Clinical trial NCT04124757: Impact of Deep Versus Standard Muscle Relaxation on Intra-operative Safety
Official title: The Impact of Deep Versus Standard Muscle Relaxation on Intra-operative Safety During Laparoscopic Surgery: a Multicenter Strategy Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Neuromuscular Blockade
Rocuronium
Anesthetics
Anesthesia Complication
Neuromuscular Blocking Agents
Surgery--Complications
Keywords: Laparoscopy
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2019-10-11
Enrollment: 731
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Classic Score>1
timeFrame: Day of surgery
Secondary outcomes:
measure: L-SRS (Leiden Surgical Rating Scale)
timeFrame: Day of surgery
measure: 30 Day Post-operative Complications
timeFrame: 30 postoperative days
measure: Quality of Recovery (QoR)
timeFrame: 2 postoperative days
measure: Quality of Life (QoL)
timeFrame: 30 postoperative days
Other outcomes:
Locations:
city: Nancy
country: France
facility: Université De Lorraine
state: Meurthe-et-Moselle
city: Milano
country: Italy
facility: Istituto Nazionale Dei Tumori
city: Nijmegen
country: Netherlands
facility: RadboudUMC
state: Gelderland
city: Leiden
country: Netherlands
facility: LUMC
state: Zuid-Holland
city: Alkmaar
country: Netherlands
facility: Noordwest ziekenhuis groep
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer institute
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Ziekenhuis
city: Valencia
country: Spain
facility: Hospital Universitari I Politecnic La Fe
Study officials:
affiliation: LUMC
name: Monique van Velzen, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.