Trial Outcomes & Findings for Bispectral Index-guided Sedation for Flexible Bronchoscopy (NCT NCT00789815)

NCT ID: NCT00789815

Last Updated: 2017-08-08

Results Overview

The hypoxemia event is defined as that when the oxyhemoglobin (SpO2) was less than 90% with any duration during the flexible bronchoscopy.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 500 participants
• Primary outcome timeframe: From the time when bronchoscope introducing patients' nose or mouth to the time when bronchoscope leaving patients' nose or mouth
• Results posted on: 2017-08-08

Participant Flow

The investigator evaluate the inclusion and exclusion criteria of patients undergoing flexible bronchoscopy (FB) at the bronchoscopic room. If patients were eligible, investigator would explain the informed concent, the safety managements and the way of sedation and FB to patients.

If patients or family refused to join the study later or if the intravenous catheter was difficultly placed on the forearm, patients were excluded before assignment.

Participant milestones

Measure	BIS-guided Propofol Infusion In the study group, induction was started using alfentanil 4\~5μg/kg bolus following repeated propofol boluses (0.5\~1.5 mg/kg) until the BIS level reached 70. During maintenance, propofol infusion (3\~12 mg/kg/hour) was given using a syringe pump (Injectomat Agilia, Fresenius Kabi, France), which was titrated to keep the BIS level between 65 and 75.	Clinical-judged Midazolam Administration In the control group, induction was started using alfentanil 4\~5μg/kg bolus following 2 mg midazolam bolus. After 2 minutes, if the patient was not well sedated, midazolam boluses were repeat by increments of 2 mg/min until conscious sedation was achieved
Overall Study STARTED	250	250
Overall Study COMPLETED	243	249
Overall Study NOT COMPLETED	7	1

Reasons for withdrawal

Measure	BIS-guided Propofol Infusion In the study group, induction was started using alfentanil 4\~5μg/kg bolus following repeated propofol boluses (0.5\~1.5 mg/kg) until the BIS level reached 70. During maintenance, propofol infusion (3\~12 mg/kg/hour) was given using a syringe pump (Injectomat Agilia, Fresenius Kabi, France), which was titrated to keep the BIS level between 65 and 75.	Clinical-judged Midazolam Administration In the control group, induction was started using alfentanil 4\~5μg/kg bolus following 2 mg midazolam bolus. After 2 minutes, if the patient was not well sedated, midazolam boluses were repeat by increments of 2 mg/min until conscious sedation was achieved
Overall Study Protocol Violation	6	1
Overall Study Intubation due to massive bleeding	1	0

Baseline Characteristics

Bispectral Index-guided Sedation for Flexible Bronchoscopy

Baseline characteristics by cohort

Measure	BIS-guided Propofol Infusion n=250 Participants In the study group, induction was started using alfentanil 4\~5μg/kg bolus following repeated propofol boluses (0.5\~1.5 mg/kg) until the BIS level reached 70. During maintenance, propofol infusion (3\~12 mg/kg/hour) was given using a syringe pump (Injectomat Agilia, Fresenius Kabi, France), which was titrated to keep the BIS level between 65 and 75.	Clinical-judged Midazolam Administration n=250 Participants In the control group, induction was started using alfentanil 4\~5μg/kg bolus following 2 mg midazolam bolus. After 2 minutes, if the patient was not well sedated, midazolam boluses were repeat by increments of 2 mg/min until conscious sedation was achieved	Total n=500 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	144 Participants n=5 Participants	124 Participants n=7 Participants	268 Participants n=5 Participants
Age, Categorical >=65 years	106 Participants n=5 Participants	125 Participants n=7 Participants	231 Participants n=5 Participants
Age, Continuous	59.9 years STANDARD_DEVIATION 13.1 • n=5 Participants	62.0 years STANDARD_DEVIATION 14.7 • n=7 Participants	60.9 years STANDARD_DEVIATION 14.0 • n=5 Participants
Sex: Female, Male Female	102 Participants n=5 Participants	111 Participants n=7 Participants	213 Participants n=5 Participants
Sex: Female, Male Male	148 Participants n=5 Participants	139 Participants n=7 Participants	287 Participants n=5 Participants
Region of Enrollment Taiwan	250 participants n=5 Participants	250 participants n=7 Participants	500 participants n=5 Participants

PRIMARY outcome

Timeframe: From the time when bronchoscope introducing patients' nose or mouth to the time when bronchoscope leaving patients' nose or mouth

Population: Patients completed the whole intervention.

