Low impact laparoscopy (low pressure pneumoperitoneum and deep neuromuscular blockade) versus standard laparoscopy during robot assisted radical prostatectomy to improve the quality of recovery and immune homeostasis; 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.
Increased IAP can cause peritoneal mesothelial injury either directly or by
compression of small vessels including capillaries, leading to a variable
degree of ischemia reperfusion injury. The compromised perfusion of the
parietal peritoneum can be visualized and quantified by a fluorescent marker
such as Indocyanine green (ICG), as shown in a previous pilot study. Hypoxic
injury of intra-abdominal organs and/or tissues may cause the release of Danger
Associated Molecular Patterns (DAMPs). It is known that after trauma and
sepsis, the release of DAMPs is associated with immunoparalysis and a higher
susceptibility to infectious complications. The use of low pressure PNP may
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.

- To establish the relationship between the use of deep neuromuscular blockade
(NMB) with low pressure pneumoperitoneum (PNP) and the quality of recovery
after RARP.
- To establish the relationship between the use of deep neuromuscular blockade
(NMB) with low pressure pneumoperitoneum (PNP) and innate immune function after
RARP.
Secondary objectives:
- To study whether low pressure PNP and/or deep NMB affects the perfusion of
the parietal peritoneal layer during RARP.

A mono-center, randomized controlled clinical trial.

The participants will be randomly assigned in a 1:1 fashion to:
- Experimental group: low impact laparoscopy (low pressure (8 mmHg) and deep
NMB (PTC 1-2))
- Control group: standard laparoscopy (standard pressure (14 mmHg) and moderate
NMB (TOF 1-2))
At the start of surgery, after intra-abdominal insufflation, 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.

The use of a deep NMB enables the safe use of low-pressure PNP. If despite a
deep NMB visibility is compromised, pressure will be increased to minimize
surgery related risks. A deep NMB is achieved by higher doses of rocuronium
which are within normal therapeutic range used in clinical practice, and is
safe to use. Depth of NMB will be monitored throughout the whole surgery. At
the end of surgery, the effects of rocuronium will be antagonized by sugammadex
to avoid residual paralysis. Indocyanine green is a registered product
routinely used to quantify tissue perfusion during this surgery. The total dose
during surgery is below the advised maximum dose of 5 mg/kg. Any possible risk
factors or interactions as mentioned in the Summary of Product Characteristics
are covered by exclusion criteria in order to fully eliminate risk of
participation. Regarding the peritoneal biopsies; peritoneal tissue is directly
visible and easily accessible during laparoscopic surgery and biopsies are
obtained in a standardized manner with hemostasis when needed under direct
vision. Therefore, no additional complications are expected. Blood samples will
be combined with routine laboratory assessment where possible. Previous studies
have shown low-pressure PNP is associated with reduced postoperative pain
scores, reduced opioid consumption and improved bowel function. This may lead
to enhanced recovery. The burden for participants is mainly related to the
evaluation of the endpoints during the early postoperative phase. Assessment of
pain scores, nausea, complications and discharge criteria are part of the
normal treatment. Questionnaires will take approximately 10-15 minutes per
time-point.