The use of postoperative IV acetaminophen does not significantly reduce the duration of hypoxemia over 48 hours among patients undergoing abdominal surgery.

According to lead author Alparslan Turan, MD, a professor and the vice chair of the Department of Outcomes Research at Cleveland Clinic in Cleveland, these results were “shocking.”

“We live in an era of opioid-related problems, and everybody is trying to use nonopioid alternatives,” Turan said. “One of these is intravenous acetaminophen, which drove a lot of attention when it was first introduced.

“We all started using it vigorously. We were giving it to almost every patient because we believed it was very effective and would decrease opioid consumption and opioid-related side effects, such as ventilatory depression and hypoxemia,” he continued. “But we had never tested it.”

To shed some light on the issue, Turan and his colleagues enrolled 580 patients (mean age, 49 years; 48% women) into this randomized, double-blind, placebo-controlled trial, which was conducted at two hospitals. All patients underwent abdominal surgery.

image

Participants received either 1 g of IV acetaminophen (n=289) or normal saline (n=291) at the onset of surgery. The dose was repeated every six hours up to 48 postoperative hours or hospital discharge, whichever occurred first.

Opioid Consumption A Secondary End Point

The trial’s primary outcome was duration of hypoxemia—defined as hemoglobin oxygen saturation less than 90%—per hour. Secondary end points included postoperative opioid consumption, pain, postoperative nausea and vomiting, sedation, and respiratory function.

“We know ventilatory depression and hypoxemia are common, yet often not monitored continuously,” Turan told Anesthesiology News. “In this study, we used continuous monitoring for hypoxemia and a variety of vital signs.”

As the researchers reported in JAMA (2020;324[4]:350-358), 570 patients completed the trial. It was found that the median duration with a blood oxygen saturation (SpO2) level less than 90% was 0.7 minutes per hour among patients in the acetaminophen group and 1.1 minutes per hour among those who received placebo (P=0.29); the estimated median difference was –0.04 minutes per hour.

“This was shocking to us,” Turan explained. “The difference is almost nothing.”

More specifically, the study found that 7% of acetaminophen patients had at least 10 minutes per hour with an SpO2 level less than 90% during the first 48 hours after surgery, compared with 9% of controls. In total, acetaminophen patients spent a median of 27 minutes in hypoxemia during the first 48 postoperative hours, compared with 39 minutes for those in the placebo group. Finally, 20% and 27% of acetaminophen and placebo patients, respectively, experienced more than four cumulative hours of hypoxemia during the first 48 postoperative hours.

The study also found no statistically significant difference between groups with respect to mean opioid consumption (expressed as morphine milligram equivalents), which was 50 mg among the acetaminophen patients and 58 mg among controls.

None of the study’s other secondary end points differed significantly between the two groups, including mean pain scores. Indeed, numerical rating scale pain scores over the first 48 postoperative hours were 4.2±1.8 among acetaminophen patients and 4.4±1.8 in the placebo group.

“Of course, there is a cost related to IV acetaminophen use,” Turan said. “Each 1-g vial costs $25 or $30. So eight doses costs at least $200, but it’s not decreasing hypoxemia, opioid consumption or pain.”

As Turan explained, the findings fly in the face of current practice, which typically sees IV acetaminophen as a common component of multimodal analgesic regimens. He therefore recommended that individual components of such regimens be tested separately for their efficacy.

“I think we need large randomized controlled trials for every intervention we think is effective,” he said. “I have seen many such studies yield negative results with different medications.”

Still a Need for IV Acetaminophen

Given these findings, clinicians no longer use IV acetaminophen in patients undergoing abdominal surgery, and are instead doing transversus abdominis plane blocks as the foundation of their analgesic regimen. That said, Turan noted there are still clinical situations where IV acetaminophen would prove to be a useful analgesic.

“If a patient cannot tolerate oral medication, I think it will be useful in those patient populations,” he noted. “But this needs to be tested in large randomized controlled trials. Head-to-head comparisons for acetaminophen have not been done on a large scale, and I think the drug needs more studies.

“But for now, we would not suggest using intravenous acetaminophen in abdominal patients to decrease hypoxemia or opioid consumption.”

For Tong Joo (T.J.) Gan, MD, acetaminophen is most effective when used as part of a multimodal regimen. “We know that multimodal approaches are an effective way to treat pain and reduce opioid consumption. That is pretty clearly demonstrated in the literature,” Gan, a professor and the chair of anesthesiology at the Renaissance School of Medicine at Stony Brook University, in New York, said.

“This study showed that acetaminophen on its own didn’t really impact opiate consumption,” said Gan, who is a member of the Anesthesiology News editorial advisory board. “But we don’t typically use acetaminophen on its own; we usually combine it with other nonopioid analgesics. By doing so, we can significantly improve a host of outcomes, such as opioid consumption and pain. And I think the hypoxemia mechanism is primarily a result of reductions in pain and opioid consumption.”

—Michael Vlessides

Turan and Gan reported no relevant financial disclosures.