Bispectral Index-guided Sedation for Flexible Bronchoscopy

NCT ID: NCT00789815

Last Updated: 2017-08-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2009-09-30

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.

Conditions

Flexible Bronchoscopy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Bispectral index guide propofol infusion

Intervention Type: DEVICE

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.

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/2min until conscious sedation was achieved

Group Type: ACTIVE_COMPARATOR

Clinical-judged midazolam administration

Intervention Type: DRUG

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.

Interventions

Bispectral 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.

Intervention Type: DEVICE

Clinical-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.

Intervention Type: DRUG

Other Intervention Names

BIS-guided profopol infusion

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chang Gung Memorial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Chang Gung Memorial Hospital

Principal Investigators

Ting-Yu Lin, MD

Role: PRINCIPAL_INVESTIGATOR

Division of Thoracic Medicine, Chang Gung Memorial hospital

Locations

Division of Thoracic Medicine, Chang Gung Memorial Hospital

Taoyuan, , Taiwan

Countries

Taiwan

References

Lo YL, Lin TY, Fang YF, Wang TY, Chen HC, Chou CL, Chung FT, Kuo CH, Feng PH, Liu CY, Kuo HP. Feasibility of bispectral index-guided propofol infusion for flexible bronchoscopy sedation: a randomized controlled trial. PLoS One. 2011;6(11):e27769. doi: 10.1371/journal.pone.0027769. Epub 2011 Nov 23.

Reference Type: DERIVED

PMID: 22132138 (View on PubMed)

Other Identifiers

97-0257B

Identifier Type: -

Identifier Source: org_study_id