Neuromuscular Block
Conditions
Keywords
deep neuromuscular block, sugammadex, stability of anesthesia, suppression of EMG activity, PQRS, General Anesthesia, Quality of Recovery
Brief summary
The investigators hypothesize that an anesthetic protocol maintaining deep neuromuscular block throughout the entire surgical procedure followed by sugammadex reversal, would suppress EMG activity and result in improved anesthetic stability by reducing the variability of the Bispectral Index of the EEG, and be beneficial by reducing the total doses of the anesthetic drugs propofol and remifentanil required to maintain an adequate level of anesthesia (BIS between 40 and 60).
Interventions
DRUGSugammadex
Reversal of deep neuromuscular block
DRUGRocuronium
Maintenance of deep neuromuscular block
Sponsors
Merck Sharp & Dohme LLC
Centro Hospitalar do Porto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients ASA I-III * Between 18 - 80 years old * Scheduled for routine cervical surgery * Minimum duration of surgery is 90 minutes and performed with total intravenous anaesthesia (TIVA) with the hypnotic propofol, the analgesic remifentanil and the neuromuscular relaxant rocuronium * Patients that are able to and do provide a signed informed consent form
Exclusion criteria
* Patients with neuromuscular diseases and severe cardiac and respiratory pathologies * Contra indication for any of the drugs used * Not able to complete the baseline PQRS test. * Indication to perform tracheal intubation using fibroscopy * Patients who are pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BIS Signal Variability Using the Measured Standard Deviation During the Maintenance Phase of Anesthesia | Maintenance of anesthesia, an average of 130 minutes | BIS (Bispetral Index of the EEG) sample standard deviation during the maintenance phase of anesthesia was used as a measure of signal variability, maintenance phase is defined as the time between the first time the BIS signal drops below 60 after loss of consciousness, until the time the BIS signal goes above 60 after the propofol infusion is stopped. BIS signal varies between 0 to 100. BIS values near 100 represent an awake clinical state while 0 denotes the maximal effect an isoelectric EEG. The aim was to maintain the BIS value within a target range of 40 to 60. The higher the BIS sample standard deviation the higher the oscillation around the sample mean. |
| Required Effect-site Concentrations of Propofol and Remifentanil | Maintenance of anesthesia, an average of 130 minutes | Mean effect-site concentration of propofol required during maintenance of anesthesia (using target controlled infusion). Mean effect-site concentration of remifentanil required during maintenance of anesthesia (using target controlled infusion). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PQRS Results at 15 and 40 Minutes After Surgery (Taking Into Account the Patient Baseline Values of the PQRS Test Done on the Preanesthetic Visit) | 15 and 40 minutes after surgery | PQRS(Post-operative Quality Recovery Scale) recovery rate at 15 minutes post surgery and PQRS recovery rate at 40 minutes post surgery. Recovery is defined as returning to PQRS baseline values. |
| PQRS Satisfaction Results at Day 3 After Surgery | 3rd day after surgery | Patient satisfaction with anesthetic care rated as: Not satisfied, A little satisfied, Moderately satisfied ,Satisfied, Totally Satisfied |
Countries
Portugal
Participant flow
Recruitment details
Recruitment started on the 2016/9/19 and finished on 2017/6/28 at Centro Hospitalar do Porto, Portugal.
Pre-assignment details
3 patients were excluded from the study after screening (signing the informed consent) but before randomization and assignment to the groups, due to: * 2 patients had their surgery postponed less than 2 hours before the schedule time * the scheduled surgical position of 1 patient was altered by the surgeon just before the start of the procedure.
Participants by arm
| Arm | Count |
|---|---|
| Standard Group Standard Clinical Practice Group - standard neuromuscular block, with a standard rocuronium dose for intubation (0.6 mg/kg). If required, the reversal of neuromuscular block is performed with neostigmine. | 32 |
| Deep NMB Group Deep Neuromuscular Block group - with a standard rocuronium dose for intubation (0.6 mg/kg), followed by a constant infusion of rocuronium (10-15 ug/kg/min) to guarantee a PTC less or equal to 2 on the TOF monitor (PTC is evaluated every 5 minutes). The reversal of neuromuscular block is performed with Sugammadex (4 mg/kg).
