Volatile Anesthetic Pharmacokinetics During Extracorporeal Membrane Oxygenation

NCT ID: NCT05680545

Last Updated: 2024-12-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-01

Study Completion Date

2026-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Respiratory Failure

Keywords

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Extracorporeal membrane oxygenation Volatile anesthetics Sedation

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Prospective, single-center, open-label, pharmacokinetic study
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Sevoflurane vaporized in ECMO machines

Patients' sedation will be managed with sevoflurane-based anesthesia directly vaporized into the ECMO machine.

Group Type EXPERIMENTAL

Sevoflurane vaporized in ECMO machines

Intervention Type OTHER

Sevoflurane will be directly vaporized into the ECMO machine through the sweep gas.

Interventions

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Sevoflurane vaporized in ECMO machines

Sevoflurane will be directly vaporized into the ECMO machine through the sweep gas.

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Physicians' Services Incorporated Foundation

OTHER

Sponsor Role collaborator

University Health Network, Toronto

OTHER

Sponsor Role lead

Responsible Party

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Diana Morales Castro

Junior Attending, MSICU Toronto General Hospital, Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Diana Morales Castro, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Central Contacts

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Diana Morales Castro, MD

Role: CONTACT

Phone: +1 416 340-3131

Email: [email protected]

Eddy Fan, MD

Role: CONTACT

Phone: +1 416 340 5483

References

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Rand A, Zahn PK, Schildhauer TA, Waydhas C, Hamsen U. Inhalative sedation with small tidal volumes under venovenous ECMO. J Artif Organs. 2018 Jun;21(2):201-205. doi: 10.1007/s10047-018-1030-9. Epub 2018 Mar 5.

Reference Type BACKGROUND
PMID: 29508167 (View on PubMed)

Ferrando C, Aguilar G, Piqueras L, Soro M, Moreno J, Belda FJ. Sevoflurane, but not propofol, reduces the lung inflammatory response and improves oxygenation in an acute respiratory distress syndrome model: a randomised laboratory study. Eur J Anaesthesiol. 2013 Aug;30(8):455-63. doi: 10.1097/EJA.0b013e32835f0aa5.

Reference Type BACKGROUND
PMID: 23545542 (View on PubMed)

McMullan V, Alston RP, Tyrrell J. Volatile anaesthesia during cardiopulmonary bypass. Perfusion. 2015 Jan;30(1):6-16. doi: 10.1177/0267659114531314. Epub 2014 Apr 14.

Reference Type BACKGROUND
PMID: 24732827 (View on PubMed)

LaGrew JE, Olsen KR, Frantz A. Volatile anaesthetic for treatment of respiratory failure from status asthmaticus requiring extracorporeal membrane oxygenation. BMJ Case Rep. 2020 Jan 15;13(1):e231507. doi: 10.1136/bcr-2019-231507.

Reference Type BACKGROUND
PMID: 31948977 (View on PubMed)

Fan E, Gattinoni L, Combes A, Schmidt M, Peek G, Brodie D, Muller T, Morelli A, Ranieri VM, Pesenti A, Brochard L, Hodgson C, Van Kiersbilck C, Roch A, Quintel M, Papazian L. Venovenous extracorporeal membrane oxygenation for acute respiratory failure : A clinical review from an international group of experts. Intensive Care Med. 2016 May;42(5):712-724. doi: 10.1007/s00134-016-4314-7. Epub 2016 Mar 23.

Reference Type BACKGROUND
PMID: 27007108 (View on PubMed)

Cheng V, Abdul-Aziz MH, Roberts JA, Shekar K. Overcoming barriers to optimal drug dosing during ECMO in critically ill adult patients. Expert Opin Drug Metab Toxicol. 2019 Feb;15(2):103-112. doi: 10.1080/17425255.2019.1563596. Epub 2019 Jan 3.

Reference Type BACKGROUND
PMID: 30582435 (View on PubMed)

Shekar K, Roberts JA, Mcdonald CI, Fisquet S, Barnett AG, Mullany DV, Ghassabian S, Wallis SC, Fung YL, Smith MT, Fraser JF. Sequestration of drugs in the circuit may lead to therapeutic failure during extracorporeal membrane oxygenation. Crit Care. 2012 Oct 15;16(5):R194. doi: 10.1186/cc11679.

Reference Type BACKGROUND
PMID: 23068416 (View on PubMed)

Shekar K, Roberts JA, Mullany DV, Corley A, Fisquet S, Bull TN, Barnett AG, Fraser JF. Increased sedation requirements in patients receiving extracorporeal membrane oxygenation for respiratory and cardiorespiratory failure. Anaesth Intensive Care. 2012 Jul;40(4):648-55. doi: 10.1177/0310057X1204000411.

Reference Type BACKGROUND
PMID: 22813493 (View on PubMed)

Bellgardt M, Ozcelik D, Breuer-Kaiser AFC, Steinfort C, Breuer TGK, Weber TP, Herzog-Niescery J. Extracorporeal membrane oxygenation and inhaled sedation in coronavirus disease 2019-related acute respiratory distress syndrome. World J Crit Care Med. 2021 Nov 9;10(6):323-333. doi: 10.5492/wjccm.v10.i6.323. eCollection 2021 Nov 9.

Reference Type BACKGROUND
PMID: 34888158 (View on PubMed)

Other Identifiers

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2022-2746

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

22-6007

Identifier Type: -

Identifier Source: org_study_id