Author: Michael Vlessides
Adding IV ketorolac to epidural morphine reduces opioid requirements after cesarean delivery without increasing estimated blood loss or blood pressure, compared with baseline.
“When it comes to ketorolac, there are a couple of main considerations that we hear from our obstetric colleagues,” said John J. Kowalczyk, MD, who is currently an instructor of anesthesiology at Harvard Medical School and a staff anesthesiologist at Beth Israel Deaconess Medical Center, both in Boston. This research was undertaken when Dr. Kowalczyk and his colleagues were at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center.
“What effect does ketorolac have on opioid sparing and estimated blood loss? And does the effect of NSAIDs [nonsteroidal anti-inflammatory drugs] on the renal vasculature lead to hypertension?” Previous studies have shown that NSAIDs may cause platelet dysfunction, uterine atony and hypertension, thereby limiting their use for post–cesarean delivery pain.
“So, our two primary goals were to evaluate the effect on estimated blood loss as well as opioid sparing,” Dr. Kowalczyk added. “Although the opioid-sparing effect of ketorolac has been evaluated in spinal anesthesia, it’s never been looked at in patients who had epidural morphine.”
To that end, the researchers enrolled 69 women undergoing cesarean delivery with combined spinal-epidural anesthesia into the trial. Of these patients, 58 remained after predetermined exclusion criteria.
Randomization was performed by the investigational pharmacy to ensure blinding. A prior power analysis determined that 58 patients were needed to detect a difference in both opioid consumption and clinically significant estimated blood loss.
The study’s primary outcome was total hydromorphone dose in the first 24 hours after cesarean delivery. Secondary outcomes included estimated blood loss and change in blood pressure compared with baseline.
The investigators reported that the median dose of hydromorphone was significantly lower in patients who received ketorolac (0.0 mg; interquartile range [IQR], 0.0-0.2 mg) than in those who did not receive it (0.2 mg; IQR, 0.0-0.4 mg) (P=0.039).
In contrast, estimated blood loss did not differ significantly between the two groups: ketorolac, 900 mL (IQR, 693-1,047 mL) versus placebo, 800 mL (IQR, 600-1,000 mL) (P=0.259).
Of note, the study also found no difference between groups with respect to change in blood pressure from baseline, with one exception. Patients who received ketorolac actually had lower systolic blood pressure at 12 hours (–8.1%; IQR, –15.0% to –3.9%) relative to their counterparts who received placebo (–2.1%; IQR, –12.3% to 4.9%) (P=0.035).
“NSAIDs are a hot topic in the obstetric literature,” Dr. Kowalczyk explained. “In June 2018, a study [Am J Obstet Gynecol 2018;218(6):616.e1-616.e8] showed that ibuprofen did not increase the blood pressure of patients with preeclampsia any higher than among patients who did not receive ibuprofen. Our findings appear to back this up.
“When it come s to NSAIDs and hemodynamic changes, the physiology of young, healthy pregnant women is discretely different than among elderly men with long-standing hypertension, for example,” he added.
“Ketorolac also has a bad rap in orthopedics,” said session co-moderator Miguel A. Cobas, MD, a professor of anesthesiology at the University of Miami Miller School of Medicine. “I’m curious, however, about what the next step is going to be at your institution after this study.”
“We’re actually using both TEG [thromboelastography] and platelet aggregometry to look deeper into this,” Dr. Kowalczyk replied. “And I think what we’re essentially going to see is a replication of earlier studies where ketorolac causes a decrease in platelet function, but without much of a clinical difference at all.
“This is exactly what we’ve seen in all the clinical studies that have examined estimated blood loss,” Dr. Kowalczyk added. “Ketorolac doesn’t cause clinically relevant increases in estimated blood loss.”
The study findings were originally presented at the 2018 annual meeting of the American Society of Anesthesiologists (abstract YI03-7).