Anesthesia
Conditions
Keywords
anesthesia, desflurane
Brief summary
The purposes of this study are to evaluate the efficacy and safety of desflurane (BLM-240) as an anesthetic agent and to demonstrate the non-inferiority of desflurane to sevoflurane in term of awakening/recovery from anesthesia.
Detailed description
The study evaluates the efficacy and safety of the use of desflurane (BLM-240) (with and without nitrous oxide) in maintenance of general anesthesia in adult patients undergoing surgical procedures typically performed under general anesthesia in Japan (thoracic, abdominal, joints, back, and neck), where analgesics and muscle relaxants are concomitantly used. The study is also intended to demonstrate the non-inferiority of desflurane with nitrous oxide to sevoflurane with nitrous oxide in time to awakening/recovery.
Interventions
DRUGdesflurane
volatile liquid for inhalation
DRUGdesflurane/nitrous oxide
volatile liquid for inhalation with gas for inhalation
volatile liquid for inhalation and gas for inhalation
Sponsors
Baxter Healthcare Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
* ASA PS 1-3 * age: older than 19 y and younger than 70 y * undergoing surgery of the thorax(thoracotomy, thoracotomy plus laparotomy, endoscopy; but excluding cardiovascular),abdomen(laparotomy,endoscopy;but excluding cesarean section), joints (including peripheral vessels), back (spine)or neck (neck, throat) * willing to be hospitalized for at least 3 days and 2 nights (from the day before surgery to the day after surgery) * having given written consent
Exclusion criteria
* need for spinal subarachnoid, epidural or local anesthesia (except local surface or infiltration anesthesia for catheter insertion or use of local anesthetic for testing before inserting epidural catheter for post-surgical pain) * contraindication for use of nitrous during surgery * anticipated need for postoperative transfer to intensive care unit and receive mechanical pulmonary ventilation * BMI of 30 kg/m2 or more * serious hepatic, renal, or circulatory disorder (Grade 3 per Notification 80 by MHW, Pharmaceutical Affairs Bureau, Safety Division) * uncontrollable hypertension (SBP 160 mmHg or higher while on antihypertensive therapy) * emergency surgery * history of hypersensitivity to components of sevoflurane, fentanyl, propofol, vecuronium or other anesthetic * contraindication to sevoflurane, fentanyl, propofol, or vecuronium * exposure or suspected exposure to inhalational halogenated anesthetic within 3 mo prior to consent * known or suspected history or family history of malignant hyperthermia * considered likely to have difficulty in receiving tracheal intubation due to conditions such as brachygnathia, micrognathia, bucked teeth, articular rheumatism or injury of cervical spine/cervical cord * known or suspected to be pregnant or lactating * participated in a clinical study within 6 mo prior to consent * history of drug dependence * history of epilepsy * otherwise judged by the investigator to be unsuitable for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Requiring Rescue Treatment During Anesthetic Maintenance | Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours) | Rescue medication includes vasopressors and depressors. |
| Number of Participants With Body Movement During Anesthetic Maintenance | Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours) | The investigator or sub-investigator observed the patient for body movement (excluding bucking) during anesthetic maintenance. |
| Number of Participants With Recall/Memory Issues During Anesthetic Maintenance | Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours) | The investigator or sub-investigator observed the patient for the presence or absence of awakening during anesthetic maintenance and interviewed the patient on the day after surgery to confirm whether the patient has any memory during anesthetic maintenance. |
| Number of Participants Not Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70% | Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours) | Rescue medication includes vasopressors and depressors. Percentage of observation points at which systolic pressure 80 to \<150 mmHg and heart rate 50 to \<100 bpm could be maintained |
| Number of Participants Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70% | Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours) | Rescue medication includes vasopressors and depressors. Percentage of observation points at which no rescue treatment was judged to be required based on blood pressure/heart rate |
| Overall Assessment of Efficacy | Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours) | Evaluation on the efficacy (ability) of BLM-240 as an anesthetic drug. |
