Individuals undergoing cardiac surgery might benefit from a pre-scheduled postoperative cocktail of intravenous (IV) acetaminophen and either propofol or dexmedetomidine, according to Harvard researchers who found the common painkiller could reduce in-hospital delirium in older patients.
Balachundhar Subramaniam, MD, MPH, and colleagues at Beth Israel Deaconess Medical Center explored the idea of IV acetaminophen (Paracetamol) in a placebo-controlled, factorial clinical trial of 120 patients undergoing on-pump coronary artery bypass graft surgery or a combination of CABG and valve surgeries at a U.S. medical center. All patients were at least 60 years old, and just 16 percent were women.
Subramaniam and co-authors said delirium is a common side effect of cardiac surgery—it’s reported in roughly half of cases—and is associated with increased length of stay, mortality, long-term cognitive decline and morbidity. Untreated pain could increase a patient’s risk of delirium, but opioids and nonsteroidal anti-inflammatory drugs could also elevate that risk, posing a particular threat to kidney health and the ability to clot blood.
“In some settings, IV acetaminophen has been shown to reduce inflammation and may confer central analgesic properties and decrease opioid consumption in both opioid-naive and exposed patients,” the authors wrote in JAMA Feb. 19. “Despite these properties, IV acetaminophen has not been studied in the context of delirium prevention.”
Subramaniam and his team randomized their subjects to one of four groups receiving post-op analgesia: those who received IV acetaminophen coupled with dexmedetomidine; those who received IV acetaminophen coupled with propofol; those who received a placebo and dexmedetomidine; and those who received a placebo with propofol. IV acetaminophen or placebo were administered every six hours for 48 hours after surgery, and postoperative sedation with either propofol or dexmedetomidine began at chest closure and continued for up to six hours.
The authors reported patients treated with IV acetaminophen had a significant reduction in delirium compared to placebo patients—10 percent prevalence versus 28 percent prevalence, respectively. There was no notable difference in delirium between dexmedetomidine and propofol (17 percent vs. 21 percent), but there were significant differences favoring acetaminophen over placebo in three prespecified secondary outcomes.
- Acetaminophen patients experienced delirium for shorter periods (1 day vs. 2 days for placebo patients).
- Acetaminophen patients saw shorter lengths of stay in the ICU (median 29.5 vs. 46.7 hours).
- Breakthrough analgesia within the first 48 hours of surgery was less common among acetaminophen patients (322.5 vs. 405.3 micrograms of morphine equivalent).
Subramanian et al. said only breakthrough analgesia was significantly different between dexmedetomidine and propofol, with averages of 328.8 versus 397.5 micrograms of morphine, respectively. The authors also noted 14 patients in the placebo-dexmedetomidine and acetaminophen-propofol groups and seven in the acetaminophen-dexmedetomidine and placebo-propofol groups developed hypotension.
“Increased inspiratory lung capacity and better pain relief with patient satisfaction favor a shorter ICU stay, both of which could potentially be achieved more effectively with a successful opioid-sparing technique,” the team wrote. “These positive benefits need further exploration in larger clinical trials, both in the setting of enhanced recovery after cardiac surgery as well as in the face of the current opioid epidemic.”
The authors said their research suggests acetaminophen could be a viable post-op pain reliever for older patients undergoing heart surgery, but more work needs to be done, including testing whether the medication could be consumed orally or rectally rather than solely through an IV.