Intraosseous Calcium vs Saline for ROSC in OHCA
Dr. Lauren Friend and Dr. Eric Krueger
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)
Design: Double-blind placebo-controlled randomized clinical trial
Time: January 2020 - April 2021
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. https://doi.org/10.1001/jama.2021.20929
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
Out-of-hospital cardiac arrests
Received at least 1 dose of epinephrine during cardiac arrest
Traumatic cardiac arrest
Receipt of epinephrine outside the trial
Clinical indication for calcium administration
Mean age 69 years
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.
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.
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.
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.
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, www.ncbi.nlm.nih.gov/pmc/articles/PMC5907484), 10.1155/2018/5825929. Accessed 31 Aug. 2020.
Morgenstern, Justin. “Calcium for of out Hospital Cardiac Arrest: The COCA Trial.” First10EM, 6 Dec. 2021, first 10em.com/calcium-for-of-out-hospital-cardiac-arrest-the-coca-trial/#:~:text=There%20are%20definitely%20indications%20for. Accessed 3 Aug. 2022.
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, pubmed.ncbi.nlm.nih.gov/31081678/, 10.1177/2048872619848883. Accessed 3 Aug. 2022.
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.