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Bispectral Index-guided Sedation for Flexible Bronchoscopy

Sedation for Flexible Bronchoscopy and Real Time Endobronchial Ultrasound -A Comparison Between Bispectral Index-guided Sedation and Conventional Sedation

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00789815
Enrollment
500
Registered
2008-11-13
Start date
2008-04-30
Completion date
2009-09-30
Last updated
2017-08-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Flexible Bronchoscopy

Keywords

flexible bronchoscopy, sedation, bispectral index

Brief summary

With the advances of flexible bronchoscopy, like metallic stent, electrocautery and real time endobronchial ultrasound, the complexity and duration of procedures are increasing. So, adequate sedation and analgesia is important for both patients and bronchoscopist. Clinical-judged midazolam administration is the current standard. However, midazolam is difficult to titrated and the clinical observations are not reliable sedative indices. Propofol is titrated easily because of its unique pharmacokinetics. Bispectral index (BIS), a real time monitor of depth-of-sedation, has been applied in general anesthesia. We design a BIS-guided propofol sedation for bronchoscopy. Through the combination of advantages of propofol and BIS, we hope to provide patients a more tolerable and safety sedation for bronchoscopy.

Detailed description

It is well known that patients undergoing bronchoscopy could be less suffering and the procedures could be carried on more smoothly if the patients have adequate sedation and analgesia. The preferred sedative and analgesic drugs are Midazolam and opioid, like Alfentanil or Morphine, which were titrated according to physicians' judgment on patients' clinical responsiveness. However, due to the pharmacokinetic characteristic of midazolam while used in intravenous injection (onset time 4-6 minutes, effective time 2-4 hours), the effective onset time may be too slow for repeated injection while patients already suffered from the bronchoscopic procedure. It is also noted that when over-sedation occurred the side effects like apnea/hypopnea, hypoxemia, and hypotension could last from dozen minutes to few hours. Although events mentioned above could be handled properly under experienced medical staff, it is still very difficult to predict the oncoming events as the pharmacokinetic effect is variant individually. Ideally, it will be more safe and efficient, during invasive procedure like bronchoscope, if the sedative drug could be onset or vanish fast and the drug effect could be titrated with an objective device directly monitoring the depth of sedation or anesthesia. Propofol is a short-acting intravenous sedative agent used for the induction of general anesthesia for children and adults; maintenance of general anesthesia; and sedation in medical contexts, such as intensive care unit (ICU) sedation for intubated, mechanically ventilated adults, and in procedures such as colonoscopy. Its mechanism of action is uncertain, but it is postulated that its primary effect may be potentiation of the Gamma-Amino Butyric Acid-A receptor, possibly by slowing the channel closing time. It has a fast onset time (1\ 2 minutes) but a short working duration (8\ 10 minutes), which vanished fast after stop administration. Bispectral Index (BIS), an non-invasive neurophysiologic monitor instrument, can transform the electroencephalogram (EEG) and electromyography of the patient to a continual numeral, ranging from 0 to 99, which provides a direct and real-time sedative depth monitor. A BIS value of 0 equals EEG silence, near 100 is the expected value in a fully awake adult, and below70 indicated the patient lose explicit memory recall but still has the ability to maintain his own vital signs. In this study, we design a sedative technique for bronchoscopy, a BIS-guided propofol administration, to compare with the traditional sedative technique, clinical-judged midazolam administration. Through the combination of the advantages of unique pharmacokinetics of propofol and real time monitor of sedative level from BIS, we hope to provide patients undergoing bronchoscopy a more satisfied and safety sedative procedure.

Interventions

DEVICEBispectral index guide propofol infusion

Induction: Alfentanil: 5μg/kg slowly push. Propofol: 0.5-1.5mg/kg slowly push till BIS value 70. Maintenance: Propofol infusion (3\ 12 mg/kg/hour) to maintain BIS around 65\ 75. Alfentanil: 5μg/kg slowly push Q15min prn if severe cough.

