Surgical Conditions
Conditions
Brief summary
A deep neuromuscular block (NMB) is often associated with improved surgical conditions especially in laparoscopic surgery. We previously showed that deep NMB is superior to a moderate NMB under propofol anesthesia. However, this may not apply to sevoflurane anesthesia and sevoflurane by itself produces some degree of muscle relaxation. We therefore plan to investigate the effect of deep NMB on surgical conditions under sevoflurane anesthesia maintenance.
Detailed description
Neuromuscular blocking agents (NMBAs) are routinely administered during general anaesthesia to facilitate endotracheal intubation and to optimize surgical conditions. Increasing data suggest superiority of a deep neuromuscular block (defined by a post-tetanic count of 1-2 twitches) in creating optimal working conditions for the surgical team. However, it is unknown whether other aspects of the anaesthetic technique, most notably the choice of anaesthetic (for example, total intravenous versus inhalational anaesthesia), influence the relationship between the depth of the neuromuscular block and surgical conditions, particularly in laparoscopic surgery. Volatile anaesthetics are known for their ability to potentiate neuromuscular blocking agents an effect that is less existent with propofol. We previously showed that surgical working conditions in laparoscopic surgery during propofol anaesthesia are highly reliant on the depth of the neuromuscular block. Whether such a relationship also exists for inhalational anaesthetics, is unknown. To investigate this, we conducted a prospective, randomized, double blind study in which patients scheduled for laparoscopic renal surgery were randomized to receive either a moderate or a deep neuromuscular block during sevoflurane anaesthesia. The primary outcome was the intraoperative surgical condition assessed by a surgeon using the validated Leiden-Surgical Rating Scale. We hypothesized that the use of an inhalational anaesthetic would obviate the need for a deep NMB due to its intrinsic muscle relaxant potentiating properties to produce optimal working conditions.
Interventions
Deep neuromuscular block will be achieved with high dose rocuronium to achieve a depth of 1-2 twitches post tetanic count
Sponsors
Merck Sharp & Dohme LLC
Leiden University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients diagnosed with renal or prostatic disease who are will undergo an elective laparoscopic renal surgical procedure or laparoscopic prostatectomy; * American Society of Anesthesiologists (ASA) class I-III * \> 18 years of age; * Ability to give oral and written informed consent.
Exclusion criteria
* Known or suspected neuromuscular disorders impairing neuromuscular function; * Allergies to muscle relaxants, anesthetics or narcotics; * A (family) history of malignant hyperthermia; * Women who are or may be pregnant or are currently breast feeding; * Renal insufficiency, as defined by glomerular filtration rate \< 30 ml/h creatinine. * Previous retroperitoneal surgery at the site of the current surgery. * Body mass index \> 35 kg/m2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Leiden Surgical Rating Scale | during surgery | During the on average 3 hour procedure, the surgical condition will be scored by the surgeon using a 5-point surgical rating scale at 15 minute intervals(1: poor ; 5: optimal) Mean and standard deviation of the average of all leiden surgical rating scale will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative Measurements and Outcomes; Sedation Levels | During post-anesthetic care unit stay (average stay 2 hours) at 15 minute intervals | Postoperative measurements and outcomes of during PACU stay, all scores are reported as means and standard deviation of the average over the follow up period -ramsay sedation levels (0 = normal alertness, eyes open, responds normal to command 1 = drowsy with open eyes, closed and opened on command 2 = drowsy with closed eyes, opened in response to light auditory stimulus 3 = eyes closed, opened in response to rubbing the shoulder or a loud auditory stimulus 4 = eyes closed and opened only briefly in response to touching the subject 5 = eyes closed, unarousable by touch, aroused by painful 6 = unarousable by pain) |
| Postoperative Measurements and Outcomes; Pain Scores | During post-anesthetic care unit stay (average stay 2 hours) at 15 minute intervals | Postoperative measurements and outcomes of during PACU stay, all scores are reported as means and standard deviation of the average over the follow up period -mean pain scores (numeric rating scale; 0 no pain - 10 worst pain imaginable) |