| Time to Extubation | Day 1 (Post-Surgery, from end of study drug inhalation to extubation) | Evaluation of Awakening/Recovery from Anesthesia from end of study drug inhalation to extubation. The patient was extubated when the following signs were observed:(1) clear consciousness, (2) ability to breathe spontaneously (minute ventilation \>=50 mL/kg/min), and (3) stable circulatory dynamics (systolic pressure: \>=100 mmHg). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Requiring Rescue Medication Due to Arrhythmia | Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours) | Rescue medication can include vasopressors and depressors. |
| Range of End-Tidal Anesthetic Percent Concentrations During Anesthetic Maintenance | Day 1 [just before the start of inhalation of study drug, during anesthetic maintenance (every 5 minutes after the start of inhalation of study drug), at the end of inhalation of study drug, immediately after awakening, and just before extubation] | Measurement by infrared absorption spectrometry. The concentrations of BLM-240 and sevoflurane at the start of inhalation were set at 3% and 1%,respectively (by vaporizer dial setting). Concentrations are monitored to determine which levels keep the patient in stable condition without requiring rescue treatment. |
| Time to Awakening | Day 1 (Post-Surgery, from the end of study drug inhalation to awakening) | Time from the end of study drug inhalation. After the end of inhalation of the study drug, the investigator commanded the patient to open his/her eyes once every minute to check whether he/she awoke and recorded the time of awakening. |
| End-Tidal Anesthetic Percent Concentrations Successfully Maintained Anesthesia | Day 1 [just before the start of inhalation of study drug, during anesthetic maintenance (every 5 minutes after the start of inhalation of study drug), at the end of inhalation of study drug, immediately after awakening, and just before extubation] | Successfully maintaining anesthesia is defined as keeping the patient in stable condition (systolic pressure 80 to \<150 mmHg and heart rate 50 to \<100bpm) without requiring rescue treatment or additional dose of opioid analgesics (\<=2 ug/kg/hr).If patient was found to have body movement, recall, or memory during anesthetic maintenance, data for such patient were to be excluded from summary statistic calculation. |
| Range of Inspired Anesthetic Concentrations Below End-Tidal Anesthetic Percent Concentrations During Anesthetic Maintenance | Day 1 [just before the start of inhalation of study drug, during anesthetic maintenance (every 5 minutes after the start of inhalation of study drug), at the end of inhalation of study drug, and just before extubation] | Measurement by infrared absorption spectrometry. Ranges reflecting when concentrations were stable. The inspired concentration was adjusted depending on the patient's condition during anesthetic maintenance (gas flow rate: 2 to 6 L/min). |
| Time to Stating Birth Date | Day 1 (Post-Surgery, after extubation) | After extubation, the investigator called and asked the patient to state the birth date once every minute and recorded the time the patient could state the birth date. Time from the end of study drug inhalation. |
| Time to Reaching an Aldrete Score >=8 (Min) | Day 1 (Post-Surgery, after extubation) | Score includes a ranking of 0-2 (higher shows improvement) in activity, respiration, circulation, consciousness, and O2 saturation (SpO2). After extubation, the investigator observed the patient's condition every 5 minutes until the Aldrete score reached \>=8 and recorded the Aldrete scores at 5-minute intervals. |
| Time to Clear Consciousness | Day 1 (Post-Surgery, from awakening to before extubation) | Clear consciousness means that patients responded to investigator's command for physical movement such as hold my finger tight. |
| Changes in Bispectral Index (BIS) Over Time During Anethetic Maintenance | Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours) | BIS is used to monitor depth of anesthesia. The BIS monitor provides a single number, which ranges from 0 (equivalent to EEG silence) to 100. A BIS value between 40 and 60 generally indicates an appropriate level for general anesthesia. |
| Number of Participants Requiring Rescue Medication Due to Rise in Blood Pressure or Heart Rate | Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours) | Rescue medication can include vasopressors and depressors. |
