Low Pressure Pneumoperitoneum and Deep Neuromuscular Block Versus Standard Laparoscopy During Robot Assisted Radical Prostatectomy to Improve the Quality of Recovery and Immune Homeostasis; Study Protocol for a Randomized Controlled Study. (RECOVER-2)

Low Pressure Pneumoperitoneum and Deep Neuromuscular Blockade Versus Standard Laparoscopy During RARP to Improve the Quality of Recovery and Immune Homeostasis; Study Protocol for a Randomized Controlled Study

Intra-abdominal pressure (IAP) needed to create sufficient workspace during laparoscopic surgery affects the surrounding organs with ischemia-reperfusion injury and a systemic immune response. This effect is related to postoperative recovery, pain scores, opioid consumption, bowel function recovery, morbidity and possibly mortality. In clinical practice standard pressures of 12-16mmHg are applied instead of the lowest possible IAP, but accumulating evidence shows lower pressure pneumoperitoneum (PNP) (6-8mmHg) to be non-compromising for sufficient workspace, when combined with deep neuromuscular blockade (NMB) in a vast majority of patients. Therefore, low impact laparoscopy, meaning low pressure PNP facilitated by deep NMB, could be a valuable addition to Enhanced Recovery After Surgery (ERAS) Protocols.

The use of low pressure PNP may also reduce hypoxic injury and the release of DAMPs and thereby contributing to a better preservation of innate immune function which may help to reduce the risk of infectious complications.

The participants will be randomly assigned to one of the experimental groups with low impact laparoscopy or one of the control groups with standard laparoscopy.

Study Overview

• Status: Completed
• Conditions: Quality of Life; Postoperative Complications; Acute Pain; Immune System Tolerance
• Intervention / Treatment: Other: Low intra-abdominal pressure; Other: Deep neuromuscular blockade (NMB); Other: Standard intra-abdominal pressure; Other: Moderate neuromuscular blockade (NMB)

Detailed Description

Intra-abdominal pressure (IAP) needed to create sufficient workspace during laparoscopic surgery affects the surrounding organs with ischemia-reperfusion injury and a systemic immune response. This effect is related to postoperative recovery, pain scores, opioid consumption, bowel function recovery, morbidity and possibly mortality. Therefore, low impact laparoscopy, meaning low pressure PNP facilitated by deep NMB, could be a valuable addition to Enhanced Recovery After Surgery (ERAS) Protocols.

The use of low pressure PNP may also reduce hypoxic injury and the release of DAMPs and thereby contributing to a better preservation of innate immune function which may help to reduce the risk of infectious complications.

The participants will be randomly assigned to the experimental group 1: low impact laparoscopy (low pressure (8 mmHg) and deep NMB (PTC 1-2)); 8 mmHg IAP after trocar introduction for perfusion measurement or the experimental group 2: low impact laparoscopy (low pressure (8 mmHg) and deep NMB (PTC 1-2)); 12 mmHg IAP after trocar introduction for perfusion measurement, or control group 1: standard laparoscopy (standard pressure (12 mmHg) and moderate NMB (TOF 1-2)); 8 mmHg IAP after trocar introduction for perfusion measurement, or control group 2: standard laparoscopy (standard pressure (12 mmHg) and moderate NMB (TOF 1-2)); 12 mmHg IAP after trocar introduction for perfusion measurement.

ICG injection will take place with starting pressure to quantify parietal peritoneum perfusion, and a parietal peritoneal biopsy will be taken. At the end of surgery, a second parietal peritoneum biopsy will be taken.

NB: After introduction of the camera trocar, insufflation of carbon dioxide is titrated to an IAP of 8mmHg in group A and C, and 14 mmHg in group B and D. After placement of the last trocar the injection of ICG and video registration of peritoneum will take place, and a peritoneal biopsy will be taken. There after surgery will take place with an IAP of 14mmHg in the control groups (C and D), and an IAP of 8mmHg in the experimental groups (A and B). In the control groups (C and D)

Pre- and postoperative a few questionnaires will be taken and blood withdrawals to evaluate the quality of recovery, and the immune response.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands
    • Canisius Wilhelmina Ziekenhuis

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:

• - Age ≥ 18 years
• Undergoing elective robot assisted radical prostatectomy (RARP)
• Obtained informed consent

Exclusion Criteria:

