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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.

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
96
Inclusion Criteria
    • Age ≥ 18 years
  • Undergoing elective robot assisted radical prostatectomy (RARP)
  • Obtained informed consent
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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Control group: Standard laparoscopyModerate neuromuscular blockade (NMB)standard laparoscopy (standard pressure (14 mmHg) and moderate NMB (TOF 1-2)
Experimental group: Low Impact laparoscopyDeep neuromuscular blockade (NMB)low impact laparoscopy (low pressure (8 mmHg) and deep NMB (PTC 1-2)
Control group: Standard laparoscopyStandard intra-abdominal pressurestandard laparoscopy (standard pressure (14 mmHg) and moderate NMB (TOF 1-2)
Experimental group: Low Impact laparoscopyLow intra-abdominal pressurelow impact laparoscopy (low pressure (8 mmHg) and deep NMB (PTC 1-2)
Primary Outcome Measures
NameTimeMethod
Quality of recovery - 40 items questionnaire score (QoR-40)at postoperative day 1

40 points (minimum: extremely poor quality of recovery) to 200 points (maximum: excellent quality of recovery)

Immune response represented by IL-10at postoperative day 1

IL-10 response upon whole blood LPS stimulation

Immune response represented by IL-6at postoperative day 1

IL-6 response upon whole blood LPS stimulation

Perfusion index of the parietal peritoneumFrom ICG injection, up to 20 seconds

calculated from the slope of ICG fluorescence intensity, and time to maximal intensity in seconds. (extracted from video registration).

Secondary Outcome Measures
NameTimeMethod
Hospital stayfrom admission up to 3 days

length of hospital stay in days

Chronic pain with McGill pain questionnaire (MPQ)3 months after surgery

range from 0 (no pain) to 78 (severe pain)

Pain score with VASDuring hospital stay up to 3 days

pain scores with VAS 0 (no pain) to 10 (severe pain)

Health status with short form survey (SF-36)day 10 and 3 months after surgery

The lower the score the more disability. The higher the score the less disability.

Quality of recovery - 40 items questionnaire score (QoR-40)day 10 after surgery

40 points (minimum: extremely poor quality of recovery) to 200 points (maximum: excellent quality of recovery)

PONVDuring hospital stay up to 3 days

With PONV impact scale score o (no PONV) to 6 (extreme PONV)

Analgesia useDuring hospital stay up to 3 days

non-cumulative and cumulative opioid use per day in morphine equivalent

Postoperative recovery timeFrom day of surgery up to 3 days

time to reach discharge criteria in days

Operating conditionsDuring operation for up to 8 hours

surgical conditions with L-SRS 0 (extremely poor work field) to 5 (excellent work field)

ComplicationsDay of surgery untill 30days after surgery

postoperative complications scored by Clavien Dindo classification; grade 0 (no deviation from ideal) grade 5 (death of patient)

Trial Locations

Locations (1)

Canisius Wilhelmina ziekenhuis

🇳🇱

Nijmegen, Netherlands

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