Anesthesia, Neuromuscular Blockade, Spinal Diseases, Surgery
Conditions
Keywords
Neuromuscular blockade, Surgical rating scale, Rocuronium, Sugammadex, Spinal surgery, General anesthesia
Brief summary
The investigators aim to investigate operating conditions, postoperative recovery and overall satisfaction of surgeons between deep neuromuscular blockade (NMB) group and restricted NMB group during spinal surgery under general anesthesia. The investigators hypothesize that this study can present good surgical conditions, postoperative recovery outcomes and overall satisfaction of surgeons in deep NMB group, thereby proving the advantages of deep NMB as well as flaws of restricted NMB in spine surgeries.
Detailed description
* Group treatment (Arms): group treated with restricted neuromuscular blockade (NMB) (Group RB); group treated with deep NMB (Group DB) → randomized allocation (subjects: motor-evoked potential \[MEP\] not monitored surgeries) * Inclusion criteria: American Society of Anesthesiologists (ASA) physical status I-II adults, aged 18-75 years, scheduled for elective spinal surgery (cervical or lumbar surgeries which have lesions no more than 3 spinal levels and not monitored by MEP) of duration \>1 hour and prone position under total intravenous anesthesia (TIVA). * Exclusion criteria: Pregnancy, the receipt of medication known to interfere with neuromuscular blockade, diseases affecting neuromuscular transmission, and the history of hypersensitivity on rocuronium or sugammadex. The patients who will have hemodynamic instability, mean blood pressure increase or fall of \> 30% from baseline (lasting for more than 5min), and blood loss \> 1 L during surgery, and MEP monitored surgeries. * Outcome Measures * Primary outcome: Mean value of peak inspiratory pressure recorded every 15 minutes. * Secondary outcomes: 1. The number of body movements (including cough or any diaphragm movement). 2. The degree of bleeding of each patient scaled by surgeons (Intraoperative scale for assessment of operating condition of surgical field: 0 - No bleeding, 1 - Slight bleeding - no suctioning of blood required, 2 - Slight bleeding - occasional suctioning required but not threatened the operative field, 3 - Slight-bleeding - frequent suctioning of blood was required that threatens the operative field a few seconds after suctioning, 4 - Moderate bleeding - frequent suctioning of blood was required which threatens the operative field directly after suctioning, 5 - Sever bleeding - continuous suctioning of blood was required which severely threatened the operative field make the surgery not possible). 3. The muscle tone of each patient scaled by surgeons (1: muscle tone is good, suitable for surgery; 2: muscle tone is moderate, but do not affect the operation; 3: muscle tone is hard, making the operation difficult.). * Three time-points of assessment of the muscle tone: ① At the placement of back muscle retractor for opening the operating site after the skin and subcutaneous incision, ② At the screw insertion through the pedicle of spine during surgery, ③ At the other period (overall muscle tone). 4. Mean value of pressure of back muscle retractor placed in the operating site (recorded every 15 minutes): measured by the pressure probe placed between the retractor and the back muscle. 5. Overall satisfaction of surgeons for the surgical condition will be assessed by the surgeons who perform surgery using numerical rating scale (NRS; 1-10) after surgery. 6. Recovery profiles including eye opening time, extubation time and sedation score (the Observer's Assessment of Alertness/ Sedation (OAA/S) score; awake, 5 to unresponsive, 1) every 10 min for 1 hour at postanesthesia care unit (PACU). 7. Postoperative adverse events
Interventions
DRUGsufficient dose of rocuronium
DRUGsugammadex 10 min after position change
Sponsors
Merck Sharp & Dohme LLC
Korea University Guro Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* American Society of Anesthesiologists (ASA) physical status I-II adult patients scheduled for elective spinal (cervical or lumbar) surgery under general anesthesia
Exclusion criteria
