CURES: The Effect of Deep Curarisation and Reversal With Sugammadex on Surgical Conditions and Perioperative Morbidity (CURES)

April 24, 2017 updated by: Pascal Vanelderen, Ziekenhuis Oost-Limburg

Effect of Deep Curarisation and Reversal With Sugammadex on Surgical Conditions and Perioperative Morbidity in Patients Undergoing Laparoscopic Gastric Bypass Surgery

The purpose of this study is to investigate if a deep neuromuscular block with a continuous infusion of rocuronium titrated to a post-tetanic count (PTC) of 1-2 responses combined with reversal of neuromuscular blockade with sugammadex results in improved surgical conditions for the surgeon and/or improved post-operative respiratory function for the patients as compared to a standard technique with an intubation dose of rocuronium and top-ups as needed to maintain a neuromuscular blockade with a train of four (TOF) count of 1-2 and reversal of neuromuscular blockade with neostigmine/glycopyrrolate.

Furthermore, we want to investigate the effect of pneumoperitoneum, and NMB with rocuronium and reversal with sugammadex or neostigmine/glycopyrrolate on cerebral tissue oxygenation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Laparoscopic bariatric surgery poses special demands on the anaesthesiologist as well as the surgeon. The surgeon requires good visualisation of the operative field while the anaesthesiologist is concerned with adequate postoperative respiratory function in these morbidly obese patients. With the advent of advanced laparoscopic techniques the time span between adequate neuromuscular blockade (NMB) and adequate postoperative recovery of respiratory muscle function is growing ever shorter with an increasing risk of postoperative residual NMB.

Even minimal postoperative residual NMB with a train of four ratio (TOF) of 0.8 is associated with impaired respiratory function as witnessed in reductions of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) in healthy volunteers. Moreover, a TOF < 0.7 correlates with increased postoperative respiratory complications due to the inability to swallow normally leading to aspiration, atelectasis and pneumonia. However, neuromuscular blocking agents not only impair respiratory function due to skeletal muscle relaxation. Also the body's response to hypoxia is impeded due to carotid body chemoreceptor suppression. Worryingly, reversal of NMB with neostigmine can lead to respiratory complications such as bronchospasm and even induce neuromuscular transmission failure in patients who already recovered from NMB.

Obese patients are at even greater risk for postoperative respiratory complications. In a recent study after bariatric surgery, 100% of patients had at least one hypoxic event (oxygen saturation <90% more then 30seconds). Restrictive ventilatory defects are clearly associated with body mass index (BMI) and obesity hypoventilation syndrome. Since respiratory failure is responsible for 11.8% of mortalities after bariatric surgery, optimal respiratory care for these patients is primordial. Optimal reversal of NMB plays an important role herein. With the advent of Sugammadex, a cyclodextrin molecule that encapsulates and inactivates rocuronium and vecuronium, rapid and dose-dependent reversal of profound NMB by high dose rocuronium is possible without the risk of impaired upper airway dilator muscle activity when given after recovery from NMB.

Furthermore, little is known about the cerebral tissue oxygen saturation (SctO2) in these morbidly obese patients during laparoscopic gastric bypass surgery. Since the unexpected finding that NMB influences hypoxic ventilatory response, more research is needed into the effect of neuromuscular blockers and their reversing agents on cerebral oxygenation. Using near infrared spectroscopy (Fore-sight®) technology absolute brain tissue oxygenation can be quantified to study these effects.

In this study we wish to investigate if a deep neuromuscular block with a continuous infusion of rocuronium titrated to a post-tetanic count (PTC) of 1-2 responses combined with reversal of NMB with sugammadex results in:

i. Improved surgical conditions for the surgeon ii. Improved post-operative respiratory function for the patients

as compared to a standard technique with an intubation dose of rocuronium and top-ups as needed to maintain a NMB with a TOF count of 1-2 and reversal of NMB with neostigmine/glycopyrrolate.

Furthermore, we wish to investigate the effect of pneumoperitoneum, and NMB with rocuronium and reversal with Sugammadex or neostigmine/glycopyrrolate on cerebral tissue oxygenation.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
    • Limburg
      • Genk, Limburg, Belgium, 3600
        • Ziekenhuis Oost-Limburg

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  1. Able to give written informed consent
  2. American Society of Anaesthesiologists class I, II or III
  3. Obese or morbid obese as defined by BMI > 30 and >40 kg/m2 respectively

Exclusion Criteria:

  1. Neuromuscular disorders
  2. Allergies to, or contraindication for muscle relaxants, neuromuscular reversing agents, anaesthetics, narcotics
  3. Malignant hyperthermia
  4. Pregnancy or lactation
  5. Renal insufficiency defined as serum creatinine of 2x the upper normal limit, glomerular filtration rate < 60ml/min, urine output of < 0.5ml/kg/h for at least 6h
  6. Chronic obstructive pulmonary disease GOLD classification 2 or higher.
  7. Clinical, radiographic or laboratory findings suggesting upper or lower airway infection
  8. Congestive heart failure.
  9. Pickwick syndrome
  10. Psychiatric illness inhibiting cooperation with study protocol or possibly obscuring results

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Deep neuromuscular blockade, reversal with sugammadex
a continuous rocuronium infusion (0.6mg/kg (lean body mass)/h,) is started and titrated to a post tetanic count of 1-2 twitches. At the end of surgery neuromuscular blockade will be reversed with Sugammadex 4mg/kg. Patients are extubated when the train of four ratio is > 0.9.
Drug: deep neuromuscular blockade with rocuronium, reversal with sugammadex
after induction of anesthesia, a rocuronium infusion (0.6mg/kg (lean body mass)/h,) is started and titrated to a post tetanic count of 1-2 twitches. At the end of surgery neuromuscular blockade will be reversed with sugammadex 4mg/kg. Patients are extubated when TOF ratio > 0.9.
Other Names:
  • rocuronium: Esmeron
  • sugammadex: Bridion
Active Comparator: normal neuromuscular blockade, reversal with neostigmine
After induction of anesthesia, top-ups of rocuronium (10mg) are given as needed to maintain a train of four count of 1-2. At the end of surgery neuromuscular blockade will be reversed with neostigmine 50μg/kg and glycopyrrolate 10μg/kg (lean body mass). Patients are extubated when TOF ratio > 0.9.
Drug: normal neuromuscular blockade reversal with rocuronium, reversal with neostigmine
After induction of anesthesia, top-ups of rocuronium (10mg) are given as needed to maintain a train of four count of 1-2. At the end of surgery neuromuscular blockade will be reversed with neostigmine 50μg/kg and glycopyrrolate 10μg/kg (lean body mass). Patients are extubated when the train of four ratio is > 0.9.
Other Names:
  • glycopyrrolate
  • rocuronium: Esmeron
  • neostigmine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Subjective Evaluation of the View on the Operating Field by the Surgeon
Time Frame: Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h

At the end of surgery, the view on the operating field will be graded by the surgeon using a 5-point rating scale:

  1. Extremely poor
  2. Poor
  3. Acceptable
  4. Good
  5. Optimal
Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h
Number of Intra-abdominal Pressure Rises > 18cmH2O
Time Frame: Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h
The number of intra-abdominal pressure rises > 18cmH2O detected by the intra-abdominal CO2 insufflator.
Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h
Duration of Surgery
Time Frame: Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h
Measured from the time of first skin incision to completion of skin closure.
Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peak Expiratory Flow
Time Frame: Measured the day before surgery and 30min after completion of surgery (when the modified observer's assessment of alertness/sedation scale is 5 (Patient responds readily to name spoken in normal tone))
Peak expiratory flow is measured with the Vitalograph® electronic portable peak flow meter. A mean of 3 measurements in the upright posture in bed before and after surgery will be used.
Measured the day before surgery and 30min after completion of surgery (when the modified observer's assessment of alertness/sedation scale is 5 (Patient responds readily to name spoken in normal tone))
Forced Expiratory Volume in 1 Second
Time Frame: Measured the day before surgery and 30min after completion of surgery (when the modified observer's assessment of alertness/sedation scale is 5 (Patient responds readily to name spoken in normal tone))
Forced expiratory volume in 1 second is measured with the Vitalograph® electronic portable peak flow meter. A mean of 3 measurements in the upright posture in bed before and after surgery will be used.
Measured the day before surgery and 30min after completion of surgery (when the modified observer's assessment of alertness/sedation scale is 5 (Patient responds readily to name spoken in normal tone))
Forced Vital Capacity
Time Frame: Measured the day before surgery and 30min after completion of surgery (when the modified observer's assessment of alertness/sedation scale is 5 (Patient responds readily to name spoken in normal tone))
Forced vital capacity is measured with the Vitalograph® electronic portable peak flow meter. A mean of 3 measurements in the upright posture in bed before and after surgery will be used.
Measured the day before surgery and 30min after completion of surgery (when the modified observer's assessment of alertness/sedation scale is 5 (Patient responds readily to name spoken in normal tone))

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ziekenhuis Oost-Limburg

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Study Chair: Pieter De Vooght, M.D., Ziekenhuis Oost-Limburg
  • Study Chair: Jeroen Van Melkebeek, M.D., Ziekenhuis Oost-Limburg
  • Study Chair: Dimitri Dylst, M.D., Ziekenhuis Oost-Limburg
  • Study Chair: Maud Beran, M.D., Ziekenhuis Oost-Limburg
  • Study Chair: Margot Vander Laenen, M.D., Ziekenhuis Oost-Limburg
  • Study Chair: Jan Van Zundert, M.D., PhD., Ziekenhuis Oost-Limburg
  • Study Chair: René Heylen, M.D., PhD., Ziekenhuis Oost-Limburg
  • Study Chair: Hans Verhelst, M.D., Ziekenhuis Oost-Limburg

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2013

Primary Completion (Actual)

January 1, 2015

Study Completion (Actual)

January 1, 2015

Study Registration Dates

First Submitted

December 6, 2012

First Submitted That Met QC Criteria

December 10, 2012

First Posted (Estimate)

December 12, 2012

Study Record Updates

Last Update Posted (Actual)

August 3, 2017

Last Update Submitted That Met QC Criteria

April 24, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PVRA-01
  • 2012-005533-37 (EudraCT Number)
  • 8616-085MISP (Other Grant/Funding Number: MISP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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