Propofol vs Propofol + Benzo/Opiates in High Risk Group

NCT ID: NCT01315158

Last Updated: 2016-10-28

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-01-31

Study Completion Date

2014-07-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Sleep Apnea, Obstructive Obesity

Keywords

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Obstructive Sleep Apnea Body Mass Index

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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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

Group Type ACTIVE_COMPARATOR

Propofol+Benzo/Opioids

Intervention Type DRUG

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

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

Group Type ACTIVE_COMPARATOR

Propofol Alone

Intervention Type DRUG

Recommended Propofol doses before considering crossover:

* Induction: 2-2.5 mg/kg
* Maintenance: 0.1-0.2 mg/kg/min

Interventions

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Propofol Alone

Recommended Propofol doses before considering crossover:

* Induction: 2-2.5 mg/kg
* Maintenance: 0.1-0.2 mg/kg/min

Intervention Type 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

Intervention Type DRUG

Other Intervention Names

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Propofol Diprivan 2,6-di-isopropofol Benzodiazepine Midazolam Versed Opioid Fentanyl

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Washington University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Faris Murad, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

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Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Countries

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United States

References

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Other Identifiers

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10-1133

Identifier Type: -

Identifier Source: org_study_id