Clinical trial NCT00789815
Conditions: Flexible Bronchoscopy
Keywords: flexible bronchoscopy sedation bispectral index
Sponsor: Chang Gung Memorial Hospital
Start date: 2008-04-01; Completion date: 2009-09-01
Enrollment: 500 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: 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 2: 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
Interventions: intervention 1: Bispectral index guide propofol infusion intervention 2: Clinical-judged midazolam administration
Intervention descriptions: intervention 1: 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 2: 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.

Protocol documents: