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

Bispectral Index-guided Sedation for Flexible Bronchoscopy

Sponsors

Lead sponsor: Chang Gung Memorial Hospital

Source Chang Gung Memorial Hospital
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.

Overall Status Completed
Start Date April 2008
Completion Date September 2009
Primary Completion Date September 2009
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
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 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 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 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 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 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 Global Tolerance for Flexible Bronchoscopy by Verbal Analogus Scale After patients recovered orientation and before they leaved the scope room.
The Global Tolerance for Flexible Bronchoscopy by Verbal Analogus Scale After patients recovered orientation and before they leaved the scope room.
The Global Tolerance for Flexible Bronchoscopy by Verbal Analogus Scale After patients recovered orientation and before they leaved the scope room.
Secondary Outcome
Measure Time Frame
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
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
The Recovery Time to Orientation After the bronchoscope leaving patients' nose or mouth to the time patients returned orientation
The Recovery Time to Ambulation After the bronchoscopy
Patients Willing Return if Repeated Bronchoscopy is Indicated. After patients recovered orientation and before they leaved the scope room.
Enrollment 500
Condition
Intervention

Intervention type: Device

Intervention name: Bispectral index guide propofol infusion

Description: 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.

Arm group label: BIS-guided propofol infusion

Other name: BIS-guided profopol infusion

Intervention type: Drug

Intervention name: Clinical-judged midazolam administration

Description: 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.

Arm group label: Clinical-judged midazolam administration

Eligibility

Criteria:

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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Ting-Yu Lin, MD Principal Investigator Division of Thoracic Medicine, Chang Gung Memorial hospital
Location
facility
Division of Thoracic Medicine, Chang Gung Memorial Hospital
Location Countries

Taiwan

Verification Date

April 2010

Responsible Party

Name title: Ting-Yu Lin

Organization: Chang Gung Memorial Hospital

Keywords
Has Expanded Access No
Number Of Arms 2
Arm Group

Arm group label: BIS-guided propofol infusion

Arm group type: Active Comparator

Description: 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.

Arm group label: Clinical-judged midazolam administration

Arm group type: Active Comparator

Description: 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/2min until conscious sedation was achieved

Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Health Services Research

Masking: None (Open Label)

Source: ClinicalTrials.gov