Propofol vs Propofol + Benzo/Opiates in High Risk Group

September 8, 2016 updated by: Washington University School of Medicine

Incidence of Sedation Related Complications With Propofol Alone Versus Propofol With Benzodiazepines and Opiates in a High Risk Group Undergoing Advanced Endoscopic Procedures: A Randomized Controlled Trial

This will be a randomized controlled trial that compares the rates of sedation related complications in high risk patients (ASA greater or equal to 3, BMI greater or equal to 30, those at risk for OSA) undergoing advanced endoscopy procedures with propofol alone compared to propofol in combination with benzodiazepines and opioids.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The use of propofol (2,6-di-isopropofol) for sedation during endoscopic procedures has increased in recent years primarily because of its favorable pharmacokinetic profile compared with traditional endoscopic sedation with benzodiazepines and opioids. Propofol has a rapid onset of action (30-45 sec) and short duration of effect (4-8 min). There also are data to support the safe use of propofol for advanced endoscopic procedures such as endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS).

There is limited information on the incidence of sedation related complications during advanced endoscopy. Prior studies were limited by controlled patient populations at low risk of developing sedation related cardiopulmonary complications. In a recent study, we defined the frequency of sedation related adverse events including the rate of airway modifications (AMs) with propofol use during advanced endoscopy. From a total of 799 patients, AMs were required in 14.4% of patients, hypoxemia in 12.8%, hypotension in 0.5% and premature termination in 0.6% of the patients. In addition, body mass index (BMI), male sex and American Society of Anesthesiologists (ASA) class of 3 or higher were independent predictors of AMs. Similarly, Wehrmann and Riphaus identified ASA class of 3 or higher, total propofol dose, history of alcohol use and having an emergency endoscopy as independent factors for sedation related complications in patients undergoing advanced procedures.

Given the alarming rates of obesity in the United States, it is believed that the prevalence of obstructive sleep apnea (OSA) may be 10% or higher and in obese adults these numbers could be as high as 25%. Using a previously validated screening tool for OSA [STOP-BANG (SB)], we reported a prevalence rate of patients at risk for OSA of 43.3% in patients undergoing advanced endoscopy procedures. Patients at risk for OSA with a positive SB score (score ≥ 3 of 8) had a higher rate of AMs (20% vs. 6.1%, adjusted relative risk 1.7) and frequency of hypoxemia (12% vs. 5.2%, adjusted relative risk 1.63) compared to those at low risk for OSA. Thus, based on the available data, it appears that ASA class 3 or higher, high BMI, and patients at risk for OSA are factors that place patients undergoing advanced endoscopy procedures at high risk for sedation related complications including airway modifications.

The optimal method for achieving deep sedation in this high risk group of patients is unclear. Propofol may accentuate airway collapse as patients become unresponsive to verbal stimulation (deep sedation). Recent studies suggest that propofol with midazolam and/or opioids may be synergistic in action and therefore the combined application of these drugs may permit smaller doses of each to be used and potentially lead to a reduction in risk of complications and in the dose of propofol needed while retaining the individual advantages of each compound. There is limited data evaluating the synergistic effect of propofol with midazolam and opioids in patients undergoing advanced endoscopy procedures. Ong and colleagues in a randomized controlled trial compared patient sedation and tolerance during ERCP using propofol alone or midazolam, ketamine and pentazocine (sedato-analgesic cocktail) for induction along with propofol for maintenance. Patient tolerance as assessed by visual analog scales by endoscopist and anesthetist were higher in the combination group. Paspatis et al reported higher dosage of intravenous propofol required in patients being sedated with propofol alone compared with that required in patients receiving oral dose of midazolam with propofol for ERCP procedures. In addition, the patients' anxiety levels before the procedure were lower in the combination group. The mean percentage decline in the oxygen saturation during the procedure was significantly greater in propofol alone group. However, these studies excluded patients deemed to be at a high risk for sedation related complications. Patients with ASA class 3 or higher were excluded, the mean BMI was less than 25, and included only patients at average risk for complications associated with sedation.

The significance of synergistic sedation in patients undergoing advanced endoscopy procedures in the high risk patients is unclear. The overall risk of sedation related complications is thought to be higher compared to standard endoscopy due to longer procedure times and the need for relatively deeper levels of sedation.

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Ability to provide informed consent
  • Age greater than or equal to 18 years

  • Presence of at least 1 of the following criteria:

    1. ASA class 3 or higher
    2. BMI of 30 or greater
    3. At risk for OSA (score of 3 or greater on the STOP-BANG screening tool)

Exclusion Criteria:

  • drug allergy to Propofol, Benzodiazepines, or Opioids
  • patients who received Benzodiazepines or Opioids within 24 hours of the procedure

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Propofol+Benzo/Opioids

If the patient is randomized into this arm the recommended Versed and Fentanyl doses are standardized:

  1. Recommended Versed:

    a. Prior to intubation

    • patient is < 50 kg = 1 mg Versed
    • patient is 50-75 kg = 1.5 mg Versed
    • patient is > 75 kg = 2 mg Versed

  2. Recommended Fentanyl

    1. Prior to intubation = 0.5 ug/kg
    2. Total procedural dose = 1 ug/kg
Drug: Propofol+Benzo/Opioids

  1. Recommended Versed:

    a. Prior to intubation

    • patient is < 50 kg = 1 mg Versed
    • patient is 50-75 kg = 1.5 mg Versed
    • patient is > 75 kg = 2 mg Versed

  2. Recommended Fentanyl

    1. Prior to intubation = 0.5 ug/kg
    2. Total procedural dose = 1 ug/kg
Other Names:
  • Versed
  • Fentanyl
  • Midazolam
  • Opioid
  • Benzodiazepine
Active Comparator: Propofol Alone

The patients randomized into the sedation with propofol alone are able to cross over if they are unable to be successfully sedated under propofol alone. The the recommended doses before considering crossover are standardized:

  • Induction Dose: 2-2.5 mg/kg
  • Maintenance Dose: 0.1-0.2 mg/kg/min
Drug: Propofol Alone

Recommended Propofol doses before considering crossover:

  • Induction: 2-2.5 mg/kg
  • Maintenance: 0.1-0.2 mg/kg/min
Other Names:
  • Diprivan
  • Propofol
  • 2,6-di-isopropofol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Experience Airway Maneuvers
Time Frame: One day (during procedure)
In high risk patients (meeting at least of 1 of 3 criteria: ASA ≥ 3, BMI ≥ 30, those at risk for OSA) undergoing advanced endoscopy procedures, compare the number of participants who experience airway maneuvers (AMs) when sedated with propofol alone versus propofol in combination with benzodiazepines and opioids.
One day (during procedure)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Experience Other Sedation Related Complications
Time Frame: One day (during procedure)
Compare the number of participants who experience other sedation related complications such as hypotension, hypoxemia and need for termination of the procedure between the two groups
One day (during procedure)
Compare Propofol Doses Between the Two Groups
Time Frame: One day (during procedure)
The dose of propofol used between the two groups will be compared
One day (during procedure)
Predictors of Sedation Related Complications as Measured by the Number of Participants Who Experience Hypoxemia (Defined as a Pulse Oximetry <90% for Any Duration)
Time Frame: One year
One year
Predictors of Sedation Related Complications as Measured by Hypopnea/Apnea (Defined as Fewer Than 6 Breaths/Minute Based on Capnography)
Time Frame: One year
One year
Predictors of Sedation Related Complications as Measured by the Incidences of Hypotension (Defined as Systolic Blood Pressure of Less Than 90mmHg or a Decrease of More Than 25% From Baseline)
Time Frame: One year
One year
Predictors of Sedation Related Complications as Measured by Early Procedure Termination for an Alternative Sedation Related Complication
Time Frame: One year
One year
Patient Tolerance as Assessed by Endoscopists
Time Frame: 24-48 hours
The frequency of symptoms of nausea and vomiting in the two groups of patients will be recorded. Patient tolerance of the procedure will be assessed independently by the endoscopist using a 100-mm visual analog scale (VAS, 0=unmanageable, 100=excellent). The patient will also score the level of tolerance using the same VAS at a routine follow-up phone call made 24-48 hours after the procedure.
24-48 hours
Number of Participants Who Experience Symptoms of Nausea and Vomiting Will be Compared Between the Two Groups
Time Frame: 24-48 hours
The number of participants who experience symptoms of nausea and vomiting in the two groups of patients will be recorded. This will be recorded during the follow-up phone call made 24-48 hours after the procedure.
24-48 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Investigators

  • Principal Investigator: Faris Murad, M.D., Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2011

Primary Completion (Actual)

July 1, 2014

Study Completion (Actual)

July 1, 2014

Study Registration Dates

First Submitted

March 11, 2011

First Submitted That Met QC Criteria

March 11, 2011

First Posted (Estimate)

March 15, 2011

Study Record Updates

Last Update Posted (Estimate)

October 28, 2016

Last Update Submitted That Met QC Criteria

September 8, 2016

Last Verified

September 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 10-1133

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Sleep Apnea, Obstructive

Clinical Trials on Propofol+Benzo/Opioids

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Jamaica

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe