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Original Investigation
November 30, 2021

Effect of Intravenous or Intraosseous Calcium vs Saline on Return of Spontaneous Circulation in Adults With Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial

Author Affiliations
  • 1Prehospital Emergency Medical Services, Central Denmark Region, Aarhus
  • 2Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark
  • 3Research Center for Emergency Medicine, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
  • 4Emergency Department, Aarhus University Hospital, Aarhus, Denmark
  • 5Department of Cardiology, Viborg Regional Hospital, Viborg, Denmark
  • 6Department of Anesthesiology and Intensive Care, Herning Regional Hospital, Herning, Denmark
  • 7Department of Anesthesiology and Intensive Care, Randers Regional Hospital, Randers, Denmark
  • 8Department of Anesthesiology and Intensive Care, Horsens Regional Hospital, Horsens, Denmark
  • 9Department of Anesthesiology and Intensive Care, Viborg Regional Hospital, Viborg, Denmark
  • 10Elective Surgery Centre, Silkeborg Regional Hospital, Silkeborg, Denmark
  • 11Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
  • 12Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark
JAMA. 2021;326(22):2268-2276. doi:10.1001/jama.2021.20929
Visual Abstract. Calcium for Return of Spontaneous Circulation in Out-of-Hospital Cardiac Arrest
Calcium for Return of Spontaneous Circulation in Out-of-Hospital Cardiac Arrest
Key Points

Question  Does administration of calcium during out-of-hospital cardiac arrest improve sustained return of spontaneous circulation?

Findings  In this randomized clinical trial that included 391 adults with out-of-hospital cardiac arrest, 19% had sustained return of spontaneous circulation after receiving treatment with intravenous or intraosseous calcium compared with 27% after receiving saline. This difference was not statistically significant, but the trial was terminated early due to concerns about harm in the calcium group.

Meaning  Treatment with intravenous or intraosseous calcium did not significantly improve sustained return of spontaneous circulation among adults with out-of-hospital cardiac arrest.

Abstract

Importance  It is unclear whether administration of calcium has a beneficial effect in patients with cardiac arrest.

Objective  To determine whether administration of calcium during out-of-hospital cardiac arrest improves return of spontaneous circulation in adults.

Design, Setting, and Participants  This double-blind, placebo-controlled randomized clinical trial included 397 adult patients with out-of-hospital cardiac arrest and was conducted in the Central Denmark Region between January 20, 2020, and April 15, 2021. The last 90-day follow-up was on July 15, 2021.

Interventions  The intervention consisted of up to 2 intravenous or intraosseous doses with 5 mmol of calcium chloride (n = 197) or saline (n = 200). The first dose was administered immediately after the first dose of epinephrine.

Main Outcomes and Measures  The primary outcome was sustained return of spontaneous circulation. The secondary outcomes included survival and a favorable neurological outcome (modified Rankin Scale score of 0-3) at 30 days and 90 days.

Results  Based on a planned interim analysis of 383 patients, the steering committee stopped the trial early due to concerns about harm in the calcium group. Of 397 adult patients randomized, 391 were included in the analyses (193 in the calcium group and 198 in the saline group; mean age, 68 [SD, 14] years; 114 [29%] were female). There was no loss to follow-up. There were 37 patients (19%) in the calcium group who had sustained return of spontaneous circulation compared with 53 patients (27%) in the saline group (risk ratio, 0.72 [95% CI, 0.49 to 1.03]; risk difference, −7.6% [95% CI, −16% to 0.8%]; P = .09). At 30 days, 10 patients (5.2%) in the calcium group and 18 patients (9.1%) in the saline group were alive (risk ratio, 0.57 [95% CI, 0.27 to 1.18]; risk difference, −3.9% [95% CI, −9.4% to 1.3%]; P = .17). A favorable neurological outcome at 30 days was observed in 7 patients (3.6%) in the calcium group and in 15 patients (7.6%) in the saline group (risk ratio, 0.48 [95% CI, 0.20 to 1.12]; risk difference, −4.0% [95% CI, −8.9% to 0.7%]; P = .12). Among the patients with calcium values measured who had return of spontaneous circulation, 26 (74%) in the calcium group and 1 (2%) in the saline group had hypercalcemia.

Conclusions and Relevance  Among adults with out-of-hospital cardiac arrest, treatment with intravenous or intraosseous calcium compared with saline did not significantly improve sustained return of spontaneous circulation. These results do not support the administration of calcium during out-of-hospital cardiac arrest in adults.

Trial Registration  ClinicalTrials.gov Identifier: NCT04153435

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