Intraosseous Calcium vs Saline for ROSC in OHCA

Dr. Lauren Friend and Dr. Eric Krueger

The Case

You receive a radio call form EMS that they are 5 minutes away with a 60-ish year-old John Doe that they have been doing CPR on for approximately 10 minutes. He was found by a member of the public who does not know the patient or have any medical history. No obvious signs of trauma.

Indications for Calcium During Cardiac Arrest? Hyperkalemia

  • High potassium levels decreased duration of survival in post-ROSC OHCA patients and were associated with reduced hemodynamic stability (4) (April 2018)

  • Serum potassium shown to have significant association with survival outcome for OHCA patients with hypokalemia associated with improved neurological outcome and survival (3)

  • High serum potassium is associated dose-dependently with poor neurological outcomes (6)

  • Serum potassium on hospital arrival is a prognostic indicator for achieving ROSC in OHCA patients (6)

The Paper

Design: Double-blind placebo-controlled randomized clinical trial

Time: January 2020 - April 2021

Location: Denmark

Journal: JAMA 2021 (Impact Factor 157.3)

Vallentin, M. F., Granfeldt, A., Meilandt, C., Povlsen, A. L., Sindberg, B., Holmberg, M. J., Iversen, B. N., Mærkedahl, R., Mortensen, L. R., Nyboe, R., Vandborg, M. P., Tarpgaard, M., Runge, C., Christiansen, C. F., Dissing, T. H., Terkelsen, C. J., Christensen, S., Kirkegaard, H., & Andersen, L. W. (2021). Effect of intravenous or intraosseous calcium vs saline on return of spontaneous circulation in adults with out-of-hospital cardiac arrest. JAMA, 326(22), 2268.

Some Background: Denmark

In 2018, Denmark had an estimated 30-day survival of 16% after out-of-hospital cardiac arrest (7). US varies from 8-16% (2).

All cardiac arrests in Denmark are responded to by an ambulance and a physician-manned mobile emergency care unit.


Administration of calcium during out-of-hospital cardiac arrest will result in improved return of spontaneous circulation.


Patients randomized to receive either 5mmol calcium or saline control

Could receive intervention via IV or IO routes

Administered immediately after first dose of epinephrine for up to 2 rounds

Primary Outcome: sustained ROSC — no further need for chest compressions x 20 minutes

Secondary Outcomes: survival at 30 days and survival at 30 days with favorable neurological outcome

Sample size calculation prior to study initiation estimated required 674 to achieve 80% power

Planned interim analysis at 50, 200, and 400 patients by independent safety monitoring committee

Inclusion Criteria

  • Out-of-hospital cardiac arrests

  • Received at least 1 dose of epinephrine during cardiac arrest

Exclusion Criteria

  • Traumatic cardiac arrest

  • Pregnancy

  • Prior enrollment

  • Receipt of epinephrine outside the trial

  • Clinical indication for calcium administration

Data Characteristics

  • Mean age 69 years

  • 29% female

Outcomes and Results

19% of patients in treatment groups sustained ROSC compared to 27% in control group (primary outcome)

At 30 days, 5.2% in treatment group vs. 9.1% in control group were alive (secondary outcome)

Favorable neurological outcome at 30 days was seen in 3.6% of treatment group vs. 7.6% of control group (secondary outcome)

*Median time from cardiac arrest to administration of drug was 18 minutes


  • Stopped early due to concerns about harm in calcium group

  • Very high ROSC rate in saline groups (about 2x generalized 2018 data)

  • Long time to drug delivery

  • Prehospital and international setting


Among out-of-hospital cardiac arrests, treatment with calcium did not significantly improve sustained ROSC.


  1. Alfonzo, A. "Survival after In-Hospital Hyperkalaemic Cardiac Arrest-Does Intravenous Calcium or Sodium Bicarbonate Influence Outcome?" Resuscitation, vol. 98, Jan. 2016, pp. A1-A2, 10.1016/j.resuscitation.2015.11.001. Accessed 1 Mar. 2020.

  2. Berger, Stuart. “Survival from Out-Of-Hospital Cardiac Arrest: Are We Beginning to See Progress?” Journal of the American Heart Association, vol. 6, no. 9, 22 Sept. 2017, 10.1161/jaha. 117.007469.

  3. Choi, Dong Sun, et al. “Relationship between Serum Potassium Level and Survival Outcome in Out-of-Hospital Cardiac Arrest Using CAPTURES Database of Korea: Does Hypokalemia Have Good Neurological Outcomes in Out-ofHospital Cardiac Arrest?" Advances in Clinical and Experimental Medicine, vol. 29, no. 6, 1 July 2020, pp. 727-734, 10.17219/acem/122178. Accessed 25 Nov. 2020.

  4. Lin, Yan-Ren, et al. “Impact of Different Serum Potassium Levels on Postresuscitation Heart Function and Hemodynamics in Patients with Nontraumatic Out-of-Hospital Cardiac Arrest." Bioinorganic Chemistry and Applications, vol. 2018, 5 Apr. 2018,, 10.1155/2018/5825929. Accessed 31 Aug. 2020.

  5. Morgenstern, Justin. “Calcium for of out Hospital Cardiac Arrest: The COCA Trial.” First10EM, 6 Dec. 2021, first Accessed 3 Aug. 2022.

  6. Shida, Haruka, et al. “Serum Potassium Level on Hospital Arrival and Survival after Out-of-Hospital Cardiac Arrest: The CRITICAL Study in Osaka, Japan." European Heart Journal. Acute Cardiovascular Care, vol. 9, no. 4_suppl, 1 Nov. 2020, pp. S175-5183,, 10.1177/2048872619848883. Accessed 3 Aug. 2022.

  7. Vallentin, Mikael Fink, et al. “Effect of Intravenous or Intraosseous Calcium vs Saline on Return of Spontaneous Circulation in Adults with Out-of-Hospital Cardiac Arrest." JAMA, vol. 326, no. 22, 14 Dec. 2021, p. 2268, 10.1001/jama.2021.20929. Accessed 8 Jan. 2022.