(Reuters Health) – Adults receiving mechanical ventilation who meet the criteria for unhealthy alcohol use have fewer agitation-related events when they’re given high-dose baclofen, a new randomized trial finds.
Researchers randomized patients with heavy alcohol use receiving mechanical ventilation to get either 50 mg to 150 mg of baclofen daily (n=159) based on their estimated glomerular filtration rate, or placebo (n=155), for up to 15 days, followed by a dose reduction over three to six days.
Patients on baclofen were significantly less likely to have agitation-related events (adjusted odds ratio 0.59), the study team reports in JAMA.
However, more patients on baclofen (8.9%) than on placebo (1.9%) had delayed awakening (without opening their eyes at 72 hours after cessation of sedatives and analgesics). Patients on baclofen also had significantly longer median time on mechanical ventilation than patients on placebo (9 days versus 8).
“Heavy alcohol users admitted in the ICU will experience a sudden stop of alcohol intake which can lead to alcohol withdrawal syndrome,” said senior study author Dr. Karim Asehnoune of the surgical intensive care unit at Nantes University Hospital, in France.
Baclofen, by suppressing alcohol cravings in patients with alcohol use disorder, may help reduce agitation-related events tied to withdrawal, Dr. Asehnoune said by email.
“Nevertheless, considering the higher rate of delayed awakening and the longer mechanical ventilation in the baclofen group, further research is needed to optimize dosing according to sedation scales,” Dr. Asehnoune said. “The long-term follow up of all the participants will bring important insights to confirm the relevance of baclofen in this indication.”
The most commonly used sedatives and analgesics in the study were propofol, midazolam and sufentanil. Patients on baclofen and placebo had similar daily doses of sedative and analgesic medications.
In the baclofen group, there were a total of 23 adverse events requiring discontinuation of the study drug, compared with 7 events in the placebo group. In addition to delayed awakening, there were more people on baclofen who had a stroke and low heart rate below 35 beats a minute.
There was no significant difference in 28-day mortality between patients on baclofen (25.3%) versus placebo (21.6%).
One limitation of the study is that the enteral route for baclofen delivery required exclusion of several patients due to concerns about the safety of intravenous administration, the study team notes. It’s also unclear whether baclofen could reduce agitation among people with heavy alcohol use who are not receiving mechanical ventilation.
The composite endpoint of agitation events also didn’t distinguish minor issues, such as removal of an IV line, versus more serious episodes that endanger patients such as falling out of bed, said Dr. Michael Reade, an intensive care physician at Royal Brisbane and Women’s Hospital, in Australia, who wrote an editorial accompanying the study.
Another limitation is that the study population was not at high risk of alcohol withdrawal, Dr. Reade said by email. The inclusion criteria of “unhealthy drinking” was more than 14 units per week for men and 7 units per week for women or men older than 65 years. Even though 75% of patients actually recruited drank at least 4 drinks a day, many might still have been at low risk of alcohol withdrawal syndrome, he explained.
“Many hospitals reserve treatments for alcohol withdrawal for patients who are actually withdrawing, and then titrate doses to effect,” Dr. Reade said. Including low-risk patients in the trial, who are unlikely to have benefit but who will manifest the negative consequences of sedation, increases the chance of showing harm over benefit.
“I think there is a good chance that if baclofen was better targeted – i.e. reserved for a higher-risk patient group, or patients showing signs of withdrawal, and then titrated to effect – its desired effects would outweigh any negative consequences of excessive sedation,” Dr. Reade said.
SOURCE: https://bit.ly/2NRBOCL and https://bit.ly/3dE6JNF JAMA, online February 23, 2021.
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