| Intraoperative Hemodynamic Conditions | Perioperative measurements at 15 minute interval (on average during 3 hours) | Perioperative average blood pressure will be reported, mean blood pressure ranging from 65 tot 110 millimeters mercury is considered normal |
| Postoperative Measurements and Outcomes; Saturation | During post-anesthetic care unit stay (average stay 2 hours) at 15 minute intervals | Postoperative measurements and outcomes of during PACU stay, all scores are reported as means and standard deviation of the average over the follow up period -blood oxygen saturation in percent levels between 95-100 are considered normal |
| Intraoperative Nociception Level | Perioperative measurements at 15 minute interval (on average during 3 hours) | The median and full range of the average nociception level index will be reported. The nociception level index consist of Ta multiparameter nonlinear combination of heart rate, heart rate variability, amplitude of the finger photoplethysmogram, skin conductance level, fluctuations in skin conductance, and their time derivatives, derived from random forest regression. Random forest is an algorithmic modeling approach that enables combining multiple parameters of different origin and discovering their complex nonlinear interactions. Normal range is between 10-20; 0 indicates no nociceptive events (in example, pain stimuli), 100 indicates severe painful stimuli. |
Countries
Netherlands
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Moderate Neuromuscular Block Moderate neuromuscular block. In patients that were randomized to receive a moderate neuromuscular block, a bolus dose of rocuronium 0.5 mg kg-1 was administered, followed by intermittent injections of rocuronium 10-20 mg, aimed at keeping the train-of-four count at 1-2 twitches. At the end of the procedure, reversal of the neuromuscular block was by administration of sugammadex (2 mg kg-1). Patients were extubated when the train-of-four ratio reached 1.0, were breathing spontaneously and were awake. | 49 |
| Deep Neuromuscular Block In patients that were randomized to receive a deep neuromuscular block, a bolus dose of rocuronium 1.0 mg kg-1 was administered, followed by a continuous rocuronium infusion. The infusion rate was started at 0.3 mg kg-1 h-1 and titrated to keep the post-tetanic count at 1-2 twitches throughout the procedure. In case the surgeon scored Leiden-Surgical Rating Scale 1 or 2 (extremely poor or poor conditions), a bolus of rocuronium 10 mg could be administered. At the end of the procedure, reversal of the neuromuscular block was achieved with the administration of sugammadex 2-4 mg kg-1. Patients were extubated when the train-of-four ratio reached 1.0. | 49 |
| Total | 98 |
Baseline characteristics
| Characteristic | Total | Deep Neuromuscular Block | Moderate Neuromuscular Block |
|---|---|---|---|
| Age, Continuous | 54 years | 51 years | 57 years |
| American Society of Anesthesiologists physical status classification system 1 | 50 Participants | 28 Participants | 22 Participants |
| American Society of Anesthesiologists physical status classification system 2 | 46 Participants | 20 Participants | 26 Participants |
| American Society of Anesthesiologists physical status classification system 3 | 2 Participants | 1 Participants | 1 Participants |
| Height (m) | 1.75 m STANDARD_DEVIATION 0.1 | 1.75 m STANDARD_DEVIATION 0.1 | 1.75 m STANDARD_DEVIATION 0.1 |
| Procedure | 98 Laparoscopic renal surgery | 49 Laparoscopic renal surgery | 49 Laparoscopic renal surgery |
| 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 | 98 Participants | 49 Participants | 49 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Netherlands | 98 participants | 49 participants | 49 participants |
| Sex: Female, Male Female | 57 Participants | 29 Participants | 28 Participants |
| Sex: Female, Male Male | 41 Participants | 20 Participants | 21 Participants |
| Weight (kg) | 80.7 kg STANDARD_DEVIATION 13.7 | 81.4 kg STANDARD_DEVIATION 13.9 | 80 kg STANDARD_DEVIATION 13.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 49 |
| other Total, other adverse events | 3 / 49 | 2 / 49 |
| serious Total, serious adverse events | 5 / 49 | 2 / 49 |
Outcome results
Primary
Leiden Surgical Rating Scale
During the on average 3 hour procedure, the surgical condition will be scored by the surgeon using a 5-point surgical rating scale at 15 minute intervals(1: poor ; 5: optimal) Mean and standard deviation of the average of all leiden surgical rating scale will be reported.