The hypoxemia event is defined as that when the oxyhemoglobin (SpO2) was less than 90% with any duration during the flexible bronchoscopy.

Outcome measures

Measure	BIS-guided Propofol Infusion n=243 Participants In the study group, induction was started using alfentanil 4\~5μg/kg bolus following repeated propofol boluses (0.5\~1.5 mg/kg) until the BIS level reached 70. During maintenance, propofol infusion (3\~12 mg/kg/hour) was given using a syringe pump (Injectomat Agilia, Fresenius Kabi, France), which was titrated to keep the BIS level between 65 and 75.	Clinical-judged Midazolam Administration n=249 Participants In the control group, induction was started using alfentanil 4\~5μg/kg bolus following 2 mg midazolam bolus. After 2 minutes, if the patient was not well sedated, midazolam boluses were repeat by increments of 2 mg/min until conscious sedation was achieved
The Number of Participants With Any Hypoxemia Event During Flexible Bronchoscopy	97 participants	88 participants

PRIMARY outcome

Timeframe: From the time when bronchoscope introducing patients' nose or mouth to the time when bronchoscope leaving patients' nose or mouth

Population: patients completed the whole intervention

The event of hypotension: when the systolic blood pressure (SBP) was less than 90mmHg with any duration.

Outcome measures

Measure	BIS-guided Propofol Infusion n=243 Participants In the study group, induction was started using alfentanil 4\~5μg/kg bolus following repeated propofol boluses (0.5\~1.5 mg/kg) until the BIS level reached 70. During maintenance, propofol infusion (3\~12 mg/kg/hour) was given using a syringe pump (Injectomat Agilia, Fresenius Kabi, France), which was titrated to keep the BIS level between 65 and 75.	Clinical-judged Midazolam Administration n=249 Participants In the control group, induction was started using alfentanil 4\~5μg/kg bolus following 2 mg midazolam bolus. After 2 minutes, if the patient was not well sedated, midazolam boluses were repeat by increments of 2 mg/min until conscious sedation was achieved
The Number of Participants With Any Hypotension Event During Flexible Bronchoscopy	18 participants	11 participants

PRIMARY outcome

Timeframe: After patients recovered orientation and before they leaved the scope room.

Population: Patients received intervention completely

The global tolerance of the entire procedure was evaluated on a 10-point verbal analogous scale (VAS, 0: no bother, 10: worst intolerable).

Outcome measures

Measure	BIS-guided Propofol Infusion n=243 Participants In the study group, induction was started using alfentanil 4\~5μg/kg bolus following repeated propofol boluses (0.5\~1.5 mg/kg) until the BIS level reached 70. During maintenance, propofol infusion (3\~12 mg/kg/hour) was given using a syringe pump (Injectomat Agilia, Fresenius Kabi, France), which was titrated to keep the BIS level between 65 and 75.	Clinical-judged Midazolam Administration n=249 Participants In the control group, induction was started using alfentanil 4\~5μg/kg bolus following 2 mg midazolam bolus. After 2 minutes, if the patient was not well sedated, midazolam boluses were repeat by increments of 2 mg/min until conscious sedation was achieved
The Global Tolerance for Flexible Bronchoscopy by Verbal Analogus Scale	0 units on a scale Interval 0.0 to 10.0	0 units on a scale Interval 0.0 to 10.0

SECONDARY outcome

Timeframe: From the time when bronchoscope introducing patients' nose or mouth to the time when bronchoscope leaving patients' nose or mouth

"Procedure interference by patients' movement" was when the bronchoscopist had to stop the procedure temporarily and our assistant had to hold down the irritant patient

Outcome measures

Measure	BIS-guided Propofol Infusion n=243 Participants In the study group, induction was started using alfentanil 4\~5μg/kg bolus following repeated propofol boluses (0.5\~1.5 mg/kg) until the BIS level reached 70. During maintenance, propofol infusion (3\~12 mg/kg/hour) was given using a syringe pump (Injectomat Agilia, Fresenius Kabi, France), which was titrated to keep the BIS level between 65 and 75.	Clinical-judged Midazolam Administration n=249 Participants In the control group, induction was started using alfentanil 4\~5μg/kg bolus following 2 mg midazolam bolus. After 2 minutes, if the patient was not well sedated, midazolam boluses were repeat by increments of 2 mg/min until conscious sedation was achieved
The Number of Participants Causing Any Procedure Interference by the Patients' Movement During Flexible Bronchoscocopy	33 participants	90 participants

SECONDARY outcome

Timeframe: From the time when bronchoscope introducing patients' nose or mouth to the time when bronchoscope leaving patients' nose or mouth

"Procedure interference by cough" was when the bronchoscopist had to stop the procedure temporarily and additional xylocaine spray and/or alfentanil had to be given to stop the cough.

