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Home » Treating Agitation in ICU Patients with AUD?

Treating Agitation in ICU Patients with AUD?

May 1, 2022
Jedidiah Perdue, MD, MPH
From The Carlat Addiction Treatment Report
Issue Links: Editorial Information | PDF of Issue

Jedidiah Perdue, MD. Dr. Perdue has disclosed no relevant financial or other interests in any commercial companies pertaining to this educational activity.

REVIEW OF: Vourc’h M et al, JAMA 2021;325(8):732–741

STUDY TYPE: Randomized clinical trial

It’s known that people who drink unhealthy amounts of alcohol are more likely to get agitated if they’re admitted to the ICU. What to do about it is less well understood. In this study, researchers reasoned that mimicking some of alcohol’s effects with the GABA-B agonist baclofen might decrease agitation in patients on mechanical ventilation. The strategy makes sense pharmacologically, and baclofen even has some evidence for treating alcohol use disorder (see CATR, May/Jun 2020), but the results here were short of a slam dunk.

This double-blind, randomized study involving 314 patients was conducted across 18 medical and surgical ICUs. Eligible patients were those with unhealthy alcohol use (greater than seven weekly standard drinks for women, greater than 14 for men) expected to require 24 hours or more of mechanical ventilation. Patients were randomized to placebo or baclofen, which was dosed based on eGFR and added to a standard anesthetic cocktail to maintain light sedation. The amount of baclofen used was quite high: 50–150 mg daily. For context, the FDA’s maximum recommended dose of baclofen is 80 mg daily. Unfortunately, the investigators did not lay out their rationale for choosing such a high dose.

This study’s primary outcome was one or more agitation-related events, such as self-extubation, pulling out lines, leaving against medical advice, and aggression. Researchers also examined a host of secondary outcomes that included 28-day mortality, oversedation, length of stay, and duration of intubation, among others.

Compared to placebo, patients receiving baclofen were significantly less likely to have an agitation-related event (29.7% vs 19.7%). However, the baclofen group had significantly longer ICU stays (14 vs 11 days), spent more time in deep sedation (7.0 vs 4.6 days), and had fewer vent-free days (14 days vs 19) than placebo. Mortality and other secondary outcomes were similar between the groups.

This study had several notable limitations. First, it lacked a validated method of quantifying alcohol intake other than self-report. We simply don’t know how much alcohol patients drank. Another limitation, probably more significant, was the lack of a delirium assessment. Other GABAergic medications, such as benzodiazepines, are associated with delirium, so baclofen could plausibly have increased rates of delirium in these patients as well—however, we don’t know if that occurred in this study. Alcohol withdrawal delirium (AWD) can be a source of agitation in itself and is treated by GABAergic medications, so it is not clear whether baclofen was treating AWD or agitation-related events stemming from some other etiology.

Carlat Take

Baclofen, at high doses, may modestly reduce agitation among ventilated patients with unhealthy alcohol use but at the cost of longer ICU stays and more time on mechanical ventilation. At this point, we would not recommend using high doses of baclofen prophylactically to prevent agitation in the ICU.

KEYWORDS alcohol use disorder delirium withdrawal
    Jedidiah Perdue, MD, MPH

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    Issue Date: May 1, 2022
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    Table Of Contents
    Urine Drug Screens: What You Need to Know
    Lab Testing for Patients with Substance Use Disorders
    Treating Agitation in ICU Patients with AUD?
    Opioid Agonist Treatment and Decreased Mortality
    Learning Objectives, Laboratory Testing, CATR, May/June 2022
    CME Post-Test - Labrotory Testing, CATR, May/June 2022
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