Cerebral Tissue Oxygenation, Laparoscopic Gastric Bypass Surgery, Obesity, Respiratory Function, Surgical Conditions
Conditions
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.
Interventions
DRUGdeep 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.
DRUGnormal 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.
Sponsors
Merck Sharp & Dohme LLC
Ziekenhuis Oost-Limburg
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Surgery | 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. |
| Number of Intra-abdominal Pressure Rises > 18cmH2O | 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. |
| Subjective Evaluation of the View on the Operating Field by the Surgeon | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Expiratory Flow | 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. |
| Forced Expiratory Volume in 1 Second | 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. |
| Forced Vital Capacity | 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. |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 30 |
| 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.
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. | 30 |
| Total | 60 |
Baseline characteristics
| Characteristic | Deep Neuromuscular Blockade, Reversal With Sugammadex | Normal Neuromuscular Blockade, Reversal With Neostigmine | Total |
|---|---|---|---|
| Age, Continuous | 41 years STANDARD_DEVIATION 13 | 42 years STANDARD_DEVIATION 11 | 41.6 years STANDARD_DEVIATION 12 |
| Body Mass Index | 40 kg/m2 STANDARD_DEVIATION 3 | 41 kg/m2 STANDARD_DEVIATION 7 | 41 kg/m2 STANDARD_DEVIATION 5 |
| Forced expiratory volume in 1 second | 2.4 L/min STANDARD_DEVIATION 0.9 | 2.2 L/min STANDARD_DEVIATION 0.6 | 2.3 L/min STANDARD_DEVIATION 0.7 |
| Forced vital capacity | 3.0 L/min STANDARD_DEVIATION 0.9 | 2.7 L/min STANDARD_DEVIATION 0.8 | 2.8 L/min STANDARD_DEVIATION 0.8 |
| Peak expiratory flow | 314 L/min STANDARD_DEVIATION 109 | 276 L/min STANDARD_DEVIATION 81 | 295 L/min STANDARD_DEVIATION 97 |
| Region of Enrollment Belgium | 30 Participants | 30 Participants | 60 Participants |
| Sex: Female, Male Female | 8 Participants | 4 Participants | 12 Participants |
| Sex: Female, Male Male | 22 Participants | 26 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 0 / 30 | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
Duration of Surgery
Measured from the time of first skin incision to completion of skin closure.
Time frame: Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Neuromuscular Blockade, Reversal With Sugammadex | Duration of Surgery | 61.3 minutes | Standard Deviation 15.1 |
| Normal Neuromuscular Blockade, Reversal With Neostigmine | Duration of Surgery | 70.6 minutes | Standard Deviation 20.8 |
p-value: 0.07Wilcoxon (Mann-Whitney)
Primary
Number of Intra-abdominal Pressure Rises > 18cmH2O
The number of intra-abdominal pressure rises \> 18cmH2O detected by the intra-abdominal CO2 insufflator.
Time frame: Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Neuromuscular Blockade, Reversal With Sugammadex | Number of Intra-abdominal Pressure Rises > 18cmH2O | 0.2 number of intra-abdominal pressure rises | Standard Deviation 0.9 |
| Normal Neuromuscular Blockade, Reversal With Neostigmine | Number of Intra-abdominal Pressure Rises > 18cmH2O | 0.3 number of intra-abdominal pressure rises | Standard Deviation 1 |
p-value: 0.69Wilcoxon (Mann-Whitney)
Primary
Subjective Evaluation of the View on the Operating Field by the Surgeon
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
Time frame: Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Neuromuscular Blockade, Reversal With Sugammadex | Subjective Evaluation of the View on the Operating Field by the Surgeon | 4.2 units on a scale | Standard Deviation 1 |
| Normal Neuromuscular Blockade, Reversal With Neostigmine | Subjective Evaluation of the View on the Operating Field by the Surgeon | 3.9 units on a scale | Standard Deviation 1.1 |
p-value: 0.16Wilcoxon (Mann-Whitney)
Secondary
Forced Expiratory Volume in 1 Second
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.
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))
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Neuromuscular Blockade, Reversal With Sugammadex | Forced Expiratory Volume in 1 Second | 45.2 percent change from baseline | Standard Deviation 36.4 |
| Normal Neuromuscular Blockade, Reversal With Neostigmine | Forced Expiratory Volume in 1 Second | 48.8 percent change from baseline | Standard Deviation 19.6 |
p-value: 0.64t-test, 1 sided
Secondary
Forced Vital Capacity
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.
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))
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Neuromuscular Blockade, Reversal With Sugammadex | Forced Vital Capacity | 51.9 percent change from baseline | Standard Deviation 16.4 |
| Normal Neuromuscular Blockade, Reversal With Neostigmine | Forced Vital Capacity | 49.0 percent change from baseline | Standard Deviation 22.6 |
p-value: 0.58t-test, 1 sided
Secondary
Peak Expiratory Flow
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.
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))
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Neuromuscular Blockade, Reversal With Sugammadex | Peak Expiratory Flow | 51.3 percent change from baseline | Standard Deviation 31.6 |
| Normal Neuromuscular Blockade, Reversal With Neostigmine | Peak Expiratory Flow | 51.5 percent change from baseline | Standard Deviation 19 |
p-value: 0.97t-test, 1 sided