Target-Controlled Infusion of Propofol for Flexible Bronchoscopy Sedation

Target-Controlled Infusion of Propofol for Flexible Bronchoscopy Sedation: Determining the Optimal Titrating Regimen

Flexible bronchoscopy (FB) sedation requires keeping sedative level in a narrow window to prevent over or under sedation. Sedative drug titration according to subjective adjustment by individual physician may cause unsteady drug concentration. Target controlled infusion (TCI) has been provided a precise pharmacokinetic control of propofol, direct control the effect side, (eg. Brain) concentration (Ce), and been applied in surgical anesthesia and variable procedure sedation. We designed this pilot study to evaluate the optimal regimen of TCI in FB sedation.

Study Overview

• Status: Terminated
• Conditions: Flexible Bronchoscopy
• Intervention / Treatment: Procedure: TCI titration by different Cet.

Detailed Description

Propofol is ideal for bronchoscopy sedation because of its fast onset and quick recovery effect. Our research and reports from different investigators demonstrate that patients received propofol sedation recover fast with excellent satisfaction for bronchoscopy. However, the amount of propofol for induction and maintenance is calculated simply by patient's body weight and physicians' experience. For those non-anesthesiologists, who perform sedative work outside the operating room, and inexperienced anesthesiologist without fully considering the individual pharmacokinetic and pharmacodynamic differences may generate unstable drug plasma concentration and increase cardio-respiration suppression. Therefore, a manner which can assess and measure objectively individual pharmacokinetic differences may improve the sedative quality and decrease the complication rate.

A model called "Target-controlled infusion"(TCI), built from massive pharmacokinetic samples of propofol, could now give precise pharmacokinetic control. Several pharmacokinetic models built-in in TCI, includes the Schnider model which use concentration of effect site (Ce, the propofol concentration in the brain) as the sedative guide. The model integrates individual variants of age, height, weight and gender to calculate the infusion profile to achieve predetermined steady "target effect site concentration" (Cet). Because of the unique consideration of individual pharmacokinetic variants and Ce targeting, TCI provides predictable sedative level and is suitable for procedures requiring narrowing therapeutic level. Beside general anesthesia, TCI has been applied in breast biopsy, upper gastrointestinal endoscopic ultrasound and endoscopic retrograde cholangiopancreatography at outpatient clinic. According to these evidences, there is potential role of TCI in bronchoscopic sedation.

Based on current evidence and our experience, we design this study to evaluate the optimal regimen for induction and procedure during bronchoscopy. We hope this study could provide the more safety and efficient bronchoscopic sedation for patients and physicians.

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taoyuan, Taiwan, 33305
    • Department of Thoracic Medicine, Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients (18 years old or more) required elective flexible bronchoscopy and sedation.

