Impact of Administration of Esmolol on Nociception Level-guided Control of Nociception. (ESMONOL)

March 21, 2024 updated by: Pascal Laferrière-Langlois, Ciusss de L'Est de l'Île de Montréal

Impact of Continuous Intraoperative Administration of Esmolol on Nociception Level-guided Control of Nociception. The EsmoNOL Randomized Controlled Trial

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Interventional

Enrollment (Estimated)

64

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Quebec
      • Montréal-Est, Quebec, Canada, H1T2M4
        • Maisonneuve-Rosemont Hospital - CIUSSS de l'Est de l'Île de Montréal
        • Contact:
        • Principal Investigator:
          • Pascal Laferrière-Langois, MD FRQS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Esmolol

In the Esmolol group, intravenous esmolol will be given as a bolus (0.5mg.kg-1) over 5 minutes, and will be started simultaneously to the remifentanil initiation.

Once the bolus of esmolol is over, a perfusion of 20 mcg.kg-1.min-1 will be programmed and maintained until the end of the surgery and completion of skin sutures
Drug: Esmolol Hydrochloride
Patients in the experimental group will receive esmolol during general anesthesia
Other Names:
  • Brevibloc
Placebo Comparator: Standard of care

In the standard of care group, intravenous saline bolus, equivalent to an esmolol bolus (0.5mg.kg-1) will be given over 5 minutes, and will be started simultaneously to the remifentanil initiation.

Once the bolus of saline is over, a saline perfusion equivalent to an esmolol infusion of 20 mcg.kg-1.min-1 will be programmed and maintained until the end of the surgery and completion of skin sutures
Drug: Saline
Patients in the standard of care group will receive saline as placebo during general anesthesia
Other Names:
  • saline serum

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intra operative remifentanil administration
Time Frame: intraoperative (from T0 = incision until Tend = end of dressing)
Quantity of remifentanil in mcg.kg-1.h-1, administered between the first surgical incision and its discontinuation at wound dressing
intraoperative (from T0 = incision until Tend = end of dressing)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The NOL Index variation before and after orotracheal intubation and first surgical incision
Time Frame: intraoperative (from T0 = nociceptive stimulation Tend = 3 minutes post stimulation)
The NOL Index variation before and after orotracheal intubation and first surgical incision
intraoperative (from T0 = nociceptive stimulation Tend = 3 minutes post stimulation)
The mean intraoperative blood pressure and heart rate
Time Frame: intraoperative (from T0 = incision until Tend = end of dressing)
The mean intraoperative blood pressure and heart rate during surgery
intraoperative (from T0 = incision until Tend = end of dressing)
doses and time weighted of norepinephrine (mg); ephedrine (mg), glycopyrrolate (mg) and atropine (mg)
Time Frame: intraoperative (from T0 = incision until Tend = end of dressing)
doses and time weighted average of norepinephrine (mg); ephedrine (mg), glycopyrrolate (mg) and atropine (mg)
intraoperative (from T0 = incision until Tend = end of dressing)
Total time with NOL value above > 25
Time Frame: intraoperative (from T0 = incision until Tend = end of dressing)
Total time and time weighted average with NOL value above > 25
intraoperative (from T0 = incision until Tend = end of dressing)
The total time and time weighted average of hypotension and/or bradycardia
Time Frame: intraoperative (from T0 = incision until Tend = end of dressing)
The total time and time weighted average of hypotension (< 20% of the baseline values of the pre-anesthesia mean arterial pressure (MAP) and/or bradycardia (HR < 60 beats/min, or HR < 50 beats/min for a profound bradycardia)) during surgery
intraoperative (from T0 = incision until Tend = end of dressing)
The time to first analgesic requirement in PACU
Time Frame: postoperative (from T0 = PACU arrival until Tend = PACU discharge)
The time to first analgesic requirement in PACU
postoperative (from T0 = PACU arrival until Tend = PACU discharge)
The amount of morphine equivalent consumption
Time Frame: postoperative (from T0 = PACU arrival until Tend = PACU discharge)
The amount of morphine equivalent consumption for postoperative pain relief in the post anesthesia care unit (PACU) in both groups
postoperative (from T0 = PACU arrival until Tend = PACU discharge)
Postoperative nausea and vomiting (PONV) and antiemetics use
Time Frame: postoperative (from T0 = PACU arrival until Tend = PACU discharge)
Postoperative outcomes such as postoperative nausea and vomiting (PONV) and amount of antiemetics used in PACU
postoperative (from T0 = PACU arrival until Tend = PACU discharge)
The time spent in PACU
Time Frame: postoperative (from T0 = PACU arrival until Tend = PACU discharge)
time spent in PACU (in minutes)
postoperative (from T0 = PACU arrival until Tend = PACU discharge)
The intensity of pain at rest and under stress
Time Frame: postoperative (from T0 = PACU arrival until Tend = PACU discharge)
The intensity of pain at rest and under stress, using a verbal rating scale from 0 to 10 : 0 being no pain, and 10 the worst pain imaginable. I'll be assessed every 30 minutes from arrival to discharge from PACU
postoperative (from T0 = PACU arrival until Tend = PACU discharge)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ciusss de L'Est de l'Île de Montréal

Investigators

  • Principal Investigator: Pascal Laferrière-Langlois, CIUSSS de l'Est de l'Ile de Montréal

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 4, 2024

Primary Completion (Estimated)

March 3, 2025

Study Completion (Estimated)

March 4, 2025

Study Registration Dates

First Submitted

February 26, 2024

First Submitted That Met QC Criteria

February 26, 2024

First Posted (Actual)

March 4, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2024

Last Update Submitted That Met QC Criteria

March 21, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-3612

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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