| Number of Participants Requiring Rescue Medication Due to Drop in Blood Pressure or Heart Rate | Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours) | Rescue medication can include vasopressors and depressors. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BLM 240 N2O Group Inhalation of BLM-240 was initiated at 3% (vaporizer dial setting) with N2O at 50-70%. The inspired concentration was adjusted depending on the patient's condition during anesthetic maintenance (gas flow rate: 2 to 6 L/min). | 111 |
| BLM 240 O2 Group Inhalation of BLM-240 was initiated at 3% (vaporizer dial setting) with o2 (\>=30%). The inspired concentration was adjusted depending on the patient's condition during anesthetic maintenance (gas flow rate: 2 to 6 L/min). | 55 |
| Sevoflurane Group Inhalation of sevoflurane was initiated at 1% (vaporizer dial setting) with N2O at 50-70%. The inspired concentration was adjusted depending on the patient's condition during anesthetic maintenance (gas flow rate: 2 to 6 L/min). | 50 |
| Total | 216 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | BLM 240 N2O Group | BLM 240 O2 Group | Sevoflurane Group | Total |
|---|---|---|---|---|
| Age, Continuous | 48.5 years STANDARD_DEVIATION 12.2 | 47.4 years STANDARD_DEVIATION 13.6 | 45.7 years STANDARD_DEVIATION 13.4 | 47.2 years STANDARD_DEVIATION 11.5 |
| Race/Ethnicity, Customized Japan | 111 participants | 55 participants | 50 participants | 216 participants |
| Sex: Female, Male Female | 60 Participants | 35 Participants | 31 Participants | 126 Participants |
| Sex: Female, Male Male | 51 Participants | 20 Participants | 19 Participants | 90 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 166 | 0 / 111 | 0 / 55 | 0 / 50 |
| other Total, other adverse events | 163 / 166 | 108 / 111 | 55 / 55 | 49 / 50 |
| serious Total, serious adverse events | 0 / 166 | 5 / 111 | 0 / 55 | 2 / 50 |
Outcome results
Primary
Number of Participants Not Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70%
Rescue medication includes vasopressors and depressors. Percentage of observation points at which systolic pressure 80 to \<150 mmHg and heart rate 50 to \<100 bpm could be maintained
Time frame: Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours)
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BLM-240 Group | Number of Participants Not Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70% | <70% | 9 participants |
| BLM-240 Group | Number of Participants Not Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70% | >=70% | 111 participants |
| BLM-240 N2O Group | Number of Participants Not Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70% | <70% | 7 participants |
| BLM-240 N2O Group | Number of Participants Not Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70% | >=70% | 68 participants |
| BLM-240 O2 Group | Number of Participants Not Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70% | >=70% | 43 participants |
| BLM-240 O2 Group | Number of Participants Not Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70% | <70% | 2 participants |
| Sevoflurane Group | Number of Participants Not Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70% | <70% | 3 participants |
| Sevoflurane Group | Number of Participants Not Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70% | >=70% | 31 participants |
Primary
Number of Participants Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70%
Rescue medication includes vasopressors and depressors. Percentage of observation points at which no rescue treatment was judged to be required based on blood pressure/heart rate
Time frame: Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours)
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BLM-240 Group | Number of Participants Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70% | >=70% | 46 participants |
| BLM-240 Group | Number of Participants Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70% | <70% | 0 participants |
| BLM-240 N2O Group | Number of Participants Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70% | <70% | 0 participants |
| BLM-240 N2O Group | Number of Participants Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70% | >=70% | 36 participants |
| BLM-240 O2 Group | Number of Participants Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70% | >=70% | 10 participants |
| BLM-240 O2 Group | Number of Participants Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70% | <70% | 0 participants |
| Sevoflurane Group | Number of Participants Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70% | >=70% | 16 participants |
| Sevoflurane Group | Number of Participants Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70% | <70% | 0 participants |
Primary
Number of Participants Requiring Rescue Treatment During Anesthetic Maintenance
Rescue medication includes vasopressors and depressors.
