Intraoperative Complications, Laparoscopy, Postoperative Complications, Surgical Complications From General Anesthesia, Ventilator-Induced Lung Injury
Conditions
Keywords
Tomography, Oximetry, Echocardiography
Brief summary
The goal of this study is to investigate the effect of depth of neuromuscular block (NMB) on global and regional (dependent versus nondependent) respiratory mechanics during laparoscopic surgery. Furthermore, we will investigate if the level of NMB influences intraoperative hemodynamic and cerebral oxygenation.
Interventions
DRUGRocuronium
Rocuronium 0.6 - 1.2 mg/kg with the dose adjusted to achieve 1-2 post-tetanic counts (Deep NMB) or 1-2 twitches in the train-on-four (Moderate NMB).
Sponsors
Merck Sharp & Dohme LLC
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Age 18 years or older * Elective patients scheduled to undergo laparoscopic surgery with expected duration \> 2h * Physical status ASA I - III
Exclusion criteria
* Pregnancy * Severe cardiac disease (NYHA class III or IV, acute coronary syndrome, or persistent ventricular tachyarrhythmia) * Previous lung surgery * History of severe chronic obstructive pulmonary disease * Gastro-esophageal pathology (including but not limited to recent gastric or esophageal surgery including bypass/banding, history of esophageal varices, known anatomical gastric or esophageal defects such as strictures, hernias or fistulas) * Mechanical ventilation within the last 30 days * Neuromuscular disease * Consented for another interventional study or refusal to participate in the present study * Hypersensitivity (e.g., anaphylaxis) to rocuronium bromide or other neuromuscular blocking agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Regional Change in Air Content (Delta Z, %) | BL; During pneumoperitoneum; Stage w/2 depths neuromuscular blockade targeted - TOF1 and Deep: 1-2 twitches in post-tetanic count (50-Hz tetanus followed by three-second pause and 15 1-Hz stimuli); and immediately after release of pneumoperitoneum | We will measure continuous respiratory flows and pressures in the intraoperative period to assess continuously the compliance and resistance of the respiratory system (T1 to T5). In addition, we will use an esophageal balloon to assess esophageal pressures and partition the global mechanical properties of the respiratory system, into their lung and chest wall components (T1 to T5). Regional lung aeration will be assessed for quantification of intraoperative lung recruitment using Electrical Impedance Tomography (EIT) (T0 to T6). Percent change was calculated using electrical impedance measurements obtained at time T0 as reference. |
| Ejection Fraction (%) | BL; During pneumoperitoneum; Stage w/2 depths neuromuscular blockade targeted - TOF1 and Deep: 1-2 twitches in post-tetanic count (50-Hz tetanus followed by three-second pause and 15 1-Hz stimuli); and immediately after release of pneumoperitoneum | To assess cardiac performance, transthoracic echocardiography will be used. Ejection fraction was measured as fractional shortening (FS). FS is the fraction of any diastolic dimension that is lost in systole. FS = 100\*(LVEDD - LVESD) / LVEDD, LVEDD = LV end-diastolic dimension (mm); LVESD = LV end-systolic dimension (mm). |
| Cerebral Oximetry (%) | BL; During pneumoperitoneum; Stage w/2 depths neuromuscular blockade targeted - TOF1 and Deep: 1-2 twitches in post-tetanic count (50-Hz tetanus followed by three-second pause and 15 1-Hz stimuli); and immediately after release of pneumoperitoneum | Regional cerebral oxygenation will be assessed continuously during the intraoperative period using NIRS technology. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative Pain | Postoperative Day 1 | The patient will be inquired about pain with a visual analogue scale (VAS). Pain will be evaluated as incisional pain using VAS (0 = no pain; 100 = worst possible pain). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Deep Neuromuscular Block (NMB) Muscle paralysis with rocuronium 0.6 - 1.2 mg/kg with the dose adjusted to achieve 1-2 post-tetanic counts (neuromuscular function monitor).
