You pick up a 58 year old patient from his home and he’s complaining of chest pain. You load him into the rig and get set to take off when he goes unconscious and unresponsive. The 12 lead you just placed on him tells you he just entered ventricular fibrillation. You immediately start high quality CPR while your partner starts searching for IV access. The monitor tells you to deliver a shock and right after the shock you administer your first suggested dose of Epinephrine. Your patient dies and you’re left to wonder how he died if you pushed Epinephrine, the drug that increases strength, pressure and rate within your heart. If you’re sitting there wondering why Epinephrine isn’t the cure all drug to any cardiac event, there have been some recently released studies that may surprise some of you.
Before we get into the blind study of Epinephrine. This drug has a lot of wonderful uses. Epinephrine is most notably used in anaphylaxis. Those with severe allergies and experiencing a severe reaction will inject a preloaded syringe into their thigh, commonly known as the EpiPen. The EpiPen delivers 0.3 mg of Epinephrine into adult patients and 0.15 mg into the pediatric population. When the Epinephrine enters the body it acts on the alpha-adrenergic receptors and causes vasodilation, or widening of the blood vessels which leads to decreased swelling. It also helps raise up the blood pressure, increase heart rate, relaxes muscles around the heart and airway to prevent compromised airways. Epinephrine can also reverse hives as well as puffy faces, lips and itchy throats. The most common side effects of an allergic reaction.
However we are here to talk about cardiac arrest and the effects Epinephrine has on the heart. Epinephrine is a high dose alpha 1 agonist. During CPR, Epi will increase the blood pressure and perfusion trying to achieve Return of Spontaneous Circulation (ROSC). After performing 2 minutes of high quality CPR and achieving an intravenous or intraosseous line, pushing 1 mg every 3 to 5 minutes is suggested. It is expected that with high quality CPR and giving repeat doses of Epinephrine every 3 to 5 minutes, you should get the heart to start and maintain perfusion after the dose. But unfortunately that’s not always the case, and for those who cannot achieve ROSC, studies suggest they have a long and challenging road ahead of them and will more likely than not experience mental and physical deficits for the remainder of their lives.
So why is Epinephrine the first line of drug for cardiac arrest if it’s not guaranteed to get essentially reverse the effects of cardiac arrest? If the drugs job is to increase the pressure and rate of the heart, why doesn’t it work essentially one hundred precent of the time? Luckily, the New England Journal of Medicine had the same questions. In August of 2018, NEJM reported a double blind trial from across the United Kingdom to test whether Epinephrine was safe and/or effective in patients in pre-hospital cardiac arrest. The test was simple, take “8014 patients with out-of-hospital cardiac arrest in the United Kingdom, paramedics at five National Health Service ambulance services administered either parenteral epinephrine (4015 patients) or saline placebo (3999 patients), along with standard care” (NEJM, 2018). The goal of the test was to measure the rate of survivability at the 30 day mark for cardiac arrest patients. Secondary to that was the rate of survivability with positive neurological outcomes post hospital discharge.
at the 30 day mark, 224 patients had survived and the difference isn’t as big as you might expect. 130 patients given doses of Epinephrine during their cardiac event survived, compared to the 94 patients given placebo doses. The secondary test showed, “There was no evidence of a significant difference in the proportion of patients who survived until hospital discharge with a favorable neurologic outcome” (NEJM, 2018). 2.2 % of those patients that received the Epinephrine medication had a favorable outcome compared to the 1.9% of those that didn’t.
In this research, the numbers are very close for the patients to receive Epinephrine and the patients to receive the placebo drug. Their survivability rates and favorable neurological outcomes are very close, and I’m sure a lot closer than most expected. There’s no denying there is a higher rate of survivability in those who receive Epinephrine. But the most important thing to take away from this trial is, “there was no significant between-group difference in the rate of a favorable neurologic outcome because more survivors had severe neurologic impairment in the epinephrine group” (NEJM, 2018).
