Volatile Anesthetic Pharmacokinetics During Extracorporeal Membrane Oxygenation

NCT05680545 | Not Yet Recruiting

• 2 other identifiers: 22-60072022-2746
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Respiratory Failure

Keywords

Extracorporeal membrane oxygenation; Volatile anesthetics; Sedation

Outcome Measures

Primary Outcomes (1)

• Sevoflurane plasma concentrations

  Plasma concentrations of sevoflurane will be measured with gas chromatography and mass spectrometry

  7 days

Secondary Outcomes (4)

• Percentage of sevoflurane in ECMO exhausted gas

  7 days

• Respiratory dynamics and respiratory effort

  7 days

• Plasma levels of ventilator-induced lung injury biomarkers

  7 days

• Required doses of sedative adjuvants

  7 days

Study Arms (1)

Sevoflurane vaporized in ECMO machines

EXPERIMENTAL

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

Other: Sevoflurane vaporized in ECMO machines

Interventions

Sevoflurane vaporized in ECMO machines OTHER

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

Sevoflurane vaporized in ECMO machines

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• The Physicians' Services Incorporated Foundation: collaborator

Related Publications (9)

• 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.

  PMID: 24732827 BACKGROUND

• 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.

  PMID: 31948977 BACKGROUND

• 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.

  PMID: 27007108 BACKGROUND

• 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.

  PMID: 30582435 BACKGROUND

• 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.

  PMID: 23068416 BACKGROUND

• 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.

  PMID: 22813493 BACKGROUND

• 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.

  PMID: 34888158 BACKGROUND

• 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.

  PMID: 29508167 BACKGROUND

• 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.

  PMID: 23545542 BACKGROUND

MeSH Terms

Conditions

Respiratory Insufficiency

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases

Study Officials

• Diana Morales Castro, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Diana Morales Castro, MD

CONTACT

+1 416 340-3131; diana.moralescastro@uhn.ca

Eddy Fan, MD

CONTACT

+1 416 340 5483

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Junior Attending, MSICU Toronto General Hospital, Principal Investigator

Model Details: Prospective, single-center, open-label, pharmacokinetic study

Study Record Dates

• First Submitted: December 16, 2022
• First Posted: January 11, 2023
• Study Start: July 1, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: December 9, 2024

Record last verified: 2024-12