So not to harp on this too much, but also at the behest of our EMS colleagues, I wanted to share a brief lit review on the efficacy of out of hospital cardiac arrest (OHCA) use, or lack thereof, of sodium bicarbonate (SB) and calcium use. This post is *different* than the prior ones as it focuses on out of hospital care! There is a TLDR at the bottom if you're a "I'm happy for you, or sorry that happened" kind of reader.
Calcium:
Calcium plays an important role in cardiac muscle contraction and is generally acknowledged for its inotropic and vasopressor effects. These effects could be beneficial 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. Since then there have been no randomized clinical trials assessing the effect of administration of calcium during cardiac arrest.
A randomized control in Denmark was done in 2020-2021 by Vallentine et al. (citation is at bottom of this post), which asked is calcium administration in OHCA improved ROSC compared to saline. Known as the Calcium for Out-of-Hospital Cardiac Arrest, or COCA Trial, patients were randomized to receiving calcium or saline after their first dose of epi. Primary outcomes were sustained ROSC for 20 minutes, and secondary outcomes were survival to 30 days and survival with favorable neurological outcome at 30 days.
This study found no significant difference between groups to get sustained ROSC. There was also no difference in survival or neurological outcomes at 30 days. Multiple follow up studies (also cited in the bottom of this post) were performed and found no improved outcomes at a year, and potential worse outcomes in the calcium group, suggesting harm.
Sodium Bicarbonate:
Sodium bicarbonate (SB) administration has been considered an important part of treatment for severe metabolic acidosis in cardiac arrest. Administration of SB seems a reasonable intervention to counteract the severe metabolic acidosis caused by hypoxia, poor perfusion and increased lactate production in cardiac arrest, in an attempt to mitigate the adverse effects of acidosis. Correction of metabolic acidosis with SB was recommended by early advanced cardiac life support (ACLS) guidelines published in 1976 and SB was the medication most frequently used during cardiac arrest until the mid-1980s. Data published in the 1970s raised concerns that SB administration during cardiac arrest can worsen the outcome after cardiac arrest and emphasized the adverse effects of bicarbonates, including increased osmolality.
ACLS guidelines this past decade have made SB a class III drug in OHCA (not recommended). However it is a class IIB (mild recommendation to give) for TCA overdose, hyperkalemia. A lit review by Velissaris et al. (again linked in the bottom of this post) summarized recent literature on the use of SB, which essentially can be summed up as, SB increases intracellular acidosis, reduces cardiac output, shifts oxygen dissociation curve to the left, hypernatremia, and hyperosmolarity. The bicarb also breaks down into CO2 and worsens tissue acidosis.
Another study, this by Kawano et al. examined the use of SB in OHCA, and found that its administration could worsen long term neuro outcomes. This was an observational study that included over 13,000 patients, and examined sustained ROSC, survival to 30 days, and favorable neurological outcomes at 30 days. SB groups had worse survival rates and worse neurological outcomes than the non-SB groups. Odds ratio for survival in SB group was 0.64, 95% CI 0.45-0.91, and the OR for favorable neuro outcome was 0.59, 95% CI 0.39-0.88. Obviously this is not a randomized control, but it does paint a poor picture of the use of this medication.
TLDR: Sodium bicarb and calcium have a litany of evidence showing they do not provide any benefit in OHCA, and there is increasing evidence that they may actually cause harm to give.
One final additional statistically tidbit I found fascinating while looking into these studies (which has less to do with SB and CC). A randomized control study on epi use in OHCA was performed in the UK by Perkins et al. This cited a number of other articles (all of which are cited below) to compare the number needed to treat for various interventions in ACLS. I wanted to present those here and let folks reflect on them.
NNT for epi in OHCA is 112
NNT for CPR by a bystander in OHCA is 15
NNT for early defibrillation in a shockable rhythm in OHCA is 5.
So second TLDR is early compressions and early application of pads during arrests are often the most life saving interventions we have! Happy reading and happy Tuesday!
Vallentin MF, Granfeldt A, Meilandt C, et al. Effect of Intravenous or Intraosseous Calcium vs Saline on Return of Spontaneous Circulation in Adults With Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA. 2021;326(22):2268–2276. doi:10.1001/jama.2021.20929
Vallentin MF, Granfeldt A, Meilandt C, Povlsen AL, Sindberg B, Holmberg MJ, Iversen BN, Mærkedahl R, Mortensen LR, Nyboe R, Vandborg MP, Tarpgaard M, Runge C, Christiansen CF, Dissing TH, Terkelsen CJ, Christensen S, Kirkegaard H, Andersen LW. Effect of calcium vs. placebo on long-term outcomes in patients with out-of-hospital cardiac arrest. Resuscitation. 2022 Oct;179:21-24. doi: 10.1016/j.resuscitation.2022.07.034. Epub 2022 Jul 30. PMID: 35917866.
Vallentin MF, Povlsen AL, Granfeldt A, Terkelsen CJ, Andersen LW. Effect of calcium in patients with pulseless electrical activity and electrocardiographic characteristics potentially associated with hyperkalemia and ischemia-sub-study of the Calcium for Out-of-hospital Cardiac Arrest (COCA) trial. Resuscitation. 2022 Dec;181:150-157. doi: 10.1016/j.resuscitation.2022.11.006. Epub 2022 Nov 18. PMID: 36403820.
Velissaris D, Karamouzos V, Pierrakos C, Koniari I, Apostolopoulou C, Karanikolas M. Use of Sodium Bicarbonate in Cardiac Arrest: Current Guidelines and Literature Review. J Clin Med Res. 2016 Apr;8(4):277-83. doi: 10.14740/jocmr2456w. Epub 2016 Feb 27. PMID: 26985247; PMCID: PMC4780490.
Kawano T, Grunau B, Scheuermeyer FX, Gibo K, Dick W, Fordyce CB, Dorian P, Stenstrom R, Straight R, Christenson J. Prehospital sodium bicarbonate use could worsen long term survival with favorable neurological recovery among patients with out-of-hospital cardiac arrest. Resuscitation. 2017 Oct;119:63-69. doi: 10.1016/j.resuscitation.2017.08.008. Epub 2017 Aug 10. PMID: 28802878.
Perkins GD, Ji C, Deakin CD, Quinn T, Nolan JP, Scomparin C, Regan S, Long J, Slowther A, Pocock H, Black JJM, Moore F, Fothergill RT, Rees N, O'Shea L, Docherty M, Gunson I, Han K, Charlton K, Finn J, Petrou S, Stallard N, Gates S, Lall R; PARAMEDIC2 Collaborators. A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. N Engl J Med. 2018 Aug 23;379(8):711-721. doi: 10.1056/NEJMoa1806842. Epub 2018 Jul 18. PMID: 30021076.
Berdowski J, Beekhuis F, Zwinderman AH, Tijssen JG, Koster RW. Importance of the first link: description and recognition of an out-of-hospital cardiac arrest in an emergency call. Circulation 2009;119:2096-2102.
Hasselqvist-Ax I, Riva G, Herlitz J, et al. Early cardiopulmonary resuscitation in out-of-hospital cardiac arrest. N Engl J Med 2015;372:2307-2315.
Kitamura T, Kiyohara K, Sakai T, et al. Public-access defibrillation and out-of-hospital cardiac arrest in Japan. N Engl J Med 2016;375:1649-1659.