Another study regarding Epinephrine use in prehospital care comes from the other side of the globe in the national out-of-hospital cardiac arrest data registry in Japan. This study is very similar in the one provided by the New England Journal of Medicine. The purpose of this study in Japan was to find, “The effect of prehospital epinephrine on neurological outcome in out-of-hospital cardiac arrest” as well as, “determine whether prehospital epinephrine administration was associated with improved outcomes in adult OHCA” (Fukuda, et. al, 2016). This study brings to light that epinephrine is being sought out all over the world, not just here in the United States.
This study looked at the nation as a whole in Japan. It was measured over the course of a two year period, from January 1, 2011 to December 31, 2012. The study included adult only out-of-hospital cardiac arrest patients treated by emergency medical personnel without delay. In all, 237,068 patients were included in the study, more specifically 16,616 patients with a shockable rhythm and 220,452 patients with a non-shockable rhythm. And to break it down even further, “A total of 4024 out of the 16,616 shockable OHCAs and 29,393 out of the 220,452 non-shockable OHCAs received prehospital epinephrine” (Fukuda, et. al, 2016). The remaining patients from these subgroups received no Epinephrine at all during the cardiac arrest event.
At the end of this study, prehospital epinephrine showed significantly poor neurological outcomes in all groups associated with the study. However, in the ancillary report, “the neurological outcome was worse as the number of epinephrine doses increased or the time to epinephrine increased, patients had a greater chance of a favorable neurological outcome only when a single dose of epinephrine was administered within 15 min of the emergency call in shockable out-of-hospital cardiac arrest” (Fukuda, et. al, 2016). With these type of findings, it could be suggested that it might not be so much that giving Epinephrine in cardiac arrest is bad for the patients. But it’s the amount of Epinephrine given in an out-of-hospital cardiac event. Perhaps a one time dose instead of repeated doses may improve neurologic outcomes for patients. All in all though the conclusion of this study showed that among all the out-of-hospital cardiac arrest patients in Japan to receive Epinephrine was associated with much smaller chance of having a favorable neurological outcome.
With these studies taking place of whether Epinephrine is good or not for out-of-hospital cardiac arrest, it’s important to have a study testing alternatives to Epinephrine and the possible positive or negative outcomes it might have. In this instance, another study reported by the New England Journal of Medicine compares the outcomes of patients given either Epinephrine or Vasopressin. Vasopressin’s goal in cardiac arrest is to increase the aortic diastolic and coronary perfusion pressure, coronary and cerebral blood flow, as well as oxygen delivery.
This study is like the other two discussed in this essay. Randomly assigned adult patients who experienced out-of-hospital cardiac arrest given either 20 IU of Vasopressin or 1 mg of Epinephrine. The end goal of this experiment was survival to hospital admission and then survival to hospital discharge. The end of the study showed, “effects of vasopressin were similar to those of epinephrine in the management of ventricular fibrillation and pulseless electrical activity, but vasopressin was superior to epinephrine in patients with asystole” (NEJM, 2004). The conclusion also suggests that Vasopressin followed by epinephrine could prove to be more helpful than just epinephrine alone in out-of-hospital cardiac arrest.
With this study reported by the New England Journal of Medicine as well as the study conducted in Japan, we saw that giving Epinephrine to patients in cardiac arrest showed favorable statistics in survivability compared to those not given any during their cardiac arrest. However, the study states those survivors who were given Epinephrine had severe neurological deficits up to hospital admittance as well as hospital discharge. The alternative we looked at suggested giving Vasopressin compared to Epinephrine didn’t show much of a difference either. So in this case I guess you need to ask yourself, is it worth giving Epinephrine as the first line drug in a major cardiac event. You have a decent chance of surviving, but at what cost if you suffer mental impairments. After reading these studies from the New England Journal of Medicine as well as the study from Japan, I am definitely more interested in finding more testings like this and finding out if Epinephrine really should be the first line drug for the next cardiac arrest case.