Neuromuscular Blockade, Rocuronium, Anesthetics, Anesthesia Complication, Neuromuscular Blocking Agents, Surgery--Complications
Conditions
Keywords
Laparoscopy
Brief summary
Muscle relaxants are routinely applied during anesthesia to facilitate endotracheal intubation and to improve surgical working conditions. Several investigations have shown that a deep neuromuscular block (NMB) improves the surgical working conditions over a moderate NMB and effectively precludes sudden deterioration of the surgical field. However, whether the improvement of surgical working conditions translates into less intra- and postoperative complications remains uncertain. Small prospective or retrospective studies shown an decrease of the incidence of intraoperative adverse events and postoperative complications after a deep NMB. There is a need to confirm these outcome data prospectively, in a large number of patients and clinics and during a variety of surgical procedures.
Detailed description
Muscle relaxants are routinely applied during anesthesia to facilitate endotracheal intubation and to improve surgical working conditions. Several investigations have shown that a deep neuromuscular block (NMB) (post tetanic count (PTC) 1-2 twitches) improves the surgical working conditions over a moderate NMB (TOF count 1-3 twitches) and effectively precludes sudden deterioration of the surgical field. However, whether the improvement of surgical working conditions translates into less intra- and postoperative complications remains uncertain. A recent retrospective analysis of neuromuscular management during laparoscopic retroperitoneal surgery showed a reduced rate of unplanned 30 day readmissions when a deep NMB over a moderate NMB was applied (3.8% vs. 12.7%).In addition, a pooled analysis of 4 randomized controlled trials comparing different levels of intra-abdominal pressure and neuromuscular blockade during laparoscopic donor nephrectomy, showed a significant reduction in the incidence of intra-operative surgical complications from 12.6% with moderate NMB to 4.8% with deep NMB. These previous observations were made in small prospective or retrospective studies. There is a need to confirm these outcome data prospectively, in a larger prospective trial for a variety of surgical procedures. We therefore propose a multi-center, randomized controlled trial, to study the effect of a deep NMB (PTC 1-2 twitches) versus standard NMB (single induction dose rocuronium) in a variety of laparoscopic surgical procedures on the incidence of intraoperative adverse events and postoperative outcome data. In this study the effect of deep neuromuscular block compared to standard neuromuscular block on intra-operative adverse events during laparoscopic surgery using the CLASSIC score system is evaluated.
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, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients scheduled for elective laparoscopic procedure with a complexity according to the BUPA classification for case complexity: 'MAJOR', 'MAJOR Plus or 'COMPLEX MAJOR' * ASA (merican society of anesthesiologists) class I-III * \> 18 years of age * Ability to give oral and written informed consent
Exclusion criteria
* Low or intermediate complexity laparoscopic procedures (BUPA 'SIMPLE' or 'INTER') * Known or suspected neuromuscular disorders impairing neuromuscular function * Allergies to muscle relaxants, anesthetics or narcotics mentioned in paragraph 5.2 * A (family) history of malignant hyperthermia * Women who are or may be pregnant or are currently breast feeding * Chronic use of any type of opioid or psychotropic drug * Use of NSAID's shorter than 5 days before surgery * Indication for rapid sequence induction * Contra-indication for sugammadex use (e.g. known sugammadex allergy or Glomerular Filtration Rate \<30 ml/min)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Classic Score>1 | Day of surgery | The incidence of symptomatic intra-operative adverse events requiring intervention or treatment (ClassIntra®grade \>1) during laparoscopic surgery in the standard of care versus the deep NMB group, as scored by the attending surgeon and anesthesiologist at the end of every procedure. A recent update of the ClassIntra®grade also involved intraoperative adverse events related to anesthesia \[Gawria et al 2023\]. This study will use both the original classic scoring, as well as an adapted version of the updated classic scoring system. The Classic score; classification of intraoperative complications, is a 6 point scale ranging from no complications (0) to fatal complications (5). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| L-SRS (Leiden Surgical Rating Scale) | Day of surgery | To study the effect of deep neuromuscular block compared to standard neuromuscular block on peroperative surgical working conditions following the Leiden Surgical Rating scale (a 5 point scale, ranging from poor (1) to excellent (5) surgical conditions. |
