Treatment of Adolescent Antimuscarinic (Anticholinergic) Toxidrome

Phase 4

Completed

Conditions: Anticholinergics Toxicity

Interventions: Drug: Physostigmine
Drug: Lorazepam

Registration Number: NCT03090620

Lead Sponsor: University of Colorado, Denver

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 19

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Physostigmine	Physostigmine	Physostigmine 0.02 mg/kg IV bolus (max of 2 mg), which can be repeated at 10 minutes, followed by a 0.02 mg/kg/hr (max of 2 mg/hr) infusion for 4 hours.
Lorazepam	Lorazepam	Lorazepam 0.05 mg/kg IV bolus (max 2 mg), which can be repeated at 10 minutes if inadequate patient response, followed by a Normal Saline infusion for 4 hours.

Primary Outcome Measures

Name	Time	Method
Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: 4 Hours	4 hours	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.
Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: Before Bolus	Baseline, immediately 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.
Comparison of RASS Score Between Physostigmine and Lorazepam: Before Bolus	Baseline, immediately 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.
Comparison of RASS Score Between Physostigmine and Lorazepam: 4 Hours	4 hours	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.
Comparison of RASS Score Between Physostigmine and Lorazepam: After Bolus	Immediately after bolus, up to 10 minutes post-Baseline	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.
Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: After Bolus	Immediately after bolus, up to 10 minutes post-Baseline	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.

Secondary Outcome Measures

Name	Time	Method
Safety and Effectiveness of Physostigmine Infusion in the Setting of Antimuscarinic Toxidrome.	Up to 4 hours	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.