The Effect of Low Pressure Pneumoperitoneum During Laparoscopic Colorectal Surgery on Innate Immune Homeostasis. (RECOVER-PLUS)

Radboud University Medical Center

Status and phase: Completed; Phase 4

Conditions: Pneumoperitoneum; Surgery; Neuromuscular Blockade; Immune Suppression

Treatments: Procedure: Low pressure pneumoperitoneum; Drug: Rocuronium bromide

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03572413

NL65290.091.18 substudy

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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100 participants in 2 patient groups

Low pressure PNP, deep NMB

Experimental group

Description:

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.

Treatment:

Drug: Rocuronium bromide

Procedure: Low pressure pneumoperitoneum

Normal pressure PNP, moderate NMB

Active Comparator group

Description:

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.

Treatment:

Drug: Rocuronium bromide