Flexible Bronchoscopy
Conditions
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
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.
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
Study design
Eligibility
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
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With Any Hypoxemia Event During Flexible Bronchoscopy | From the time when bronchoscope introducing patients' nose or mouth to the time when bronchoscope leaving patients' nose or mouth | The 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 Bronchoscopy | From the time when bronchoscope introducing patients' nose or mouth to the time when bronchoscope leaving patients' nose or mouth | The 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 Scale | After 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
| Measure | Time frame | Description |
|---|---|---|
| The Recovery Time to Ambulation | 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. |
| The Number of Participants Causing Any Procedure Interference by the Patients' Movement During Flexible Bronchoscocopy | 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 |
| 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 Cough | 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. |
| The Recovery Time to Orientation | 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 |
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
| Arm | Count |
|---|---|
| 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 |
| Total | 500 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Intubation due to massive bleeding | 1 | 0 |
| Overall Study | Protocol Violation | 6 | 1 |
Baseline characteristics
| Characteristic | Clinical-judged Midazolam Administration | BIS-guided Propofol Infusion | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 125 Participants | 106 Participants | 231 Participants |
| Age, Categorical Between 18 and 65 years | 124 Participants | 144 Participants | 268 Participants |
| Age, Continuous | 62.0 years STANDARD_DEVIATION 14.7 | 59.9 years STANDARD_DEVIATION 13.1 | 60.9 years STANDARD_DEVIATION 14 |
| Region of Enrollment Taiwan | 250 participants | 250 participants | 500 participants |
| Sex: Female, Male Female | 111 Participants | 102 Participants | 213 Participants |
| Sex: Female, Male Male | 139 Participants | 148 Participants | 287 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 115 / 250 | 100 / 250 |
| serious Total, serious adverse events | 2 / 250 | 0 / 250 |
Outcome results
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BIS-guided Propofol Infusion | The Global Tolerance for Flexible Bronchoscopy by Verbal Analogus Scale | 0 units on a scale |
| Clinical-judged Midazolam Administration | The Global Tolerance for Flexible Bronchoscopy by Verbal Analogus Scale | 0 units on a scale |
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIS-guided Propofol Infusion | The Number of Participants With Any Hypotension Event During Flexible Bronchoscopy | 18 participants |
| Clinical-judged Midazolam Administration | The Number of Participants With Any Hypotension Event During Flexible Bronchoscopy | 11 participants |
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIS-guided Propofol Infusion | The Number of Participants With Any Hypoxemia Event During Flexible Bronchoscopy | 97 participants |
| Clinical-judged Midazolam Administration | The Number of Participants With Any Hypoxemia Event During Flexible Bronchoscopy | 88 participants |
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIS-guided Propofol Infusion | Patients Willing Return if Repeated Bronchoscopy is Indicated. | 171 participants |
| Clinical-judged Midazolam Administration | Patients Willing Return if Repeated Bronchoscopy is Indicated. | 169 participants |
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIS-guided Propofol Infusion | The Number of Participants Causing Any Procedure Interference by Cough | 73 participants |
| Clinical-judged Midazolam Administration | The Number of Participants Causing Any Procedure Interference by Cough | 110 participants |
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIS-guided Propofol Infusion | The Number of Participants Causing Any Procedure Interference by the Patients' Movement During Flexible Bronchoscocopy | 33 participants |
| Clinical-judged Midazolam Administration | The Number of Participants Causing Any Procedure Interference by the Patients' Movement During Flexible Bronchoscocopy | 90 participants |
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIS-guided Propofol Infusion | The Recovery Time to Ambulation | 30.0 Minutes | Standard Deviation 18.2 |
| Clinical-judged Midazolam Administration | The Recovery Time to Ambulation | 55.7 Minutes | Standard Deviation 40.6 |
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIS-guided Propofol Infusion | The Recovery Time to Orientation | 11.7 minutes | Standard Deviation 10.2 |
| Clinical-judged Midazolam Administration | The Recovery Time to Orientation | 30.0 minutes | Standard Deviation 26.8 |