Time frame: Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours)
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BLM-240 Group | Number of Participants Requiring Rescue Treatment During Anesthetic Maintenance | No | 120 participants |
| BLM-240 Group | Number of Participants Requiring Rescue Treatment During Anesthetic Maintenance | Yes | 46 participants |
| BLM-240 N2O Group | Number of Participants Requiring Rescue Treatment During Anesthetic Maintenance | Yes | 36 participants |
| BLM-240 N2O Group | Number of Participants Requiring Rescue Treatment During Anesthetic Maintenance | No | 75 participants |
| BLM-240 O2 Group | Number of Participants Requiring Rescue Treatment During Anesthetic Maintenance | No | 45 participants |
| BLM-240 O2 Group | Number of Participants Requiring Rescue Treatment During Anesthetic Maintenance | Yes | 10 participants |
| Sevoflurane Group | Number of Participants Requiring Rescue Treatment During Anesthetic Maintenance | No | 34 participants |
| Sevoflurane Group | Number of Participants Requiring Rescue Treatment During Anesthetic Maintenance | Yes | 16 participants |
Primary
Number of Participants With Body Movement During Anesthetic Maintenance
The investigator or sub-investigator observed the patient for body movement (excluding bucking) during anesthetic maintenance.
Time frame: Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours)
Population: Full Analysis Set (FAS) - subjects assigned to treatment groups, excluding subjects with significant GCP violations (significant violations regarding informed consent and study procedures), subjects who did not receive the allocated study drug, subjects whose ASA status was not Class I, II, III, or subjects for whom no data were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BLM-240 Group | Number of Participants With Body Movement During Anesthetic Maintenance | No | 165 participants |
| BLM-240 Group | Number of Participants With Body Movement During Anesthetic Maintenance | Yes | 1 participants |
| BLM-240 N2O Group | Number of Participants With Body Movement During Anesthetic Maintenance | Yes | 0 participants |
| BLM-240 N2O Group | Number of Participants With Body Movement During Anesthetic Maintenance | No | 111 participants |
| BLM-240 O2 Group | Number of Participants With Body Movement During Anesthetic Maintenance | No | 54 participants |
| BLM-240 O2 Group | Number of Participants With Body Movement During Anesthetic Maintenance | Yes | 1 participants |
| Sevoflurane Group | Number of Participants With Body Movement During Anesthetic Maintenance | No | 50 participants |
| Sevoflurane Group | Number of Participants With Body Movement During Anesthetic Maintenance | Yes | 0 participants |
Primary
Number of Participants With Recall/Memory Issues During Anesthetic Maintenance
The investigator or sub-investigator observed the patient for the presence or absence of awakening during anesthetic maintenance and interviewed the patient on the day after surgery to confirm whether the patient has any memory during anesthetic maintenance.
Time frame: Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours)
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BLM-240 Group | Number of Participants With Recall/Memory Issues During Anesthetic Maintenance | No | 165 participants |
| BLM-240 Group | Number of Participants With Recall/Memory Issues During Anesthetic Maintenance | Unevaluable | 1 participants |
| BLM-240 Group | Number of Participants With Recall/Memory Issues During Anesthetic Maintenance | Yes | 0 participants |
| BLM-240 N2O Group | Number of Participants With Recall/Memory Issues During Anesthetic Maintenance | No | 110 participants |
| BLM-240 N2O Group | Number of Participants With Recall/Memory Issues During Anesthetic Maintenance | Unevaluable | 1 participants |
| BLM-240 N2O Group | Number of Participants With Recall/Memory Issues During Anesthetic Maintenance | Yes | 0 participants |
| BLM-240 O2 Group | Number of Participants With Recall/Memory Issues During Anesthetic Maintenance | Yes | 0 participants |
| BLM-240 O2 Group | Number of Participants With Recall/Memory Issues During Anesthetic Maintenance | No | 55 participants |
| BLM-240 O2 Group | Number of Participants With Recall/Memory Issues During Anesthetic Maintenance | Unevaluable | 0 participants |
| Sevoflurane Group | Number of Participants With Recall/Memory Issues During Anesthetic Maintenance | No | 50 participants |
| Sevoflurane Group | Number of Participants With Recall/Memory Issues During Anesthetic Maintenance | Unevaluable | 0 participants |
| Sevoflurane Group | Number of Participants With Recall/Memory Issues During Anesthetic Maintenance | Yes | 0 participants |
Primary
Overall Assessment of Efficacy
Evaluation on the efficacy (ability) of BLM-240 as an anesthetic drug.
