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IV Acetaminophen May Combat Delirium After Cardiac Surgery

In the first days after cardiac surgery, adding IV acetaminophen (Ofirmev) and a sedative to other pain management reduced postoperative delirium among older patients in a randomized trial.

IV acetaminophen plus either IV dexmedetomidine (Precedex) or propofol (Diprivan) cut the likelihood of in-hospital delirium 2.8-fold compared with placebo plus sedative (10% vs 28%, P=0.01), reported Balachundhar Subramaniam, MD, MPH, of Beth Israel Deaconess Medical Center in Boston, and colleagues in JAMA.

Acetaminophen also significantly reduced breakthrough analgesia (median 322.5 vs 405.3 μg morphine equivalents), ICU length of stay (median 29.5 vs 46.7 hours), and delirium duration (median 1 vs 2 days).

The two-by-two factorial design also compared the two sedatives but turned up no significant differences in delirium between propofol and dexmedetomidine (21% vs 17%, P=0.54).

Postoperative delirium is a common but devastating complication after cardiac surgery among elderly patients, noted Subramaniam. “So far, we have not had any effective treatment at all in the sense of effective prophylaxis. So I think for the first time, we have found a commonly-used drug, which is routinely used for 48 hours following surgery. It can effectively reduce the incidence of delirium,” Subramaniam told MedPage Today.

When it comes to clinical practice, “I think other institutions will start using postoperative IV acetaminophen as a routine drug following surgery in their patients for 2 days and that will effectively cut down the use of opioids plus also give effective analgesia,” he continued.

Subramaniam’s group evaluated 120 patients ages 60 and older getting coronary artery bypass graft (CABG) surgery, with or without a valve replacement, requiring cardiopulmonary bypass at a U.S. medical facility. The median age was 69, and 15.8% women.

Patients were randomized to placebo and propofol (n=30), placebo and dexmedetomidine (n=30), acetaminophen and dexmedetomidine (n=29), or acetaminophen and propofol (n=31). Participants received postoperative sedation with propofol or dexmedetomidine beginning at chest closure and used for a maximum of 6 hours; postoperative analgesia with placebo or IV acetaminophen was administered every 6 hours for 48 hours.

When comparing propofol and dexmedetomidine, breakthrough analgesia was the only significantly different outcome (median 397.5 vs 328.8 μg).

Hypotension was similar between groups in both drug comparisons.

“It’s a one center study, so we have to do a multicenter study, and prove the findings,” Subramaniam acknowledged. “And of course, there are people who claim that Tylenol can also have the same effects, but following cardiac surgery at least for 24 to 36 hours, there is a problem in terms of gastric absorption.”

“Additional research, including comparison of IV versus oral acetaminophen and other potentially opioid-sparing analgesics on the incidence of postoperative delirium, is warranted,” the researchers concluded.

The study was supported by Mallinckrodt Pharmaceuticals.

Subramaniam disclosed relationships with Mallinckrodt Pharmaceuticals and the National Institutes of Health.