Low Pressure Pneumoperitoneum and Deep Neuromuscular Block vs. Standard During RARP to Improve Quality of Recovery; a Randomized Controlled Study.

Not Applicable

Completed

Conditions: Quality of Life
Postoperative Complications
Acute Pain
Immune System Tolerance

Interventions: Other: Standard intra-abdominal pressure
Other: Low intra-abdominal pressure
Other: Moderate neuromuscular blockade (NMB)
Other: Deep neuromuscular blockade (NMB)

Registration Number: NCT04250883

Lead Sponsor: Radboud University Medical Center

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 97

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Control group: Standard laparoscopy	Moderate neuromuscular blockade (NMB)	standard laparoscopy (standard pressure (14 mmHg) and moderate NMB (TOF 1-2)
Experimental group: Low Impact laparoscopy	Deep neuromuscular blockade (NMB)	low impact laparoscopy (low pressure (8 mmHg) and deep NMB (PTC 1-2)
Control group: Standard laparoscopy	Standard intra-abdominal pressure	standard laparoscopy (standard pressure (14 mmHg) and moderate NMB (TOF 1-2)
Experimental group: Low Impact laparoscopy	Low intra-abdominal pressure	low impact laparoscopy (low pressure (8 mmHg) and deep NMB (PTC 1-2)

Primary Outcome Measures

Name	Time	Method
Quality of Recovery - 40 Items Questionnaire Score (QoR-40)	Pre-operative	40 points (minimum: extremely poor quality of recovery) to 200 points (maximum: excellent quality of recovery)

Secondary Outcome Measures

Name	Time	Method
Health Status With Short Form Survey (SF-36)	Measure pre-operative, on day 12 and at 3 months after surgery	Total score on a scale of 0-100 points. The lower the score the more disability. The higher the score the less disability.
Chronic Pain With McGill Pain Questionnaire (MPQ)	3 months after surgery	Number of words Chosen according the user manual of the questionnaire
Operating Conditions	During operation for up to 8 hours	surgical conditions with L-SRS 0 (extremely poor work field) to 5 (excellent work field)
Pain Score With NRS	Preset timepoints during hospital stay (1hr, 6hrs, 12hrs, day1), up to 3 days maximum. No measurements after discharge to home.	pain scores with NRS 0 (no pain) to 10 (severe pain)
Postoperative Nausea and Vomiting (PONV)	During hospital stay up to 3 days	Presence of symptoms yes/no
Analgesia Use	During hospital stay up to 3 days	Cumulative opioid use in morphine equivalent (in mg)
Hospital Stay	from admission up to 3 days	length of hospital stay in days
Complications	Day of surgery untill 30days after surgery	Postoperative complications scored by Clavien Dindo classification; grade 0 (no deviation from ideal) grade 5 (death of patient)
Perfusion Index of the Parietal Peritoneum	From ICG injection, up to 20 seconds	Angle minimal to maximal, calculated from the slope of ICG fluorescence intensity (extracted from video registration).
Immune Response Represented by IL-10	Pre-operative, postoperative day 1 and 12	IL-10 response upon whole blood LPS stimulation
Immune Response Represented by IL-6	Pre-operative, postoperative day 1 and 12	IL-6 response upon whole blood LPS stimulation