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Oxygen Thresholds and Mortality During Extracorporeal Life Support in Adult Patients*

Munshi, Laveena MD1; Kiss, Alex PhD2; Cypel, Marcelo MD3,4; Keshavjee, Shaf MD3,4; Ferguson, Niall D. MD5–7,3; Fan, Eddy MD4,8

doi: 10.1097/CCM.0000000000002643
Clinical Investigations
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Objectives: Extracorporeal life support can lead to rapid reversal of hypoxemia and shock; however, it can also result in varying degrees of hyperoxia. Recent data have suggested an association between hyperoxia and mortality; however, this conclusion has not been consistent across the literature. We evaluated the association between oxygenation thresholds and mortality in three cohorts of extracorporeal life support patients.

Design: We performed a retrospective cohort study using the Extracorporeal Life Support Organization Registry.

Setting: We evaluated the relationship between oxygenation measured 24 hours after extracorporeal membrane oxygenation onset and mortality (2010–2015).

Patients: The extracorporeal life support cohorts were as follows: 1) veno-venous extracorporeal membrane oxygenation for respiratory failure, 2) veno-arterial extracorporeal membrane oxygenation for cardiogenic shock, and 3) extracorporeal cardiopulmonary resuscitation.

Interventions: The relationships between hypoxemia (Pao2 < 60mm Hg), normoxia (Pao2 60–100mm Hg), moderate hyperoxia (Pao2 101–300mm Hg), extreme hyperoxia (Pao2 > 300 mm Hg), and mortality were evaluated across three extracorporeal life support cohorts.

Measurements and Main Results: Seven hundred sixty-five patients underwent veno-venous extracorporeal membrane oxygenation, 775 patients underwent veno-arterial extracorporeal membrane oxygenation, and 412 underwent extracorporeal cardiopulmonary resuscitation. During veno-venous extracorporeal membrane oxygenation, hypoxemia (odds ratio, 1.68; 95% CI, 1.09–2.57) and moderate hyperoxia (odds ratio, 1.66; 95% CI, 1.11–2.50) were associated with increased mortality compared with normoxia. There was no association between oxygenation and mortality for veno-arterial extracorporeal membrane oxygenation. Moderate hyperoxia was associated with increased mortality during extracorporeal cardiopulmonary resuscitation compared with normoxia (odds ratio, 1.77; 95% CI, 1.03–3.30). An exploratory analysis did not find more specific Pao2 thresholds associated with mortality within moderate hyperoxia.

Conclusions: Moderate hyperoxia was associated with increased mortality in patients undergoing veno-venous extracorporeal membrane oxygenation for respiratory failure and extracorporeal cardiopulmonary resuscitation. Hypoxemia was associated with an increased mortality in veno-venous extracorporeal membrane oxygenation. No association was seen between oxygenation and mortality in veno-arterial extracorporeal membrane oxygenation which may be due to early death driven by the underlying disease.

1Interdepartmental Division of Critical Care Medicine, Department of Medicine, Sinai Health System, University of Toronto, Toronto, ON, Canada.

2Institute for Clinical Evaluative Sciences.

3Extracorporeal Life Support Program, Toronto General Hospital, University of Toronto, ON, Canada.

4Division of Thoracic Surgery, Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, ON, Canada.

5Interdepartmental Division of Critical Care Medicine, Departments of Medicine and Physiology, Institute of Health Policy Management and Evaluation, University of Toronto, Toronto, ON, Canada.

6Toronto General Research Institute, Toronto, ON, Canada.

7Department of Medicine, Division of Respirology, University Health Network and Mount Sinai Hospitals, Toronto, ON, Canada.

8Interdepartmental Division of Critical Care Medicine, Department of Medicine, Institute of Health Policy, Management and Evaluation, Toronto General Hospital, University of Toronto, Toronto, ON, Canada.

*See also p. 2106.

This work was performed at Sinai Health System/University Health Network.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Supported, in part, by a grant from the Extracorporeal Life Support Organization (ELSO). ELSO had no role in the design nor results of the study.

Dr. Munshi is supported by a Fellowship Grant, Canadian Institutes of Health Research (CIHR), and the Eliot Philipson Clinician Scientist Training Program, University of Toronto; she received funding from the Extracorporeal Life Support Organization. Dr. Fan is supported by a New Investigator Award, CIHR. The remaining authors have disclosed that they do not have any potential conflicts of interest. The funding organizations had no role in the design and conduct of the study, management, analysis, or interpretation of the data or article preparation or approval.

For information regarding this article, E-mail: Laveena.munshi@sinaihealthsystem.ca

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