Deep Neuromuscular Relaxation in Patients for Thoraco-laparoscopic Esophagectomy

Study Overview
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Brief Summary
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Rationale: Endoscopic (thoraco-laparoscopic) esophageal surgery is a high risk procedure where the use of deep neuromuscular block (NMB) may increase field visibility and anaesthesia conditions. Under these conditions, boluses of muscle relaxants can be given on indication only OR by continuous infusion. We hypothesize that deep NMB by continuous infusion of rocuronium as compared to on demand bolus administration facilitates surgical and anesthesia conditions during thoraco-laparoscopic esophageal resection but higher doses of sugammadex are needed to reverse NMB at the end of surgery. Objective: Primary objective is to evaluate the use of deep muscle relaxation versus on indication only on surgical and anesthesia conditions in patients for endoscopic esophageal resection. Secondary objectives are to evaluate the (hypothetical) dose of sugammadex needed in both groups in an economical perspective and to compare the intra-operative cardiac and respiratory incidents and post-operative complication rate of both groups. Study design: a single-center randomized controlled double-blinded intervention study. Study population: All patients > 18 years to undergo a thoracolaparoscopic esophageal resection.I Intervention: Patients are randomized to receive either continuous infusion of rocuronium 0.6 mg/kg/hr (group 1) or continuous infusion of NaCl 0.9% 0.06 ml/kg/hr (group 2). On demand boluses of Rocuronium 0.3 mg/kg can be given in both groups. Main study parameters/endpoints: The primary outcome parameter of this study is the SRS during the abdominal phase of thoracolaparoscopic esophageal surgery. Secondary outcomes measured are SRS during the thoracic phase, the number of on demand boluses infused, the dose of Sugammadex needed in both groups to reach a TOF of > 90%, duration of surgery, a cost-analysis, the incidence of intra-operative cardiac and respiratory incidents and the ability of surgeons to estimate which neuromuscular blocking regime was given to the patient.

Official Title
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A Randomized Controlled Double-blinded Trial Comparing the Effect of on Demand vs Deep Neuromuscular Relaxation on Rating of Surgical and Anesthesia Conditions in Patients Undergoing Thoraco-laparoscopic Esophagectomy

Conditions
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Neuromuscular Block, Esophageal Cancer, Surgery

Intervention / Treatment
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* Drug: Rocuronium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients, undergoing elective thoraco-laparoscopic esophageal resection (either Ivor Lewis or McKeown variant) Written informed consent Exclusion Criteria: pregnancy Known allergies for aminosteroid-type muscle relaxants or sugammadex. Severe kidney dysfunction (GFR < 30), patients on dialysis Liver function disorders Myasthenia Gravis or other (neuro)muscular diseases Patients with carcinomatosis Use of anti-epileptics and lithium or drugs containing Kinin

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: deep neuromuscular relaxation<br>continuous infusion of rocuronium 0.6 mg/kg/hr (group 1). On demand bolus rocuronium can be given if demanded by anesthesiologist or surgeon | Drug: Rocuronium<br>* Rocuronium given continuously to reach deep neuromuscular block<br>* Other names: Esmeron;|
| No Intervention: on demand neuromuscular relaxation<br>continuous infusion of NaCl 0.9% 0.06 ml/kg/hr (group 2) On demand bolus of Rocuronium will be given when demanded by anesthesiologist or surgeon. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rating of surgical conditions (SRS) during the abdominal phase of the operation. |  | during operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rating of SRS during thoracic phase of the operation. |  | during operation | 
| Number of on demand boluses infused, indication of on demand bolus administration |  | during operation | 
| Rating of anesthesia conditions | peak and mean respiratory pressure, incidence peak insufflation pressure >35 mmHg. Depth of NBM at the end of surgery. Time until spontaneous breathing, time until extubation. Peroperative cardiac and respiratory incidents, peroperative surgical complications.Tiem to reversal of NMB, % of recurarisation | during operation | 
| Costs (euro's) associated with use of Rocuronium, Sugammadex, operation time and length of stay ICU. | amount of rocuronium used (mg); Dose of sugammadex needed (mg), duration of surgery, hypothetical need for post-operative ventilation if sugammadex would not be available(%). | during operation and an average of 4 weeks thereafter | 
| Number of correct estimates of group randomization by surgeons | Surgeons will guess in which group the patient was randomized (%) and the reason for this choice will be registrated. Accordingly we can estimate whether the surgeons complaints of inadequate NMB are justified and additionally, the chance of bias affecting main outcome parameter. | directly after operation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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surgical rating scale, neuromuscular relaxation, Anaesthesia, minimally invasive esophagectomy