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Original ArticleFree Preview

Blood-Pressure Targets in Comatose Survivors of Cardiac Arrest

List of authors.
  • Jesper Kjaergaard, M.D., D.M.Sc.,
  • Jacob E. Møller, M.D., D.M.Sc.,
  • Henrik Schmidt, M.D., D.M.Sc.,
  • Johannes Grand, M.D., Ph.D.,
  • Simon Mølstrøm, M.D.,
  • Britt Borregaard, R.N., Ph.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.,
  • Laust E.R. Obling, M.D.,
  • Matias G. Lindholm, M.D., Ph.D.,
  • Martin Frydland, M.D., Ph.D.,
  • Martin A.S. Meyer, M.D.,
  • Matilde Winther-Jensen, 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.,
  • Søren A. Madsen, M.D.,
  • Vibeke L. Jørgensen, M.D., Ph.D.,
  • and Christian Hassager, M.D., D.M.Sc.

Abstract

Background

Evidence to support the choice of blood-pressure targets for the treatment of comatose survivors of out-of-hospital cardiac arrest who are receiving intensive care is limited.

Methods

In a double-blind, randomized trial with a 2-by-2 factorial design, we evaluated a mean arterial blood-pressure target of 63 mm Hg as compared with 77 mm Hg in comatose adults who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause; patients were also assigned to one of two oxygen targets (reported separately). The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category (CPC) of 3 or 4 within 90 days (range, 0 to 5, with higher categories indicating more severe disability; a category of 3 or 4 indicates severe disability or coma). Secondary outcomes included neuron-specific enolase levels at 48 hours, death from any cause, scores on the Montreal Cognitive Assessment (range, 0 to 30, with higher scores indicating better cognitive ability) and the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at 3 months, and the CPC at 3 months.

Results

A total of 789 patients were included in the analysis (393 in the high-target group and 396 in the low-target group). A primary-outcome event occurred in 133 patients (34%) in the high-target group and in 127 patients (32%) in the low-target group (hazard ratio, 1.08; 95% confidence interval [CI], 0.84 to 1.37; P=0.56). At 90 days, 122 patients (31%) in the high-target group and 114 patients (29%) in the low-target group had died (hazard ratio, 1.13; 95% CI, 0.88 to 1.46). The median CPC was 1 (interquartile range, 1 to 5) in both the high-target group and the low-target group; the corresponding median modified Rankin scale scores were 1 (interquartile range, 0 to 6) and 1 (interquartile range, 0 to 6), and the corresponding median Montreal Cognitive Assessment scores were 27 (interquartile range, 24 to 29) and 26 (interquartile range, 24 to 29). The median neuron-specific enolase level at 48 hours was also similar in the two groups. The percentages of patients with adverse events did not differ significantly between the groups.

Conclusions

Targeting a mean arterial blood pressure of 77 mm Hg or 63 mm Hg in patients who had been resuscitated from cardiac arrest did not result in significantly different percentages of patients dying or having 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 in the trial and their relatives; the staff at the participating sites — in particular, the nursing staff of the intensive care units at both sites for committing themselves to diligent adherence to the trial protocol; the medical Technical Department at Copenhagen University Hospital Rigshospitalet for the careful offsetting of the blood-pressure modules that constituted the basis for the double-blind design of the trial; Mette Krefeld Bentzen (Department of Clinical Biochemistry, Copenhagen University Hospital Rigshospitalet) for technical assistance in analyzing the biobank samples for neuron-specific enolase; and Jesper Nyvold Larsen for contributing a system for proxy consent that substantially reduced the time to randomization in the trial.

Author Affiliations

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

Dr. Kjaergaard can be contacted at or at the Department of Cardiology, the Heart Center, Copenhagen University Hospital Rigshospitalet, 9 Blegdamsvej, DK2100 Copenhagen East, Denmark.