Clinical trial NCT01748643: CURES: The Effect of Deep Curarisation and Reversal With Sugammadex on Surgical Conditions and Perioperative Morbidity
Official title: Effect of Deep Curarisation and Reversal With Sugammadex on Surgical Conditions and Perioperative Morbidity in Patients Undergoing Laparoscopic Gastric Bypass Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Obesity
Laparoscopic Gastric Bypass Surgery
Surgical Conditions
Respiratory Function
Cerebral Tissue Oxygenation
Lead sponsor: Ziekenhuis Oost-Limburg
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2012-12-12
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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 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

Primary outcomes:
measure: Subjective Evaluation of the View on the Operating Field by the Surgeon
timeFrame: Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h
measure: Number of Intra-abdominal Pressure Rises > 18cmH2O
timeFrame: Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h
measure: Duration of Surgery
timeFrame: Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h
Secondary outcomes:
measure: Peak Expiratory Flow
timeFrame: 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))
measure: Forced Expiratory Volume in 1 Second
timeFrame: 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))
measure: Forced Vital Capacity
timeFrame: 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))
Other outcomes:
Locations:
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg
state: Limburg
Study officials:
affiliation: Ziekenhuis Oost-Limburg
name: Pieter De Vooght, M.D.
role: STUDY_CHAIR
affiliation: Ziekenhuis Oost-Limburg
name: Jeroen Van Melkebeek, M.D.
role: STUDY_CHAIR
affiliation: Ziekenhuis Oost-Limburg
name: Dimitri Dylst, M.D.
role: STUDY_CHAIR
affiliation: Ziekenhuis Oost-Limburg
name: Maud Beran, M.D.
role: STUDY_CHAIR
affiliation: Ziekenhuis Oost-Limburg
name: Margot Vander Laenen, M.D.
role: STUDY_CHAIR
affiliation: Ziekenhuis Oost-Limburg
name: Jan Van Zundert, M.D., PhD.
role: STUDY_CHAIR
affiliation: Ziekenhuis Oost-Limburg
name: René Heylen, M.D., PhD.
role: STUDY_CHAIR
affiliation: Ziekenhuis Oost-Limburg
name: Hans Verhelst, M.D.
role: STUDY_CHAIR
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