Clinical trial NCT04250883: Low Pressure Pneumoperitoneum and Deep Neuromuscular Block vs. Standard During RARP to Improve Quality of Recovery; a Randomized Controlled Study.
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Quality of Life
Postoperative Complications
Acute Pain
Immune System Tolerance
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2020-01-31
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Randomized
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Quality of Recovery - 40 Items Questionnaire Score (QoR-40)
timeFrame: at postoperative day 1
measure: Quality of Recovery - 40 Items Questionnaire Score (QoR-40)
timeFrame: day 12 after surgery
measure: Quality of Recovery - 40 Items Questionnaire Score (QoR-40)
timeFrame: Pre-operative
Secondary outcomes:
measure: Health Status With Short Form Survey (SF-36)
timeFrame: Measure pre-operative, on day 12 and at 3 months after surgery
measure: Chronic Pain With McGill Pain Questionnaire (MPQ)
timeFrame: 3 months after surgery
measure: Operating Conditions
timeFrame: During operation for up to 8 hours
measure: Pain Score With NRS
timeFrame: Preset timepoints during hospital stay (1hr, 6hrs, 12hrs, day1), up to 3 days maximum. No measurements after discharge to home.
measure: Postoperative Nausea and Vomiting (PONV)
timeFrame: During hospital stay up to 3 days
measure: Analgesia Use
timeFrame: During hospital stay up to 3 days
measure: Hospital Stay
timeFrame: from admission up to 3 days
measure: Complications
timeFrame: Day of surgery untill 30days after surgery
measure: Perfusion Index of the Parietal Peritoneum
timeFrame: From ICG injection, up to 20 seconds
measure: Immune Response Represented by IL-10
timeFrame: Pre-operative, postoperative day 1 and 12
measure: Immune Response Represented by IL-6
timeFrame: Pre-operative, postoperative day 1 and 12
measure: Chronic Pain With McGill Pain Questionnaire (MPQ)
timeFrame: 3 months after surgery
measure: Perfusion Index of the Parietal Peritoneum
timeFrame: From ICG injection, up to 20 seconds
Other outcomes:
measure: Duration of Surgery
timeFrame: 0-350minutes
measure: Duration of Pneumoperitoneum
timeFrame: 0-350 minutes
measure: Estimated Blood Loss
timeFrame: During operation
Locations:
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina ziekenhuis
Study officials:
affiliation: Radboud University Medical Center
name: Michiel Warle, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Reijnders-Boerboom GTJA, Jacobs LMC, Helder LS, Panhuizen IF, Brouwer MPJ, Albers KI, Loonen T, Scheffer GJ, Keijzer C, van Basten JA, Warle MC. Recovery and immune function after low pressure pneumoperitoneum during robot-assisted radical prostatectomy: a randomised controlled trial. BJU Int. 2024 Sep;134(3):416-425. doi: 10.1111/bju.16397. Epub 2024 May 24.