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Probability Ramp Control of Propofol for EGD

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ClinicalTrials.gov Identifier: NCT01838304
Recruitment Status : Completed
First Posted : April 24, 2013
Results First Posted : January 23, 2018
Last Update Posted : January 23, 2018
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania

Brief Summary:
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 or disease Intervention/treatment Phase
Gastrointestinal Disease Device: Probability ramp control Device: Monitoring Not Applicable

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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)
Study Start Date : March 2013
Actual Primary Completion Date : May 2013
Actual Study Completion Date : May 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Endoscopy
Drug Information available for: Propofol

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Number of Participants Requiring Adjustment in Propofol Dosing [ Time Frame: Intraprocedure (average of 9 minutes) ]
    Following initial sedation, an infusion rate for propofol is determined by the CRNA (control) or software (experimental). If this rate is appropriate for the duration of the brief procedure, no adjustment to the rate will be required. A greater requirement for rate changes suggests that the anesthesia provider needs to be immediately available to perform these adjustments.


Secondary Outcome Measures :
  1. Decrease in Minute Ventilation From Baseline [ Time Frame: Duration of sedation (average of 25 minutes) ]
    Minute ventilation as determined by respiratory inductance plethysmography from initiation of sedation until emergence.

  2. Time Spent Below a Saturation of 80% [ Time Frame: Duration of sedation (mean 25 minutes) ]
    Number of seconds spent below saturation of 80%, reported as the total per group

  3. Procedure Time [ Time Frame: Procedure time (average of 9 minutes) ]
    Time from endoscopic intubation until completion of the procedure. This is not really an outcome measure, but is used to assess balance between groups.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • scheduled for elective EGD

Exclusion Criteria:

  • Unable to provide informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Publications:
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01838304     History of Changes
Other Study ID Numbers: 817166
First Posted: April 24, 2013    Key Record Dates
Results First Posted: January 23, 2018
Last Update Posted: January 23, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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
Anesthetics, Intravenous
Anesthetics, General
Anesthetics