Intraoperative infusions of esmolol reduced intraoperative opioid use, PACU opioid use and PACU pain scores, and may be effective as part of a multimodal analgesic regimen in certain patient populations.
“Esmolol can obviously decrease risk for conditions like opioid-induced hyperalgesia, and perhaps should be used for specific subsets of patients, such as those undergoing ambulatory surgery and those expected to have mild postoperative pain,” said Thomas Anthony Anderson, MD, PhD, an anesthesiologist at Massachusetts General Hospital and assistant professor of anesthesia at Harvard Medical School, in Boston.
Although opioids are fairly ubiquitous in the operating room and a common component of perioperative analgesia, they also are associated with a large number of side effects—ileus, nausea, hyperalgesia, sedation and respiratory depression—all of which can prolong PACU or hospital length of stay.
“As anesthesiologists, finding an adjunct that we can use to decrease those risks and the need for opioids is important,” said Dr. Anderson, who noted that reduction in the use of opioids perioperatively has been shown to enhance recovery and decrease morbidity in adults. “A number of research studies have suggested that esmolol has analgesic properties, so we investigated the role of intraoperative esmolol infusions on postoperative pain and opioid consumption.”
For this analysis, Dr. Anderson and his colleagues searched the following databases: PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Pubget and Google Scholar. All randomized, placebo-controlled or opioid-controlled trials written in English and performed on patients aged 18 years or older were included in the study. A review of the literature showed 23 studies that explored the intraoperative use of esmolol compared with opioid/placebo control and recorded postoperative pain scores and opioid consumption.
As Dr. Anderson reported at the International Anesthesia Research Society 2017 annual meeting (abstract 1566), PACU opioid consumption was reduced in the group receiving esmolol, an ultrashort beta-1 receptor antagonist commonly used to address tachycardia. In 609 patients from 11 trials, patients randomly assigned to esmolol in the PACU were administered less morphine compared with the control groups (standardized mean difference [SMD], –1.21; 95% CI, –1.66 to –0.77; P≤0.001).
Not surprisingly, said Dr. Anderson, intraoperative opioid consumption also favored the esmolol group. In 527 patients from nine trials, patients randomly assigned to esmolol received lessmorphine equivalents intraoperatively than patients in the control groups (SMD, –1.60; 95% CI, –2.25 to –0.96; P≤0.001). When split into remifentanil (Ultiva, Mylan) and fentanyl control groups, patients randomly assigned to esmolol still showed a decrease in intraoperative opioid consumption.
“This is important because recent research has shown the relationship between the intraoperative opioid dose and postoperative 30-day readmission rates,” Dr. Anderson said. “Thus, the dose of opioid given intraoperatively matters not only for the aforementioned side effects, but there may be further associations that are going to be revealed down the road.”
Investigators also examined intraoperative hemodynamic parameters and postoperative nausea and vomiting (PONV). Although the studies were underpowered to yield statistical significance, none reported major issues with bradycardia or hypotension in patients receiving esmolol. Moreover, researchers observed a trend suggesting a decrease in PONV in patients receiving intraoperative esmolol. In the first hour after surgery, however, visual analog scale pain scores for those randomly assigned to esmolol were equivalent postoperatively to those who did not, the authors noted.
“There’s a fair amount of variability in the time in which pain scores are assessed,” Dr. Anderson said. “In the future, it would be useful to study how long these decreases in pain and opioid consumption last following surgery.”
For now, however, the researchers reported that intraoperative esmolol could be beneficial in certain subsets of patients, namely, those undergoing ambulatory surgery, those at risk for postoperative respiratory compromise, and those with an existing chronic pain diagnosis or who are at risk for developing chronic pain.
How Does Esmolol Work?
Moderator of the session, Anis Dizdarevic, MD, assistant professor of anesthesiology and pain management at NewYork-Presbyterian/Columbia University Medical Center, in New York City, inquired about the proposed mechanism of action.
“Is there a hypothesis as to why beta blockers or esmolol would be involved in reducing pain scores and/or opioid consumption?” Dr. Dizdarevic asked.
“The reasons for the opioid-sparing properties of esmolol are still unclear,” Dr. Anderson said, “but there are a number of theories involving voltage-gated calcium channels and regulation of the NMDA [N-methyl-D-aspartate] subtype of glutamate receptors. Although nobody knows for sure, I think the simplest proposed explanation is that esmolol acts as an indirect NMDA receptor antagonist, preventing sympathetic surge and agonism activity at the NMDA receptor.”