
It is time to reassess our long and established approach to out-of-hospital cardiac arrest management, writes Dr. Bryan E. Bledsoe.
In the late 1980s, as a young resident physician, I remember responding to a cardiac arrest on a medical floor in the hospital. The patient was an elderly person. I was not the senior person there and resuscitation was being run by a third-year internal medicine resident. This patient was reportedly admitted for altered mental status and the workup was underway. The patient was found unresponsive by nursing staff and CPR had been started. I remember that we performed compressions and ventilations for almost 45 minutes. The patient received multiple medications including epinephrine, atropine, sodium bicarbonate, calcium chloride, aminophylline, lidocaine and others. We emptied a whole drawer of medications from the resuscitation cart into this patient.
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Ultimately, the senior resident determined that resuscitation efforts were futile and the patient was pronounced dead. As the senior resident was walking out of the room, he looked at me and said: “At least we know his electrolytes were in balance.” I thought to myself: “I doubt his family could care less about the patient’s electrolyte balance. They want to know if he’s going to come home for Thanksgiving dinner.” But, in that era, there was nothing that was done during that resuscitation that was wrong based upon the science of the day. The problem was that the science regarding medications in cardiac arrest resuscitation was very limited and almost anecdotal. Today, we know more. But, in many instances, protocols and guidelines have not changed and our patients are not benefiting from what we are doing. Here are some facts (as of this writing):
1. No medication has been shown to improve long-term survival in human cardiac arrest.
It’s that simple. No medication has been shown to improve survival in human cardiac arrest. Every medication used in the past for cardiac arrest was given with presumptive benefit. Epinephrine was thought to stimulate the heart and to constrict peripheral blood vessels to increase blood pressure. Vasopressin was often given for the same reasons. Sodium bicarbonate was given to buffer the known metabolic acidosis associated with cardiac arrest. Atropine was often given based on the theory that the cardiac arrest may have been caused by an unexplained increase in vagal tone, thus slowing or stopping the heart. Various antidysrhythmic medications (lidocaine, procainamide, bretylium, amiodarone and others) were given to stabilize the cell membranes in the heart and treat and prevent dysrhythmias and improve the odds of successful defibrillation. Multiple other medications have been recommended such as aminophylline, dexamethasone, glucose, insulin and others. None have shown improvement in long term survival.
2. Empiric sodium bicarbonate in cardiac arrest is of no proven benefit.
Cardiac arrest results in both respiratory and metabolic acidosis. If the patient is not breathing or the heart is not beating, metabolic acids and carbon dioxide (CO2) levels will quickly rise and systemic acidosis will result. It seemed intuitive that giving an alkalizing agent (sodium bicarbonate) would slow or correct the acidosis and chances of successful resuscitation would be enhanced. However, when the role of sodium bicarbonate in cardiac arrest was studied, no long-term benefit could be discerned. A systematic review and meta-analysis of the use of sodium bicarbonate in cardiac arrest was recently completed and published. The researchers found eight studies that addressed out-of-hospital cardiac arrest (OHCA). The analysis of these papers showed that use of sodium bicarbonate was not associated with improvement in survival to discharge, return of spontaneous circulation (ROSC), rate of sustained ROSC and good neurological outcomes at hospital discharge. Until further evidence is found, emergency personnel are advised not to routinely administer sodium bicarbonate in OHCA patients.1 A similar meta-analysis and systemic review of sodium bicarbonate use in pediatric cardiac arrest found no discernable benefit.2 In 2010, the American Heart Association (AHA) recommended against routinely giving sodium bicarbonate in cardiac arrest. Yet, it is still widely used in EMS.3 When questioned about this practice, several reasons are often given. Some will hypothesize that since the patient is dying, what’s the harm of giving the drug? While there may be no harm, the safety of empiric sodium bicarbonate has never been studied. It may, in fact, be harmful. Some report giving it “just in case” the patient has a metabolic abnormality. Some state that hyperkalemia may be present. First, hyperkalemia is most common in patients with chronic kidney disease (e.g., dialysis patients). Sodium bicarbonate has never been shown to significantly lower potassium levels in hyperkalemia.4 Others give it “just in case” the cardiac arrest is due to overdose with tricyclic antidepressant (TCA) medications. Sodium bicarbonate does play a role in the treatment of serious TCA overdoses.5 However, TCAs are rarely used anymore as there are numerous safer and more effective medications available. Giving empiric sodium bicarbonate “just in case” the patient has overdosed on TCAs or might have a metabolic abnormality is poor medicine and not recommended.
