Probability Ramp Control of Propofol for EGD

NCT ID: NCT01838304

Last Updated: 2018-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2013-05-31

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.

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.

Conditions

Gastrointestinal Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Monitoring

Standard of care sedation by CRNA using proposal with manual recording of drug dosing

Group Type: ACTIVE_COMPARATOR

Monitoring

Intervention Type: DEVICE

Manual recording of drug doses determined by CRNA

Probability ramp control

Propofol titrated to deep sedation using PRC software.

Group Type: EXPERIMENTAL

Probability ramp control

Intervention Type: DEVICE

Decision support software that calculates propofol doses appropriate for age and weight of the patient

Interventions

Probability ramp control

Decision support software that calculates propofol doses appropriate for age and weight of the patient

Intervention Type: DEVICE

Monitoring

Manual recording of drug doses determined by CRNA

Intervention Type: DEVICE

Other Intervention Names

Manual recording of drug doses determined by CRNA

Eligibility Criteria

Inclusion Criteria

• scheduled for elective EGD

Exclusion Criteria

• Unable to provide informed consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeff E Mandel, MD MS

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

Endoscopy Center, Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 22467886 (View on PubMed)

Other Identifiers

817166

Identifier Type: -

Identifier Source: org_study_id