Sugammadex: Reversal of deep neuromuscular block
Rocuronium: Maintenance of deep neuromuscular block | 31 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | BIS monitoring failed. | 1 | 1 |
| Overall Study | Patients' data files were corrupted. | 1 | 1 |
| Overall Study | Time of the procedure less than 90 min. | 1 | 2 |
Baseline characteristics
| Characteristic | Standard Group | Deep NMB Group | Total |
|---|---|---|---|
| Age, Continuous | 52.4 years STANDARD_DEVIATION 10.7 | 52.6 years STANDARD_DEVIATION 7.9 | 52.5 years STANDARD_DEVIATION 9.3 |
| Mean Arterial Pressure | 105.6 mmHg STANDARD_DEVIATION 12.8 | 101.4 mmHg STANDARD_DEVIATION 12.5 | 103.5 mmHg STANDARD_DEVIATION 12.7 |
| 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 32 Participants | 31 Participants | 63 Participants |
| Region of Enrollment Portugal | 32 Participants | 31 Participants | 63 Participants |
| Sex: Female, Male Female | 18 Participants | 17 Participants | 35 Participants |
| Sex: Female, Male Male | 14 Participants | 14 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 35 |
| other Total, other adverse events | 2 / 35 | 6 / 35 |
| serious Total, serious adverse events | 0 / 35 | 0 / 35 |
Outcome results
Primary
BIS Signal Variability Using the Measured Standard Deviation During the Maintenance Phase of Anesthesia
BIS (Bispetral Index of the EEG) sample standard deviation during the maintenance phase of anesthesia was used as a measure of signal variability, maintenance phase is defined as the time between the first time the BIS signal drops below 60 after loss of consciousness, until the time the BIS signal goes above 60 after the propofol infusion is stopped. BIS signal varies between 0 to 100. BIS values near 100 represent an awake clinical state while 0 denotes the maximal effect an isoelectric EEG. The aim was to maintain the BIS value within a target range of 40 to 60. The higher the BIS sample standard deviation the higher the oscillation around the sample mean.
Time frame: Maintenance of anesthesia, an average of 130 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Group | BIS Signal Variability Using the Measured Standard Deviation During the Maintenance Phase of Anesthesia | 7.6 units on a scale | Standard Deviation 1.6 |
| Deep NMB Group | BIS Signal Variability Using the Measured Standard Deviation During the Maintenance Phase of Anesthesia | 7.8 units on a scale | Standard Deviation 1.6 |
Comparison: Sample size calculation was performed with a power of 0.80 and an α of 0.05, considering the primary hypothesis of a reduction in the BIS variability (measured as the standard deviation). A 25% reduction on the BIS variability (standard deviation) was considered clinically relevant, and gave a minimum sample size of 26 per group.p-value: 0.651t-test, 2 sided
Primary
Required Effect-site Concentrations of Propofol and Remifentanil
Mean effect-site concentration of propofol required during maintenance of anesthesia (using target controlled infusion). Mean effect-site concentration of remifentanil required during maintenance of anesthesia (using target controlled infusion).
Time frame: Maintenance of anesthesia, an average of 130 minutes
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Group | Required Effect-site Concentrations of Propofol and Remifentanil | Propofol | 3000 ng/ml | Standard Deviation 560 |
| Standard Group | Required Effect-site Concentrations of Propofol and Remifentanil | Remifentanil | 3.26 ng/ml | Standard Deviation 1.02 |
| Deep NMB Group | Required Effect-site Concentrations of Propofol and Remifentanil | Propofol | 2450 ng/ml | Standard Deviation 550 |
| Deep NMB Group | Required Effect-site Concentrations of Propofol and Remifentanil | Remifentanil | 2.84 ng/ml | Standard Deviation 1.12 |
Comparison: This statistical analysis applies to the propofol effect-site concentration. Sample size calculation was performed with a power of 0.80 and an α of 0.05 also a reduction in the propofol drug consumption (measured as the average effect-site concentration) during maintenance of anesthesia. A reduction on propofol mean effect-site concentration of 20% was considered clinically relevant, giving a minimum of 34 patients per groupp-value: <0.001t-test, 2 sided
Comparison: This statistical analysis applies to the remifentanil effect-site concentration.~Sample size calculation was performed with a power of 0.80 and an α of 0.05 also a reduction in the remifentanil drug consumption (measured as the average effect-site concentration) during maintenance of anesthesia. A reduction on on remifentanil average effect-site concentration of 20% was considered clinically relevant, giving a minimum of 24 patients per groupp-value: 0.245t-test, 2 sided
Secondary
PQRS Results at 15 and 40 Minutes After Surgery (Taking Into Account the Patient Baseline Values of the PQRS Test Done on the Preanesthetic Visit)
PQRS(Post-operative Quality Recovery Scale) recovery rate at 15 minutes post surgery and PQRS recovery rate at 40 minutes post surgery. Recovery is defined as returning to PQRS baseline values.