DRUGClinical-judged midazolam administration

Induction: Alfentanil: 5μg/kg slowly push. Midazolam: 2 mg slowly push followed by increments of 2 mg/ 2min till OAA/S\* 2\ 3. Maintenance: Midazolam: 2 mg/ 2min prn to keep OAA/S\* 2\ 3 or if intolerance of procedure. Alfentanil as study arm. \*Observer's assessment of alertness/sedation (OAA/S): Class 5: Responds readily to name spoken in normal tone. Class 4: Lethargic response to name called in normal tone. Class 3: Responds only to name called loudly. Class 2: Responds only to shaking. Class 1: No response to shaking.

Sponsors

Chang Gung Memorial Hospital
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* Patients (\>18 years old) requiring elective flexible bronchoscopy or Real time endobronchial ultrasound with transbronchial needle aspiration.

Exclusion criteria

* American Society of Anesthesiologists classification of physical status 4 and 5, including hepatic or renal failure, severe obstructive sleep apnea and severe chronic obstructive pulmonary disease. * Significant Central nervous system disorders or other factors contributing to access consciousness difficultly. * Allergic history to study drugs. * A history of glaucoma in the midazolam arm.

Design outcomes

Primary

MeasureTime frameDescription
The Number of Participants With Any Hypoxemia Event During Flexible BronchoscopyFrom the time when bronchoscope introducing patients' nose or mouth to the time when bronchoscope leaving patients' nose or mouthThe hypoxemia event is defined as that when the oxyhemoglobin (SpO2) was less than 90% with any duration during the flexible bronchoscopy.
The Number of Participants With Any Hypotension Event During Flexible BronchoscopyFrom the time when bronchoscope introducing patients' nose or mouth to the time when bronchoscope leaving patients' nose or mouthThe event of hypotension: when the systolic blood pressure (SBP) was less than 90mmHg with any duration.
The Global Tolerance for Flexible Bronchoscopy by Verbal Analogus ScaleAfter patients recovered orientation and before they leaved the scope room.The global tolerance of the entire procedure was evaluated on a 10-point verbal analogous scale (VAS, 0: no bother, 10: worst intolerable).

Secondary

MeasureTime frameDescription
The Recovery Time to AmbulationAfter the bronchoscopyThe recovery time to ambulation defined as the time between finishing flexible bronchoscopy to the moment when patients could walk without assistance.
The Number of Participants Causing Any Procedure Interference by the Patients' Movement During Flexible BronchoscocopyFrom the time when bronchoscope introducing patients' nose or mouth to the time when bronchoscope leaving patients' nose or mouthProcedure interference by patients' movement was when the bronchoscopist had to stop the procedure temporarily and our assistant had to hold down the irritant patient
Patients Willing Return if Repeated Bronchoscopy is Indicated.After patients recovered orientation and before they leaved the scope room.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.
The Number of Participants Causing Any Procedure Interference by CoughFrom the time when bronchoscope introducing patients' nose or mouth to the time when bronchoscope leaving patients' nose or mouthProcedure 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.
The Recovery Time to OrientationAfter the bronchoscope leaving patients' nose or mouth to the time patients returned orientationThe 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

Countries

Taiwan

Participant flow

Recruitment details

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.

Pre-assignment details

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.

Participants by arm

ArmCount
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.
250
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
250
Total500

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyIntubation due to massive bleeding10
Overall StudyProtocol Violation61

Baseline characteristics

CharacteristicClinical-judged Midazolam AdministrationBIS-guided Propofol InfusionTotal
Age, Categorical
<=18 years
1 Participants0 Participants1 Participants
Age, Categorical
>=65 years
125 Participants106 Participants231 Participants
Age, Categorical
Between 18 and 65 years
124 Participants144 Participants268 Participants
Age, Continuous62.0 years
STANDARD_DEVIATION 14.7
59.9 years
STANDARD_DEVIATION 13.1
60.9 years
STANDARD_DEVIATION 14
Region of Enrollment
Taiwan
250 participants250 participants500 participants
Sex: Female, Male
Female
111 Participants102 Participants213 Participants
Sex: Female, Male
Male
139 Participants148 Participants287 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
115 / 250100 / 250
serious
Total, serious adverse events
2 / 2500 / 250

