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.

Frostbite

Frostbite is a condition that occurs when skin and underlying tissues freeze due to exposure to cold temperatures. It occurs due to vasoconstriction, resulting in decreased blood flow (which would deliver heat) to tissues, and this leads to ice crystal formation. Frostbite most often occurs due to exposure at temperatures of less than -20°C (that includes wind chill). Freezing alone typically does not cause tissue damage. Thawing is what worsens the damage by disrupting the endothelium of cells. The blood flow of skin is normally around 250 ml/min, but in tissue damaged by frostbite, drops to 20-50 ml/min. This endothelial damage leads to swelling, platelet aggregation, and potentially thrombosis (in the form of microthrombi due to decreased intravascular flow). 

Exposed and wet skin are the most likely to be damaged. Most likely areas are feet, hands, ears, lips, and nose. Risk factors for frostbite include patients that are colder temperatures, wind chill, no shelter, prolonged exposure, exposure while wet, patients with EtOH use. Patients with medical conditions that impact vasculature are also at increased risk, including diabetes, PVD, and smokers.

Classifications of Frostbite:

1. First Degree: Involves superficial skin freezing, causing redness and irritation, but usually has good recover

   • Symptoms include stinging and burning, eventually throbbing

   • Patients typically develop erythema, swelling, and have desquamation later

2. Second Degree: Involves freezing of the skin and deeper tissues, resulting in blistering and swelling, but usually has good recovery

   • Symptoms include numbness, then followed by aching and throbbing

   • Patients typically have extensive edema for hours, then develop blisters after that, and desquamate over the course of days

3. Third Degree: Involves freezing extending to subcutaneous tissues, leading to deep tissue damage, usually has poor recovery

   • Symptoms include extremities feeling heavy, then burning, throbbing, and shooting pains

   • Patient with third degree frostbite will develop hemorrhagic blisters

4. Fourth Degree: The most severe form, involving freezing of muscles, tendons, and bone, often leading to irreversible damage

   • Symptoms include a deep, aching pain

   • Skin becomes mottled, and deep eschar forms

Management:

• Treat hypothermia first! Rewarm core temperature, otherwise at risk of reinjuring the patient if their extremities are re-exposed to cold again

• Remove wet clothing

• Place extremities in a 40-42°C bath for 20-30 min

  • Care should be made to not rewarm too quickly, otherwise you risk worsening reperfusion injuries

  • For areas that can not be placed in a bath (nose, ears, etc) can use a warm, wet towel

• Rewarming is considerably painful and should be treated with aggressive pain control

• Wound care should be undertaken

  • Wrap wounds with sterile, dry gauze

  • Keep effected extremities elevated

  • Do not remove blisters

  • Have a high clinical suspicion for possible compartment syndrome

• Patients with full thickness injuries and no evidence of reperfusion after rewarming should be considered for tPa therapy which may reduce the risk of digital amputation

• Patients should receive tetanus vaccination

Complications of frostbite

Patients can develop hypersensitivity to the cold with pain and ongoing numbness. Many patients can develop arthritis, can have loss of nails, cracked skin, atrophy of muscles. If tissue ischemia is severe, debridement may end up being necessary for extreme cases.

Example of Stage 3 injury

Basit H, Wallen TJ, Dudley C. Frostbite. [Updated 2023 Jun 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-Available from: https://www.ncbi.nlm.nih.gov/books/NBK536914/

Handford C, Thomas O, Imray CHE. Frostbite. Emerg Med Clin N Am. 2017;35(2):281–299.

Frostbite. Orthobullets. (n.d.). https://www.orthobullets.com/hand/12105/frostbite 

Hypothermia

Hypothermia is a medical emergency characterized by a core body temperature below the normal range of 95°F (35°C).