3. Empiric administration of calcium salts in cardiac arrest is of no proven benefit.
As with sodium bicarbonate, many continue to administer calcium salts (calcium chloride, calcium gluconate) in cardiac arrest. However, there have been no studies that show benefit in cardiac arrest and it is not recommended.6,7 While there may be some benefit to calcium salts in cardiac arrest in dialysis or chronic kidney disease patients because of hyperkalemia, these conditions are not frequently encountered in most cardiac arrest cases. Routine administration of calcium salts in cardiac arrest is not recommended.
4. Empiric administration of antidysrhythmic medications in cardiac arrest is of no proven benefit.
Numerous antidysrhythmic medications have been used in cardiac arrest resuscitation. However, to date, none have shown any improvement in long-term survival or other benefit. A systematic review and meta-analysis found that, based on the current literature and data, there is no conclusive evidence that any antidysrhythmic medication improves the rates of ROSC, survival to admission, survival to discharge or neurological outcomes. Also, many of these medications have significant side-effects. Given the side-effects of some of these agents, further research is needed before they are placed in current cardiopulmonary resuscitation guidelines.8
5. Despite the American Heart Association’s guidelines, routine use of epinephrine in cardiac arrest is of no proven benefit.
Epinephrine (adrenaline) has been used in the treatment of cardiac arrest since the late 1800s. In fact, all the way to the modern era, epinephrine has been the primary drug used in cardiac arrest resuscitation attempts. However, supporting literature as to the benefit of epinephrine has been limited or of poor quality. More recently, several studies have been published that have taken a critical look at the use of epinephrine in cardiac arrest.
The PARAMEDIC 2 study was published in 2018. It was a randomized double-blind placebo-controlled study where patients either received normal saline (placebo) or epinephrine (EMS personnel did not know what was in the syringes). The 30-day survival was better for the patients who received epinephrine (3.2% for those who received epinephrine and 2.4% for those who received saline). However, neurological outcomes were worse for those who received epinephrine (31% with serious neurological injury for those receiving epinephrine versus 17.8% for those who received saline). Epinephrine did not improve survival with good neurological outcomes.9
An Australian randomized double-blind placebo-controlled study comparing epinephrine to normal saline (placebo) and found that while epinephrine improved the rate of ROSC, it did not result in improved survival to hospital discharge.10
A Japanese before and after study found similar results. While epinephrine was associated with improved ROSC, it was not associated with improved long-term survival. In fact, it had a negative effect on both long-term survival and neurologic impairment.11 Similar studies demonstrated the same outcomes (improved ROSC, but no change in long-term survival or neurologic status).12
Some have recommended the administration of epinephrine before defibrillation. However, the benefits of this strategy have never been demonstrated. In fact, some studies have shown worsened outcomes with this regimen. Survival was worse for patients who received epinephrine before defibrillation.13
Despite the evidence to the contrary, the AHA still recommends the routine use of epinephrine in cardiac arrest. However, there is an evolving push from the scientific community to base the AHA guidelines on the prevailing science.14,15 Overall, while more studies are needed, there is no significant evidence of benefit from routine administration of epinephrine in cardiac arrest and there is a clear propensity for worsened neurological outcomes.
6. If they are going die anyway, what’s the harm of giving these medications?
There are several issues here. Concerns about the administration of pharmacological agents may take away from the only therapies proven to improve outcomes and survival in cardiac arrest—early defibrillation and high-quality CPR. Worries about medications, intravenous lines, definitive airways, mechanical CPR devices, pulse checks, POCUS and similar issues can detract from providing the only therapies with proven benefit. Furthermore, if the patient fails to respond to early defibrillation and high-quality CPR, transport to the hospital for continued resuscitative measures is unlikely to be of benefit. The United States is behind other parts of the world in EMS termination of cardiac arrest resuscitation efforts in the out-of-hospital setting.16,17 Oftentimes, EMS personnel will fail to obtain ROSC on scene yet transport to the hospital with poor-quality CPR and poor ventilation continued during the transport. Once in the emergency department, resuscitative measures are continued but, more often than not, are futile and unsuccessful.
