Innate Inflammatory Response, Neuromuscular Blockade, Postoperative Complications, Quality of Life
Conditions
Brief summary
Monocenter randomized controlled trial to compare the effect of deep neuromuscular blockade (NMB) versus moderate NMB during total hip replacement surgery on postoperative quality of recovery and innate immune function.
Detailed description
Rationale: Neuromuscular blockade agents (NMB) may enable surgeons to optimize exposure during hip surgery. With an increasing depth of NMB, manipulation of muscles and adjunctive tissues may be easier, therefore reducing damage to muscles and adjunct tissues. Accumulating evidence exists that the use of deep NMB in laparoscopic surgery is associated with a better quality of recovery and lower pain scores. However, whether this accounts for open surgery is still unknown. In addition, surgery is associated with postoperative immune suppression. Surgical stress and damage cause the release of Danger Associated Molecular Patterns (DAMPs). After trauma and sepsis, the release of DAMPs is associated with immune paralysis and a higher susceptibility to infectious complications. Previous research indicates that DAMPS are the origin of postoperative immune suppression. The use of deep NMB in hip surgery may reduce surgical damage and thereby lead to a better quality of recovery and secondarily a better preservation of immune cell function. Primary objective: To establish the relationship between the use of deep neuromuscular blockade (NMB) versus moderate NMB and the quality of recovery after total hip replacement surgery (THR) Secondary objective: To establish the relationship between the use of deep NMB versus moderate NMB and innate immune function after THR surgery Study design: A monocenter, blinded, randomized controlled clinical trial Study population: adults who are scheduled for primary or secondary hip replacement surgery under general anaesthesia. Intervention: Patients will be randomized between a deep NMB (post tetanic count (PTC) 1-2) and moderate NMB (Train-of-four (TOF) 1-2) Primary endpoint: Quality of Recovery score (QoR-40) at postoperative day 1. Secondary endpoints: postoperative innate immune function, QoR-40 at postoperative day 30, 30-day postoperative (infectious) complications, postoperative pain scores and opioid consumption
Interventions
DRUGRocuronium Bromide
Moderate NMB (TOF 1-2)
Sponsors
Merck Sharp & Dohme LLC
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age of 18 years or older * Scheduled for total hip replacement surgery under general anaesthesia * Informed consent obtained
Exclusion criteria
* Insufficient control of the Dutch language to read the patient information and to fill out de questionnaires * Known or suspected hypersensitivity to rocuronium or sugammadex * Deficiency of vitamin K dependent clotting factors or coagulopathy * Severe renal disease (creatinine clearance \<30 ml/min), including patients on dialysis * Severe liver disease (Child-Pugh Classification C) * Known or suspected neuromuscular disorders impairing neuromuscular function * Women who are or may be pregnant or currently breastfeeding * Chronic use of psychotropic drugs * Use of immunomodulatory medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Recovery 40 (QoR-40) questionnaire score | Postoperative day 1 | 40 points (minimum: extremely poor quality of recovery) to 200 points (maximum: excellent quality of recovery) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immune function represented by serum cytokine | Postoperative day 1 | Serum cytokine IL-6 level |
| Immune function represented by IL-10 | Postoperative day 1 | Serum cytokine IL-10 level |
| Immune function represented by TNF-a | Postoperative day 1 | Serum cytokine TNF-a level |
| Immune function represented by ex-vivo IL-6 production capacity | Postoperative day 1 | Ex-vivo IL-6 production capacity upon whole blood Lipopolysaccharide(LPS) stimulation |
| Quality of Recovery 40 (QoR-40) questionnaire score | Postoperative day 30 | 40 points (minimum: extremely poor quality of recovery) to 200 points (maximum: excellent quality of recovery) |
| Pain score by numeric pain rating (NRS) scale | During hospital admission up to 3 days postoperative | pain scores with NRS 0 (no pain) to 10 (severe pain) |
| Postoperative complications | 30 postoperative days | postoperative complications scored by Clavien-Dindo classification; grade 0 (no deviation from ideal) grade 5 (death of patient) |
| Infectious postoperative complications | 30 postoperative days | Postoperative infectious complications scored the definitions of the StEP-COMPAC group initiative |
| Analgesia consumption | During hospital admission up to 3 days postoperative | non-cumulative and cumulative opioid use per day in morphine equivalent |
| Immune function represented by ex-vivo IL-10 production capacity | Postoperative day 1 | Ex-vivo IL-10 production capacity upon whole blood LPS stimulation |
Countries
Netherlands
Outcome results
None listed