Time frame: 15 and 40 minutes after surgery
Population: 10 patients were not able to complete the PQRS test at 15 minutes, since they were not able to communicate or understand the questions.~1 patient was not able to complete the PQRS test at 15 and 40 minutes due to problems in the vocal cords.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Standard Group | PQRS Results at 15 and 40 Minutes After Surgery (Taking Into Account the Patient Baseline Values of the PQRS Test Done on the Preanesthetic Visit) | 15 minutes | Overall recovery | 2 Participants |
| Standard Group | PQRS Results at 15 and 40 Minutes After Surgery (Taking Into Account the Patient Baseline Values of the PQRS Test Done on the Preanesthetic Visit) | 15 minutes | Did not recovered | 24 Participants |
| Standard Group | PQRS Results at 15 and 40 Minutes After Surgery (Taking Into Account the Patient Baseline Values of the PQRS Test Done on the Preanesthetic Visit) | 40 minutes | Overall recovery | 0 Participants |
| Standard Group | PQRS Results at 15 and 40 Minutes After Surgery (Taking Into Account the Patient Baseline Values of the PQRS Test Done on the Preanesthetic Visit) | 40 minutes | Did not recovered | 32 Participants |
| Deep NMB Group | PQRS Results at 15 and 40 Minutes After Surgery (Taking Into Account the Patient Baseline Values of the PQRS Test Done on the Preanesthetic Visit) | 40 minutes | Did not recovered | 27 Participants |
| Deep NMB Group | PQRS Results at 15 and 40 Minutes After Surgery (Taking Into Account the Patient Baseline Values of the PQRS Test Done on the Preanesthetic Visit) | 15 minutes | Overall recovery | 5 Participants |
| Deep NMB Group | PQRS Results at 15 and 40 Minutes After Surgery (Taking Into Account the Patient Baseline Values of the PQRS Test Done on the Preanesthetic Visit) | 40 minutes | Overall recovery | 3 Participants |
| Deep NMB Group | PQRS Results at 15 and 40 Minutes After Surgery (Taking Into Account the Patient Baseline Values of the PQRS Test Done on the Preanesthetic Visit) | 15 minutes | Did not recovered | 21 Participants |
Comparison: The null hypothesis was that PQRS overall recovery at 15 minutes was independent from the study group.p-value: 0.419Fisher Exact
Comparison: The null hypothesis was that PQRS overall recovery at 40 minutes was independent from the study group.p-value: 0.107Fisher Exact
Secondary
PQRS Satisfaction Results at Day 3 After Surgery
Patient satisfaction with anesthetic care rated as: Not satisfied, A little satisfied, Moderately satisfied ,Satisfied, Totally Satisfied
Time frame: 3rd day after surgery
Population: 4 patients did not complete the questionnaire on the 3rd day, since they did not pick up the phone.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard Group | PQRS Satisfaction Results at Day 3 After Surgery | Satisfied | 3 Participants |
| Standard Group | PQRS Satisfaction Results at Day 3 After Surgery | A little satisfied | 0 Participants |
| Standard Group | PQRS Satisfaction Results at Day 3 After Surgery | Moderately satisfied | 0 Participants |
| Standard Group | PQRS Satisfaction Results at Day 3 After Surgery | Not satisfied | 0 Participants |
| Standard Group | PQRS Satisfaction Results at Day 3 After Surgery | Totally satisfied | 27 Participants |
| Deep NMB Group | PQRS Satisfaction Results at Day 3 After Surgery | Not satisfied | 0 Participants |
| Deep NMB Group | PQRS Satisfaction Results at Day 3 After Surgery | Totally satisfied | 27 Participants |
| Deep NMB Group | PQRS Satisfaction Results at Day 3 After Surgery | Satisfied | 2 Participants |
| Deep NMB Group | PQRS Satisfaction Results at Day 3 After Surgery | Moderately satisfied | 0 Participants |
| Deep NMB Group | PQRS Satisfaction Results at Day 3 After Surgery | A little satisfied | 0 Participants |
Comparison: The null hypothesis was that PQRS satisfaction with anesthetic care was independent of the study group.p-value: 0.669Chi-squared