• Laparoscopic radical prostatectomy without robot assistance
• Insufficient control of the Dutch language to read the patient information and to fill out de questionnaires
• Neo-adjuvant chemotherapy
• Chronic use of analgesics or psychotropic drugs
• Use of NSAID's shorter than 5 days before surgery
• Severe liver- or renal disease
• Neuromuscular disease
• Hyperthyroidism or thyroid adenomas
• Deficiency of vitamin K dependent clotting factors or coagulopathy
• Planned diagnostics or treatment with radioactive iodine < 1 week after surgery
• Indication for rapid sequence induction
• BMI >35kg/m2
• Known of suspected hypersensitivity to ICG, sodium iodide, iodine, rocuronium or sugammadex
• Use of medication interfering with ICG absorption as listed in the summary of product characteristics (SPC); anticonvulsants, bisulphite compounds, haloperidol, heroin, meperidine, metamizol, methadone, morphium, nitrofurantoin, opium alkaloids, phenobarbital, phenylbutazone, cyclopropane, probencid

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group: Low Impact laparoscopy; low impact laparoscopy (low pressure (8 mmHg) and deep NMB (PTC 1-2)	Other: Low intra-abdominal pressure; 8 mmHg; Other: Deep neuromuscular blockade (NMB); Deep NMB (PTC1-2)
Active Comparator: Control group: Standard laparoscopy; standard laparoscopy (standard pressure (14 mmHg) and moderate NMB (TOF 1-2)	Other: Standard intra-abdominal pressure; 14 mmHg; Other: Moderate neuromuscular blockade (NMB); Moderate NMB (TOF 1-2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of recovery - 40 items questionnaire score (QoR-40)	40 points (minimum: extremely poor quality of recovery) to 200 points (maximum: excellent quality of recovery)	at postoperative day 1
Immune response represented by IL-6	IL-6 response upon whole blood LPS stimulation	at postoperative day 1
Immune response represented by IL-10	IL-10 response upon whole blood LPS stimulation	at postoperative day 1
Perfusion index of the parietal peritoneum	calculated from the slope of ICG fluorescence intensity, and time to maximal intensity in seconds. (extracted from video registration).	From ICG injection, up to 20 seconds

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of recovery - 40 items questionnaire score (QoR-40)	40 points (minimum: extremely poor quality of recovery) to 200 points (maximum: excellent quality of recovery)	day 10 after surgery
Health status with short form survey (SF-36)	The lower the score the more disability. The higher the score the less disability.	day 10 and 3 months after surgery
Chronic pain with McGill pain questionnaire (MPQ)	range from 0 (no pain) to 78 (severe pain)	3 months after surgery
Pain score with VAS	pain scores with VAS 0 (no pain) to 10 (severe pain)	During hospital stay up to 3 days
Analgesia use	non-cumulative and cumulative opioid use per day in morphine equivalent	During hospital stay up to 3 days
PONV	With PONV impact scale score o (no PONV) to 6 (extreme PONV)	During hospital stay up to 3 days
Hospital stay	length of hospital stay in days	from admission up to 3 days
Postoperative recovery time	time to reach discharge criteria in days	From day of surgery up to 3 days
Operating conditions	surgical conditions with L-SRS 0 (extremely poor work field) to 5 (excellent work field)	During operation for up to 8 hours
Complications	postoperative complications scored by Clavien Dindo classification; grade 0 (no deviation from ideal) grade 5 (death of patient)	Day of surgery untill 30days after surgery

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 24, 2020
• Primary Completion (Actual): December 9, 2021
• Study Completion (Actual): March 7, 2022

Study Registration Dates

• First Submitted: January 29, 2020
• First Submitted That Met QC Criteria: January 30, 2020
• First Posted (Actual): January 31, 2020

Study Record Updates

• Last Update Posted (Actual): May 13, 2022
• Last Update Submitted That Met QC Criteria: May 9, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Peritoneal Diseases; Pain; Neurologic Manifestations; Pneumoperitoneum; Acute Pain; Postoperative Complications; Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Trace Elements; Micronutrients; Iodine
• Other Study ID Numbers: NL72780.091.20; 2020-000411-79 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: All data will be analyzed for publication. After that it belongs to Radboud umc where other researchers of Radboud umc may or may not include this database to their study. But there will be no active sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No