Rocuronium: Rocuronium 0.6 - 1.2 mg/kg with the dose adjusted to achieve 1-2 post-tetanic counts (Deep NMB) or 1-2 twitches in the train-on-four (Moderate NMB). | 16 |
| Moderate Neuromuscular Block (NMB) Muscle paralysis with rocuronium 0.6 - 1.2 mg/kg with the dose adjusted to achieve 1-2 twitches in the train-on-four (neuromuscular function monitor).
Rocuronium: Rocuronium 0.6 - 1.2 mg/kg with the dose adjusted to achieve 1-2 post-tetanic counts (Deep NMB) or 1-2 twitches in the train-on-four (Moderate NMB). | 19 |
| Total | 35 |
Baseline characteristics
| Characteristic | Moderate Neuromuscular Block (NMB) | Total | Deep Neuromuscular Block (NMB) |
|---|---|---|---|
| Age, Continuous | 60.7 years STANDARD_DEVIATION 9.6 | 58.7 years STANDARD_DEVIATION 10.8 | 56.6 years STANDARD_DEVIATION 11.9 |
| ASA Physical Status Classification I | 2 Participants | 3 Participants | 1 Participants |
| ASA Physical Status Classification II | 17 Participants | 32 Participants | 15 Participants |
| Body Mass Index | 28.0 kg/m^2 STANDARD_DEVIATION 4.5 | 28.3 kg/m^2 STANDARD_DEVIATION 7.7 | 29.7 kg/m^2 STANDARD_DEVIATION 8.1 |
| Region of Enrollment United States | 19 Participants | 35 Participants | 16 Participants |
| Sex: Female, Male Female | 4 Participants | 9 Participants | 5 Participants |
| Sex: Female, Male Male | 15 Participants | 26 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 16 | 0 / 19 |
| serious Total, serious adverse events | 0 / 16 | 0 / 19 |
Outcome results
Primary
Cerebral Oximetry (%)
Regional cerebral oxygenation will be assessed continuously during the intraoperative period using NIRS technology.
Time frame: BL; During pneumoperitoneum; Stage w/2 depths neuromuscular blockade targeted - TOF1 and Deep: 1-2 twitches in post-tetanic count (50-Hz tetanus followed by three-second pause and 15 1-Hz stimuli); and immediately after release of pneumoperitoneum
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Neuromuscular Block (NMB): Deep (1st) of Deep-TOF1-Deep | Cerebral Oximetry (%) | 74 percent cerebral saturation | Standard Deviation 6 |
| Deep Neuromuscular Block (NMB): MODERATE of of Deep-TOF1-Deep | Cerebral Oximetry (%) | 73 percent cerebral saturation | Standard Deviation 5 |
| Deep Neuromuscular Block (NMB): Deep (2nd) of Deep-TOF1-Deep | Cerebral Oximetry (%) | 74 percent cerebral saturation | Standard Deviation 6 |
| Moderate Neuromuscular Block (NMB): MOD(1st) of TOF1-Deep-TOF1 | Cerebral Oximetry (%) | 75 percent cerebral saturation | Standard Deviation 6 |
| Moderate Neuromuscular Block (NMB): Deep of TOF1-Deep-TOF1 | Cerebral Oximetry (%) | 75 percent cerebral saturation | Standard Deviation 6 |
| Moderate Neuromuscular Block (NMB): MOD(2nd) of TOF1-Deep-TOF1 | Cerebral Oximetry (%) | 75 percent cerebral saturation | Standard Deviation 7 |
Primary
Ejection Fraction (%)
To assess cardiac performance, transthoracic echocardiography will be used. Ejection fraction was measured as fractional shortening (FS). FS is the fraction of any diastolic dimension that is lost in systole. FS = 100\*(LVEDD - LVESD) / LVEDD, LVEDD = LV end-diastolic dimension (mm); LVESD = LV end-systolic dimension (mm).