* Pregnancy * Present medication known to interfere with neuromuscular blockade * Diseases affecting neuromuscular transmission * History of hypersensitivity on rocuronium or sugammadex * Emergent spinal surgery * Spinal surgeries which have lesions more than 3 spinal levels * Spinal surgeries which have duration less than 1 hour * Spinal surgeries which are not performed under prone position * Spinal surgeries which are not performed under total intravenous anesthesia (TIVA). * Patients who will have hemodynamic instability (mean blood pressure increase or fall of \> 30% from baseline lasting for more than 5 min) during surgery * Patients who will have blood loss \> 1 L during surgery * MEP monitored spinal surgeries
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Value of Peak Inspiratory Pressure | Every 15 minutes during anesthesia, up to 3 hours | This outcome is the mean value of the peak inspiratory pressure measured at each 15 minute during the anesthesia, which can reflect the degree of the tone of respiratory muscles. As muscle tone increases, airway pressure usually increases due to increased tone of abdominal muscle and respiratory muscles including diaphragm. The longer the surgery goes, the higher the airway pressure gets. Also, as neurospinal surgeries are operated in the prone position, the potential for increased airway pressure is high. As airway pressure gets higher, intrathoracic pressure and intraabdominal pressure also become higher. These consequences may bring about similar results with detrimental effects derived from marked increase in intraabdominal pressure in laparoscopic abdominal surgeries |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Satisfaction of Surgeons for the Surgical Condition | After surgery | Overall satisfaction of surgeons for the surgical condition will be assessed by the surgeons who perform surgery using numerical rating scale (NRS; 1-10) after surgery (1, worst; 10, best). |
| The Muscle Tone | at the screw insertion through the pedicle of spine during surgery | The muscle tone of each patient at the screw insertion through the pedicle of spine during surgery scaled by surgeons (1: muscle tone is good, suitable for surgery; 2: muscle tone is moderate, but do not affect the operation; 3: muscle tone is hard, making the operation difficult.). |
| The Number of Body Movements | At the occurrence of the event during surgery, up to 3 hours | The number of body movements (including cough or any diaphragm movement) observed during the surgery. |
| Mean Value of Pressure of Back Muscle Retractor | Every 15 minutes at the period of the retractor placement during surgery, up to 2 hours | Mean value of pressure of back muscle retractor placed in the operating site (recorded every 15 minutes during the placement of the retractor): measured by the pressure probe placed between the retractor and the back muscle. |
| Recovery Time (Time to Reach Sedation Score 5 at Postanesthesia Care Unit (PACU). | every 10 min for 1 hour at PACU. | the time to reach sedation score 5 (the Observer's Assessment of Alertness/ Sedation (OAA/S) score; awake, 5 to unresponsive, 1) at PACU |
| Adverse Events : The Postoperative Nausea and Vomiting Occurrence in Subject | during the postoperative 24 hours | The occurrence of any adverse events was recorded in the post-anesthesia care unit (PACU) and a ward during the postoperative 24 hours. |
| The Degree of Bleeding | Continuously observed during the whole period of surgery, up to 3 hours | 2.The degree of bleeding of each patient scaled by surgeons (Intraoperative scale for assessment of operating condition of surgical field: 0 - No bleeding, 1 - Slight bleeding - no suctioning of blood required, 2 - Slight bleeding - occasional suctioning required but not threatened the operative field, 3 - Slight-bleeding - frequent suctioning of blood was required that threatens the operative field a few seconds after suctioning, 4 - Moderate bleeding - frequent suctioning of blood was required which threatens the operative field directly after suctioning, 5 - Severe bleeding - continuous suctioning of blood was required which severely threatened the operative field make the surgery not possible). |
Countries
South Korea
Participant flow
Recruitment details
This study was a single-site study recruited and performed at Korea University Guro Hospital, a general hospital, Seoul, South Korea, from 15 May 2016 to 16 February 2017.
Pre-assignment details
No enrolled participants were excluded from the study before assignment to arms or groups.
