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Original Investigation
September 29, 2021

Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest: A Randomized Clinical Trial

Author Affiliations
  • 1Research Center for Emergency Medicine, Department of Clinical Medicine and Emergency Department, Aarhus University and Aarhus University Hospital, Aarhus, Denmark
  • 2Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark
  • 3Prehospital Emergency Medical Services, Central Denmark Region, Aarhus, Denmark
  • 4Department of Anesthesia, Centre of Head and Orthopedics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  • 5Department of Cardiology, The Heart Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  • 6Department of Anesthesiology and Intensive Care, Odense University Hospital, Odense, Denmark
  • 7Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
  • 8Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
  • 9Department of Anesthesia and Intensive Care, Aalborg University Hospital, Aalborg, Denmark
  • 10Department of Medicine, Randers Regional Hospital, Randers, Denmark
  • 11Department of Emergency Medicine, Herlev and Gentofte University Hospital, Copenhagen, Denmark
  • 12Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
  • 13Department of Internal Medicine, Herlev and Gentofte University Hospital, Copenhagen, Denmark
  • 14Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, Pennsylvania
  • 15Unit of Clinical Simulation and Education, Herlev and Gentofte University Hospital, Copenhagen, Denmark
  • 16Department of Anesthesiology and Intensive Care, Viborg Regional Hospital, Viborg, Denmark
  • 17Department of Anesthesiology and Intensive Care, Horsens Regional Hospital, Horsens, Denmark
  • 18Department of Cardiology, Herlev and Gentofte University Hospital, Copenhagen, Denmark
  • 19Copenhagen Emergency Medical Services, University of Copenhagen, Copenhagen, Denmark
  • 20Department of Anesthesiology, Zealand University Hospital, Køge, Denmark
  • 21Center for Resuscitation Science, Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
  • 22Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
  • 23Institute of Public Health, Charité-Universitätsmedizin Berlin, Berlin, Germany
  • 24Department of Cardiology, Viborg Regional Hospital, Viborg, Denmark
JAMA. Published online September 29, 2021. doi:10.1001/jama.2021.16628
Visual Abstract. Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in In-Hospital Cardiac Arrest
Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in In-Hospital Cardiac Arrest
Key Points

Question  Does the combination of vasopressin and methylprednisolone administered during in-hospital cardiac arrest improve return of spontaneous circulation?

Findings  In this randomized trial that included 501 patients with in-hospital cardiac arrest in Denmark, the proportion of patients who achieved return of spontaneous circulation was 42% in the vasopressin and methylprednisolone group and 33% in the placebo group, a difference that was statistically significant.

Meaning  Among patients with in-hospital cardiac arrest, administration of vasopressin and methylprednisolone compared with placebo significantly increased the likelihood of return of spontaneous circulation, but it is uncertain whether there is benefit or harm for long-term survival.

Abstract

Importance  Previous trials have suggested that vasopressin and methylprednisolone administered during in-hospital cardiac arrest might improve outcomes.

Objective  To determine whether the combination of vasopressin and methylprednisolone administered during in-hospital cardiac arrest improves return of spontaneous circulation.

Design, Setting, and Participants  Multicenter, randomized, double-blind, placebo-controlled trial conducted at 10 hospitals in Denmark. A total of 512 adult patients with in-hospital cardiac arrest were included between October 15, 2018, and January 21, 2021. The last 90-day follow-up was on April 21, 2021.

Intervention  Patients were randomized to receive a combination of vasopressin and methylprednisolone (n = 245) or placebo (n = 267). The first dose of vasopressin (20 IU) and methylprednisolone (40 mg), or corresponding placebo, was administered after the first dose of epinephrine. Additional doses of vasopressin or corresponding placebo were administered after each additional dose of epinephrine for a maximum of 4 doses.

Main Outcomes and Measures  The primary outcome was return of spontaneous circulation. Secondary outcomes included survival and favorable neurologic outcome at 30 days (Cerebral Performance Category score of 1 or 2).

Results  Among 512 patients who were randomized, 501 met all inclusion and no exclusion criteria and were included in the analysis (mean [SD] age, 71 [13] years; 322 men [64%]). One hundred of 237 patients (42%) in the vasopressin and methylprednisolone group and 86 of 264 patients (33%) in the placebo group achieved return of spontaneous circulation (risk ratio, 1.30 [95% CI, 1.03-1.63]; risk difference, 9.6% [95% CI, 1.1%-18.0%]; P = .03). At 30 days, 23 patients (9.7%) in the intervention group and 31 patients (12%) in the placebo group were alive (risk ratio, 0.83 [95% CI, 0.50-1.37]; risk difference: −2.0% [95% CI, −7.5% to 3.5%]; P = .48). A favorable neurologic outcome was observed in 18 patients (7.6%) in the intervention group and 20 patients (7.6%) in the placebo group at 30 days (risk ratio, 1.00 [95% CI, 0.55-1.83]; risk difference, 0.0% [95% CI, −4.7% to 4.9%]; P > .99). In patients with return of spontaneous circulation, hyperglycemia occurred in 77 (77%) in the intervention group and 63 (73%) in the placebo group. Hypernatremia occurred in 28 (28%) and 27 (31%), in the intervention and placebo groups, respectively.

Conclusions and Relevance  Among patients with in-hospital cardiac arrest, administration of vasopressin and methylprednisolone, compared with placebo, significantly increased the likelihood of return of spontaneous circulation. However, there is uncertainty whether this treatment results in benefit or harm for long-term survival.

Trial Registration  ClinicalTrials.gov Identifier: NCT03640949

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