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

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ClinicalTrials.gov Identifier: NCT01748643
Recruitment Status : Completed
First Posted : December 12, 2012
Results First Posted : August 3, 2017
Last Update Posted : August 3, 2017
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Pascal Vanelderen, Ziekenhuis Oost-Limburg

Brief Summary:

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.


Condition or disease Intervention/treatment 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

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  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, 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
Study Start Date : April 2013
Actual Primary Completion Date : January 2015
Actual Study Completion Date : January 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

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:
  • rocuronium: Esmeron
  • neostigmine
  • glycopyrrolate



Primary Outcome Measures :
  1. 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

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01748643


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

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 ( EudraCT Number )
8616-085MISP ( Other Grant/Funding Number: MISP )
First Posted: December 12, 2012    Key Record Dates
Results First Posted: August 3, 2017
Last Update Posted: August 3, 2017
Last Verified: April 2017

Additional relevant MeSH terms:
Disease
Pathologic Processes
Rocuronium
Neostigmine
Glycopyrrolate
Neuromuscular Nondepolarizing Agents
Neuromuscular Blocking Agents
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Parasympathomimetics
Autonomic Agents
Adjuvants, Anesthesia
Muscarinic Antagonists
Cholinergic Antagonists