Impact of Deep Neuromuscular Blockade During Total Hip Replacement Surgery on Postoperative Recovery and Immune Function

Study Overview
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Brief Summary
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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
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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

Official Title
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Deep Versus Moderate Neuromuscular Blockade During Total HIP Replacement Surgery to Improve POstoperative Quality of Recovery and Immune Function: a Randomized Controlled Study

Conditions
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Innate Inflammatory Response, Quality of Life, Postoperative Complications, Neuromuscular Blockade

Intervention / Treatment
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* Drug: Rocuronium Bromide
* Drug: Rocuronium Bromide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deep neuromuscular blockade<br>Participant will receive deep neuromuscular blockade (PTC 1-2) | Drug: Rocuronium Bromide<br>* Deep NMB (PTC 1-2)<br>* Other names: Bridion;|
| Active Comparator: Moderate neuromuscular blockade<br>Participant will receive moderate neuromuscular blockade (TOF 1-2) | Drug: Rocuronium Bromide<br>* Moderate NMB (TOF 1-2)<br>* Other names: Bridion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Recovery 40 (QoR-40) questionnaire score | 40 points (minimum: extremely poor quality of recovery) to 200 points (maximum: excellent quality of recovery) | Postoperative day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Recovery 40 (QoR-40) questionnaire score | 40 points (minimum: extremely poor quality of recovery) to 200 points (maximum: excellent quality of recovery) | Postoperative day 30 | 
| Immune function represented by serum cytokine | Serum cytokine IL-6 level | Postoperative day 1 | 
| Immune function represented by IL-10 | Serum cytokine IL-10 level | Postoperative day 1 | 
| Immune function represented by TNF-a | Serum cytokine TNF-a level | Postoperative day 1 | 
| Immune function represented by ex-vivo IL-6 production capacity | Ex-vivo IL-6 production capacity upon whole blood Lipopolysaccharide(LPS) stimulation | Postoperative day 1 | 
| Immune function represented by ex-vivo IL-10 production capacity | Ex-vivo IL-10 production capacity upon whole blood LPS stimulation | Postoperative day 1 | 
| Pain score by numeric pain rating (NRS) scale | pain scores with NRS 0 (no pain) to 10 (severe pain) | During hospital admission up to 3 days postoperative | 
| Postoperative complications | postoperative complications scored by Clavien-Dindo classification; grade 0 (no deviation from ideal) grade 5 (death of patient) | 30 postoperative days | 
| Infectious postoperative complications | Postoperative infectious complications scored the definitions of the StEP-COMPAC group initiative | 30 postoperative days | 
| Analgesia consumption | non-cumulative and cumulative opioid use per day in morphine equivalent | During hospital admission up to 3 days postoperative |