Deep Neuromuscular Relaxation in Patients for Thoraco-laparoscopic Esophagectomy (DEPTH)

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

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.

Study Overview

• Status: Completed
• Conditions: Esophageal Cancer; Surgery; Neuromuscular Block
• Intervention / Treatment: Drug: Rocuronium

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1105 AZ
      • Academic Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: deep neuromuscular relaxation; 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; Rocuronium given continuously to reach deep neuromuscular block; Other Names: Esmeron
No Intervention: on demand neuromuscular relaxation; 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?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Time Frame
length of stay ICU/PACU	participants will be followed for the duration of hospital stay, an expected average of 4 weeks
need for re-intubation	participants will be followed for the duration of hospital stay, an expected average of 4 weeks
post-operative surgical complications	participants will be followed for the duration of hospital stay, an expected average of 4 weeks
VAS-scores	24-hours post operation
Abdominal and thoracic insufflation pressures	During operation

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Chair: Markus W Hollmann, prof, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Principal Investigator: Denise P Veelo, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Publications and helpful links

General Publications

• Veelo DP, Gisbertz SS, Binnekade JM, Hannivoort RA, Bosman JA, Geerts BF, Blobner M, van Berge Henegouwen MI, Hollmann MW. On-demand versus continuous rocuronium infusion for deep neuromuscular relaxation in patients undergoing thoraco-laparoscopic esophagectomy: a randomized-controlled clinical trial (DEPTH). Can J Anaesth. 2019 Sep;66(9):1062-1074. doi: 10.1007/s12630-019-01373-0. Epub 2019 Apr 25.
• Veelo DP, Gisbertz SS, Hannivoort RA, van Dieren S, Geerts BF, van Berge Henegouwen MI, Hollmann MW. The effect of on-demand vs deep neuromuscular relaxation on rating of surgical and anaesthesiologic conditions in patients undergoing thoracolaparoscopic esophagectomy (DEPTH trial): study protocol for a randomized controlled trial. Trials. 2015 Aug 5;16:331. doi: 10.1186/s13063-015-0849-0.

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: December 12, 2014
• First Submitted That Met QC Criteria: December 16, 2014
• First Posted (Estimate): December 19, 2014

Study Record Updates

• Last Update Posted (Estimate): September 19, 2016
• Last Update Submitted That Met QC Criteria: September 16, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Anaesthesia; minimally invasive esophagectomy; surgical rating scale; neuromuscular relaxation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Neuromuscular Agents; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Rocuronium
• Other Study ID Numbers: 2014-211; 2014-002147-18 (EudraCT Number); MISP51412 (Other Grant/Funding Number: Merck Sharp & Dohme BV)