Impact of Administration of Esmolol on Nociception Level-guided Control of Nociception.

NCT ID: NCT06291363

Last Updated: 2024-07-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

64 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-04-16

Study Completion Date

2025-03-04

Brief Summary

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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.

Detailed Description

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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

Conditions

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Opioid Use, Unspecified Anesthesia Nociceptive Pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Two groups of patients randomized into Group "ESMOLOL" for esmolol and group "Standard of Care" for a total of 64 participants.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Randomization will be done prior to the entrance in the OR, the day of the surgery.

Study Groups

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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

Group Type EXPERIMENTAL

Esmolol Hydrochloride

Intervention Type DRUG

Patients in the experimental group will receive esmolol during general anesthesia

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

Group Type PLACEBO_COMPARATOR

Saline

Intervention Type DRUG

Patients in the standard of care group will receive saline as placebo during general anesthesia

Interventions

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Esmolol Hydrochloride

Patients in the experimental group will receive esmolol during general anesthesia

Intervention Type DRUG

Saline

Patients in the standard of care group will receive saline as placebo during general anesthesia

Intervention Type DRUG

Other Intervention Names

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Brevibloc saline serum

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ciusss de L'Est de l'Île de Montréal

OTHER

Sponsor Role lead

Responsible Party

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Pascal Laferrière-Langlois

MD, MSc, FRQS, Assistant Professor, Principal Investigator, Anesthesiologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Pascal Laferrière-Langlois

Role: PRINCIPAL_INVESTIGATOR

Ciusss de L'Est de l'Île de Montréal

Locations

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Maisonneuve-Rosemont Hospital - CIUSSS de l'Est de l'Île de Montréal

Montreal East, Quebec, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Pascal Laferrière-Langlois

Role: CONTACT

+1-819-432-5847

Nadia Godin

Role: CONTACT

514-252-3400 ext. 3193

Facility Contacts

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Pascal Laferrière-Langois, MD FRQS

Role: primary

+1-819-432-5847

References

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Angst MS, Clark JD. Opioid-induced hyperalgesia: a qualitative systematic review. Anesthesiology. 2006 Mar;104(3):570-87. doi: 10.1097/00000542-200603000-00025.

Reference Type BACKGROUND
PMID: 16508405 (View on PubMed)

Asouhidou I, Trikoupi A. Esmolol reduces anesthetic requirements thereby facilitating early extubation; a prospective controlled study in patients undergoing intracranial surgery. BMC Anesthesiol. 2015 Nov 28;15:172. doi: 10.1186/s12871-015-0154-1.

Reference Type BACKGROUND
PMID: 26615516 (View on PubMed)

Bergeron C, Brulotte V, Pelen F, Clairoux A, Belanger ME, Issa R, Urbanowicz R, Tanoubi I, Drolet P, Fortier LP, Verdonck O, Fortier A, Espitalier F, Richebe P. Impact of chronic treatment by beta1-adrenergic antagonists on Nociceptive-Level (NOL) index variation after a standardized noxious stimulus under general anesthesia: a cohort study. J Clin Monit Comput. 2022 Feb;36(1):109-120. doi: 10.1007/s10877-020-00626-4. Epub 2021 Jan 4.

Reference Type BACKGROUND
PMID: 33398545 (View on PubMed)

Bohringer C, Astorga C, Liu H. The Benefits of Opioid Free Anesthesia and the Precautions Necessary When Employing It. Transl Perioper Pain Med. 2020;7(1):152-157.

Reference Type BACKGROUND
PMID: 31712783 (View on PubMed)

Celebi N, Cizmeci EA, Canbay O. [Intraoperative esmolol infusion reduces postoperative analgesic consumption and anaesthetic use during septorhinoplasty: a randomized trial]. Rev Bras Anestesiol. 2014 Sep-Oct;64(5):343-9. doi: 10.1016/j.bjan.2013.10.013. Epub 2014 Jun 21. Portuguese.

