Baclofen may reduce alcohol-related agitation in ICU

Daily doses of baclofen may help reduce the risk of agitation among individuals with unhealthy alcohol use admitted to the intensive care unit (ICU), according to results of the BACLOREA* trial presented at eCCR 2021.

The study involved 314 adults aged 18–80 years (mean age 57 years, 17.2 percent female) with an alcohol intake exceeding the NIAAA threshold** (median five units/day) and who were receiving mechanical ventilation (expected ≥24 hours) at one of 18 ICUs. They were randomized to receive either baclofen or placebo. Following a loading dose of trial drug (50–150 mg) with dose dependent on estimated glomerular filtration rate, patients received the same dose in three administrations from day 2–15 (eg, 30-20-50 mg dose for those receiving 100 mg). After day 15, extubation, or tracheotomy, the dose was gradually tapered off over 3–6 days depending on renal function.

The number of patients with ≥1 agitation-related events (unplanned extubation; pulling out lines, catheters, or drains; falling out of bed; elopement from ICU; removal of immobilization device; self-aggression or aggression towards staff) was significantly lower in the baclofen vs the placebo group (19.7 percent vs 29.7 percent; adjusted odds ratio [adjOR], 0.58; p=0.04). [eCCR 2021; JAMA 2021;325:732-741]

Incidence of agitation by day 28 did not differ between the baclofen and placebo groups (27.8 percent vs 34.8 percent; adjOR, 0.72; p=0.19), nor did ICU-acquired infection (23.1 percent vs 20.6 percent; adjOR, 1.14; p=0.63), agitation-related event or mortality by day 28 (42.9 percent vs 45.8 percent; p=0.39), or death by day 28 (25.3 percent vs 20.6 percent; adjOR, 1.24; p=0.44) or day 90 (29.9 percent vs 25.0 percent; p=0.35).

There were significant reductions in the total number of events over the treatment period (n=45 vs 79; p=0.003), total number of agitation-related events (n=70 vs 111; rate ratio, 0.63; p=0.003), and number of ventilator-free days (median 14 vs 19 days; p=0.01) in the baclofen vs placebo group. Conversely, duration of mechanical ventilation (median 9 vs 8 days; p=0.02) and ICU admission (median 14 vs 11 days; p=0.01) was longer in the baclofen vs placebo group. Common agitation-related events in both groups were medical disposal removal, unplanned extubation, and self-aggression or aggression towards staff.

The duration of Ricker Sedation Agitation Scale 1–3 over the 28 days was longer in the baclofen vs placebo group (mean 7.0 vs 4.6 days; p=0.01). Median daily dose of sedatives or analgesics by day 28 did not significantly differ between groups.

Study author Dr Mickael Vourc’h from the University Hospital of Nantes, Nantes, France, noted that the between-group difference for the primary outcome was lower than the study was powered to detect. Furthermore, the baclofen dose used was higher than the current recommendations and was not adjusted according to sedation scales.

The role for baclofen

Previous studies have shown that unhealthy alcohol consumption is associated with an increased risk of ICU-acquired infection and in-ICU mortality up to 1 year post-discharge, regardless of alcohol abuse or dependence, said co-author Dr Karim Asehnoune, also from from the University Hospital of Nantes.

Agitation can have multiple consequences including hindrance of medical care and aggression towards medical staff in the short-term, longer duration of ventilation and ICU-acquired infection in the middle-term, and psychological outcomes in the long-term, he said.

There are currently no recommendations for the prevention of agitation or delirium in the ICU among patients with unhealthy alcohol use, said Asehnoune.

Baclofen has been reported to suppress alcohol cravings in individuals with alcohol use disorder and since 2014, has been recommended for use in outpatients in France. However, there is no evidence to support the use of high-dose baclofen (>150 mg/day) in ICU-admitted patients, he continued.

“In patients with unhealthy alcohol use under mechanical ventilation, high-dose baclofen in addition to standard of care reduced agitation-related events compared with placebo,” said Vourc’h.

“Nevertheless, [this measure] could also increase the depth of sedation and the length of stay in the ICU,” he said, highlighting that dosing should be adjusted according to renal function and sedation scales.