Outcome measures

Measure	BIS-guided Propofol Infusion n=243 Participants In the study group, induction was started using alfentanil 4\~5μg/kg bolus following repeated propofol boluses (0.5\~1.5 mg/kg) until the BIS level reached 70. During maintenance, propofol infusion (3\~12 mg/kg/hour) was given using a syringe pump (Injectomat Agilia, Fresenius Kabi, France), which was titrated to keep the BIS level between 65 and 75.	Clinical-judged Midazolam Administration n=249 Participants In the control group, induction was started using alfentanil 4\~5μg/kg bolus following 2 mg midazolam bolus. After 2 minutes, if the patient was not well sedated, midazolam boluses were repeat by increments of 2 mg/min until conscious sedation was achieved
The Number of Participants Causing Any Procedure Interference by Cough	73 participants	110 participants

SECONDARY outcome

Timeframe: After the bronchoscope leaving patients' nose or mouth to the time patients returned orientation

The time to orientation defined as the time between finishing flexible bronchoscopy to the moment when patients could open their eyes spontaneously, could recall their date of birth, and perform a finger-nose test correctly

Outcome measures

Measure	BIS-guided Propofol Infusion n=243 Participants In the study group, induction was started using alfentanil 4\~5μg/kg bolus following repeated propofol boluses (0.5\~1.5 mg/kg) until the BIS level reached 70. During maintenance, propofol infusion (3\~12 mg/kg/hour) was given using a syringe pump (Injectomat Agilia, Fresenius Kabi, France), which was titrated to keep the BIS level between 65 and 75.	Clinical-judged Midazolam Administration n=249 Participants In the control group, induction was started using alfentanil 4\~5μg/kg bolus following 2 mg midazolam bolus. After 2 minutes, if the patient was not well sedated, midazolam boluses were repeat by increments of 2 mg/min until conscious sedation was achieved
The Recovery Time to Orientation	11.7 minutes Standard Deviation 10.2	30.0 minutes Standard Deviation 26.8

SECONDARY outcome

Timeframe: After the bronchoscopy

The recovery time to ambulation defined as the time between finishing flexible bronchoscopy to the moment when patients could walk without assistance.

Outcome measures

Measure	BIS-guided Propofol Infusion n=243 Participants In the study group, induction was started using alfentanil 4\~5μg/kg bolus following repeated propofol boluses (0.5\~1.5 mg/kg) until the BIS level reached 70. During maintenance, propofol infusion (3\~12 mg/kg/hour) was given using a syringe pump (Injectomat Agilia, Fresenius Kabi, France), which was titrated to keep the BIS level between 65 and 75.	Clinical-judged Midazolam Administration n=249 Participants In the control group, induction was started using alfentanil 4\~5μg/kg bolus following 2 mg midazolam bolus. After 2 minutes, if the patient was not well sedated, midazolam boluses were repeat by increments of 2 mg/min until conscious sedation was achieved
The Recovery Time to Ambulation	30.0 Minutes Standard Deviation 18.2	55.7 Minutes Standard Deviation 40.6

SECONDARY outcome

Timeframe: After patients recovered orientation and before they leaved the scope room.

Population: Patients who answered the question in the questionnaire after bronchoscopy

Patients were asked their willingness to return for another FB if needed by means of a five-point scale (definitely not, probably not, unsure, probably would, and definitely would return). Both "probably would", and "definitely would return" were defined as patients agreed to return.

