Opioids are currently the gold standard for perioperative pain control and allow for
proper intraoperative hemodynamic stability. However, their use presents several major
challenges, as demonstrated by the opioid crisis intensifying over the years in North
America and increasingly in Europe. Besides commonly described adverse effects such as
postoperative nausea, vomiting, respiratory depression, ileus, or pruritus, opioids are
associated with induced hyperalgesia. In this context, several opioid-sparing strategies
have been explored. The use of esmolol, a short-acting beta-blocker, can reduce
sympathetic stimulation induced by perioperative nociceptive stimuli. Integrated into a
multimodal strategy, it reduces the need for intraoperative opioid administration and
postoperative analgesic consumption. Concurrently, multiparametric monitoring of
nociception via the Nociception-Level Index (NOL index) also allows for a reduction in
intraoperative opioids and decreased pain scores in the post anesthesia care unit (PACU).
The aim of this trial will be to explore the combination of these two strategies and
assess the impact of continuous esmolol infusion on Nociception-Level-guided
intraoperative remifentanil administration in patients under general anesthesia
undergoing gynecological or general surgery via laparoscopy or lower abdominal
laparotomy.
This single center randomized controlled trial will be conducted in a Canadian academic
hospital. Participants aged between 18 and 65 years undergoing gynecological or general
surgery by laparoscopy or lower abdominal laparotomy will be included in this study.
Induction of general anesthesia will be achieved with propofol in combination with
target-controlled infusion (TCI) remifentanil at 3 ng.ml-1 for intubation, then guided by
the NOL Index during the procedure. Hypnosis will be maintained by the administration of
sevoflurane with a target minimum alveolar concentration (MAC) between 0.7 and 1.2 to
sustain a bispectral Index (BIS)between 40 and 60. Intervention group participants will
receive esmolol as follows: an initial bolus of 0.5 mg.kg-1 at induction of anesthesia
followed by a continuous infusion of 20mcg.kg-1.min-1 until the end of the intervention.
A saline solution infusion will be administered to control group participants under the
same conditions. The primary outcome will be the amount of remifentanil administered
intraoperatively in mcg.kg-1.h-1. Secondary outcomes will include variations in the NOL
Index during nociceptive stimuli, average heart rate and blood pressure, the
intraoperative doses and time weighted average of norepinephrine (mg); ephedrine (mg),
glycopyrrolate (mg) and atropine (mg), the total time and time weighted average of
hypotension and or bradycardia during surgery, the time to first analgesic requirement,
amount of morphine equivalent consumption for postoperative pain relief in PACU,
intensity of pain at rest and under stress, using a verbal rating scale (VRS), from
arrival to discharge from PACU.
The main objective of the study is to evaluate the impact of continuous intraoperative
infusion of esmolol on intraoperative remifentanil administration in patients undergoing
general anesthesia with NOL-guided nociception management.
Secondary objectives are listed below.
Based on a recent unpublished trial recently held at Maisonneuve-Rosemont Hospital
focusing on colorectal surgeries, the investigators assumed a mean intraoperative
remifentanil consumption of 5.59 mcg.kg-1.h-1 and 7.98, respectively in the intervention
and control group, with a combined standard deviation of ± 3.24. This data is aligned
with recently published international data. With an alpha risk of 5%, a power of 80.0%, a
two-tailed test, and an estimated dropout ratio of 10.0%, it was calculated that 32
participants would be required in each group, to detect a 30% reduction in intraoperative
remifentanil administration.
Study duration: 12 months
Study Center: Maisonneuve-Rosemont Hospital, Integrated University Health and Social
Services Centre (CIUSSS) de l'Est de l'Ile de Montreal (CEMTL), University of Montreal,
Montreal, Quebec, Canada.
Adverse Events: there is very little risk involved with participation in this study, side
effects that may be associated with the use of esmolol includes bradycardia and/or
hypotension