Time frame: Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours)
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BLM-240 Group | Overall Assessment of Efficacy | Excellent Ability | 111 participants |
| BLM-240 Group | Overall Assessment of Efficacy | Sufficient Ability | 9 participants |
| BLM-240 Group | Overall Assessment of Efficacy | Some Ability | 44 participants |
| BLM-240 Group | Overall Assessment of Efficacy | Insufficient Ability | 1 participants |
| BLM-240 Group | Overall Assessment of Efficacy | Inadequate | 0 participants |
| BLM-240 Group | Overall Assessment of Efficacy | Unevaluable | 1 participants |
| BLM-240 N2O Group | Overall Assessment of Efficacy | Unevaluable | 1 participants |
| BLM-240 N2O Group | Overall Assessment of Efficacy | Insufficient Ability | 0 participants |
| BLM-240 N2O Group | Overall Assessment of Efficacy | Excellent Ability | 68 participants |
| BLM-240 N2O Group | Overall Assessment of Efficacy | Some Ability | 35 participants |
| BLM-240 N2O Group | Overall Assessment of Efficacy | Sufficient Ability | 7 participants |
| BLM-240 N2O Group | Overall Assessment of Efficacy | Inadequate | 0 participants |
| BLM-240 O2 Group | Overall Assessment of Efficacy | Sufficient Ability | 2 participants |
| BLM-240 O2 Group | Overall Assessment of Efficacy | Some Ability | 9 participants |
| BLM-240 O2 Group | Overall Assessment of Efficacy | Insufficient Ability | 1 participants |
| BLM-240 O2 Group | Overall Assessment of Efficacy | Unevaluable | 0 participants |
| BLM-240 O2 Group | Overall Assessment of Efficacy | Inadequate | 0 participants |
| BLM-240 O2 Group | Overall Assessment of Efficacy | Excellent Ability | 43 participants |
| Sevoflurane Group | Overall Assessment of Efficacy | Inadequate | 0 participants |
| Sevoflurane Group | Overall Assessment of Efficacy | Unevaluable | 0 participants |
| Sevoflurane Group | Overall Assessment of Efficacy | Sufficient Ability | 3 participants |
| Sevoflurane Group | Overall Assessment of Efficacy | Insufficient Ability | 0 participants |
| Sevoflurane Group | Overall Assessment of Efficacy | Excellent Ability | 31 participants |
| Sevoflurane Group | Overall Assessment of Efficacy | Some Ability | 16 participants |
Primary
Time to Extubation
Evaluation of Awakening/Recovery from Anesthesia from end of study drug inhalation to extubation. The patient was extubated when the following signs were observed:(1) clear consciousness, (2) ability to breathe spontaneously (minute ventilation \>=50 mL/kg/min), and (3) stable circulatory dynamics (systolic pressure: \>=100 mmHg).
Time frame: Day 1 (Post-Surgery, from end of study drug inhalation to extubation)
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BLM-240 Group | Time to Extubation | 9.8 minutes | Standard Deviation 5 |
| BLM-240 N2O Group | Time to Extubation | 10.1 minutes | Standard Deviation 4.6 |
| BLM-240 O2 Group | Time to Extubation | 9.3 minutes | Standard Deviation 5.7 |
| Sevoflurane Group | Time to Extubation | 14.8 minutes | Standard Deviation 8.4 |
95% CI: [-6.6, -2.7]
Secondary
Changes in Bispectral Index (BIS) Over Time During Anethetic Maintenance
BIS is used to monitor depth of anesthesia. The BIS monitor provides a single number, which ranges from 0 (equivalent to EEG silence) to 100. A BIS value between 40 and 60 generally indicates an appropriate level for general anesthesia.