Time frame: BL; During pneumoperitoneum; Stage w/2 depths neuromuscular blockade targeted - TOF1 and Deep: 1-2 twitches in post-tetanic count (50-Hz tetanus followed by three-second pause and 15 1-Hz stimuli); and immediately after release of pneumoperitoneum
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Neuromuscular Block (NMB): Deep (1st) of Deep-TOF1-Deep | Ejection Fraction (%) | 36 % fractional shortening | Standard Deviation 5 |
| Deep Neuromuscular Block (NMB): MODERATE of of Deep-TOF1-Deep | Ejection Fraction (%) | 34 % fractional shortening | Standard Deviation 5 |
| Deep Neuromuscular Block (NMB): Deep (2nd) of Deep-TOF1-Deep | Ejection Fraction (%) | 35 % fractional shortening | Standard Deviation 4 |
| Moderate Neuromuscular Block (NMB): MOD(1st) of TOF1-Deep-TOF1 | Ejection Fraction (%) | 35 % fractional shortening | Standard Deviation 5 |
| Moderate Neuromuscular Block (NMB): Deep of TOF1-Deep-TOF1 | Ejection Fraction (%) | 36 % fractional shortening | Standard Deviation 2 |
| Moderate Neuromuscular Block (NMB): MOD(2nd) of TOF1-Deep-TOF1 | Ejection Fraction (%) | 37 % fractional shortening | Standard Deviation 6 |
Primary
Regional Change in Air Content (Delta Z, %)
We will measure continuous respiratory flows and pressures in the intraoperative period to assess continuously the compliance and resistance of the respiratory system (T1 to T5). In addition, we will use an esophageal balloon to assess esophageal pressures and partition the global mechanical properties of the respiratory system, into their lung and chest wall components (T1 to T5). Regional lung aeration will be assessed for quantification of intraoperative lung recruitment using Electrical Impedance Tomography (EIT) (T0 to T6). Percent change was calculated using electrical impedance measurements obtained at time T0 as reference.
Time frame: BL; During pneumoperitoneum; Stage w/2 depths neuromuscular blockade targeted - TOF1 and Deep: 1-2 twitches in post-tetanic count (50-Hz tetanus followed by three-second pause and 15 1-Hz stimuli); and immediately after release of pneumoperitoneum
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Neuromuscular Block (NMB): Deep (1st) of Deep-TOF1-Deep | Regional Change in Air Content (Delta Z, %) | 14.5 percent change | Standard Deviation 51.6 |
| Deep Neuromuscular Block (NMB): MODERATE of of Deep-TOF1-Deep | Regional Change in Air Content (Delta Z, %) | 29.0 percent change | Standard Deviation 43 |
| Deep Neuromuscular Block (NMB): Deep (2nd) of Deep-TOF1-Deep | Regional Change in Air Content (Delta Z, %) | 43.3 percent change | Standard Deviation 39.9 |
| Moderate Neuromuscular Block (NMB): MOD(1st) of TOF1-Deep-TOF1 | Regional Change in Air Content (Delta Z, %) | -14.0 percent change | Standard Deviation 40.2 |
| Moderate Neuromuscular Block (NMB): Deep of TOF1-Deep-TOF1 | Regional Change in Air Content (Delta Z, %) | 19.4 percent change | Standard Deviation 41.2 |
| Moderate Neuromuscular Block (NMB): MOD(2nd) of TOF1-Deep-TOF1 | Regional Change in Air Content (Delta Z, %) | 29.8 percent change | Standard Deviation 38.2 |
Secondary
Postoperative Pain
The patient will be inquired about pain with a visual analogue scale (VAS). Pain will be evaluated as incisional pain using VAS (0 = no pain; 100 = worst possible pain).
Time frame: Postoperative Day 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Neuromuscular Block (NMB): Deep (1st) of Deep-TOF1-Deep | Postoperative Pain | 3.5 units on a scale | Standard Deviation 2 |
| Deep Neuromuscular Block (NMB): MODERATE of of Deep-TOF1-Deep | Postoperative Pain | 3.1 units on a scale | Standard Deviation 2.2 |