Dataset Information

Effect of High-Dose Baclofen on Agitation-Related Events Among Patients With Unhealthy Alcohol Use Receiving Mechanical Ventilation: A Randomized Clinical Trial.

ABSTRACT:

Importance

Unhealthy alcohol use can lead to agitation in the intensive care unit (ICU).

Objective

To assess whether high-dose baclofen reduces agitation-related events compared with placebo in patients with unhealthy alcohol use receiving mechanical ventilation.

Design, settings, and participants

This phase 3, double-blind, placebo-controlled, randomized clinical trial conducted in 18 ICUs in France recruited adults receiving mechanical ventilation who met criteria for unhealthy alcohol use. Patients were enrolled from June 2016 to February 2018; the last follow-up was in May 2019.

Interventions

Baclofen (n = 159), adjusted from 50 to 150 mg per day based on estimated glomerular filtration rate, or placebo (n = 155) during mechanical ventilation up to a maximum of 15 days before gradual dose reduction over 3 to 6 days.

Main outcomes and measures

The primary end point was the percentage of patients with at least 1 agitation-related event over the treatment period. Secondary outcomes included duration of mechanical ventilation, length of ICU stay, and 28-day mortality.

Results

Among 314 patients who were randomized (mean age, 57 years; 60 [17.2%] women), 313 (99.7%) completed the trial. There was a statistically significant decrease in the percentage of patients who experienced at least 1 agitation-related event in the baclofen group vs the placebo group (31 [19.7%] vs 46 [29.7%]; difference, -9.93% [95% CI, -19.45% to -0.42%]; adjusted odds ratio, 0.59 [95% CI, 0.35-0.99]). Of 18 prespecified secondary end points, 14 were not significantly different. Compared with the placebo group, the baclofen group had a significantly longer median length of mechanical ventilation (9 vs 8 days; difference, 2.00 [95% CI, 0.00-3.00]; hazard ratio [HR] for extubation, 0.76 [95% CI, 0.60-0.97]) and stay in the ICU (14 vs 11 days; difference, 2.00 [95% CI, 0.00-4.00]; HR for discharge, 0.70 [95% CI, 0.54-0.90]). At 28 days, there was no significant difference in mortality in the baclofen vs placebo group (25.3% vs 21.6%; adjusted odds ratio, 1.24 [95% CI, 0.72-2.13]). Delayed awakening (no eye opening at 72 hours after cessation of sedatives and analgesics) occurred in 14 patients (8.9%) in the baclofen group vs 3 (1.9%) in the placebo group.

Conclusions and relevance

Among patients with unhealthy alcohol use receiving mechanical ventilation, treatment with high-dose baclofen, compared with placebo, resulted in a statistically significant reduction in agitation-related events. However, considering the modest effect and the totality of findings for the secondary end points and adverse events, further research is needed to determine the possible role of baclofen in this setting and to potentially optimize dosing.

Trial registration

ClinicalTrials.gov Identifier: NCT02723383.

SUBMITTER: Vourc'h M

PROVIDER: S-EPMC7903253 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAlcohol is the leading psychoactive substance consumed in France, with about 15 million regular consumers. The National institute on Alcohol Abuse and Alcoholism (NIAAA) considers alcohol abuse to be more than 14 units of alcohol a week for men and 7 units for women. The specific complication of alcoholism is the alcohol withdrawal syndrome. Its incidence reaches up to 30 % and its main complications are delirium tremens, restlessness, extended hospital stay, higher morbidity, and psychiatric and cognitive impairment. Without appropriate treatment, delirium tremens can lead to death in up to 50 % of patients.Methods/designThis prospective, double-blind, randomised controlled study versus placebo will be conducted in twelve French intensive care units (ICU). Patients with an alcohol intake level higher than the NIAAA threshold, who are under mechanical ventilation, will be included. The primary objective is to determine whether baclofen is more efficient than placebo in preventing restlessness-related side effects in the ICU. Secondary outcomes include mechanical ventilation duration, length of ICU stay, and cumulative doses of sedatives and painkillers received within 28 days of ICU admission. Restlessness-related side effects in the ICU are defined as unplanned extubation, medical disposal removal (such as urinary catheter, venous or arterial line or surgical drain), falling out of bed, ICU runaway (leaving ICU without physician's approval), immobilisation device removal, self-aggression or aggression towards medical staff. Daily doses of baclofen/placebo will be guided by daily creatinine clearance assessment.DiscussionRestlessness in alcoholic patients is a life-threatening issue in ICUs. BACLOREA is a randomised study assessing the capacity of baclofen to prevent agitation in mechanically ventilated patients. Enrolment of 314 patients will begin in June 2016 and is expected to end in October 2018.Trial registrationClinicalTrials.gov Identifier: NCT02723383 , registered on 3 March 2016.

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