Participants by arm
| Arm | Count |
|---|---|
| Deep Neuromuscular Blockade This arm will be given sufficient dose of rocuronium. In this Arm group, rocuronium will be administered to maintain deep neuromuscular blockade \[NMB\] (TOF count 0, post-tetanic count \[PTC\] of 1-2 twitches) until the end of surgery and the reversal of NMB will be performed by sugammadex 4 mg/kg at the end of surgery'.
sufficient dose of rocuronium | 43 |
| Restricted Neuromuscular Blockade This arm will be given restricted (not sufficient) dose of rocuronium. In this Arm group, sugammadex will be administered according to the prescribing indications (4 mg/kg for deep neuromuscular blockade \[NMB\] state or 2 mg/kg for moderate NMB or less) to reverse the NMB 10 min after position change (sugammadex 10 min after position change \[a prone position\]). Thereafter, muscle relaxants will not be injected any more throughout the surgery except the following situations: If the patients show any body movement during surgery or if surgeons express any complaint about muscle tone (the muscle tone: grade 3), rescue rocuronium 5 mg will be administered and the number of body movements and rescue rocuronium administration (dose) will be recorded.
sugammadex 10 min after position change | 40 |
| Total | 83 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 2 | 5 |
Baseline characteristics
| Characteristic | Deep Neuromuscular Blockade | Total | Restricted Neuromuscular Blockade |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 13 Participants | 22 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 61 Participants | 31 Participants |
| Age, Continuous | 61 years | 60 years | 60 years |
| Height (m) | 1.59 meter STANDARD_DEVIATION 0.07 | 1.59 meter STANDARD_DEVIATION 0.07 | 1.58 meter STANDARD_DEVIATION 0.08 |
| Race/Ethnicity, Customized Korean | 43 Participants | 83 Participants | 40 Participants |
| Region of Enrollment South Korea | 43 Participants | 83 Participants | 40 Participants |
| Sex: Female, Male Female | 31 Participants | 60 Participants | 29 Participants |
| Sex: Female, Male Male | 12 Participants | 23 Participants | 11 Participants |
| Weight (kg) | 59.8 kg STANDARD_DEVIATION 8.5 | 59.9 kg STANDARD_DEVIATION 7.7 | 60 kg STANDARD_DEVIATION 6.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 40 |
| other Total, other adverse events | 11 / 43 | 8 / 40 |
| serious Total, serious adverse events | 0 / 43 | 0 / 40 |
Outcome results
Primary
Mean Value of Peak Inspiratory Pressure
This outcome is the mean value of the peak inspiratory pressure measured at each 15 minute during the anesthesia, which can reflect the degree of the tone of respiratory muscles. As muscle tone increases, airway pressure usually increases due to increased tone of abdominal muscle and respiratory muscles including diaphragm. The longer the surgery goes, the higher the airway pressure gets. Also, as neurospinal surgeries are operated in the prone position, the potential for increased airway pressure is high. As airway pressure gets higher, intrathoracic pressure and intraabdominal pressure also become higher. These consequences may bring about similar results with detrimental effects derived from marked increase in intraabdominal pressure in laparoscopic abdominal surgeries
Time frame: Every 15 minutes during anesthesia, up to 3 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Neuromuscular Blockade | Mean Value of Peak Inspiratory Pressure | 18.4 cmH2O | Standard Deviation 1.1 |
| Restricted Neuromuscular Blockade | Mean Value of Peak Inspiratory Pressure | 20.2 cmH2O | Standard Deviation 1.1 |
p-value: <0.001t-test, 2 sided
Secondary
Adverse Events : The Postoperative Nausea and Vomiting Occurrence in Subject
The occurrence of any adverse events was recorded in the post-anesthesia care unit (PACU) and a ward during the postoperative 24 hours.
Time frame: during the postoperative 24 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Deep Neuromuscular Blockade | Adverse Events : The Postoperative Nausea and Vomiting Occurrence in Subject | 11 Participants |
| Restricted Neuromuscular Blockade | Adverse Events : The Postoperative Nausea and Vomiting Occurrence in Subject | 8 Participants |
p-value: 0.202Chi-squared
Secondary
Mean Value of Pressure of Back Muscle Retractor
Mean value of pressure of back muscle retractor placed in the operating site (recorded every 15 minutes during the placement of the retractor): measured by the pressure probe placed between the retractor and the back muscle.
