Clinical trial NCT03572413: The Effect of Low Pressure Pneumoperitoneum During Laparoscopic Colorectal Surgery on Innate Immune Homeostasis.
Official title: The Effectiveness of Low Pressure Pneumoperitoneum During Laparoscopic Colorectal Surgery in Preserving Innate Immune Homeostasis by Reducing Peritoneal Mesothelial Cell Injury.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pneumoperitoneum
Neuromuscular Blockade
Surgery
Immune Suppression
Keywords: Laparoscopic surgery
Deep neuromuscular block
Low pressure pneumoperitoneum
Postoperative immune suppression
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2018-06-28
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Substudy of the RECOVER trial (a randomised controlled trial comparing the effect of low pressure pneumoperitoneum with deep neuromuscular block versus normal pressure pneumoperitoneum with moderate neuromuscular block during laparoscopic colorectal surgery on early quality of recovery) investigating innate immune homeostasis after laparoscopic colorectal surgery.

Detailed description: Rationale: 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.

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

Study design: a multi-center, blinded, randomized controlled clinical trial.

Study population: adult individuals scheduled for laparoscopic colorectal surgery with a primary colonic anastomosis.

Intervention: participants will be randomly assigned in a 1:1 fashion to either the experimental group (group A): low pressure PNP (8 mmHg) with deep NMB (PTC 1-2) or the control group (group B): normal pressure PNP (12 mmHg) with moderate NMB (TOF count 1-2).

Primary endpoint: mononuclear cell responsiveness ex-vivo as reflected by TNFα release upon LPS stimulation.

Secondary endpoints: mononuclear cell responsiveness ex-vivo as reflected by IL-6, IL-10 and IL-1beta release upon LPS stimulation. Peritoneal mesothelial hypoxia as reflected by peritoneal HIF1α mRNA expression, histological peritoneal mesothelial cell injury and plasma levels of DAMPs and cytokines.

Eligibility criteria: Inclusion Criteria:

* Scheduled for laparoscopic colorectal surgery with a primary anastomosis
* Obtained informed consent
* Age over 18 years

Exclusion Criteria:

* Insufficient control of the Dutch language to read the patient information and to fill out the questionnaires
* Primary colostomy
* Neo-adjuvant chemotherapy
* Chronic use of analgesics or psychotropic drugs
* Use of NSAIDs shorter than 5 days before surgery
* Known or suspected allergy to rocuronium of sugammadex
* Neuromuscular disease
* Indication for rapid sequence induction
* Severe liver- or renal disease (creatinine clearance \<30ml/min)
* BMI \>35 kg/m²
* Deficiency of vitamin K dependent clotting factors or coagulopathy

Primary outcomes:
measure: Mononuclear cell responsiveness ex vivo
timeFrame: Before surgery, 24 and 72 hours after surgery
Secondary outcomes:
measure: Mononuclear cell responsiveness ex-vivo
timeFrame: Before surgery, 24 and 72 hours after surgery
measure: Serum DAMPs and cytokines
timeFrame: Before surgery, at the end of surgery and 24 hours after surgery
measure: HLA-DR mRNA expression
timeFrame: Before surgery, 24 and 72 hours after surgery
measure: Peritoneal histology and HIF1alpha expression
timeFrame: At the start and end of surgery
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Hospital
state: Gelderland
Study officials:
affiliation: Radboud University Medical Center
name: Kim I Albers, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radboud University Medical Center
name: Michiel C Warlé, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: