This study aims to evaluate esmolol's perfusion impact during induction and maintenance of general anesthesia, using Nociception-Level-guided control of nociception, in adult patients undergoing laparoscopic and lower abdominal surgery, on intraoperative remifentanil consumption and postoperative pain in the Post-Anesthesia Care Unit.

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

Inclusion Criteria:

• Fully consented, American Society of Anesthesiologists Classification Score 1-3 patients from 18yo to 65yo
• Undergoing laparoscopic surgery associated with sub umbilical mini-laparotomy. Eligible surgeries will be hysterectomy (excluding vaginal approach) and left hemicolectomy, of duration time expected under 180 minutes, under general anesthesia
• No allergy to one of the medications used in this study

Exclusion Criteria:

Contraindication to the use of the study drug (esmolol) is an exclusion criterion :

• Hypotension
• Sinus bradycardia
• Sick sinus syndrome
• Second and third degree A-V block
• Pulmonary hypertension
• Right ventricular failure secondary to pulmonary hypertension
• Decompensated heart failure
• Cardiogenic shock
• Nontreated pheochromocytoma
• Known hypersensitivity to esmolol or any of the inactive ingredients of the product
• Allergy to esmolol or other beta blockers (cross-sensitivity is possible)
• Renal dysfunction
• Airway disease such as asthma or chronic obstructive pulmonary disease
• Thyrotoxicosis
• Myasthenia gravis
• Raynaud's disease or peripheral circulatory disorder

Other situations leading to exclusion :

• Severe mental impairment
• Chronic use of opioids, β-adrenergic receptors antagonists
• High risk of conversion to laparotomy according to the surgical team (>25%)

Patients will automatically be excluded after recruitment if they withdraw their consent, or if laparoscopy is converted to laparotomy.

Randomization will be done prior to the entrance in the OR, the day of the surgery.