| 30 Day Post-operative Complications | 30 postoperative days | To study the effect of deep neuromuscular block compared to standard neuromuscular block on 30 day post-operative complications according the Clavien-Dindo score en Comprehensive Complication Index and unplanned readmissions |
| Quality of Recovery (QoR) | 2 postoperative days | To study the effect of deep neuromuscular block compared to standard neuromuscular block on Quality of Recovery at post-operative day 1, 2 according to the Quality of Recovery-40 |
| Quality of Life (QoL) | 30 postoperative days | To study the effect of deep neuromuscular block compared to standard neuromuscular block on Quality of life at post-operative day 30 Short Form-36 |
Countries
France, Italy, Netherlands, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard Neuromuscular Blockade Subjects will receive regular rocuronium induction dose, followed by bolus foses of 10 mg in case of insufficient conditions | 362 |
| Deep Neuromuscular Block Subjects will receive high dose rocuronium induction dose followed by continuous rocuronium administration, to achieve a depth of neuromuscular block of 1-2 twitches post tetanic count
Deep neuromuscular block: Deep neuromuscular block will be achieved with high dose rocuronium to achieve a depth of 1-2 twitches post tetanic count | 361 |
| Total | 723 |
Baseline characteristics
| Characteristic | Standard Neuromuscular Blockade | Deep Neuromuscular Block | Total |
|---|---|---|---|
| Age, Continuous | 58.4 year STANDARD_DEVIATION 13.7 | 58.0 year STANDARD_DEVIATION 13.5 | 58.2 year STANDARD_DEVIATION 13.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 362 Participants | 361 Participants | 723 Participants |
| Sex: Female, Male Female | 150 Participants | 139 Participants | 289 Participants |
| Sex: Female, Male Male | 212 Participants | 222 Participants | 434 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 361 | 0 / 362 |
| other Total, other adverse events | 65 / 361 | 51 / 362 |
| serious Total, serious adverse events | 24 / 361 | 23 / 362 |
Outcome results
Primary
Classic Score>1
The incidence of symptomatic intra-operative adverse events requiring intervention or treatment (ClassIntra®grade \>1) during laparoscopic surgery in the standard of care versus the deep NMB group, as scored by the attending surgeon and anesthesiologist at the end of every procedure. A recent update of the ClassIntra®grade also involved intraoperative adverse events related to anesthesia \[Gawria et al 2023\]. This study will use both the original classic scoring, as well as an adapted version of the updated classic scoring system. The Classic score; classification of intraoperative complications, is a 6 point scale ranging from no complications (0) to fatal complications (5).
Time frame: Day of surgery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Neuromuscular Blockade | Classic Score>1 | 66 participants |
| Deep Neuromuscular Block | Classic Score>1 | 54 participants |
Secondary
30 Day Post-operative Complications
To study the effect of deep neuromuscular block compared to standard neuromuscular block on 30 day post-operative complications according the Clavien-Dindo score en Comprehensive Complication Index and unplanned readmissions
Time frame: 30 postoperative days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Neuromuscular Blockade | 30 Day Post-operative Complications | 142 Participants |
| Deep Neuromuscular Block | 30 Day Post-operative Complications | 139 Participants |
Secondary
L-SRS (Leiden Surgical Rating Scale)
To study the effect of deep neuromuscular block compared to standard neuromuscular block on peroperative surgical working conditions following the Leiden Surgical Rating scale (a 5 point scale, ranging from poor (1) to excellent (5) surgical conditions.
Time frame: Day of surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Neuromuscular Blockade | L-SRS (Leiden Surgical Rating Scale) | 4.6 units on a scale | Standard Deviation 0.5 |
| Deep Neuromuscular Block | L-SRS (Leiden Surgical Rating Scale) | 4.9 units on a scale | Standard Deviation 0.3 |
Secondary
Quality of Life (QoL)
To study the effect of deep neuromuscular block compared to standard neuromuscular block on Quality of life at post-operative day 30 Short Form-36
Time frame: 30 postoperative days
Secondary
Quality of Recovery (QoR)
To study the effect of deep neuromuscular block compared to standard neuromuscular block on Quality of Recovery at post-operative day 1, 2 according to the Quality of Recovery-40
Time frame: 2 postoperative days