Increased ketorolac doses reduce opioid use following caesarean delivery

In women undergoing caesarean section (C-section), six scheduled doses of ketorolac reduced postoperative opioid use as opposed to having only two doses.

“We hypothesized that giving ketorolac at regular intervals for an additional 24 hours would decrease opioid use compared with no NSAID administration,” said Dr Jean Hostage from Tufts Medical Center, Boston, Massachusetts, US, at SMFM 2023.

Indeed, the primary outcome of median total morphine milligram equivalents within the first 72 hours following C-section was halved in patients who received additional ketorolac doses compared with women who received placebo after the initial two ketorolac doses (30 vs 60; p<0.001). [SMFM 2023, abstract 9]

Moreover, more women in the ketorolac arm were able to hold off on postop opioids than those in the placebo arm (n=24 vs 9; p=0.003).

This trial comprised 148 women (mean age 32.5 years) without hypertensive disorders who delivered via C-section. All received an opioid as part of neuraxial anaesthesia. Participants were given IV ketorolac 30 mg around the time of delivery and another dose 6 hours later. They were then randomized 1:1 to receive four additional doses of ketorolac or placebo Q6H. They also received NSAIDs, acetaminophen, and opioids every 4 to 6 hours as needed. Fifty-two women in each arm participated in the 2-week post-partum survey.

Other secondary outcomes

Women who received prolonged ketorolac prescription were less likely to have pain scores >3 than those in the placebo arm. The differences were more pronounced at 30 and 36 hours postop (p=0.005 for both timepoints).

There were no differences between the ketorolac and the placebo arms in terms of postop changes in haematocrit (–5.5 percent for both arms; p=0.94) and creatinine (0.61 vs 0.62 mg/dL; p=0.26).

In terms of the effect of ketorolac on renal function, the data on creatinine is ‘reassuring’, Hostage stressed. “[Based on evidence,] any renal injury caused by ketorolac is usually multimodal in nature and due to many aspects following surgery in addition to just giving ketorolac itself … Our data supported that.”

There were similar percentages of participants in the ketorolac and the placebo arms who were ‘satisfied’ or ‘very strongly satisfied’ with their post-partum experience (94 percent vs 96 percent) and pain control (94 percent vs 90 percent). “[Hence,] patients on ketorolac used less opioids but they were just as satisfied as patients on placebo,” Hostage said.

Further trials needed

Of note, participants were given oral ibuprofen at 12–30 hours following delivery. This could have mitigated the treatment effect observed in the study, according to Hostage.

Other limitations that should be taken into account are the exclusion of women with hypertensive disorder, the inclusion of women who delivered via C-section with neuraxial anaesthesia only, and the use of data from a single academic centre. “[Also,] oral NSAIDs were not begun until study medication was completed,” she added.

“We shall explore the efficacy and safety of increased ketorolac among patients with hypertensive disorder in future studies,” Hostage said. She added that they would also compare the efficacy of increased ketorolac against oral ibuprofen, and would also look into the need for opioids post-discharge in future trials.