Calcium and Sodium Bicarbonate Efficacy in Out of Hospital Cardiac Arrest

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.

EMS Protocol of the Week - Adult Respiratory Distress

Hi EM friends,

Time to take your breath away with another EMS protocol of the week. This week's focus will be on adult respiratory distress and how our prehospital counterparts initiate patient care prior to handing them off to us. A few months ago, we discussed the respiratory distress protocol for pediatric patients - a lot of overlap here except EMS providers have a couple more tricks up their sleeves when it comes to adults.

The prehospital approach to respiratory distress exists as a progression of care based on the provider's level of training. CFRs start with ABCs and monitoring vital signs. If needed, these providers can implement airway adjuncts and administer supplemental O2. All patients will be started off on a NRB unless the mask is not tolerated in which case O2 will be given via NC. At this level of training, CFRs can then address potential drug overdose. 

BLS crews can address all of the above and will then transport these patients to the hospital. They can additionally request ALS backup while en route. If available, CPAP therapy can be utilized for patients with persistent distress. 

If the on-scene team is ALS-trained, they can perform advanced airway management as necessary. From here, ALS providers will start cardiac monitoring, EKG interpretation, and establish IV access during transport. They can even assess and treat for a tension pneumothorax or administer Nitroglycerin for suspected flash pulmonary edema.

There is not a lot to be aware of from an OLMC standpoint, but providers have the option of authorizing Lasix to be given to patients that may benefit.

Also important to note, ALL patients who are received by EMS crews in respiratory arrest MUST receive ventilatory assistance unless an official DNR order and/or MOLST form is provided to the crew.

More words to read at www.nycremsco.org.

Best,

Zachary Kim, MD

PGY-2 Emergency Medicine

EMS Protocol of the Week - Undifferentiated Shock (Adult)

The new protocol for the adult patient in undifferentiated shock puts a lot of tools in the hands of paramedics. To be clear, the approach changes if there is a clear etiology for the shock, but for the patient who is in shock without a clear reason why, there’s now a protocol to assist! Providers at the BLS level will initiate transport procedures while checking a blood glucose level. ALS providers will obtain vascular access and check an EKG to look for a cardiac cause of the shock, after which they will initiate a 20mL/kg crystalloid bolus. If this doesn’t resolve the shock, paramedics can either administer a repeat bolus or start a vasopressor agent – options include infusions of norepinephrine or dopamine, or push-doses of epinephrine. After choosing an agent, if crews want to switch to a different agent (or give an additional one), OLMC can be used for additional orders. OLMC also has the option of authorizing vasopressin administration as another option.

Check the attached pdf for specifics in dosing, but overall this is a great summary of what’s now available in the paramedic’s toolbox for shock. Protocol binder or www.nycremsco.org for more.

Dave