Epinephrine Death Watch

Yesterday the American Medical Association published a landmark study (nonrandomized, observational) challenging conventional wisdom and possibly tolling the death knell for the use of epinephrine in cardiac arrest. In a study encompassing over 400,000 out-of-hospital cardiac arrests in Japan from 2005-2008, researchers are declaring that epinephrine in cardiac arrest may lead to worse survival and neurological outcomes than no drug at all. While their study also shows epinephrine leads to increased rates of return of spontaneous circulation (18% to 5%), despite this seemingly positive link to return of circulation, they are suggesting the longer term deleterious effects of the epinephrine may outweigh the short term positive effects. This study now clears the way for what previously would have been an unethical (because epi has been the standard of care) study – a randomized, blinded trial of epinephrine versus placebo.

The article and accompanying editorial are available to be read at the following links.

Prehospital Epinephrine Use and Survival Among Patients With Out-of-Hospital Cardiac Arrest

Questioning the Use of Epinephrine to Treat Cardiac Arrest

Twenty years in the field have taught me that getting pulses back with epi, particularly on a patient with asystole or PEA, does not mean the patient is going to walk out of the hospital. It feels great to get pulses and pressure back and have the patient start to breathe on their own, but in most cases, their name shows up in the obituaries within a week or two. They either die or their family faced with confirmed brain death agrees to pull the plug. I did a call a week ago – a patient in asystole who with a quick combitube, good CPR, and two doses of epi had pulses back. Some dopamine, normal saline, a fourth floor carry down and transport with no loss of circulation, had us all shaking each other’s hands. Yet each day, I check the obits looking for the patient’s name, just as I did a month ago for another patient who came back from asystole with a single dose of epi only to show up in the death pages a week later. Epi seems to jump start their hearts, but its effect on the brain may be a different story. Most of my true saves have been people who have dropped in public, gotten bystander CPR and come back with defibrillation. Years ago they said high-dose epi was bad for the patient, today it looks like any epi at all may be bad.

Now I am on a new death watch. As I have checked the obits for the names of my patients, in 2015, I will check the new AHA guidelines checking for epinephrine’s demise.


  • Brett says:

    So CPR, Delay Tube and use BLS Airway if it works, Defib, and no epi… Im not seeing a need for paramedic care if this trend continues. Combi-Tubes could be handled by BLS crews and an AED removes my LP-15. Epi is all i have left!

  • Peter says:

    Good observation, Brett-

    This major study (below) showed that ALS care makes no difference in cardiac arrest outcome.

    N Engl J Med. 2004 Aug 12;351(7):647-56.
    Advanced cardiac life support in out-of-hospital cardiac arrest.
    Stiell IG, Wells GA, Field B, Spaite DW, Nesbitt LP, De Maio VJ, Nichol G, Cousineau D, Blackburn J, Munkley D, Luinstra-Toohey L, Campeau T, Dagnone E, Lyver M; Ontario Prehospital Advanced Life Support Study Group.
    SourceDepartment of Emergency Medicine, Ottawa Health Research Institute, University of Ottawa, Ottawa Ont, Canada. istiell@ohri.ca

    BACKGROUND: The Ontario Prehospital Advanced Life Support (OPALS) Study tested the incremental effect on the rate of survival after out-of-hospital cardiac arrest of adding a program of advanced life support to a program of rapid defibrillation.

    METHODS: This multicenter, controlled clinical trial was conducted in 17 cities before and after advanced-life-support programs were instituted and enrolled 5638 patients who had had cardiac arrest outside the hospital. Of those patients, 1391 were enrolled during the rapid-defibrillation phase and 4247 during the subsequent advanced-life-support phase. Paramedics were trained in standard advanced life support, which includes endotracheal intubation and the administration of intravenous drugs.

    RESULTS: From the rapid-defibrillation phase to the advanced-life-support phase, the rate of admission to a hospital increased significantly (10.9 percent vs. 14.6 percent, P<0.001), but the rate of survival to hospital discharge did not (5.0 percent vs. 5.1 percent, P=0.83). The multivariate odds ratio for survival after advanced life support was 1.1 (95 percent confidence interval, 0.8 to 1.5); after an arrest witnessed by a bystander, 4.4 (95 percent confidence interval, 3.1 to 6.4); after cardiopulmonary resuscitation administered by a bystander, 3.7 (95 percent confidence interval, 2.5 to 5.4); and after rapid defibrillation, 3.4 (95 percent confidence interval, 1.4 to 8.4). There was no improvement in the rate of survival with the use of advanced life support in any subgroup.

    CONCLUSIONS: The addition of advanced-life-support interventions did not improve the rate of survival after out-of-hospital cardiac arrest in a previously optimized emergency-medical-services system of rapid defibrillation. In order to save lives, health care planners should make cardiopulmonary resuscitation by citizens and rapid-defibrillation responses a priority for the resources of emergency-medical-services systems.

    Copyright 2004 Massachusetts Medical Society

  • Joe B says:

    Since cardiac arrest is less than 1% of calls, you will still have some other things to do on other patients. How about letting dopamine go on the death march right next to epinephrine?

  • mpatk says:


    Epi may still be of use, but in a subset of cases and not all of them. We need to recognize at not all systole/PEA arrests are the same; and focus on reversible causes while quality compressions are done, rather than the “Epi for everyone!” approach.

  • Almost Jesus says:

    Maybe we should be looking into tweaking the dose of epi rather than simply not giving it. When you give a patient a milligram of epi and they are awake, they quickly start down the road towards death. This seems counter-intuitive. We give people 0.3-0.5mg of epi for anaphylaxis and they improve. We give 4mL of Epi 1:100,000 as a push dose pressor and we raise their BP. A milligram of epi in a code situation is given with the thought that only part of it will reach the patient. Once ROSC happens, suddenly you have 1+ milligrams of epi floating around their system, this is likely to have a deleterious effect.
    I’d be interested to see a study where 0.1-0.3mg of epi IV is given during cardiac arrest and compare it to 1 milligram and no epi and see if it makes a difference in positive neuro outcomes.

  • Rogue Medic says:

    50 years of giving epinephrine in cardiac arrest with no evidence of improved survival, but growing evidence of harm.

    Still, people claim that we must prove that epinephrine is the cause of the harm and they are offended at the suggestion that they be required to provide evidence of improved survival to be permitted to continue to push epi in cardiac arrest.

    Where is our concern for our patients?


  • RP says:

    I have a funny idea that the strength of Paramedicine isn’t based in what drugs and ALS interventions we can push on our patients. It is rooted in the idea that we may perform an ALS assessment that will populate a differential diagnosis that may lead to options of treatment that will benefit the patient. Often this process is handed over to the receiving facilities’ staff for continued analysis and we therefore do not get the *self-serving* benefit of treating the problem, but rather we play a vital of a *team* approach in identifying a viable solution.
    This would mean that asking tough questions of what we thought & were told worked, what studies exist (or should exist)and how am I participating in the development of the team (or community).

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