Impact of Deep Versus Standard Muscle Relaxation on Intra-operative Safety

NCT ID: NCT04124757

Last Updated: 2025-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 731 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-11
• Study Completion Date: 2024-06-01

Brief Summary

Muscle relaxants are routinely applied during anesthesia to facilitate endotracheal intubation and to improve surgical working conditions. Several investigations have shown that a deep neuromuscular block (NMB) improves the surgical working conditions over a moderate NMB and effectively precludes sudden deterioration of the surgical field. However, whether the improvement of surgical working conditions translates into less intra- and postoperative complications remains uncertain. Small prospective or retrospective studies shown an decrease of the incidence of intraoperative adverse events and postoperative complications after a deep NMB. There is a need to confirm these outcome data prospectively, in a large number of patients and clinics and during a variety of surgical procedures.

Detailed Description

Muscle relaxants are routinely applied during anesthesia to facilitate endotracheal intubation and to improve surgical working conditions. Several investigations have shown that a deep neuromuscular block (NMB) (post tetanic count (PTC) 1-2 twitches) improves the surgical working conditions over a moderate NMB (TOF count 1-3 twitches) and effectively precludes sudden deterioration of the surgical field. However, whether the improvement of surgical working conditions translates into less intra- and postoperative complications remains uncertain. A recent retrospective analysis of neuromuscular management during laparoscopic retroperitoneal surgery showed a reduced rate of unplanned 30 day readmissions when a deep NMB over a moderate NMB was applied (3.8% vs. 12.7%).In addition, a pooled analysis of 4 randomized controlled trials comparing different levels of intra-abdominal pressure and neuromuscular blockade during laparoscopic donor nephrectomy, showed a significant reduction in the incidence of intra-operative surgical complications from 12.6% with moderate NMB to 4.8% with deep NMB.

These previous observations were made in small prospective or retrospective studies. There is a need to confirm these outcome data prospectively, in a larger prospective trial for a variety of surgical procedures. We therefore propose a multi-center, randomized controlled trial, to study the effect of a deep NMB (PTC 1-2 twitches) versus standard NMB (single induction dose rocuronium) in a variety of laparoscopic surgical procedures on the incidence of intraoperative adverse events and postoperative outcome data.

In this study the effect of deep neuromuscular block compared to standard neuromuscular block on intra-operative adverse events during laparoscopic surgery using the CLASSIC score system is evaluated.

Conditions

Neuromuscular Blockade; Rocuronium; Anesthetics; Anesthesia Complication; Neuromuscular Blocking Agents; Surgery--Complications

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Standard neuromuscular blockade

Subjects will receive regular rocuronium induction dose, followed by bolus foses of 10 mg in case of insufficient conditions

Group Type: NO_INTERVENTION

No interventions assigned to this group

Deep neuromuscular block

Subjects will receive high dose rocuronium induction dose followed by continuous rocuronium administration, to achieve a depth of neuromuscular block of 1-2 twitches post tetanic count

Group Type: EXPERIMENTAL

Deep neuromuscular block

Intervention Type: OTHER

Deep neuromuscular block will be achieved with high dose rocuronium to achieve a depth of 1-2 twitches post tetanic count

Interventions

Deep neuromuscular block

Deep neuromuscular block will be achieved with high dose rocuronium to achieve a depth of 1-2 twitches post tetanic count

Intervention Type: OTHER

Other Intervention Names

High dose rocuronium

Eligibility Criteria

Inclusion Criteria

• Patients scheduled for elective laparoscopic procedure with a complexity according to the BUPA classification for case complexity: 'MAJOR', 'MAJOR Plus or 'COMPLEX MAJOR'
• ASA (merican society of anesthesiologists) class I-III
• > 18 years of age
• Ability to give oral and written informed consent

Exclusion Criteria

• Low or intermediate complexity laparoscopic procedures (BUPA 'SIMPLE' or 'INTER')
• Known or suspected neuromuscular disorders impairing neuromuscular function
• Allergies to muscle relaxants, anesthetics or narcotics mentioned in paragraph 5.2
• A (family) history of malignant hyperthermia
• Women who are or may be pregnant or are currently breast feeding
• Chronic use of any type of opioid or psychotropic drug
• Use of NSAID's shorter than 5 days before surgery
• Indication for rapid sequence induction
• Contra-indication for sugammadex use (e.g. known sugammadex allergy or Glomerular Filtration Rate <30 ml/min)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Martijn Boon

Prinicipal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Monique van Velzen, PhD