Causes of Hypothermia:

1. Increased heat loss

   • Homeless population

   • Elderly patients

   • Submersion injuries

   • Drugs, EtOH, CO poisoning can all cause increased vasodilation, leading to increased heat loss

2. Decreased heat production

   • Endocrine (hypothyroidism, hypoadrenalism, hypoglycemia)

   • Erythrodermas (psoriasis, exfoliative dermatitis, eczema, burns)

   • Impaired shivering

   • Impaired thermoregulation

   • Sepsis

Swiss Hypothermia Staging System:

Stage 1: Mild (32-35°C) - Shivering, mild confusion, awake

Stage 2: Moderate (28-32°C) - Severe shivering, altered mental status

Stage 3: Severe (20-28°C) - Loss of consciousness, bradycardia, shivering may cease

Stage 4: Profound (<20°C) – Unobtainable vital signs

Associated Complications:

1. Cardiac dysfunction

   1. Dysrhythmias can occur when body temperature drops below 30°C

   2. There is typically a drop in temperature and MAP after rewarming is started due to vasoconstriction

2. Cold injuries (frostbite, etc. Maybe there will be more on this at a later date)

3. Coagulopathy (patient may be coagulopathic despite normal labs because the lab rewarms the sample)

   1. Impaired clotting function

   2. Thromboembolism (due to hemoconcentration and poor circulation)

   3. DIC

4. Impaired pharmacology

   1. Protein binding increases when temperature drops, rendering drugs ineffective

   2. Oral meds are not absorbed well due to decreased GI motility

   3. IM route is impaired due to vasoconstriction

5. Rhabdomyolysis

General Management:

1. Airway, Breathing, Circulation (ABCs)

   • Hypothermia causes a leftward shift in oxygen curve so support with oxygen, and prepare for intubation depending on how profound the hypothermia is

2. ECG Findings

   • Patients usually have sinus bradycardia, can progress to a fib with slow ventricular response

   • Severe cases can develop v fib

   • Osborn or "J" waves (associated with moderate to severe hypothermia)
     

3. Remove Wet Clothing - Prevent further heat loss

4. Passive External Rewarming - Insulate the patient, provide warm blankets

5. Active External Rewarming (should be done for moderate hypothermia)

   • Use forced warm air blankets or radiant heaters – our ED uses the Bair Hugger

6. Active Internal Rewarming (for severe hypothermia)

   • Warmed intravenous fluids (warmed to 38-42°C)

• Heated humidified oxygen

• Various lavages (Thoracic, peritoneal, bladder, GI)

Management during Cardiac Arrest:

1. CPR – initiate if patient does not have a pulse (should also assess if patient is still breathing)

   • It is challenging to assess vital signs in hypothermic patients - use end tidal or POCUS to help assist to see if patient is breathing and has cardiac function

   • Starting CPR if the patient does have a pulse may precipitate ventricular rhythms

   • Hypothermic patients have higher chances of improved neurological outcome and survival than normothermic patients that arrest

2. Defibrillation

   • Use defibrillation if indicated, but note that hypothermic patients may not respond to defibrillation until adequately warmed

3. ECMO

   • Patients with refractory hypothermia should be considered for ECMO

   • Patients with out-of-hospital-cardiac-arrest that are hypothermic should ideally be transported to an ECMO center

   • If patient is unstable (dysrhythmia, severe hypothermia, etc) ECMO teams should be contacted early in the ED visit

Stay warm out there this weekend!

Paal P, Pasquier M, Darocha T, Lechner R, Kosinski S, Wallner B, Zafren K, Brugger H. Accidental Hypothermia: 2021 Update. Int J Environ Res Public Health. 2022 Jan 3;19(1):501. doi: 10.3390/ijerph19010501. PMID: 35010760; PMCID: PMC8744717.

Baumgartner EA, Belson M, Rubin C, Patel M. Hypothermia and other cold-related morbidity emergency department visits: United States, 1995-2004. Wilderness Environ Med 2008;19:233-237

Brown et al., Accidental Hypothermia. N Engl J Med 2012; 367:1930-1938