Time frame: Every 15 minutes at the period of the retractor placement during surgery, up to 2 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Neuromuscular Blockade | Mean Value of Pressure of Back Muscle Retractor | 81.2 mmHg | Standard Deviation 9.1 |
| Restricted Neuromuscular Blockade | Mean Value of Pressure of Back Muscle Retractor | 100 mmHg | Standard Deviation 7.3 |
p-value: <0.001t-test, 2 sided
Secondary
Overall Satisfaction of Surgeons for the Surgical Condition
Overall satisfaction of surgeons for the surgical condition will be assessed by the surgeons who perform surgery using numerical rating scale (NRS; 1-10) after surgery (1, worst; 10, best).
Time frame: After surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Neuromuscular Blockade | Overall Satisfaction of Surgeons for the Surgical Condition | 8 Scores on a scale (NRS; 1-10) | Standard Deviation 1.3 |
| Restricted Neuromuscular Blockade | Overall Satisfaction of Surgeons for the Surgical Condition | 3.1 Scores on a scale (NRS; 1-10) | Standard Deviation 1.2 |
p-value: <0.001t-test, 2 sided
Secondary
Recovery Time (Time to Reach Sedation Score 5 at Postanesthesia Care Unit (PACU).
the time to reach sedation score 5 (the Observer's Assessment of Alertness/ Sedation (OAA/S) score; awake, 5 to unresponsive, 1) at PACU
Time frame: every 10 min for 1 hour at PACU.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Neuromuscular Blockade | Recovery Time (Time to Reach Sedation Score 5 at Postanesthesia Care Unit (PACU). | 10.5 minute | Standard Deviation 7.9 |
| Restricted Neuromuscular Blockade | Recovery Time (Time to Reach Sedation Score 5 at Postanesthesia Care Unit (PACU). | 17 minute | Standard Deviation 11.4 |
p-value: 0.06t-test, 2 sided
Secondary
The Degree of Bleeding
2.The degree of bleeding of each patient scaled by surgeons (Intraoperative scale for assessment of operating condition of surgical field: 0 - No bleeding, 1 - Slight bleeding - no suctioning of blood required, 2 - Slight bleeding - occasional suctioning required but not threatened the operative field, 3 - Slight-bleeding - frequent suctioning of blood was required that threatens the operative field a few seconds after suctioning, 4 - Moderate bleeding - frequent suctioning of blood was required which threatens the operative field directly after suctioning, 5 - Severe bleeding - continuous suctioning of blood was required which severely threatened the operative field make the surgery not possible).
Time frame: Continuously observed during the whole period of surgery, up to 3 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Neuromuscular Blockade | The Degree of Bleeding | 1.8 Scores on a scale (NRS; 0-5) | Standard Deviation 0.7 |
| Restricted Neuromuscular Blockade | The Degree of Bleeding | 3.3 Scores on a scale (NRS; 0-5) | Standard Deviation 0.7 |
p-value: <0.001t-test, 2 sided
Secondary
The Muscle Tone
The muscle tone of each patient at the screw insertion through the pedicle of spine during surgery scaled by surgeons (1: muscle tone is good, suitable for surgery; 2: muscle tone is moderate, but do not affect the operation; 3: muscle tone is hard, making the operation difficult.).
Time frame: at the screw insertion through the pedicle of spine during surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Neuromuscular Blockade | The Muscle Tone | 1.3 Scores on a scale (NRS; 1-3) | Standard Deviation 0.7 |
| Restricted Neuromuscular Blockade | The Muscle Tone | 2.5 Scores on a scale (NRS; 1-3) | Standard Deviation 0.7 |
p-value: <0.001Chi-squared
Secondary
The Number of Body Movements
The number of body movements (including cough or any diaphragm movement) observed during the surgery.
Time frame: At the occurrence of the event during surgery, up to 3 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Neuromuscular Blockade | The Number of Body Movements | 0 number of event | Standard Deviation 0 |
| Restricted Neuromuscular Blockade | The Number of Body Movements | 2 number of event | Standard Deviation 1 |
p-value: <0.001Chi-squared