Role: PRINCIPAL_INVESTIGATOR

LUMC

Locations

Université De Lorraine

Nancy, Meurthe-et-Moselle, France

Istituto Nazionale Dei Tumori

Milan, , Italy

RadboudUMC

Nijmegen, Gelderland, Netherlands

LUMC

Leiden, South Holland, Netherlands

Noordwest ziekenhuis groep

Alkmaar, , Netherlands

Netherlands Cancer institute

Amsterdam, , Netherlands

Canisius Wilhelmina Ziekenhuis

Nijmegen, , Netherlands

Hospital Universitari I Politecnic La Fe

Valencia, , Spain

Countries

France; Italy; Netherlands; Spain

References

Boon M, Martini C, Yang HK, Sen SS, Bevers R, Warle M, Aarts L, Niesters M, Dahan A. Impact of high- versus low-dose neuromuscular blocking agent administration on unplanned 30-day readmission rates in retroperitoneal laparoscopic surgery. PLoS One. 2018 May 23;13(5):e0197036. doi: 10.1371/journal.pone.0197036. eCollection 2018.

Reference Type: BACKGROUND

PMID: 29791482 (View on PubMed)

Torensma B, Martini CH, Boon M, Olofsen E, In 't Veld B, Liem RS, Knook MT, Swank DJ, Dahan A. Deep Neuromuscular Block Improves Surgical Conditions during Bariatric Surgery and Reduces Postoperative Pain: A Randomized Double Blind Controlled Trial. PLoS One. 2016 Dec 9;11(12):e0167907. doi: 10.1371/journal.pone.0167907. eCollection 2016.

Reference Type: BACKGROUND

PMID: 27936214 (View on PubMed)

Martini CH, Boon M, Bevers RF, Aarts LP, Dahan A. Evaluation of surgical conditions during laparoscopic surgery in patients with moderate vs deep neuromuscular block. Br J Anaesth. 2014 Mar;112(3):498-505. doi: 10.1093/bja/aet377. Epub 2013 Nov 15.

Reference Type: BACKGROUND

PMID: 24240315 (View on PubMed)

Rosenthal R, Hoffmann H, Clavien PA, Bucher HC, Dell-Kuster S. Definition and Classification of Intraoperative Complications (CLASSIC): Delphi Study and Pilot Evaluation. World J Surg. 2015 Jul;39(7):1663-71. doi: 10.1007/s00268-015-3003-y.

Reference Type: BACKGROUND

PMID: 25665678 (View on PubMed)

Madsen MV, Scheppan S, Mork E, Kissmeyer P, Rosenberg J, Gatke MR. Influence of deep neuromuscular block on the surgeons assessment of surgical conditions during laparotomy: a randomized controlled double blinded trial with rocuronium and sugammadex. Br J Anaesth. 2017 Sep 1;119(3):435-442. doi: 10.1093/bja/aex241.

Reference Type: BACKGROUND

PMID: 28969327 (View on PubMed)

Ozdemir-van Brunschot DMD, Braat AE, van der Jagt MFP, Scheffer GJ, Martini CH, Langenhuijsen JF, Dam RE, Huurman VA, Lam D, d'Ancona FC, Dahan A, Warle MC. Deep neuromuscular blockade improves surgical conditions during low-pressure pneumoperitoneum laparoscopic donor nephrectomy. Surg Endosc. 2018 Jan;32(1):245-251. doi: 10.1007/s00464-017-5670-2. Epub 2017 Jun 22.

Reference Type: BACKGROUND

PMID: 28643056 (View on PubMed)

Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. doi: 10.1097/01.sla.0000133083.54934.ae.

Reference Type: BACKGROUND

PMID: 15273542 (View on PubMed)

Honing M, Reijnders-Boerboom G, Dell-Kuster S, van Velzen M, Martini C, Valenza F, Proto P, Cambronero OD, Broens S, Panhuizen I, Roozekrans M, Fuchs-Buder T, Boon M, Dahan A, Warle M. The impact of deep versus standard neuromuscular block on intraoperative safety during laparoscopic surgery: an international multicenter randomized controlled double-blind strategy trial - EURO-RELAX TRIAL. Trials. 2021 Oct 26;22(1):744. doi: 10.1186/s13063-021-05638-2.

Reference Type: DERIVED

PMID: 34702332 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.assessurgery.com/

Link to calculate comprehensive complication index

Other Identifiers

P19.065

Identifier Type: -

Identifier Source: org_study_id