Comparison of Low Versus Normal Pressure Pneumoperitoneum - With Profound Low Versus Normal Pressure Pneumoperitoneum -With Profound Muscle Relaxation- During Laparoscopic Donor Nephrectomy (LEOPARD2)

A Phase IV, Blinded, Randomized Controlled Trial to Compare the Effectiveness of Low Pressure Pneumoperitoneum - With Profound Muscle Relaxation - During Laparoscopic Donor Nephrectomy to Optimize the Quality-of-recovery During the Early Post-operative Phase

As both patients with end-stage kidney disease and society benefit tremendously from live kidney donation, the safety and well-being of kidney donors are highly important objectives in live kidney donation. Laparoscopic donor nephrectomy has several advantages over open nephrectomy, such as less post-operative pain, better quality of life and shorter hospital stay. Therefore, laparoscopic donor nephrectomy is nowadays the treatment of choice in most countries.

So far, modifications of the technique of laparoscopic donor nephrectomy, i.e. hand-assisted and/or retroperitoneoscopic approaches, did not show a significant benefit with regard to safety as reflected by the conversion to open and postoperative complications rate. We therefore believe that further research should focus on the optimization of early postoperative pain and its concomitant use of opioids. Since non-steroidal anti-inflammatory drugs are contra-indicated before and after nephrectomy, the management of postoperative pain largely depends on the administration of opioids. Measures to reduce postoperative pain would also reduce the occurrence of postoperative nausea and vomitus, and postoperative bowel dysfunction.

A recent pilot study performed by our group showed that the use of low pressure pneumoperitoneum was feasible and significantly reduced deep intra-abdominal and referred pain score during the first 72 hours after surgery. Previous studies performed by others show that low pressure pneumoperitoneum is associated with reduction of systemic inflammatory response, post-operative pain and analgesic consumption. Martini et al have shown that deep neuromuscular block improves surgical conditions during laparoscopic surgery with standard intra-abdominal pressure. To facilitate the use of low pressure pneumoperitoneum, deep neuromuscular block improves surgical conditions and might become a prerequisite for the use of low pressure pneumoperitoneum.

Our hypothesis is that the combination of low pressure pneumoperitoneum and deep neuromuscular block improves quality of recovery in the early post-operative phase.

Study Overview

• Status: Completed
• Conditions: Renal Disease
• Intervention / Treatment: Procedure: Normal pressure pneumoperitoneum (12 mmHg); Procedure: Deep neuromuscular block; Procedure: Low pressure pneumoperitoneum

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6500HB
      • 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

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 non-steroidal anti-inflammatory drugs shorter than 5 days before surgery
• known or suspect allergy to rocuronium or sugammadex
• significant liver* or renal** dysfunction
• neuromuscular disease
• pregnant of breastfeeding

• indication for rapid sequence induction

  • liver dysfunction is defined as alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) > twice the upper limit (extremely rare in live kidney donors) ** renal dysfunction is defined as serum creatinine twice the normal level and/or glomerular filtration rate < 60 ml/min (extremely rare in live kidney donors)

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
Active Comparator: Normal pressure pneumoperitoneum & deep neuromuscular block; Normal pressure pneumoperitoneum	Procedure: Normal pressure pneumoperitoneum (12 mmHg); Procedure: Deep neuromuscular block
Experimental: Low pressure pneumoperitoneum & deep neuromuscular block; Low pressure pneumoperitoneum	Procedure: Deep neuromuscular block; Procedure: Low pressure pneumoperitoneum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Quality-of-Recovery 40 scale	day 1

Secondary Outcome Measures

Outcome Measure	Time Frame
Cumulative use of opioids	Day -1;0;1;2;3 and Mon3
Cumulative use of other analgetics	Day -1;0;1;2;3
Post-operative complications	Day 0;1;2;3 and Month 3
Time to reach discharge criteria	Day 0;1;2;3

Other Outcome Measures

Outcome Measure	Time Frame
Operation time	Peri-operative
Length of pneumoperitoneum	Peri-operative
Estimated blood loss	Peri-operative
Intra-operative complications	Peri-operative

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Michiel Warlé, MD PhD, Radboud University Medical Center

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.
• Ozdemir-van Brunschot DMD, Scheffer GJ, van der Jagt M, Langenhuijsen H, Dahan A, Mulder JEEA, Willems S, Hilbrands LB, Donders R, van Laarhoven CJHM, d'Ancona FA, Warle MC. Quality of Recovery After Low-Pressure Laparoscopic Donor Nephrectomy Facilitated by Deep Neuromuscular Blockade: A Randomized Controlled Study. World J Surg. 2017 Nov;41(11):2950-2958. doi: 10.1007/s00268-017-4080-x. Erratum In: World J Surg. 2017 Aug 18;:
• Ozdemir-van Brunschot DM, Scheffer GJ, Dahan A, Mulder JE, Willems SA, Hilbrands LB, d'Ancona FC, Donders RA, van Laarhoven KJ, Warle MC. Comparison of the effectiveness of low pressure pneumoperitoneum with profound muscle relaxation during laparoscopic donor nephrectomy to optimize the quality of recovery during the early post-operative phase: study protocol for a randomized controlled clinical trial. Trials. 2015 Aug 12;16:345. doi: 10.1186/s13063-015-0887-7.

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: May 21, 2014
• First Submitted That Met QC Criteria: May 21, 2014
• First Posted (Estimate): May 23, 2014

Study Record Updates

• Last Update Posted (Estimate): November 10, 2015
• Last Update Submitted That Met QC Criteria: November 9, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Low pressure pneumoperitoneum; Deep neuromuscular block
• Additional Relevant MeSH Terms: Digestive System Diseases; Peritoneal Diseases; Pneumoperitoneum
• Other Study ID Numbers: MISP#51414