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

Neuromuscular Blockade Clinical Trial

— EURORELAX  

Official title:

The Impact of Deep Versus Standard Muscle Relaxation on Intra-operative Safety During Laparoscopic Surgery: a Multicenter Strategy Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04124757
• Other study ID #: P19.065
• Status: Recruiting
• Phase: N/A
• Start date: February 11, 2020
• Est. completion date: June 1, 2024

Study information

• Verified date: January 2024
• Source: Leiden University Medical Center
• Contact: Gijsbert HM Honing, PhD
• Phone: 0031 71 526 2301
• Email: g.h.m.honing[@]lumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 922
• Est. completion date: June 1, 2024
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
France	Université De Lorraine	Nancy	Meurthe-et-Moselle
Italy	Istituto Nazionale Dei Tumori	Milano
Netherlands	Noordwest ziekenhuis groep	Alkmaar
Netherlands	Netherlands Cancer institute	Amsterdam
Netherlands	LUMC	Leiden	Zuid-Holland
Netherlands	Canisius Wilhelmina Ziekenhuis	Nijmegen
Netherlands	RadboudUMC	Nijmegen	Gelderland
Spain	Hospital Universitari I Politecnic La Fe	Valencia

Sponsors (2)

Lead Sponsor	Collaborator
Leiden University Medical Center	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

France,  Italy,  Netherlands,  Spain, 

References & Publications (7)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Classic score	The incidence of symptomatic intra-operative adverse events requiring intervention or treatment (ClassIntra®grade = 2) during laparoscopic surgery in the standard of care versus the deep NMB group, as scored by the attending surgeon and anesthesiologist at the end of every procedure. A recent update of the ClassIntra®grade also involved intraoperative adverse events related to anesthesia [Gawria et al 2023]. This study will use both the original classic scoring, as well as an adapted version of the updated classic scoring system.; The Classic score; classification of intraoperative complications, is a 6 point scale ranging from no complications (0) to fatal complications (5).	Day of surgery
Secondary	L-SRS (Leiden Surgical Rating Scale)	To study the effect of deep neuromuscular block compared to standard neuromuscular block on peroperative surgical working conditions following the Leiden Surgical Rating scale (a 5 point scale, ranging from poor (1) to excellent (5) surgical conditions.	Day of surgery
Secondary	30 day post-operative complications	To study the effect of deep neuromuscular block compared to standard neuromuscular block on 30 day post-operative complications according the Clavien-Dindo score en Comprehensive Complication Index and unplanned readmissions	30 postoperative days
Secondary	Quality of recovery (QoR)	To study the effect of deep neuromuscular block compared to standard neuromuscular block on Quality of Recovery at post-operative day 1, 2 according to the Quality of Recovery-40	2 postoperative days
Secondary	Quality of life (QoL)	To study the effect of deep neuromuscular block compared to standard neuromuscular block on Quality of life at post-operative day 30 Short Form-36	30 postoperative days

External Links

•   Link to calculate comprehensive complication index