Deep Versus Moderate Muscle Relaxation During Laparoscopic Donor Nephrectomy in Enhancing Postoperative Recovery (RELAX)

The Effectiveness of Deep Versus Moderate Muscle Relaxation During Laparoscopic Donor Nephrectomy in Enhancing Postoperative Recovery

Postoperative recovery after live donor nephrectomy (LDN) is largely determined by the consequences of postoperative pain and analgesia consumptions. The investigators' goal is to establish the relationship between the use of deep neuromuscular blockade (NMB) during laparoscopic donor nephrectomy (LDN) and the early quality of recovery. Therefore, the investigators designed a trial in which patients scheduled for living donor nephrectomy are randomized into a group with deep NMB or moderate NMB. The primary outcome measurement will be the Quality of Recovery-40 questionnaire (overall score) at 48 hours after extubation.

Study Overview

• Status: Completed
• Conditions: Surgery; Neuromuscular Block; Renal Transplant Donor of Left Kidney; Renal Transplant Donor of Right Kidney
• Intervention / Treatment: Other: Rocuronium; Other: No additional Rocuronium

Detailed Description

Rationale: Postoperative recovery after live donor nephrectomy (LDN) is largely determined by the consequences of postoperative pain and analgesia consumptions. The use of deep neuromuscular blockade (NMB) has shown to reduce postoperative pain scores after laparoscopic surgery. With this study the investigators will investigate if deep NMB also improves the early quality of recovery after LDN.

Objective: To establish the relationship between the use of deep neuromuscular blockade (NMB) during laparoscopic donor nephrectomy (LDN) - with standard pressure pneumoperitoneum - and the early quality of recovery.

Study design: A multicenter, blinded, randomized controlled trial

Study population: 96 adult patients (18 years or older), scheduled for living donor nephrectomy, will be randomized into a group with deep or moderate neuromuscular blockade. Deep neuromuscular blockade is defined as post tetanic count 1-2.

Main study parameters/endpoints: The primary outcome measurement will be the Quality of Recovery-40 questionnaire (overall score) at 48 hours after extubation.

Secondary outcomes measured are: intra-operative parameters (e.g. surgical conditions, operation time, length of pneumoperitoneum, first warm ischemia time, estimated blood loss, conversion to open or hand-assisted donor nephrectomy, intra-operative complications, cumulative use of rocuronium and sugammadex), the total score of the quality of Recovery-40 questionnaire at 48 hours after extubation, post-operative pain (components of pain scores); postoperative nausea and vomiting (NRS), the cumulative use of analgesics and anti-emetics, time to reach discharge criteria and postoperative complications.

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands
    • LUMC
  • Nijmegen, Netherlands
    • Radboudumc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

All adult individuals, who are scheduled for living kidney donation.

Inclusion Criteria:

• obtained informed consent
• age over 18 years

Exclusion Criteria:

