Clinical trial NCT03090620: Treatment of Adolescent Antimuscarinic (Anticholinergic) Toxidrome
Official title: A Randomized Trial Comparing Physostigmine vs Lorazepam for Treatment of Adolescent Antimuscarinic (Anticholinergic) Toxidrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Anticholinergics Toxicity
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: American Academy of Clinical Toxicology
First posted: 2017-03-27
Enrollment: 19
Sex: ALL
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Comparison of RASS Score Between Physostigmine and Lorazepam: Before Bolus
timeFrame: Baseline, immediately before bolus
measure: Comparison of RASS Score Between Physostigmine and Lorazepam: After Bolus
timeFrame: Immediately after bolus, up to 10 minutes post-Baseline
measure: Comparison of RASS Score Between Physostigmine and Lorazepam: 4 Hours
timeFrame: 4 hours
measure: Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: Before Bolus
timeFrame: Baseline, immediately before bolus
measure: Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: After Bolus
timeFrame: Immediately after bolus, up to 10 minutes post-Baseline
measure: Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: 4 Hours
timeFrame: 4 hours
Secondary outcomes:
measure: Safety and Effectiveness of Physostigmine Infusion in the Setting of Antimuscarinic Toxidrome.
timeFrame: Up to 4 hours
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus, Children's Hospital Colorado
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: George S Wang, MD
role: PRINCIPAL_INVESTIGATOR
References: