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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified December 2012 by Ziekenhuis Oost-Limburg
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Pascal Vanelderen, Ziekenhuis Oost-Limburg
ClinicalTrials.gov Identifier:
NCT01748643
First received: December 6, 2012
Last updated: December 10, 2012
Last verified: December 2012
  Purpose

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 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/glycopyrolate on cerebral tissue oxygenation.


Condition Intervention Phase
Obesity
Laparoscopic Gastric Bypass Surgery
Surgical Conditions
Respiratory Function
Cerebral Tissue Oxygenation
Drug: deep neuromuscular blockade with rocuronium, reversal with sugammadex
Drug: normal neuromuscular blockade reversal with rocuronium, reversal with neostigmine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Effect of Deep Curarisation and Reversal With Sugammadex on Surgical Conditions and Perioperative Morbidity in Patients Undergoing Laparoscopic Gastric Bypass Surgery

Resource links provided by NLM:


Further study details as provided by Ziekenhuis Oost-Limburg:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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

  • Number of intra-abdominal pressure rises > 15cmH2O [ Time Frame: Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h ] [ Designated as safety issue: No ]
    The number of intra-abdominal pressure rises > 15cmH2O detected by the intra-abdominal CO2 insufflator.


Secondary Outcome Measures:
  • Respiratory function [ 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)) ] [ Designated as safety issue: Yes ]
    Respiratory function will be assessed by measuring peak expiratory flow (PEF) and forced expiratory volume in 1 second (FEV1) 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.

  • Oxygen saturation [ 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)) ] [ Designated as safety issue: Yes ]
    Oxygen saturation will be measured non-invasively with a pulse oxymeter

  • Effect of pneumoperitoneum on cerebral tissue oxygenation. [ Time Frame: Participants will be followed for an expected average of 5min after the start of intra-abdominal CO2 insufflation by the surgeon ] [ Designated as safety issue: No ]
    Using near infrared spectroscopy (Fore-sight®) technology, absolute brain tissue oxygenation can be quantified non-invasively by applying 2 skin electrodes to the forehead of the patient.

  • Effect of neuromuscular blockade on cerebral tissue oxygenation [ Time Frame: Participants will be followed for an expected average of 5min after the intravenous injection of rocuronium ] [ Designated as safety issue: No ]
    Using near infrared spectroscopy (Fore-sight®) technology, absolute brain tissue oxygenation can be quantified non-invasively by applying 2 skin electrodes to the forehead of the patient.

  • The effect of reversal of neuromuscular blockade (with sugammadex or neostigmine) on cerebral tissue oxygenation [ Time Frame: Participants will be followed for an expected average of 5min after the intravenous injection of sugammadex or neostigmine ] [ Designated as safety issue: No ]
    Using near infrared spectroscopy (Fore-sight®) technology, absolute brain tissue oxygenation can be quantified non-invasively by applying 2 skin electrodes to the forehead of the patient.


Estimated Enrollment: 60
Study Start Date: January 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • rocuronium: Esmeron
  • neostigmine
  • glycopyrrolate

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01748643

Contacts
Contact: Pascal Vanelderen, M.D. +3289325298 pascal.vanelderen@gmail.com
Contact: Margot Vander Laenen, M.D. +3289325214 margot.vander.laenen@telenet.be

Locations
Belgium
Ziekenhuis Oost-Limburg Not yet recruiting
Genk, Limburg, Belgium, 3600
Contact: Pascal Vanelderen, M.D.    +3289325298    pascal.vanelderen@gmail.com   
Principal Investigator: Pascal Vanelderen, M.D.         
Sub-Investigator: Pieter De Vooght, M.D.         
Sub-Investigator: Jeroen Van Melkebeek, M.D.         
Sub-Investigator: Dimitri Dylst, M.D.         
Sub-Investigator: Maud Beran, M.D.         
Sub-Investigator: Margot Vander Laenen, M.D.         
Sub-Investigator: Jan Van Zundert, M.D., PhD.         
Sub-Investigator: René Heylen, M.D., PhD.         
Sub-Investigator: Hans Verhels, M.D.         
Sponsors and Collaborators
Ziekenhuis Oost-Limburg
Merck Sharp & Dohme Corp.
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
  More Information

Publications:

Responsible Party: Pascal Vanelderen, M.D., Principal Investigator, Ziekenhuis Oost-Limburg
ClinicalTrials.gov Identifier: NCT01748643     History of Changes
Other Study ID Numbers: PVRA-01, 2012-005533-37, 8616-085MISP
Study First Received: December 6, 2012
Last Updated: December 10, 2012
Health Authority: Belgium: Ethics Committee
Belgium: Federal Agency for Medicinal Products and Health Products

Additional relevant MeSH terms:
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Glycopyrrolate
Neostigmine
Rocuronium
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Cholinesterase Inhibitors
Enzyme Inhibitors
Parasympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Neuromuscular Nondepolarizing Agents
Neuromuscular Blocking Agents
Neuromuscular Agents

ClinicalTrials.gov processed this record on July 22, 2014