4 (combative). Scores closer to 0 indicate a better outcome for this measurement.

Time frame: Baseline, immediately before bolus

Comparison of RASS Score Between Physostigmine and Lorazepam: After Bolus

Time frame: Immediately after bolus, up to 10 minutes post-Baseline

Comparison of RASS Score Between Physostigmine and Lorazepam: 4 Hours

Time frame: 4 hours

Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: Before Bolus

Determine the effectiveness of physostigmine as compared with lorazepam in the reversal of antimuscarinic delirium. Confusion Assessment Method for the ICU (CAM-ICU) scores will be evaluated throughout the study. This measurement is a dichotomous outcome ("yes" or "no" for presence of delirium is indicated rather than a score). The number of participants exhibiting delirium is reported.

Time frame: Baseline, immediately before bolus

Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: After Bolus

Time frame: Immediately after bolus, up to 10 minutes post-Baseline

Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: 4 Hours

Time frame: 4 hours

Secondary Outcomes

Safety and Effectiveness of Physostigmine Infusion in the Setting of Antimuscarinic Toxidrome.

Evaluation of clinical antimuscarinic symptoms, along with presence of any adverse effects, during the infusion to report tolerability, safety profile, and effectiveness of the infusion. the number of participants exhibiting adverse events will be reported, by type.

Time frame: Up to 4 hours