Bispectral Index-guided Sedation for Flexible Bronchoscopy

This study has been completed.
Sponsor:
Information provided by:
Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier:
NCT00789815
First received: November 10, 2008
Last updated: April 1, 2010
Last verified: April 2010
  Purpose

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.


Condition Intervention Phase
Flexible Bronchoscopy
Device: Bispectral index guide propofol infusion
Drug: Clinical-judged midazolam administration
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Health Services Research
Official Title: Sedation for Flexible Bronchoscopy and Real Time Endobronchial Ultrasound -A Comparison Between Bispectral Index-guided Sedation and Conventional Sedation

Resource links provided by NLM:


Further study details as provided by Chang Gung Memorial Hospital:

Primary Outcome Measures:
  • The Number of Participants With Any Hypoxemia Event During Flexible Bronchoscopy [ Time Frame: From the time when bronchoscope introducing patients' nose or mouth to the time when bronchoscope leaving patients' nose or mouth ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: From the time when bronchoscope introducing patients' nose or mouth to the time when bronchoscope leaving patients' nose or mouth ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: After patients recovered orientation and before they leaved the scope room. ] [ Designated as safety issue: No ]
    The global tolerance of the entire procedure was evaluated on a 10-point verbal analogous scale (VAS, 0: no bother, 10: worst intolerable).


Secondary Outcome Measures:
  • The Number of Participants Causing Any Procedure Interference by the Patients' Movement During Flexible Bronchoscocopy [ Time Frame: From the time when bronchoscope introducing patients' nose or mouth to the time when bronchoscope leaving patients' nose or mouth ] [ Designated as safety issue: No ]
    "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

  • The Number of Participants Causing Any Procedure Interference by Cough [ Time Frame: From the time when bronchoscope introducing patients' nose or mouth to the time when bronchoscope leaving patients' nose or mouth ] [ Designated as safety issue: No ]
    "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 [ Time Frame: After the bronchoscope leaving patients' nose or mouth to the time patients returned orientation ] [ Designated as safety issue: Yes ]
    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

  • The Recovery Time to Ambulation [ Time Frame: After the bronchoscopy ] [ Designated as safety issue: Yes ]
    The recovery time to ambulation defined as the time between finishing flexible bronchoscopy to the moment when patients could walk without assistance.

  • Patients Willing Return if Repeated Bronchoscopy is Indicated. [ Time Frame: After patients recovered orientation and before they leaved the scope room. ] [ Designated as safety issue: No ]
    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.


Enrollment: 500
Study Start Date: April 2008
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Device: 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.

Other Name: BIS-guided profopol infusion
Active Comparator: 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
Drug: 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.

Other Name: Clinical-judged midazolam administration

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00789815

Locations
Taiwan
Division of Thoracic Medicine, Chang Gung Memorial Hospital
5. Fu-Hsing street.Gueishan Township, Taoyuan, Taiwan, 333
Sponsors and Collaborators
Chang Gung Memorial Hospital
Investigators
Principal Investigator: Ting-Yu Lin, MD Division of Thoracic Medicine, Chang Gung Memorial hospital
  More Information

No publications provided by Chang Gung Memorial Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ting-Yu Lin, Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier: NCT00789815     History of Changes
Other Study ID Numbers: 97-0257B
Study First Received: November 10, 2008
Results First Received: February 3, 2010
Last Updated: April 1, 2010
Health Authority: Taiwan: Institutional Review Board

Keywords provided by Chang Gung Memorial Hospital:
flexible bronchoscopy
sedation
bispectral index

Additional relevant MeSH terms:
Propofol
Midazolam
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Adjuvants, Anesthesia
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 01, 2014