Time frame: Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours)
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BLM-240 Group | Changes in Bispectral Index (BIS) Over Time During Anethetic Maintenance | Before Extubation | 90.1 score on a scale | Standard Deviation 11.9 |
| BLM-240 Group | Changes in Bispectral Index (BIS) Over Time During Anethetic Maintenance | After Awakening | 84.8 score on a scale | Standard Deviation 15.4 |
| BLM-240 Group | Changes in Bispectral Index (BIS) Over Time During Anethetic Maintenance | Prior to start of inhalation | 50.7 score on a scale | Standard Deviation 13.2 |
| BLM-240 Group | Changes in Bispectral Index (BIS) Over Time During Anethetic Maintenance | End of inhalation | 46.3 score on a scale | Standard Deviation 12.9 |
| BLM-240 Group | Changes in Bispectral Index (BIS) Over Time During Anethetic Maintenance | 5 minutes after extubation | 93.5 score on a scale | Standard Deviation 6.7 |
| BLM-240 N2O Group | Changes in Bispectral Index (BIS) Over Time During Anethetic Maintenance | After Awakening | 88.2 score on a scale | Standard Deviation 10.8 |
| BLM-240 N2O Group | Changes in Bispectral Index (BIS) Over Time During Anethetic Maintenance | Prior to start of inhalation | 48.6 score on a scale | Standard Deviation 14.8 |
| BLM-240 N2O Group | Changes in Bispectral Index (BIS) Over Time During Anethetic Maintenance | End of inhalation | 57.3 score on a scale | Standard Deviation 18.6 |
| BLM-240 N2O Group | Changes in Bispectral Index (BIS) Over Time During Anethetic Maintenance | Before Extubation | 90.8 score on a scale | Standard Deviation 10.8 |
| BLM-240 N2O Group | Changes in Bispectral Index (BIS) Over Time During Anethetic Maintenance | 5 minutes after extubation | 95.2 score on a scale | Standard Deviation 5.3 |
| BLM-240 O2 Group | Changes in Bispectral Index (BIS) Over Time During Anethetic Maintenance | 5 minutes after extubation | 93.4 score on a scale | Standard Deviation 6.1 |
| BLM-240 O2 Group | Changes in Bispectral Index (BIS) Over Time During Anethetic Maintenance | Before Extubation | 90.9 score on a scale | Standard Deviation 9.9 |
| BLM-240 O2 Group | Changes in Bispectral Index (BIS) Over Time During Anethetic Maintenance | Prior to start of inhalation | 49.8 score on a scale | Standard Deviation 12.6 |
| BLM-240 O2 Group | Changes in Bispectral Index (BIS) Over Time During Anethetic Maintenance | After Awakening | 87.4 score on a scale | Standard Deviation 11.2 |
| BLM-240 O2 Group | Changes in Bispectral Index (BIS) Over Time During Anethetic Maintenance | End of inhalation | 48.8 score on a scale | Standard Deviation 11.8 |
Secondary
End-Tidal Anesthetic Percent Concentrations Successfully Maintained Anesthesia
Successfully maintaining anesthesia is defined as keeping the patient in stable condition (systolic pressure 80 to \<150 mmHg and heart rate 50 to \<100bpm) without requiring rescue treatment or additional dose of opioid analgesics (\<=2 ug/kg/hr).If patient was found to have body movement, recall, or memory during anesthetic maintenance, data for such patient were to be excluded from summary statistic calculation.
Time frame: Day 1 [just before the start of inhalation of study drug, during anesthetic maintenance (every 5 minutes after the start of inhalation of study drug), at the end of inhalation of study drug, immediately after awakening, and just before extubation]
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BLM-240 Group | End-Tidal Anesthetic Percent Concentrations Successfully Maintained Anesthesia | 3.97 percentage | Standard Deviation 1.17 |
| BLM-240 N2O Group | End-Tidal Anesthetic Percent Concentrations Successfully Maintained Anesthesia | 3.69 percentage | Standard Deviation 1.06 |
| BLM-240 O2 Group | End-Tidal Anesthetic Percent Concentrations Successfully Maintained Anesthesia | 4.48 percentage | Standard Deviation 1.21 |
| Sevoflurane Group | End-Tidal Anesthetic Percent Concentrations Successfully Maintained Anesthesia | 1.30 percentage | Standard Deviation 0.39 |
Secondary
Number of Participants Requiring Rescue Medication Due to Arrhythmia
Rescue medication can include vasopressors and depressors.
