Although typically used to promote hemodynamic stability, beta blockers may have another purpose, according to a team of Montreal researchers: reducing postoperative pain. Their systematic review concluded that continuous beta-blocker infusions during surgery can decrease postoperative opioid consumption, the incidence of nausea and PACU length of stay, all with few side effects.
“We know that postoperative pain is an important factor in determining patients’ overall quality of recovery, as well as satisfaction,” said Stephen S. Yang, MD, a resident at McGill University Health Centre, in Montreal. “Controlling postoperative pain decreases overall length of stay in the hospital and hospital costs as well.
“Opioids are usually prescribed for postoperative pain, but there’s a dose-dependent relationship in terms of side effects, such as nausea, vomiting, sedation and even respiratory depression,” he said.
“This is why most of us advocate for a multimodal approach to analgesia, which targets different parts of the pathway to reduce pain.
“Although there are multiple medications that have been looked at as part of multimodal analgesia—including NSAIDs [nonsteroidal anti-inflammatory drugs], acetaminophen and ketamine—one of the medications that’s been described very little in the literature in this respect is beta blockers.”
To help shed some light on this knowledge gap, Dr. Yang and his colleagues performed a systematic review to evaluate the effect of intraoperative beta-blocker usage on postoperative outcomes.
They searched three databases (Medline, Embase and the Cochrane Central Register of Controlled Trials) to identify randomized controlled trials that used a control group to compare the effects of these agents on postoperative pain outcomes.
From a total of 12 randomized controlled trials identified between 1970 and 2014, the researchers selected five (comprising a total of 130 patients) that were of high quality and had a low risk for bias. Patients in all five studies received intraoperative esmolol (Brevibloc, Baxter).
“In most of the studies, they gave a 0.5-mg/kg loading dose at induction followed by an infusion,” Dr. Yang described.
“The infusion dose varied widely since it was titrated to hemodynamic effect. So it could range from 20 mcg/kg per minute up to 100 mcg/kg per minute, in some cases.”
Reduced Post-op Opioids And Nausea/Vomiting
As Dr. Yang reported at the 2016 annual meeting of the Canadian Anesthesiologists’ Society (abstract 151137), patients receiving esmolol consumed significantly less postoperative opioids (–8.55 mg; 95% CI, –12.31 to –4.79 mg) than their counterparts who did not.
The investigators also found a reduction in the mean PACU length of stay (–24.7 minutes; 95% CI, –52.6 to 3.2 minutes) and incidence of postoperative nausea and vomiting (odds ratio, 0.31; 95% CI, 0.18-0.54).
“I think this is likely secondary to a decrease in opioid consumption,” he explained.
With the decrease in nausea and vomiting, there also was a significant decrease in the use of antiemetics.
“In terms of mean postop erative pain score, although there was a trend toward a decrease in patients receiving beta blockers [–0.49; 95% CI, 1.35-0.37], it did not reach statistical significance,” Dr. Yang said. There was no increase in the incidence of hemodynamic complications in patients receiving esmolol.
Determining how beta blockers work in this regard is open to interpretation, as Dr. Yang discussed. “There have been three different mechanisms that have been described in the literature,” he said:
“Number one is that beta blockers block the activation of norepinephrine from the hippocampus, reducing pain by acting on NMDA [N-methyl-D-aspartate] receptors.
The second mechanism might be that it blocks the inhibitory G-protein receptor, which activates the entire cascade leading to pain.
And the third mechanism—which is not exactly clear—is that it somehow acts synergistically with intraoperative opioids, potentially prolonging their effect.”
As Girish P. Joshi, MBBS, MD, told Anesthesiology News, the systematic review adds to the store of current knowledge regarding the role of analgesic adjuncts in improving postoperative pain management.
Yet as Dr. Joshi discussed, the analysis is not without its limitations, namely, small sample size, heterogeneity regarding the dose and duration of esmolol infusion, and lack of information regarding pain management after discharge from the PACU. Dr. Joshi is professor of anesthesiology and pain management at the University of Texas Southwestern Medical School, in Dallas.
“In addition to the mechanisms proposed by the authors, I think that the use of intraoperative esmolol allows avoidance/reduction of intraoperative opioid administration, which may prevent/limit acute opioid tolerance and/or opioid-induced hyperalgesia, clinically relevant phenomena that are often underappreciated by anesthesiologists,” he added.
With this in mind, Dr. Joshi referred readers to an article by Hayhurst and Durieux: “Differential Opioid Tolerance and Opioid-Induced Hyperalgesia: A Clinical Reality” (Anesthesiology 2016;124:483-488).