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

Surgery Clinical Trial

— RECOVER-PLUS  

Official title:

The Effectiveness of Low Pressure Pneumoperitoneum During Laparoscopic Colorectal Surgery in Preserving Innate Immune Homeostasis by Reducing Peritoneal Mesothelial Cell Injury.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03572413
• Other study ID #: NL65290.091.18 substudy
• Status: Completed
• Phase: Phase 4
• Start date: October 24, 2018
• Est. completion date: December 1, 2020

Study information

• Verified date: March 2021
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: December 1, 2020
• Est. primary completion date: August 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Immune Suppression
• Neuromuscular Blockade
• Pneumoperitoneum
• Surgery

Intervention

Procedure:
• Low pressure pneumoperitoneum
Lowering intra-abdominal pressure during laparoscopic surgery

Drug:
• Rocuronium bromide
Deep (PTC 1-2) versus moderate (TOF count 1-2) neuromuscular block

Locations

Country	Name	City	State
Netherlands	Canisius Wilhelmina Hospital	Nijmegen	Gelderland

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mononuclear cell responsiveness ex vivo	TNFalpha release upon LPS stimulation	Before surgery, 24 and 72 hours after surgery
Secondary	Mononuclear cell responsiveness ex-vivo	IL-6, IL-10 and IL-1beta release upon LPS stimulation	Before surgery, 24 and 72 hours after surgery
Secondary	Serum DAMPs and cytokines	Danger associated molecular patterns, TNFalpha, IL-6 and IL-10	Before surgery, at the end of surgery and 24 hours after surgery
Secondary	HLA-DR mRNA expression	MHC-II antigen presenting immune receptor	Before surgery, 24 and 72 hours after surgery
Secondary	Peritoneal histology and HIF1alpha expression	Histology and HIF1alpha mRNA expression of a peritoneal biopsy	At the start and end of surgery