Outcome measures

Measure	BIS-guided Propofol Infusion n=221 Participants In the study group, induction was started using alfentanil 4\~5μg/kg bolus following repeated propofol boluses (0.5\~1.5 mg/kg) until the BIS level reached 70. During maintenance, propofol infusion (3\~12 mg/kg/hour) was given using a syringe pump (Injectomat Agilia, Fresenius Kabi, France), which was titrated to keep the BIS level between 65 and 75.	Clinical-judged Midazolam Administration n=226 Participants In the control group, induction was started using alfentanil 4\~5μg/kg bolus following 2 mg midazolam bolus. After 2 minutes, if the patient was not well sedated, midazolam boluses were repeat by increments of 2 mg/min until conscious sedation was achieved
Patients Willing Return if Repeated Bronchoscopy is Indicated.	171 participants	169 participants

Adverse Events

BIS-guided Propofol Infusion

Serious events: 2 serious events

Other events: 115 other events

Deaths: 0 deaths

Clinical-judged Midazolam Administration

Serious events: 0 serious events

Other events: 100 other events

Deaths: 0 deaths

Serious adverse events

Measure	BIS-guided Propofol Infusion n=250 participants at risk In the study group, induction was started using alfentanil 4\~5μg/kg bolus following repeated propofol boluses (0.5\~1.5 mg/kg) until the BIS level reached 70. During maintenance, propofol infusion (3\~12 mg/kg/hour) was given using a syringe pump (Injectomat Agilia, Fresenius Kabi, France), which was titrated to keep the BIS level between 65 and 75.	Clinical-judged Midazolam Administration n=250 participants at risk In the control group, induction was started using alfentanil 4\~5μg/kg bolus following 2 mg midazolam bolus. After 2 minutes, if the patient was not well sedated, midazolam boluses were repeat by increments of 2 mg/min until conscious sedation was achieved
Respiratory, thoracic and mediastinal disorders Intubation due to massive bleeding after bronchial biopsy	0.40% 1/250 • Number of events 1 • During bronchoscopy and after recovery within 3 days. The adverse events is the primary outcome of this study. So, regular assessment would be done during bronchoscopy and after recovery. In this study, all adverse events recovered spontaneously or after proper managements.	0.00% 0/250 • During bronchoscopy and after recovery within 3 days. The adverse events is the primary outcome of this study. So, regular assessment would be done during bronchoscopy and after recovery. In this study, all adverse events recovered spontaneously or after proper managements.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.40% 1/250 • Number of events 1 • During bronchoscopy and after recovery within 3 days. The adverse events is the primary outcome of this study. So, regular assessment would be done during bronchoscopy and after recovery. In this study, all adverse events recovered spontaneously or after proper managements.	0.00% 0/250 • During bronchoscopy and after recovery within 3 days. The adverse events is the primary outcome of this study. So, regular assessment would be done during bronchoscopy and after recovery. In this study, all adverse events recovered spontaneously or after proper managements.

Other adverse events

Measure	BIS-guided Propofol Infusion n=250 participants at risk In the study group, induction was started using alfentanil 4\~5μg/kg bolus following repeated propofol boluses (0.5\~1.5 mg/kg) until the BIS level reached 70. During maintenance, propofol infusion (3\~12 mg/kg/hour) was given using a syringe pump (Injectomat Agilia, Fresenius Kabi, France), which was titrated to keep the BIS level between 65 and 75.	Clinical-judged Midazolam Administration n=250 participants at risk In the control group, induction was started using alfentanil 4\~5μg/kg bolus following 2 mg midazolam bolus. After 2 minutes, if the patient was not well sedated, midazolam boluses were repeat by increments of 2 mg/min until conscious sedation was achieved
Respiratory, thoracic and mediastinal disorders Hypoxemia during flexible bronchoscopy	38.8% 97/250 • Number of events 131 • During bronchoscopy and after recovery within 3 days. The adverse events is the primary outcome of this study. So, regular assessment would be done during bronchoscopy and after recovery. In this study, all adverse events recovered spontaneously or after proper managements.	35.6% 89/250 • Number of events 131 • During bronchoscopy and after recovery within 3 days. The adverse events is the primary outcome of this study. So, regular assessment would be done during bronchoscopy and after recovery. In this study, all adverse events recovered spontaneously or after proper managements.
Cardiac disorders Hypotension during flexible bronchoscopy	7.2% 18/250 • Number of events 37 • During bronchoscopy and after recovery within 3 days. The adverse events is the primary outcome of this study. So, regular assessment would be done during bronchoscopy and after recovery. In this study, all adverse events recovered spontaneously or after proper managements.	4.4% 11/250 • Number of events 27 • During bronchoscopy and after recovery within 3 days. The adverse events is the primary outcome of this study. So, regular assessment would be done during bronchoscopy and after recovery. In this study, all adverse events recovered spontaneously or after proper managements.

Additional Information

Ting-Yu Lin

Chung Gung Memorial Hospital

Phone: 886 3 3281200

Email: yuebaoyuebao@yahoo.com.tw

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place