• insufficient control of the Dutch language to read the patient information and to fill out the questionnaires
• chronic use of analgesics or psychotropic drugs
• use of NSAIDs shorter than 5 days before surgery
• known or suspect allergy to rocuronium of sugammadex
• neuromuscular disease
• indication for rapid sequence induction
• deficiency of vitamin K-dependent clotting factors, coagulopathy or active use of coumarin derivates.
• Peri-operative use of fusidic acid or flucloxacillin
• Severe renal impairment (creatinine clearance <30ml/min)
• Morbid obesity (BMI>35 kg/m2)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: Deep Neuromuscular blockade; An extra bolus of rocuronium after intubation followed by infusion	Other: Rocuronium; A bolus of 0.7 mg/kg rocuronium is administered just after tracheal intubation and then an infusion of rocuronium (0.3 to 0.4 mg/kg) is started when post-tetanic count (PTC) is more than 0 and titrated towards PTC 1-2.
Sham Comparator: Group B: Moderate neuromuscular Blockade; Moderate neuromuscular Blockade No additional rocuronium after intubation.	Other: No additional Rocuronium; No additional rocuronium is administered after tracheal intubation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Score of the Quality of Recovery-40 Questionnaire (QoR-40)	The QoR-40 is a validated assessment tool for measuring a patient's self-assessed quality of recovery after surgery. It consists of 40 questions measuring 5 dimensions: patient support, comfort, emotions, physical independence and pain. Each item is rated on a scale of 1 to 5, giving a minimal score of 40 and a maximum score of 200. Higher values represent a better outcome	Day 1: 24 hours after detubation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgical Conditions	Surgical rating score, concerning the quality of the surgical field, scored with the surgical rating scale (SRS) A likert scale from 1 to 5. Higher scores represent better outcomes.; = extremely poor conditions; = poor conditions; = acceptable conditions; =good conditions; = optimal conditions	Day 0: Intraoperative, average of scores up to 240 minutes (assessed each 15 minutes)
Length of Pneumoperitoneum	Intraoperative parameter of duration of pneumoperitoneum	Day 0: once, up to 240 minutes
Warm Ischemia Time	Intraoperative parameter measuring the time (in minutes) between dissection of the renal artery and flushing of the kidney after retrieval	Day 0: once, up to 240 minutes
Estimated Blood Loss	Intraoperative parameter	Day 0: once, up to 240 minutes
Conversion	Number of Participants with conversion to open or hand-assisted donor nephrectomy	Day 0: once, up to 240 minutes
Intra-operative Complications	Number of Participants with Complications which occurred during surgery	Day 0: once, up to 240 minutes
Cumulative Use of Rocuronium	Total amount of rocuronium administered during surgery	Day 0: once, up to 240 minutes
Total Score of the Quality of Recovery-40 Questionnaire	The QoR-40 is a validated assessment tool for measuring a patient's self-assessed quality of recovery after surgery. It consists of 40 questions measuring 5 dimensions: patient support, comfort, emotions, physical independence and pain. Each item is rated on a scale of 1 to 5, giving a minimal score of 40 and a maximum score of 200. Higher values represent a better outcome.	Day 2: 48 hours after detubation
Postoperative Pain	components of pain scores after 1 hour, 6 hours, on postoperative day 1 (POD1) and postoperative day 2 (POD2). Likert scale from 0 to 10. Higher scores represent more pain.	Day 0: 1h, 6h, day 1: 24h and day 2: 48 hours (and if still admitted 72h) after detubation
Postoperative Complications	Number of participants with postoperative complications that occurred up to 8 weeks after surgery	24 and 48 hours (and if still admitted 72h) after detubation and 4 and 8 weeks after surgery
Discharge Criteria	Scoring the following criteria: adequate pain control with oral medication, passage of flatus or defecation, intake of solid food tolerated, patient is mobilized and independent and patient accepts discharge.	24 and 48 hours after detubation
Pain Scores	Total amount of pain 4 weeks after surgery Likert scale from 0 to 10. Higher scores represent more pain (worse outcome).	once, 4 weeks after surgery

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Michiel Warle, Dr., Radboud University Medical Center; Principal Investigator: Moira Bruintjes, Msc., Radboud University Medical Center; Principal Investigator: Andries E Braat, Dr., LUMC

Publications and helpful links

General Publications

• Reijnders-Boerboom GTJA, van Helden EV, Minnee RC, Albers KI, Bruintjes MHD, Dahan A, Martini CH, d'Ancona FCH, Scheffer GJ, Keijzer C, Warle MC. Deep neuromuscular block reduces the incidence of intra-operative complications during laparoscopic donor nephrectomy: a pooled analysis of randomized controlled trials. Perioper Med (Lond). 2021 Dec 9;10(1):56. doi: 10.1186/s13741-021-00224-1.
• Albers KI, van Helden EV, Dahan A, Martini CH, Bruintjes MHD, Scheffer GJ, Steegers MAH, Keijzer C, Warle MC. Early postoperative pain after laparoscopic donor nephrectomy predicts 30-day postoperative infectious complications: a pooled analysis of randomized controlled trials. Pain. 2020 Jul;161(7):1565-1570. doi: 10.1097/j.pain.0000000000001842.
• Bruintjes MHD, Krijtenburg P, Martini CH, Poyck PP, d'Ancona FCH, Huurman VAL, van der Jagt M, Langenhuijsen JF, Nijboer WN, van Laarhoven CJHM, Dahan A, Warle MC; RELAX collaborator group. Efficacy of profound versus moderate neuromuscular blockade in enhancing postoperative recovery after laparoscopic donor nephrectomy: A randomised controlled trial. Eur J Anaesthesiol. 2019 Jul;36(7):494-501. doi: 10.1097/EJA.0000000000000992.
• Bruintjes MH, Braat AE, Dahan A, Scheffer GJ, Hilbrands LB, d'Ancona FC, Donders RA, van Laarhoven CJ, Warle MC. Effectiveness of deep versus moderate muscle relaxation during laparoscopic donor nephrectomy in enhancing postoperative recovery: study protocol for a randomized controlled study. Trials. 2017 Mar 4;18(1):99. doi: 10.1186/s13063-017-1785-y.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): November 2, 2017
• Study Completion (Actual): December 2, 2017

Study Registration Dates

• First Submitted: June 29, 2016
• First Submitted That Met QC Criteria: July 15, 2016
• First Posted (Estimate): July 20, 2016

Study Record Updates

• Last Update Posted (Actual): September 19, 2019
• Last Update Submitted That Met QC Criteria: August 16, 2019
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Laparoscopic donor nephrectomy; Early quality of recovery
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Neuromuscular Agents; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Rocuronium
• Other Study ID Numbers: NL58160.091.16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO