Probability Ramp Control of Propofol for EGD

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01838304
First received: April 12, 2013
Last updated: May 21, 2013
Last verified: March 2013
  Purpose

Endoscopic sedation requires titration of propofol to deep sedation without minimum overshoot into general anesthesia. This skill is demanding and acquired slowly. Probability Ramp Control (PRC) simplifies this by providing the clinician with a simple infusion sequence that permits gradual titration of propofol. The purpose of this study is to compare the performance of this technology to that of experienced anesthesia providers in endoscopic sedation.


Condition Intervention
Gastrointestinal Disease
Device: Probability ramp control
Device: Monitoring

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Randomized Comparison of Depth of Sedation With Propofol Titrated by Probability Ramp Control to Control by Anesthesia Providers During Esophagogastroduodenoscopy (EGD)

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Depth of sedation, as assessed by SEDLine processed EEG. [ Time Frame: Intraprocedure ] [ Designated as safety issue: Yes ]
    SEDLine® is a device that analyzes the electroencephalogram (EEG) with a proprietary algorithm and produces a number between zero and 100 that is related to the depth of anesthesia.


Secondary Outcome Measures:
  • Predicted effect site concentrations for propofol [ Time Frame: Intraprocedure ] [ Designated as safety issue: No ]
  • Minute ventilation, as assessed by calibrated RIP [ Time Frame: Intraprocedure ] [ Designated as safety issue: Yes ]
    Respiratory Inductance Plethysmography (RIP) utilizes fabric bands with a coil that is energized with an alternating current. The magnetic inductance is related to the area enclosed by the coil, which is proportional to lung volume. By calibration against a spirometer, continuous estimates of minute ventilation can be made.

  • Hemoglobin saturation, as assessed by pulse oximetry [ Time Frame: Intraprocedure ] [ Designated as safety issue: Yes ]
  • Endoscopist satisfaction, as assessed by 10 point Likert scale [ Time Frame: At completion of the procedure ] [ Designated as safety issue: No ]
  • Patient Satisfaction by 10 point Likert scale [ Time Frame: Prior to discharge from endoscopy suite, typically 30 minutes ] [ Designated as safety issue: No ]
    Patient satisfaction with sedation experience


Enrollment: 40
Study Start Date: March 2013
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Monitoring
Standard of care sedation by CRNA using proposal with manual recording of drug dosing
Device: Monitoring
Manual recording of drug doses determined by CRNA
Other Name: Manual recording of drug doses determined by CRNA
Experimental: Probability ramp control
Propofol titrated to deep sedation using PRC software.
Device: Probability ramp control
Decision support software that calculates propofol doses appropriate for age and weight of the patient

Detailed Description:

Administration of propofol to achieve a target of moderate sedation is a challenging task for which anesthesia providers receive minimal training. Undersedation results in a noncompliant patient, while oversedation results in airway obstruction, respiratory depression, and hypotension. Considerable variability in patient pharmacokinetics (the distribution of drug within the body) and pharmacodynamics (the translation of drug concentration to clinical effect) has been demonstrated. The skill of titrating propofol to the desired target and maintaining this state is slowly acquired in the clinical environment of the endoscopy center with frequent reliance on rescue skills. An automated system that facilitates this process would be useful.

Pharmacokinetic models allow us to make predictions of the results of drug administration. If we know the age and size of the patient, we can determine a quantity of propofol that will attain a desired concentration at some point in the future (within the predictive accuracy of the model). If they are old, this is less than if they are young. If they are obese, this is more than if they are thin. By adjusting the dosing, we can achieve similar concentrations at a specified time in a wide range of patients.

Pharmacodynamic models allow us to relate drug concentration to a probability of response. Sensitivity is a randomly distributed variable, and the cumulative probability of response to propofol is well represented by a sigmoid curve. While we do not know the concentration that will suffice for a given individual, we can determine the probability that this individual will lose responsiveness within an interval of concentrations. For example, the probability of loss of responsiveness between 1 µg/ml and 6 µg/ml is around 99%. For any given age and size, an infusion sequence can be determined so that we traverse this interval smoothly. The infusion sequence is determined by minimization of the difference between the simulated probability and the target (1). We predict that 90% of 50 year old 70 kg patients will lose responsiveness between one minute and three minutes after initiating the infusion, and 99% by five minutes. The infusion sequence for this patient is comprised of a bolus of 287 µg/kg followed by an initial infusion of 216 µg/kg/min, with an increase to 550 µg/kg/min after 147 seconds. By selecting the infusion sequence based on the age and size of the patient, all patients will track the same target line. These infusion rates are determined prior to initiation of sedation, and the clinician can verify that they are appropriate for the patient before beginning sedation.

Once the endpoint of adequate sedation is observed, the effect site concentration associated with this endpoint is inferred, and the infusion that will maintain this concentration can be determined. This allows the clinical observation to be translated into an infusion rate, much as a driver accelerates to a desired speed and then engages the cruise control to maintain that speed.

The intent of this study is to demonstrate equivalent safety and efficacy of PRC to control by a skilled clinician.

References

1. Mandel JE, Sarraf E. The Variability of Response to Propofol Is Reduced When a Clinical Observation Is Incorporated in the Control: A Simulation Study. Anesthesia & Analgesia. 2012;114:1221-9.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • scheduled for elective EGD

Exclusion Criteria:

  • Unable to provide informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01838304

Locations
United States, Pennsylvania
Endoscopy Center, Perelman Center for Advanced Medicine
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Investigators
Principal Investigator: Jeff E Mandel, MD MS University of Pennsylvania
  More Information

Publications:
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01838304     History of Changes
Other Study ID Numbers: 817166
Study First Received: April 12, 2013
Last Updated: May 21, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pennsylvania:
propofol sedation endoscopy

Additional relevant MeSH terms:
Gastrointestinal Diseases
Digestive System Diseases
Propofol
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anesthetics, Intravenous
Anesthetics, General
Anesthetics

ClinicalTrials.gov processed this record on July 31, 2014