Calcium does not significantly improve return of spontaneous circulation in adults with out-of-hospital cardiac arrest

1. Among adult patients with out-of-hospital cardiac arrest, treatment with intravenous or intraosseous calcium compared with saline did not significantly improve sustained return of spontaneous circulation.

2. Calcium administration during out-of-hospital cardiac arrest in adults is not supported by the study findings and currently not recommended.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Calcium plays an essential role in the regulation and contraction of cardiac myocytes with inotropic and vasopressor effects. However, it is unclear whether administration of calcium has any beneficial effects in the setting of cardiac arrest. This double-blind, randomized, placebo-controlled clinical trial from Denmark sought to address the hypothesis that administration of calcium during out-of-hospital cardiac arrest would result in improved return of spontaneous circulation. The main endpoint was sustained return of spontaneous circulation. The secondary endpoints included survival and a favorable neurological outcome (modified Rankin Scale score of 0-3) at 30 days and 90 days. Among 391 patients with out-of-hospital cardiac arrest, 19% achieved sustained return of spontaneous circulation after administration of intravenous or intraosseous calcium compared to 27% after saline administration, a nonsignificant difference. However, the trial was stopped early due to concerns about harm in the group receiving calcium. These findings suggested that treatment with intravenous or intraosseous calcium did not significantly improve sustained return of spontaneous circulation in adults with out-of-hospital cardiac arrest. Thus, calcium administration during out-of-hospital cardiac arrest in adults is not supported by the study findings and currently not recommended. A limitation of this study was the premature termination of the trial resulting in a smaller sample size than originally planned. However, given the results of the interim analysis, enrollment of further patients in the trial to achieve more precise estimates of the treatment effect was not ethically justified.

Click to read the study in JAMA

Relevant Reading: Calcium administration during cardiac arrest: a systematic review

In-Depth [randomized controlled trial]: This double-blind, placebo-controlled randomized clinical trial included 391 patients (mean age [SD], 68 [14] years; 114 [29%] female) with out-of-hospital cardiac arrest from the Central Denmark Region between January 2020 and April 2021, with follow-up until July 2021. The intervention consisted of up to 2 intravenous or intraosseous doses of calcium chloride (n = 193) or saline (n = 198). No patients were lost to follow-up. However, based on a planned interim analysis of 383 patients, the trial was terminated early due to concerns about harm in the calcium group. In total, 37 patients (19%) in the calcium group sustained return of spontaneous circulation compared with 53 patients (27%) in the saline group (RR, 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 (RR, 0.57 [95%CI, 0.27 to 1.18]; risk difference, −3.9% [95%CI, −9.4%to 1.3%]; P = .17), where a favorable neurological outcome was observed in 7 patients (3.6%) in the calcium group and 15 patients (7.6%) in the saline group (RR, 0.48 [95%CI, 0.20 to 1.12]; risk difference, −4.0% [95%CI, −8.9%to 0.7%]; P = .12). Lastly, among 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.

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