Time frame: Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours)
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BLM-240 Group | Number of Participants Requiring Rescue Medication Due to Arrhythmia | 3 participants |
| BLM-240 N2O Group | Number of Participants Requiring Rescue Medication Due to Arrhythmia | 1 participants |
| BLM-240 O2 Group | Number of Participants Requiring Rescue Medication Due to Arrhythmia | 2 participants |
| Sevoflurane Group | Number of Participants Requiring Rescue Medication Due to Arrhythmia | 0 participants |
p-value: 1Fisher Exact
Secondary
Number of Participants Requiring Rescue Medication Due to Drop in Blood Pressure or Heart Rate
Rescue medication can include vasopressors and depressors.
Time frame: Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours)
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BLM-240 Group | Number of Participants Requiring Rescue Medication Due to Drop in Blood Pressure or Heart Rate | 40 participants |
| BLM-240 N2O Group | Number of Participants Requiring Rescue Medication Due to Drop in Blood Pressure or Heart Rate | 32 participants |
| BLM-240 O2 Group | Number of Participants Requiring Rescue Medication Due to Drop in Blood Pressure or Heart Rate | 8 participants |
| Sevoflurane Group | Number of Participants Requiring Rescue Medication Due to Drop in Blood Pressure or Heart Rate | 16 participants |
Secondary
Number of Participants Requiring Rescue Medication Due to Rise in Blood Pressure or Heart Rate
Rescue medication can include vasopressors and depressors.
Time frame: Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours)
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BLM-240 Group | Number of Participants Requiring Rescue Medication Due to Rise in Blood Pressure or Heart Rate | 6 participants |
| BLM-240 N2O Group | Number of Participants Requiring Rescue Medication Due to Rise in Blood Pressure or Heart Rate | 4 participants |
| BLM-240 O2 Group | Number of Participants Requiring Rescue Medication Due to Rise in Blood Pressure or Heart Rate | 2 participants |
| Sevoflurane Group | Number of Participants Requiring Rescue Medication Due to Rise in Blood Pressure or Heart Rate | 0 participants |
p-value: 0.3113Fisher Exact
Secondary
Range of End-Tidal Anesthetic Percent Concentrations During Anesthetic Maintenance
Measurement by infrared absorption spectrometry. The concentrations of BLM-240 and sevoflurane at the start of inhalation were set at 3% and 1%,respectively (by vaporizer dial setting). Concentrations are monitored to determine which levels keep the patient in stable condition without requiring rescue treatment.
Time frame: Day 1 [just before the start of inhalation of study drug, during anesthetic maintenance (every 5 minutes after the start of inhalation of study drug), at the end of inhalation of study drug, immediately after awakening, and just before extubation]
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BLM-240 Group | Range of End-Tidal Anesthetic Percent Concentrations During Anesthetic Maintenance | Low Range | 3 percentage |
| BLM-240 Group | Range of End-Tidal Anesthetic Percent Concentrations During Anesthetic Maintenance | High Range | 4 percentage |
| BLM-240 N2O Group | Range of End-Tidal Anesthetic Percent Concentrations During Anesthetic Maintenance | Low Range | 4 percentage |
| BLM-240 N2O Group | Range of End-Tidal Anesthetic Percent Concentrations During Anesthetic Maintenance | High Range | 5 percentage |
| BLM-240 O2 Group | Range of End-Tidal Anesthetic Percent Concentrations During Anesthetic Maintenance | Low Range | 1.2 percentage |
| BLM-240 O2 Group | Range of End-Tidal Anesthetic Percent Concentrations During Anesthetic Maintenance | High Range | 1.4 percentage |
Secondary
Range of Inspired Anesthetic Concentrations Below End-Tidal Anesthetic Percent Concentrations During Anesthetic Maintenance
Measurement by infrared absorption spectrometry. Ranges reflecting when concentrations were stable. The inspired concentration was adjusted depending on the patient's condition during anesthetic maintenance (gas flow rate: 2 to 6 L/min).
