RECOVER study: the effect of low- versus normal pressure pneumoperitoneum during laparoscopic colorectal surgery on the early quality of recovery with perioperative care according to the enhanced recovery principles.
Substudy: the effectiveness of low pressure pneumoperitoneum during laparoscopic colorectal surgery in preserving innate immune homeostasis by reducing peritoneal mesothelial cell injury.

The laparoscopic approach reduced trauma as compared to open surgery, however,
the pressure used to create a PNP with sufficient surgical workspace still
leads to significant tissue injury. Prior studies show that the use of
low-pressure pneumoperitoneum (PNP) during laparoscopic surgery reduced
postoperative pain scores, cumulative opioid consumption and improved bowel
function recovery. Deep neuromuscular blockade (NMB) as compared to moderate
NMB decreases the amount of intra-abdominal pressure required to achieve
similar surgical conditions and enables the use of low-pressure PNP without
compromising the quality of the surgical field and patient safety. Therefore,
the use of deep NMB with low-pressure PNP could be a significant addition to
the conventional Enhanced Recovery After Surgery (ERAS) protocols.
Increased intra-abdominal pressure can cause peritoneal mesothelial cell injury
either directly or by compression of the capillary vessels, causing a variable
degree of ischemia reperfusion injury. The immune system can identify damage to
host cells by recognising Danger-Associated Molecular Patterns (DAMPs) that are
released upon cell death in an uncontrolled fashion, such as during surgical
trauma. DAMPs elicit an immune response similar to the response to invading
pathogens and induce an anti-inflammatory immune response strongly related to
postoperative recovery, infectious complications and mortality. Low pressure
PNP is associated with lower levels of serum pro- and anti-inflammatory
cytokines and better preservation of innate immune function.

Main study: to establish the relationship between the use of low pressure
pneumoperitoneum with deep neuromuscular blockade and the early quality of
recovery after laparoscopic colorectal surgery with perioperative care
according to the enhanced recovery principles.

Substudy: To establish the relationship between the use of low pressure
pneumoperitoneum with deep neuromuscular blockade and innate immune function
after laparoscopic colorectal surgery.

A multi-center, blinded, randomized controlled clinical trial.

Participants will be randomly assigned in a 1:1 fashion to:
Group A: low pressure PNP (8 mmHg) with deep NMB (PTC 1-2)
Group B (standard treatment, control group): normal pressure PNP (12 mmHg) with
moderate NMB (TOF 1-2)

Recent studies show that the use of a deep NMB enables safe use of low-pressure
PNP(1-3). If visibility is compromised at low pressure, pressure will be
increased to ensure no additional risks related to the surgery. A deep NMB is
achieved by higher doses of rocuronium that are within normal therapeutical
range used in clinical practice, and can safely be used (4). Depth of NMB will
be monitored throughout the whole surgery. At the end of surgery, the effects
of rocuronium are antagonized by suggamadex to ensure no extended effects.
Randomized controlled trails have shown sugammadex can be safely administered
(5). Regarding the substudy, peritoneal tissue is directly visible and easily
accessible during laparoscopic colorectal surgery. Biopsies are obtained in a
standardized manner previously used in other studies (6,7) who report no
complications. After biopsy, hemostasis will be established under direct vision
and therefore no additional complications are to be expected. Therefore, risks
of participating in the study are minimal. Previous studies have shown
low-pressure PNP is associated with reduced postoperative pain scores, reduced
opioid consumption and improved bowel function (2,3,8,9). This may lead to
enhanced recovery. Blood samples will be combined with routine laboratory
assessment as much as possible. Assessment of pain, nausea, complications and
discharge criteria are part of the normal treatment. The burden for
participants is mainly related to the evaluation of the endpoints during the
early postoperative phase. Questionnaires will take approximately 10-15 minutes
per time-point.

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(5)
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