It is time to reassess our long and established approach to OHCA management.EMS personnel should assess cardiac arrest victims for factors that can adversely impact cardiac arrest survival (no ROSC prior to transport, no shock delivered, no bystander CPR and the arrest was not witnessed by bystanders or EMS). The use of various medications in cardiac arrest, despite years of historical use, provides no added benefit. Our approach to cardiac arrest survival should focus on bystander CPR, early defibrillation, high-quality (uninterrupted CPR) and similar factors. When reviewing the science, it is important to distinguish the in-hospital cardiac arrest (IHCA) literature from OHCA literature. The distinction between the two is significant. IHCA is common in hospitalized patients in the United States. As compared with patients who suffer an OHCA, patients who experience an IHCA tend to have more medical comorbidities, have a witnessed arrest, and be attended to by professional first responders. Also, providers resuscitating patients from IHCA commonly have access to tools and information not readily available to the OHCA responders. Despite these differences, EMS guidelines for OHCA are often based upon data from with IHCA (and vice versa). In terms of OHCA, patients who do not respond to validated and proven treatment measures should be considered for field termination of resuscitation. EMS protocols and guidelines should reflect the current, and not historic, OHCA science.18
References
1. Alshahrani MS, Aldandan HW. Use of sodium bicarbonate in out-of-hospital cardiac arrest: a systematic review and meta-analysis. Int J Emerg Med. 2021;14(1):21.
2. Chang CY, Wu PH, Hsiao CT, Chang CP, Chen YC, Wu KH. Sodium bicarbonate administration during in-hospital pediatric cardiac arrest: A systematic review and meta-analysis. Resuscitation. 2021;162:188-197.
3. Glover BM, Brown SP, Morrison L, et al. Wide variability in drug use in out-of-hospital cardiac arrest: a report from the resuscitation outcomes consortium. Resuscitation. 2012;83(11):1324-1330.
4. Abuelo JG. Treatment of severe hyperkalemia: confronting 4 fallacies. Kidney Int Rep. 2018;3(1):47-55.
5. Mirrakhimov AE, Ayach T, Barbaryan A, Talari G, Chadha R, Gray A. The role of sodium bicarbonate in the management of some toxic ingestions. Int J Nephrol. 2017;2017:7831358.
6. Landry A, Foran M, Koyfman A. Does calcium administration during cardiopulmonary resuscitation improve survival for patients in cardiac arrest? Ann Emerg Med. 2014;64(2):187-189.
7. Kette F, Ghuman J, Parr M. Calcium administration during cardiac arrest: a systematic review. Eur J Emerg Med. 2013;20(2):72-78.
8. Chowdhury A, Fernandes B, Melhuish TM, White LD. Antiarrhythmics in cardiac arrest: a systematic review and meta-analysis. Heart Lung Circ. 2018;27(3):280-290.
9. Perkins GD, Ji C, Deakin CD, et al. A randomized trial of epinephrine in out-of-hospital cardiac arrest. N Engl J Med. 2018;379(8):711-721.
10. Jacobs IG, Finn JC, Jelinek GA, Oxer HF, Thompson PL. Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial. Resuscitation. 2011;82(9):1138-1143.
11. Hagihara A, Hasegawa M, Abe T, Nagata T, Wakata Y, Miyazaki S. Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest. JAMA. 2012;307(11):1161-1168
12. Olasveengen TM, Wik L, Sunde K, Steen PA. Outcome when adrenaline (Epinephrine) was actually given vs. not given – post hoc analysis of a randomized clinical trial. Resuscitation. 2012;83(3):327-332.
13. Evans E, Swanson MB, Mohr N, et al. Epinephrine before defibrillation in patients with shockable in-hospital cardiac arrest: propensity matched analysis. BMJ. 2021;375:e066534.
14. Bornstein K, Long B, Porta AD, Weinberg G. After a century, Epinephrine’s role in cardiac arrest resuscitation remains controversial. Am J Emerg Med. 2021;39:168-172
15. Long B, Koyfman A. Emergency medicine myths: epinephrine in cardiac arrest. J Emerg Med. 2017;52(6):809-814.
16. Libby C, Skinner RB, Rawal AR. Ems termination of resuscitation and pronouncement of death. In: StatPearls. StatPearls Publishing; 2022.
17. Morrison LJ, Verbeek PR, Vermeulen MJ, et al. Derivation and evaluation of a termination of resuscitation clinical prediction rule for advanced life support providers. Resuscitation. 2007;74(2):266-275.
18. Moskowitz A, Holmberg MJ, Donnino MW, Berg KM. In-hospital cardiac arrest: are we overlooking a key distinction? Curr Opin Crit Care. 2018;24(3):151-157.