The Effect of Low Pressure Pneumoperitoneum During Laparoscopic Colorectal Surgery on Innate Immune Homeostasis.

NCT ID: NCT03572413

Last Updated: 2021-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-24
• Study Completion Date: 2020-12-01

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.

Conditions

Pneumoperitoneum; Neuromuscular Blockade; Surgery; Immune Suppression

Keywords

Laparoscopic surgery; Deep neuromuscular block; Low pressure pneumoperitoneum; Postoperative immune suppression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Low pressure PNP, deep NMB

Low pressure pneumoperitoneum of 8 mmHg with deep neuromuscular block (post tetanic count of 1-2) reached by titration with continuous infusion of Rocuronium bromide.

Group Type: EXPERIMENTAL

Low pressure pneumoperitoneum

Intervention Type: PROCEDURE

Lowering intra-abdominal pressure during laparoscopic surgery

Rocuronium bromide

Intervention Type: DRUG

Deep (PTC 1-2) versus moderate (TOF count 1-2) neuromuscular block

Normal pressure PNP, moderate NMB

Normal pressure pneumoperitoneum of 12 mmHg with moderate neuromuscular block (TOF count of 1-2) reached by titration with bolus or continuous infusion of a low dose of Rocuronium bromide.

Group Type: ACTIVE_COMPARATOR

Rocuronium bromide

Intervention Type: DRUG

Deep (PTC 1-2) versus moderate (TOF count 1-2) neuromuscular block

Interventions

Low pressure pneumoperitoneum

Lowering intra-abdominal pressure during laparoscopic surgery

Intervention Type: PROCEDURE

Rocuronium bromide

Deep (PTC 1-2) versus moderate (TOF count 1-2) neuromuscular block

Intervention Type: DRUG

Other Intervention Names

Low intra-abdominal pressure; Deep muscle relaxation

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kim I Albers, MD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Michiel C Warlé, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

Canisius Wilhelmina Hospital

Nijmegen, Gelderland, Netherlands

Countries

Netherlands

Other Identifiers

NL65290.091.18 substudy

Identifier Type: -

Identifier Source: org_study_id