Propranolol as an Anxiolytic to Reduce the Use of Sedatives From Critically-ill Adults Receiving Mechanical Ventilation
Status:
Recruiting
Trial end date:
2021-07-01
Target enrollment:
Participant gender:
Summary
The COVID-19 pandemic has led to shortages of intravenous sedatives due to increased ICU
patient admissions and greater use of mechanical ventilation. A shortage of sedatives is as
concerning as a shortage of mechanical ventilators since critically ill patients require
sedation for comfort and to tolerate mechanical ventilation. Anti-adrenergic medications are
increasingly recognized for their role in sedation of critically ill patients. Propranolol is
a plentiful and inexpensive, non-selective beta-adrenergic blocker with good penetration of
the blood-brain barrier, which can reduce agitation and arousal. The study team published a
single-centre retrospective study of 64 mechanically-ventilated patients which found the
initiation of propranolol was associated with an 86% reduction in propofol dose and a roughly
50% reduction in midazolam dose while maintaining the same level of sedation. Propranolol has
the potential to mitigate the threat posed by worldwide sedative shortages and improve
critical care management of patients who require mechanical ventilation.
This study seeks to evaluate whether the addition of propranolol to a standard sedation
regimen reduces the dose of sedative needed in critically ill patients requiring mechanical
ventilation. This study is an open-label randomized controlled trial, single-blinded with 1:1
allocation. Both arms will receive sedation according to usual intensive care unit practice
with a sedative agent. The intervention arm will additionally receive enteral propranolol
20-60mg q6h titrated up over 24-48h until intravenous sedative doses have fallen to a minimal
level (propofol <0.5mg/kg/h or midazolam <0.5mg/h) or the maximum dose of propranolol is
reached. Intravenous sedative doses will be titrated downwards in response to sympatholysis
produced by the propranolol, as evidenced by a decreasing heart rate or blood pressure. The
control arm will receive sedation without the addition or propranolol.
The primary outcome will be the change in primary sedative dose from baseline to Day 3 of
enrollment. Analysis of the primary outcome will be a difference in differences; the change
in sedative dose from baseline to Day 3 in the intervention group versus the same change in
the control group. The Mann-Whitney U test will be used as a nonparametric test of
independent samples for this outcome.
Phase:
Phase 3
Details
Lead Sponsor:
Ottawa Hospital Research Institute
Collaborators:
Hamilton Health Sciences Corporation McMaster University Sinai Health System The Ottawa Hospital Toronto General Hospital University Health Network, Toronto