Reference Type BACKGROUND
PMID: 25168439 (View on PubMed)

Colvin LA, Bull F, Hales TG. Perioperative opioid analgesia-when is enough too much? A review of opioid-induced tolerance and hyperalgesia. Lancet. 2019 Apr 13;393(10180):1558-1568. doi: 10.1016/S0140-6736(19)30430-1.

Reference Type BACKGROUND
PMID: 30983591 (View on PubMed)

Fletcher D, Martinez V. Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis. Br J Anaesth. 2014 Jun;112(6):991-1004. doi: 10.1093/bja/aeu137.

Reference Type BACKGROUND
PMID: 24829420 (View on PubMed)

Gelineau AM, King MR, Ladha KS, Burns SM, Houle T, Anderson TA. Intraoperative Esmolol as an Adjunct for Perioperative Opioid and Postoperative Pain Reduction: A Systematic Review, Meta-analysis, and Meta-regression. Anesth Analg. 2018 Mar;126(3):1035-1049. doi: 10.1213/ANE.0000000000002469.

Reference Type BACKGROUND
PMID: 29028742 (View on PubMed)

Martini CH, Boon M, Broens SJ, Hekkelman EF, Oudhoff LA, Buddeke AW, Dahan A. Ability of the nociception level, a multiparameter composite of autonomic signals, to detect noxious stimuli during propofol-remifentanil anesthesia. Anesthesiology. 2015 Sep;123(3):524-34. doi: 10.1097/ALN.0000000000000757.

Reference Type BACKGROUND
PMID: 26154185 (View on PubMed)

Paloheimo MP, Sahanne S, Uutela KH. Autonomic nervous system state: the effect of general anaesthesia and bilateral tonsillectomy after unilateral infiltration of lidocaine. Br J Anaesth. 2010 May;104(5):587-95. doi: 10.1093/bja/aeq065. Epub 2010 Mar 30.

Reference Type BACKGROUND
PMID: 20354006 (View on PubMed)

Renaud-Roy E, Stockle PA, Maximos S, Brulotte V, Sideris L, Dube P, Drolet P, Tanoubi I, Issa R, Verdonck O, Fortier LP, Richebe P. Correlation between incremental remifentanil doses and the Nociception Level (NOL) index response after intraoperative noxious stimuli. Can J Anaesth. 2019 Sep;66(9):1049-1061. doi: 10.1007/s12630-019-01372-1. Epub 2019 Apr 17.

Reference Type BACKGROUND
PMID: 30997633 (View on PubMed)

Richebe P, Capdevila X, Rivat C. Persistent Postsurgical Pain: Pathophysiology and Preventative Pharmacologic Considerations. Anesthesiology. 2018 Sep;129(3):590-607. doi: 10.1097/ALN.0000000000002238.

Reference Type BACKGROUND
PMID: 29738328 (View on PubMed)

Sabourdin N, Burey J, Tuffet S, Thomin A, Rousseau A, Al-Hawari M, Taconet C, Louvet N, Constant I. Analgesia Nociception Index-Guided Remifentanil versus Standard Care during Propofol Anesthesia: A Randomized Controlled Trial. J Clin Med. 2022 Jan 11;11(2):333. doi: 10.3390/jcm11020333.

Reference Type BACKGROUND
PMID: 35054027 (View on PubMed)

Shahiri TS, Richebe P, Richard-Lalonde M, Gelinas C. Description of the validity of the Analgesia Nociception Index (ANI) and Nociception Level Index (NOL) for nociception assessment in anesthetized patients undergoing surgery: a systematized review. J Clin Monit Comput. 2022 Jun;36(3):623-635. doi: 10.1007/s10877-021-00772-3. Epub 2021 Nov 16.

Reference Type BACKGROUND
PMID: 34783941 (View on PubMed)

Shanthanna H, Ladha KS, Kehlet H, Joshi GP. Perioperative Opioid Administration. Anesthesiology. 2021 Apr 1;134(4):645-659. doi: 10.1097/ALN.0000000000003572.

Reference Type BACKGROUND
PMID: 32991672 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Other Identifiers

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2024-3612

Identifier Type: -

Identifier Source: org_study_id

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