Pneumoperitoneum, Neuromuscular Blockade, Surgery, Immune Suppression
Conditions
Keywords
Laparoscopic surgery, Deep neuromuscular block, Low pressure pneumoperitoneum, Postoperative immune suppression
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.
Interventions
PROCEDURELow pressure pneumoperitoneum
Lowering intra-abdominal pressure during laparoscopic surgery
DRUGRocuronium bromide
Deep (PTC 1-2) versus moderate (TOF count 1-2) neuromuscular block
Sponsors
Merck Sharp & Dohme LLC
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mononuclear cell responsiveness ex vivo | Before surgery, 24 and 72 hours after surgery | TNFalpha release upon LPS stimulation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mononuclear cell responsiveness ex-vivo | Before surgery, 24 and 72 hours after surgery | IL-6, IL-10 and IL-1beta release upon LPS stimulation |
| Serum DAMPs and cytokines | Before surgery, at the end of surgery and 24 hours after surgery | Danger associated molecular patterns, TNFalpha, IL-6 and IL-10 |
| HLA-DR mRNA expression | Before surgery, 24 and 72 hours after surgery | MHC-II antigen presenting immune receptor |
| Peritoneal histology and HIF1alpha expression | At the start and end of surgery | Histology and HIF1alpha mRNA expression of a peritoneal biopsy |
Countries
Netherlands
Outcome results
None listed