Time frame: Day 1 [just before the start of inhalation of study drug, during anesthetic maintenance (every 5 minutes after the start of inhalation of study drug), at the end of inhalation of study drug, and just before extubation]
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BLM-240 Group | Range of Inspired Anesthetic Concentrations Below End-Tidal Anesthetic Percent Concentrations During Anesthetic Maintenance | Low Range | 0.3 percentage |
| BLM-240 Group | Range of Inspired Anesthetic Concentrations Below End-Tidal Anesthetic Percent Concentrations During Anesthetic Maintenance | High Range | 0.5 percentage |
| BLM-240 N2O Group | Range of Inspired Anesthetic Concentrations Below End-Tidal Anesthetic Percent Concentrations During Anesthetic Maintenance | Low Range | 0.1 percentage |
| BLM-240 N2O Group | Range of Inspired Anesthetic Concentrations Below End-Tidal Anesthetic Percent Concentrations During Anesthetic Maintenance | High Range | 0.3 percentage |
Secondary
Time to Awakening
Time from the end of study drug inhalation. After the end of inhalation of the study drug, the investigator commanded the patient to open his/her eyes once every minute to check whether he/she awoke and recorded the time of awakening.
Time frame: Day 1 (Post-Surgery, from the end of study drug inhalation to awakening)
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BLM-240 Group | Time to Awakening | 6.8 minutes | Standard Deviation 4 |
| BLM-240 N2O Group | Time to Awakening | 7.2 minutes | Standard Deviation 3.7 |
| BLM-240 O2 Group | Time to Awakening | 6.2 minutes | Standard Deviation 4.6 |
| Sevoflurane Group | Time to Awakening | 10.4 minutes | Standard Deviation 5.5 |
p-value: 0.15t-test, 2 sided
Secondary
Time to Clear Consciousness
Clear consciousness means that patients responded to investigator's command for physical movement such as hold my finger tight.
Time frame: Day 1 (Post-Surgery, from awakening to before extubation)
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BLM-240 Group | Time to Clear Consciousness | 7.7 minutes | Standard Deviation 4.4 |
| BLM-240 N2O Group | Time to Clear Consciousness | 8.1 minutes | Standard Deviation 4.2 |
| BLM-240 O2 Group | Time to Clear Consciousness | 6.9 minutes | Standard Deviation 4.7 |
| Sevoflurane Group | Time to Clear Consciousness | 12.3 minutes | Standard Deviation 7.4 |
Secondary
Time to Reaching an Aldrete Score >=8 (Min)
Score includes a ranking of 0-2 (higher shows improvement) in activity, respiration, circulation, consciousness, and O2 saturation (SpO2). After extubation, the investigator observed the patient's condition every 5 minutes until the Aldrete score reached \>=8 and recorded the Aldrete scores at 5-minute intervals.
Time frame: Day 1 (Post-Surgery, after extubation)
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BLM-240 Group | Time to Reaching an Aldrete Score >=8 (Min) | 13.6 minutes | Standard Deviation 5.2 |
| BLM-240 N2O Group | Time to Reaching an Aldrete Score >=8 (Min) | 13.9 minutes | Standard Deviation 4.8 |
| BLM-240 O2 Group | Time to Reaching an Aldrete Score >=8 (Min) | 13.1 minutes | Standard Deviation 6 |
| Sevoflurane Group | Time to Reaching an Aldrete Score >=8 (Min) | 18.7 minutes | Standard Deviation 8.4 |
Secondary
Time to Stating Birth Date
After extubation, the investigator called and asked the patient to state the birth date once every minute and recorded the time the patient could state the birth date. Time from the end of study drug inhalation.
Time frame: Day 1 (Post-Surgery, after extubation)
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BLM-240 Group | Time to Stating Birth Date | 11.4 minutes | Standard Deviation 5.4 |
| BLM-240 N2O Group | Time to Stating Birth Date | 11.8 minutes | Standard Deviation 5.3 |
| BLM-240 O2 Group | Time to Stating Birth Date | 10.6 minutes | Standard Deviation 5.6 |
| Sevoflurane Group | Time to Stating Birth Date | 16.2 minutes | Standard Deviation 8.7 |
p-value: 0.0001t-test, 2 sided