Time frame: during surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moderate Neuromuscular Block | Leiden Surgical Rating Scale | 4.8 score on a scale | Standard Deviation 0.4 |
| Deep Neuromuscular Block | Leiden Surgical Rating Scale | 4.8 score on a scale | Standard Deviation 0.3 |
p-value: 0.94GEEGLM
Secondary
Intraoperative Hemodynamic Conditions
Perioperative average blood pressure will be reported, mean blood pressure ranging from 65 tot 110 millimeters mercury is considered normal
Time frame: Perioperative measurements at 15 minute interval (on average during 3 hours)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Moderate Neuromuscular Block | Intraoperative Hemodynamic Conditions | 84 millimeters mercury |
| Deep Neuromuscular Block | Intraoperative Hemodynamic Conditions | 85 millimeters mercury |
Secondary
Intraoperative Nociception Level
The median and full range of the average nociception level index will be reported. The nociception level index consist of Ta multiparameter nonlinear combination of heart rate, heart rate variability, amplitude of the finger photoplethysmogram, skin conductance level, fluctuations in skin conductance, and their time derivatives, derived from random forest regression. Random forest is an algorithmic modeling approach that enables combining multiple parameters of different origin and discovering their complex nonlinear interactions. Normal range is between 10-20; 0 indicates no nociceptive events (in example, pain stimuli), 100 indicates severe painful stimuli.
Time frame: Perioperative measurements at 15 minute interval (on average during 3 hours)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Moderate Neuromuscular Block | Intraoperative Nociception Level | 11 score on a scale |
| Deep Neuromuscular Block | Intraoperative Nociception Level | 13 score on a scale |
Secondary
Postoperative Measurements and Outcomes; Pain Scores
Postoperative measurements and outcomes of during PACU stay, all scores are reported as means and standard deviation of the average over the follow up period -mean pain scores (numeric rating scale; 0 no pain - 10 worst pain imaginable)
Time frame: During post-anesthetic care unit stay (average stay 2 hours) at 15 minute intervals
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moderate Neuromuscular Block | Postoperative Measurements and Outcomes; Pain Scores | 2.9 units on a scale | Standard Deviation 1.9 |
| Deep Neuromuscular Block | Postoperative Measurements and Outcomes; Pain Scores | 3.2 units on a scale | Standard Deviation 1.8 |
Secondary
Postoperative Measurements and Outcomes; Saturation
Postoperative measurements and outcomes of during PACU stay, all scores are reported as means and standard deviation of the average over the follow up period -blood oxygen saturation in percent levels between 95-100 are considered normal
Time frame: During post-anesthetic care unit stay (average stay 2 hours) at 15 minute intervals
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moderate Neuromuscular Block | Postoperative Measurements and Outcomes; Saturation | 98 percentage of blood oxygen saturation | Standard Deviation 1 |
| Deep Neuromuscular Block | Postoperative Measurements and Outcomes; Saturation | 98 percentage of blood oxygen saturation | Standard Deviation 1 |
Secondary
Postoperative Measurements and Outcomes; Sedation Levels
Postoperative measurements and outcomes of during PACU stay, all scores are reported as means and standard deviation of the average over the follow up period -ramsay sedation levels (0 = normal alertness, eyes open, responds normal to command 1 = drowsy with open eyes, closed and opened on command 2 = drowsy with closed eyes, opened in response to light auditory stimulus 3 = eyes closed, opened in response to rubbing the shoulder or a loud auditory stimulus 4 = eyes closed and opened only briefly in response to touching the subject 5 = eyes closed, unarousable by touch, aroused by painful 6 = unarousable by pain)
Time frame: During post-anesthetic care unit stay (average stay 2 hours) at 15 minute intervals
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moderate Neuromuscular Block | Postoperative Measurements and Outcomes; Sedation Levels | 0.9 units on a scale | Standard Deviation 0.6 |
| Deep Neuromuscular Block | Postoperative Measurements and Outcomes; Sedation Levels | 1.0 units on a scale | Standard Deviation 0.6 |