Volatile Anesthetic Pharmacokinetics During Extracorporeal Membrane Oxygenation (Vol-ECMO)

November 28, 2023 updated by: Diana Morales Castro, University Health Network, Toronto

Volatile Anesthetic Pharmacokinetics During Extracorporeal Membrane

The goal of this study is to design a pilot trial evaluating the safety, feasibility, pharmacokinetic modeling, and physiological effects of a volatile anesthetic, sevoflurane, directly administered in extracorporeal membrane oxygenation machines.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a life-saving therapy for catastrophic respiratory failure, including severe COVID-19. Optimal drug dosing in critically ill patients is challenging due to concomitant organ dysfunction, and with the addition of ECMO, the level of complexity significantly increases.

ECMO PK interactions with intravenous (IV) sedatives are complex and therapeutic failures are often encountered, highlighting the need for alternative sedation strategies. To overcome these limitations, volatile anesthetics are a potential solution for sedation and analgesia. Nevertheless, their use has been limited during ECMO support due to the low respiratory volumes associated with the lung-protective strategies, and the concerns of bioavailability given the compromised native lung function. The overarching aim of this project is to evaluate a strategy to mitigate the influence of ECMO on sedatives pharmacokinetics, using volatile anesthetics directly vaporized into ECMO oxygenators.

The study will consist of two phases: the ex-vivo trial an the in-vivo trial. For the ex-vivo trial, two ECMO circuits primed with Ringer's lactate will be used to design the dosing recommendations for the feasibility trial. Vaporized sevoflurane will be delivered directly into the membrane oxygenator with the ECMO gas and evacuated through the wall suction. Sevoflurane concentrations will be monitored with an infrared multi-gas analyzer sensor at the ECMO gas outlet. The test will be performed with different sweep flows and sevoflurane concentrations. Sevoflurane concentrations will be measured in the fluid to design a dosing model to conduct the in-vivo trial.

The in-vivo trial will be a prospective, single-center, open-label, pilot feasibility/PK study of 10 patients receiving venovenous ECMO (VV ECMO) in the Medical-Surgical Intensive Care Unit (MSICU) at the Toronto General Hospital. Following informed consent, these patients will be enrolled and managed with sevoflurane-based anesthesia directly delivered into the ECMO machine. During their ECMO run, samples will be taken and sevoflurane concentrations analyzed with headspace gas chromatography and mass spectrometry. Sedation scales, surrogates of respiratory dynamics and effort, and biotrauma inflammatory cytokines levels will be obtained at the same time.

Study Type

Interventional

Enrollment (Estimated)

10

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Eddy Fan, MD
  • Phone Number: +1 416 340 5483

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

adult patients expected to be on VV ECMO support for a time frame of more than 24 hours and receiving a sevoflurane-based sedation protocol.

Exclusion Criteria:

  • lack of informed consent for participation
  • pregnancy
  • serum bilirubin > 150 μmol/L
  • ongoing massive blood transfusion requirement (> 50% blood volume transfused in the previous 8 hours)
  • therapeutic plasma exchange and/or renal replacement therapy in the preceding 24 hours
  • expected death or withdrawal of life support in the next 48 hours.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sevoflurane vaporized in ECMO machines
Patients' sedation will be managed with sevoflurane-based anesthesia directly vaporized into the ECMO machine.
Other: Sevoflurane vaporized in ECMO machines
Sevoflurane will be directly vaporized into the ECMO machine through the sweep gas.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sevoflurane plasma concentrations
Time Frame: 7 days
Plasma concentrations of sevoflurane will be measured with gas chromatography and mass spectrometry
7 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of sevoflurane in ECMO exhausted gas
Time Frame: 7 days
The volume/volume percentage of sevoflurane will be measured with an infrared multi-gas analyzer sensor at the sweep gas outlet
7 days
Respiratory dynamics and respiratory effort
Time Frame: 7 days
Driving pressure, occlusion pressure, and P0.1 pressures will be measured with the patients mechanical ventilator daily
7 days
Plasma levels of ventilator-induced lung injury biomarkers
Time Frame: 7 days
As a surrogate for ventilator-induced lung injury, plasma levels of interleukins 6 and 8, and necrosis tumor factor will be measured daily
7 days
Required doses of sedative adjuvants
Time Frame: 7 days
The doses of other sedatives and analgesics, including opioids, antipsychotics, benzodiazepines, ketamine and propofol will be recorded
7 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Collaborators

The Physicians' Services Incorporated Foundation

Investigators

  • Principal Investigator: Diana Morales Castro, MD, University Health Network, Toronto

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2024

Primary Completion (Estimated)

December 30, 2024

Study Completion (Estimated)

June 30, 2025

Study Registration Dates

First Submitted

December 16, 2022

First Submitted That Met QC Criteria

December 26, 2022

First Posted (Actual)

January 11, 2023

Study Record Updates

Last Update Posted (Actual)

November 29, 2023

Last Update Submitted That Met QC Criteria

November 28, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 22-6007
  • 2022-2746 (Other Grant/Funding Number: PSI Foundation)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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