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Original ArticleFree Preview

Oxygen Targets in Comatose Survivors of Cardiac Arrest

List of authors.
  • Henrik Schmidt, M.D., D.M.Sc.,
  • Jesper Kjaergaard, M.D., D.M.Sc.,
  • Christian Hassager, M.D., D.M.Sc.,
  • Simon Mølstrøm, M.D.,
  • Johannes Grand, M.D., Ph.D.,
  • Britt Borregaard, Ph.D.,
  • Laust E. Roelsgaard Obling, M.D.,
  • Søren Venø, M.D.,
  • Laura Sarkisian, M.D., Ph.D.,
  • Dmitry Mamaev, M.D.,
  • Lisette O. Jensen, M.D., D.M.Sc.,
  • Benjamin Nyholm, M.D.,
  • Dan E. Høfsten, M.D., Ph.D.,
  • Jakob Josiassen, M.D., Ph.D.,
  • Jakob H. Thomsen, M.D., Ph.D.,
  • Jens J. Thune, M.D., Ph.D.,
  • Matias G. Lindholm, M.D., Ph.D.,
  • Martin A. Stengaard Meyer, M.D.,
  • Matilde Winther-Jensen, Ph.D.,
  • Marc Sørensen, M.D.,
  • Martin Frydland, M.D., Ph.D.,
  • Rasmus P. Beske, M.D.,
  • Ruth Frikke-Schmidt, M.D., D.M.Sc.,
  • Sebastian Wiberg, M.D., Ph.D.,
  • Søren Boesgaard, M.D., D.M.Sc.,
  • Vibeke Lind Jørgensen, M.D., Ph.D.,
  • and Jacob E. Møller, M.D., D.M.Sc.

Abstract

Background

The appropriate oxygenation target for mechanical ventilation in comatose survivors of out-of-hospital cardiac arrest is unknown.

Methods

In this randomized trial with a 2-by-2 factorial design, we randomly assigned comatose adults with out-of-hospital cardiac arrest in a 1:1 ratio to either a restrictive oxygen target of a partial pressure of arterial oxygen (Pao2) of 9 to 10 kPa (68 to 75 mm Hg) or a liberal oxygen target of a Pao2 of 13 to 14 kPa (98 to 105 mm Hg); patients were also assigned to one of two blood-pressure targets (reported separately). The primary outcome was a composite of death from any cause or hospital discharge with severe disability or coma (Cerebral Performance Category [CPC] of 3 or 4; categories range from 1 to 5, with higher values indicating more severe disability), whichever occurred first within 90 days after randomization. Secondary outcomes were neuron-specific enolase levels at 48 hours, death from any cause, the score on the Montreal Cognitive Assessment (ranging from 0 to 30, with higher scores indicating better cognitive ability), the score on the modified Rankin scale (ranging from 0 to 6, with higher scores indicating greater disability), and the CPC at 90 days.

Results

A total of 789 patients underwent randomization. A primary-outcome event occurred in 126 of 394 patients (32.0%) in the restrictive-target group and in 134 of 395 patients (33.9%) in the liberal-target group (hazard ratio, 0.95; 95% confidence interval, 0.75 to 1.21; P=0.69). At 90 days, death had occurred in 113 patients (28.7%) in the restrictive-target group and in 123 (31.1%) in the liberal-target group. On the CPC, the median category was 1 in the two groups; on the modified Rankin scale, the median score was 2 in the restrictive-target group and 1 in the liberal-target group; and on the Montreal Cognitive Assessment, the median score was 27 in the two groups. At 48 hours, the median neuron-specific enolase level was 17 μg per liter in the restrictive-target group and 18 μg per liter in the liberal-target group. The incidence of adverse events was similar in the two groups.

Conclusions

Targeting of a restrictive or liberal oxygenation strategy in comatose patients after resuscitation for cardiac arrest resulted in a similar incidence of death or severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.)

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Funding and Disclosures

Supported by a grant (NNF17OC0028706) from the Novo Nordisk Foundation. Dr. Hassager’s work is funded by a grant (R186-2015-2132) from the Lundbeck Foundation.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

This article was published on August 27, 2022, at NEJM.org.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

We thank the patients who participated in this trial, their relatives, and the staff members at the participating sites, including members of the nursing staff in the cardiac intensive care units for their diligent adherence to the trial protocol; and Jesper Nyvold Larsen for developing a system for proxy patient consent, which helped to reduce the interval between admission and randomization.

Author Affiliations

From the Departments of Anesthesiology and Intensive Care (H.S., S.M., S.V., D.M.) and Cardiology (B.B., L.S., L.O.J., J.E.M.), Odense University Hospital, and the Department of Clinical Research, University of Southern Denmark (H.S., C.H., B.B., L.O.J., J.E.M.), Odense, and the Departments of Cardiology (J.K., C.H., J.G., L.E.R.O., B.N., D.E.H., J.J., J.H.T., M.G.L., M.A.S.M., M.F., M.W.-J., R.P.B., R.F.-S., S.W., S.B., J.E.M.) and Cardiothoracic Anesthesiology (M.S., V.L.J.), the Heart Center, and the Department of Clinical Biochemistry, Center of Diagnostic Investigation (R.F.-S.), Copenhagen University Hospital Rigshospitalet, the Department of Clinical Medicine, University of Copenhagen (J.K., C.H., R.F.-S.), and the Department of Cardiology, Copenhagen University Hospital Bispebjerg (J.J.T.), Copenhagen — all in Denmark.

Dr. Møller can be contacted at or at the Department of Cardiology, Odense University Hospital, Winsløvvej 4, 5000 Odense C, Denmark.