Outcome results

Primary

The Global Tolerance for Flexible Bronchoscopy by Verbal Analogus Scale

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

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

Population: Patients received intervention completely

ArmMeasureValue (MEDIAN)
BIS-guided Propofol InfusionThe Global Tolerance for Flexible Bronchoscopy by Verbal Analogus Scale0 units on a scale
Clinical-judged Midazolam AdministrationThe Global Tolerance for Flexible Bronchoscopy by Verbal Analogus Scale0 units on a scale
Comparison: The null hypothesis: the global tolerance of patients in study is worse than that in the control group.p-value: 0.05Wilcoxon (Mann-Whitney)
Primary

The Number of Participants With Any Hypotension Event During Flexible Bronchoscopy

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

Time frame: 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

ArmMeasureValue (NUMBER)
BIS-guided Propofol InfusionThe Number of Participants With Any Hypotension Event During Flexible Bronchoscopy18 participants
Clinical-judged Midazolam AdministrationThe Number of Participants With Any Hypotension Event During Flexible Bronchoscopy11 participants
Comparison: The null hypothesis: the incidence of hypotension during FB in patients of study group is higher than that in the control group.p-value: 0.05Chi-squared
Primary

The Number of Participants With Any Hypoxemia Event During Flexible Bronchoscopy

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

Time frame: 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.

ArmMeasureValue (NUMBER)
BIS-guided Propofol InfusionThe Number of Participants With Any Hypoxemia Event During Flexible Bronchoscopy97 participants
Clinical-judged Midazolam AdministrationThe Number of Participants With Any Hypoxemia Event During Flexible Bronchoscopy88 participants
Comparison: The null hypothesis: the incidence of hypoxemia occured during FB with BIS-guided propofol infusion is higher than that with clinical-judged midazolam administration.~Power calculation is described below.p-value: 0.05Chi-squared
Secondary

Patients Willing Return if Repeated Bronchoscopy is Indicated.

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.

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

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

ArmMeasureValue (NUMBER)
BIS-guided Propofol InfusionPatients Willing Return if Repeated Bronchoscopy is Indicated.171 participants
Clinical-judged Midazolam AdministrationPatients Willing Return if Repeated Bronchoscopy is Indicated.169 participants
p-value: 0.05Chi-squared
Secondary

The Number of Participants Causing Any Procedure Interference by Cough

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.

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

ArmMeasureValue (NUMBER)
BIS-guided Propofol InfusionThe Number of Participants Causing Any Procedure Interference by Cough73 participants
Clinical-judged Midazolam AdministrationThe Number of Participants Causing Any Procedure Interference by Cough110 participants
p-value: 0.05Chi-squared
Secondary

The Number of Participants Causing Any Procedure Interference by the Patients' Movement During Flexible Bronchoscocopy

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

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

ArmMeasureValue (NUMBER)
BIS-guided Propofol InfusionThe Number of Participants Causing Any Procedure Interference by the Patients' Movement During Flexible Bronchoscocopy33 participants
Clinical-judged Midazolam AdministrationThe Number of Participants Causing Any Procedure Interference by the Patients' Movement During Flexible Bronchoscocopy90 participants
p-value: 0.05Chi-squared
Secondary

The Recovery Time to Ambulation

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

Time frame: After the bronchoscopy

ArmMeasureValue (MEAN)Dispersion
BIS-guided Propofol InfusionThe Recovery Time to Ambulation30.0 MinutesStandard Deviation 18.2
Clinical-judged Midazolam AdministrationThe Recovery Time to Ambulation55.7 MinutesStandard Deviation 40.6
p-value: 0.05t-test, 2 sided
Secondary

The Recovery Time to 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

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

ArmMeasureValue (MEAN)Dispersion
BIS-guided Propofol InfusionThe Recovery Time to Orientation11.7 minutesStandard Deviation 10.2
Clinical-judged Midazolam AdministrationThe Recovery Time to Orientation30.0 minutesStandard Deviation 26.8
p-value: 0.05t-test, 2 sided

Source: ClinicalTrials.gov · Data processed: Mar 27, 2026