Probability Ramp Control of Propofol for EGD

Study Description

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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 Design

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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

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Outcome Measures

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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.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• scheduled for elective EGD

Exclusion Criteria:

• Unable to provide informed consent

Contacts and Locations

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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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

Mandel JE, Sarraf E. The variability of response to propofol is reduced when a clinical observation is incorporated in the control: a simulation study. Anesth Analg. 2012 Jun;114(6):1221-9. doi: 10.1213/ANE.0b013e31824cb853. Epub 2012 Mar 30.

Responsible Party:	University of Pennsylvania
ClinicalTrials.gov Identifier:	NCT01838304 History of Changes
Other Study ID Numbers:	817166
First Posted:	April 24, 2013
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