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.
• Mallampati score 4 or 5.
• Significant Central nervous system disorders or other factors contributing to access consciousness difficultly.
• Men with body mass index(BMI) large than 42，Females with BMI large than 35.
• Allergic history to study drugs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Titration by target effect site concentration (Cet) 0.5μg/ml; The investigator will titrate the Cet to keep stable vital signs and sedative level during the flexible bronchoscopy. The criteria for titration is descried in the intervention.	Procedure: TCI titration by different Cet.; Induction: After topical xylocaine and alfentanil 5μg/kg iv 1 minute before, Cet 2.0μg/ml is started on the TCI pump ('Vial" Injectomat TIVA Agilia syringe infusion pump, Fresenius Kabi, France). The sedative level will be accessed by sedation scale "OAA/S" every 30 seconds till OAA/S ≦3(Responds only to name called loudly). The current Ce will be set as the maintenance Cet. If desired OAA/S is not achieved after reaching 2.0μg/ml,Cet will be increased every 90 seconds by the regimens be assigned until OAA/S ≦3. The current Ce will be set as the maintenance Cet. Maintenance: The Cet will be increased according to the assigned regimens if: Patients become irritant and interfere procedures.; Patients open eyes or talk to express uncomfortable. The Cet will be decreased if: Systolic blood pressure is less than 90mmHg;; Mean arterial blood pressure is less than 65mmHg;; Oxyhemoglobin saturation is less than 90 % with any duration.
Active Comparator: Titration by Cet 0.2μg/ml; The investigator will titrate the Cet to keep stable vital signs and sedative level during the flexible bronchoscopy. The criteria for titration is descried in the intervention.	Procedure: TCI titration by different Cet.; Induction: After topical xylocaine and alfentanil 5μg/kg iv 1 minute before, Cet 2.0μg/ml is started on the TCI pump ('Vial" Injectomat TIVA Agilia syringe infusion pump, Fresenius Kabi, France). The sedative level will be accessed by sedation scale "OAA/S" every 30 seconds till OAA/S ≦3(Responds only to name called loudly). The current Ce will be set as the maintenance Cet. If desired OAA/S is not achieved after reaching 2.0μg/ml,Cet will be increased every 90 seconds by the regimens be assigned until OAA/S ≦3. The current Ce will be set as the maintenance Cet. Maintenance: The Cet will be increased according to the assigned regimens if: Patients become irritant and interfere procedures.; Patients open eyes or talk to express uncomfortable. The Cet will be decreased if: Systolic blood pressure is less than 90mmHg;; Mean arterial blood pressure is less than 65mmHg;; Oxyhemoglobin saturation is less than 90 % with any duration.
Active Comparator: Titration by Cet 0.1μg/ml; The investigator will titrate the Cet to keep stable vital signs and sedative level during the flexible bronchoscopy. The criteria for titration is descried in the intervention.	Procedure: TCI titration by different Cet.; Induction: After topical xylocaine and alfentanil 5μg/kg iv 1 minute before, Cet 2.0μg/ml is started on the TCI pump ('Vial" Injectomat TIVA Agilia syringe infusion pump, Fresenius Kabi, France). The sedative level will be accessed by sedation scale "OAA/S" every 30 seconds till OAA/S ≦3(Responds only to name called loudly). The current Ce will be set as the maintenance Cet. If desired OAA/S is not achieved after reaching 2.0μg/ml,Cet will be increased every 90 seconds by the regimens be assigned until OAA/S ≦3. The current Ce will be set as the maintenance Cet. Maintenance: The Cet will be increased according to the assigned regimens if: Patients become irritant and interfere procedures.; Patients open eyes or talk to express uncomfortable. The Cet will be decreased if: Systolic blood pressure is less than 90mmHg;; Mean arterial blood pressure is less than 65mmHg;; Oxyhemoglobin saturation is less than 90 % with any duration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Patients With Hypoxemia During Flexible Bronchoscopy	Hypoxemia is defined as: Oxyhemoglobin saturation (SPO2) is less than 90 % with any duration	During sedative induction and bronchoscopy
The Number of Changes in Target Effect Site Concentration During Flexible Bronchoscopy	The investigator will titrate the target effect site concentration (Cet) during bronchoscopy according to protocol to keep stable vital signs and sedative levels. The numbers of adjustment will be recorded to show which regimen required less adjustment to keep stable sedative levels and vital signs.	During sedative induction and bronchoscopy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Recovery Time to Orientation	The recovery time to orientation was defined as the time between finishing bronchoscopy to the time when the patients could spontaneously open their eyes, recall their date of birth, and correctly perform finger-nose test.	after bronchosocpy
The Total Doses of Propofol During Induction and Overall Procedures	The dosses of propofol used during induction and overall flexible bronchoscopy will be recored from the screen of the TCI pump.	after bronchoscopy
The Cooperation of Patients From the View of Bronchoscopists	After the bronchoscopy, the bronchoscopist will be asked by 10-point Verbal Analogus Scale (0: the best cooperation, 10: the worst cooperation) to express how they fell about the cooperation of patients undergoing the bronchoscopy.	After bronchoscopy
The Global Tolerance for Flexible Bronchoscopy	After the recovery, patients will be asked about the tolerance of bronchoscopy performed to them by 10-point Verbal Analogus Scale (0: best tolerance, 10: worst tolerance)	After recovery

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Investigators: Principal Investigator: Ting-Yu Lin, MD, Department of Thoracic Medicine, Chang Gung Memorial Hospital

Publications and helpful links

General Publications

• Fanti L, Agostoni M, Arcidiacono PG, Albertin A, Strini G, Carrara S, Guslandi M, Torri G, Testoni PA. Target-controlled infusion during monitored anesthesia care in patients undergoing EUS: propofol alone versus midazolam plus propofol. A prospective double-blind randomised controlled trial. Dig Liver Dis. 2007 Jan;39(1):81-6. doi: 10.1016/j.dld.2006.09.004. Epub 2006 Oct 16.
• Lin TY, Lo YL, Hsieh CH, Ni YL, Wang TY, Lin HC, Wang CH, Yu CT, Kuo HP. The potential regimen of target-controlled infusion of propofol in flexible bronchoscopy sedation: a randomized controlled trial. PLoS One. 2013 Apr 24;8(4):e62744. doi: 10.1371/journal.pone.0062744. Print 2013.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: April 7, 2010
• First Submitted That Met QC Criteria: April 8, 2010
• First Posted (Estimate): April 12, 2010

Study Record Updates

• Last Update Posted (Estimate): December 8, 2011
• Last Update Submitted That Met QC Criteria: November 5, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Keywords: propofol; Target-controlled infusion,; bronchoscopy,; sedation,
• Other Study ID Numbers: 98-3441A3