Bowel Obstruction, Cholecystitis, Chronic Kidney Disease, Endometriosis, Fibroids, Prostate Cancer, Uterine Prolapse
Conditions
Keywords
Neuromuscular blockade
Brief summary
This is a two period cross-over study randomizing patients undergoing laparoscopic surgery into 2 different groups: group 1 in which patients receive deep neuromuscular blockade in the beginning portion of their laparoscopic surgery followed by a period of moderate blockade and, group 2 in which patients receive moderate neuromuscular blockade in the beginning portion of their laparoscopic surgery followed by a period of deep blockade. The deep neuromuscular block is defined as post tetanic count of 1 to 2 and the moderate neuromuscular block is defined as 1-2 twitches. In all patients, sugammadex is used to reverse the block at the end of surgery in order to obtain optimal extubating conditions.
Detailed description
Neuromuscular blockade (NMB) is frequently utilized in laparoscopic procedures to improve surgical conditions by relaxing the abdominal muscles and thus facilitating insufflation with carbon dioxide to optimize surgical view. Increased airway pressures can lead to an increase in alveolar and perivascular edema, a decline in dynamic lung compliance and hypoxemia. Several studies have investigated surgical view under deep vs. moderate neuromuscular blockade. Literature supports deep neuromuscular blockade providing better operating conditions/view by a surgeon and low airway pressures but, potentially, longer duration to extubation and worse respiratory mechanics at the end of anesthesia versus moderate neuromuscular blockade which shows worse operating conditions/view by a surgeon and worse airway pressures but possibly shorter duration to extubation and better respiratory mechanics at the end of anesthesia. Thus, there is clearly equipoise with regard to the comparative effectiveness of deep vs medium NMB. Therefore, this study is designed to ascertain if a deep neuromuscular block will decrease the airway pressures in patients undergoing laparoscopic procedures compared to those under a moderate block. A reduction in airway pressures may lead to a decrease in the complications associated with elevated airway pressures including hypoxemia, total static lung compliance, alveolar edema, and long term morbidity. Additionally, the study aims to determine if time from administration of sugammadex to reversal is different between patients that have a moderate NMB as compared to a deep NMB.
Interventions
PROCEDUREDeep to Moderate NMB
Rocuronium infusion will be paused and the Train of Four (TOF) monitor will be set to every 1-2 min. Once the patient has achieved a moderate NMB state (one to two twitches), the infusion of the muscle relaxant will be resumed at a low dose to maintain the patient at this level of blockade.
PROCEDUREModerate to Deep NMB
Rocuronium infusion will be increased in increments of 0.1-0.2 mg/kg/hr. and the TOF monitor will be set to every 1-2 min. Once the patient has no twitches and a PTC of 0-1 (deep NMB) the infusion will be adjusted to maintain the patient at this level of NMB.
DRUGRocuronium
Sponsors
Merck Sharp & Dohme LLC
Stony Brook University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Each participant must be willing and able to provide written informed consent for the study. * Each participant must be American Society of Anesthesiologists (ASA) class I, II or III. * Each participant must be scheduled for elective laparoscopic surgery (this includes robotic laparoscopic surgery). * Expected surgical duration of 60 min or longer
Exclusion criteria
* Inability to give informed oral or written consent * Known or suspected neuromuscular disorders impairing neuromuscular function; * True allergies as defined as hypotension, bronchospasm, or anaphylaxis to muscle relaxants, anesthetics or opioids * A history (patient or family) of malignant hyperthermia * A contraindication for neostigmine administration * Renal insufficiency, as defined by serum creatinine levels at 2.5 fold the normal level * Body mass index \>40 kg/m\^2 * Significant respiratory disease. * Planned postoperative mechanical ventilation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Airway Pressures | Intra-operative, from intubation time to extubation time | To determine if a deep NMB can lead to lower peak airway pressures in patients undergoing laparoscopic procedures when compared to a moderate NMB |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Abdominal Insufflation Pressure | Intra-operative, from intubation time to extubation time | To compare surgical operating condition by Abdominal Insufflation Pressure in patients undergoing laparoscopic procedures using deep NMB versus moderate NMB |
| Surgical Rating Scale | Intra-operative, from intubation time to extubation time | To compare surgical operating condition by Surgical Rating Scale (SRS) in patients undergoing laparoscopic procedures using deep NMB versus moderate NMB Surgical Rating Score scores are on a 1-5 scale with 1 = extremely poor conditions, 2 = poor conditions, 3 = adequate conditions, 4 = good conditions, 5= excellent conditions. Higher scores mean a better outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Deep to Moderate NMB This group will undergo deep neuromuscular blockade, defined as post tetanic count (PTC) of 1 to 2, in the beginning portion of the surgery followed by a period of moderate blockade. | 29 |
| Moderate to Deep NMB This group will undergo moderate neuromuscular blockade, defined as 1-2 twitches, in the beginning portion of the surgery followed by a period of deep blockade. | 24 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | nonevaluable data sets | 6 | 6 |
| Period 1 | Post randomization screen failure | 5 | 9 |
Baseline characteristics
| Characteristic | Moderate to Deep NMB | Total | Deep to Moderate NMB |
|---|---|---|---|
| Age, Continuous | 50.8 years STANDARD_DEVIATION 15.4 | 51.8 years STANDARD_DEVIATION 15.15 | 52.8 years STANDARD_DEVIATION 14.9 |
| Procedure General | 15 Participants | 41 Participants | 26 Participants |
| Procedure General/Gynecology | 2 Participants | 3 Participants | 1 Participants |
| Procedure Gynecology | 5 Participants | 7 Participants | 2 Participants |
| Procedure Urology | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 24 Participants | 53 Participants | 29 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 14 Participants | 31 Participants | 17 Participants |
| Sex: Female, Male Male | 10 Participants | 22 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 0 / 53 |
| other Total, other adverse events | 0 / 53 | 0 / 53 |
| serious Total, serious adverse events | 0 / 53 | 0 / 53 |
Outcome results
Primary
Peak Airway Pressures
To determine if a deep NMB can lead to lower peak airway pressures in patients undergoing laparoscopic procedures when compared to a moderate NMB
Time frame: Intra-operative, from intubation time to extubation time
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Deep NMB | Peak Airway Pressures | Mean | 25.5 cm H2O |
| Deep NMB | Peak Airway Pressures | Maximum | 28 cm H2O |
| Moderate NMB | Peak Airway Pressures | Mean | 28.3 cm H2O |
| Moderate NMB | Peak Airway Pressures | Maximum | 30 cm H2O |
p-value: 0.01Wilcoxon (Mann-Whitney)
Secondary
Abdominal Insufflation Pressure
To compare surgical operating condition by Abdominal Insufflation Pressure in patients undergoing laparoscopic procedures using deep NMB versus moderate NMB
Time frame: Intra-operative, from intubation time to extubation time
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Deep NMB | Abdominal Insufflation Pressure | 15 mmHg |
| Moderate NMB | Abdominal Insufflation Pressure | 15 mmHg |
p-value: 0.28Wilcoxon (Mann-Whitney)
Secondary
Surgical Rating Scale
To compare surgical operating condition by Surgical Rating Scale (SRS) in patients undergoing laparoscopic procedures using deep NMB versus moderate NMB Surgical Rating Score scores are on a 1-5 scale with 1 = extremely poor conditions, 2 = poor conditions, 3 = adequate conditions, 4 = good conditions, 5= excellent conditions. Higher scores mean a better outcome.
Time frame: Intra-operative, from intubation time to extubation time
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Deep NMB | Surgical Rating Scale | 5 units on a scale |
| Moderate NMB | Surgical Rating Scale | 5 units on a scale |
p-value: 0.63Wilcoxon (Mann-Whitney)