Calcium plays a key role in cardiac muscle contraction and is generally known for its inotropic and vasopressor effects, which could be helpful in the setting of cardiac arrest.
"Two small, randomized trials from 1985, including a total of 163 patients, found that administration of calcium did not result in a significant increase in return of spontaneous circulation for patients with out-of-hospital cardiac arrest and asystole or pulseless electrical activity. However, both trials had point estimates that favored calcium," Dr. Lars W. Andersen with Prehospital Emergency Medical Services in Aarhus, Denmark, and colleagues note in JAMA.
To investigate further, they conducted the Calcium for Out-of-Hospital Cardiac Arrest trial, randomly assigning adults with out-of-hospital cardiac arrest to up to two intravenous or intraosseous doses of 5 mmol calcium chloride or saline, with the first dose administered immediately after the first dose of epinephrine.
The steering committee stopped the trial early over concerns about possible harm in the calcium group.
The primary outcome of sustained return of spontaneous circulation occurred in more patients in the saline group (53 of 198, 27%) than the calcium group (37 of 193, 19%), a difference approaching statistical significance (P=0.09). At 30 days, more patients in the saline group than the calcium group were alive (9.1% vs. 5.2%, P=0.17).
"Although not reaching statistical significance, patients receiving calcium had worse outcomes, including worse 30-day survival with a favorable neurological outcome. At 90 days, fewer patients in the calcium group had a favorable neurological outcome and quality of life was lower in survivors," the study team reports.
Among the patients with calcium values measured who had return of spontaneous circulation, 74% in the calcium group had hypercalcemia versus 2% in the saline group.
The researchers say strengths of the study include blinded administration of calcium, delivered quickly after epinephrine, and with few protocol deviations.
Limitations include the early halt to the trial. "Even though continuing the trial would have resulted in more precise estimates of the treatment effect, it was not considered ethically justified to continue after the results of the interim analysis were evident. This decision was consistent with the recommendations from the independent data and safety monitoring committee," the researchers write.
The trial also only tested one dosing regime and timing and the results cannot necessarily be extrapolated to other doses or a different timing interval.
The authors note that calcium is often administered to patients with in-hospital cardiac arrest, a situation not addressed by their study; they say the rationale for this practice is "unclear."
Their findings suggest that the "administration of calcium to an unselected cardiac arrest population is unlikely to result in improved outcomes and may in fact result in worse outcomes," the researchers conclude.
Results of the study were presented in part on a Critical Care Reviews livestream on November 30, 2021.
SOURCE: https://bit.ly/3d1OS1x JAMA, online November 30, 2021.
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