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

Abstract

IMPORTANCEIt 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 PARTICIPANTSThis 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. INTERVENTIONSThe 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 MEASURESThe 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. RESULTSBased 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.

Calcium use during cardiac arrest: A systematic review

“…Forty-one studies were selected for full text analysis, ten studies were included for qualitative review, and nine were included for meta-analysis. Among them, three RCTs 7 , 8 , 11 and seven NRSI 5 , 10 , 21 , 22 , 23 , 24 , 25 were identified. One study included only patients with hyperkalemia measured during the cardiac arrest 10 and for this reason, we decided to exclude it from the quantitative analysis.…”

“…The three RCTs were blinded and compared calcium chloride with placebo (normal saline). 7 , 8 , 11 Two trials used a dose of 500 mg, 7 , 8 and the most recent trial used a 735 mg dose. 11 Calcium was administered only one time in the trials that used the 500 mg dose, 7 , 8 however, up to two doses were administered in the most recent trial.…”

“…The aforementioned study was stopped early due to concerns for possible harm. 11 The latest American Heart Association (AHA) guidelines from 2020 do not recommend the routine administration of calcium, chiefly based on non-randomised studies of this intervention. 12 Nevertheless, despite guideline recommendations, the use of calcium in intra-hospital cardiac arrest (IHCA) has increased since the 2000s.…”

Pre-hospital blood products and calcium replacement protocols in UK critical care services: A survey of current practice

“…The COCA trial of calcium in out of hospital medical cardiac arrest found no benefit and, although not reaching statistical significance, there was a trend for worse outcomes in patients who received calcium. 20 Studies have suggested that high levels of calcium immediately after administration may cause cytosolic and mitochondrial calcium overload during cardiac arrest leading to cardiac hypercontraction, 21. , 22.…”

Journal update monthly top five

“…This double-blinded, placebo-controlled randomised clinical trial (RCT) from Denmark examined the benefit of intravenous calcium during an OHCA for improving rates of sustained return of spontaneous circulation (ROSC). Previous RCTs reported improved point estimates with intravenous calcium, though not significant 2 3…”