Without evidence of benefit, an intervention should not be presumed to be beneficial or safe.

- Rogue Medic

ACLS Excuses for Causing Harm with Epinephrine


The next ACLS guidelines are available for review and comment, before they are finalized. The Consensus on Science with Treatment Recommendations (CoSTR) from the International Liaison Committee on Resuscitation (ILCOR) are available for two guidelines:

Vasopressors in Adult Cardiac Arrest

Advanced Airway Management During Adult Cardiac Arrest

We have been using these interventions for so long, that there should be great evidence to show that benefits and harms of both interventions, but there is no good evidence to support either intervention.

For epinephrine (adrenaline in Commonwealth countries), the most commonly used vasopressor and the only one rally being considered, there is no evidence of actual benefit – increased survival without severe brain damage.

Nothing else matters.

There is no valid evidence that increasing any surrogate endpoint improves survival without severe brain damage. The evidence cited by ILCOR shows that epinephrine increases the rate of severe brain damage.

Intervention: Vasopressor or a combination of vasopressors provided intravenously or intraosseously during cardiopulmonary resuscitation.[1]


Here are the outcomes that are supposed to indicate that the patient is better.

Outcomes: Short-term survival (return of spontaneous circulation (ROSC) and survival to hospital admission), mid-term survival (survival to hospital discharge, 28 days, 30 days, or 1 month), mid-term favorable neurological outcomes (Cerebral Performance Category score of 1-2 or modified Rankin Scale 0-3 at hospital discharge, 28 days, 30 days, or 1 month) and long-term favorable and poor (modified Rankin Score 4-5) neurological outcomes (after 1 month).[1]


Is ROSC an improvement?

We aren’t supposed to ask that question. These are faulty assumption that the guidelines are based on.

1. Doing something more is better than only doing things supported by valid evidence of improved survival without severe brain damage.


How much harm is being caused in this rush to get a pulse back?

We are supposed to ignore our understanding of research, look at a statistically insignificant “trend”, and extrapolate that statistically insignificant “trend” to support the prejudice that our intervention has not been harmful.

That is not good science.

That is not good medicine.

Why aren’t there any studies large enough to show improved survival without severe brain damage for anything other than rapid defibrillation (when indicated VF/pulseless VT) and chest compressions?

The research has only produced excuses and surrogate endpoint. Surrogate endpoints are for hypothesis generation and sales pitches to the least knowledgeable, but not for treatment guidelines.

ILCOR has told us this before, but that was because the choice was between large doses of epinephrine and small doses of epinephrine, not between epinephrine and no epinephrine.

The choice is the same.

Is the more aggressive intervention helping?

The answer is the same. No. That is not the conclusion of the evidence.

In adults with out-of-hospital cardiac arrest, the use of epinephrine resulted in a significantly higher rate of 30-day survival than the use of placebo, but 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.[2]


If the goal is a pulse with more severe brain damage, then epinephrine is the way to go.

If the goal is increased survival without severe brain damage, we have to keep looking.

We should limit the use of epinephrine to well controlled research until there is evidence of improvement in outcomes that matter.

If this evidence is never found, our patients will not have been harmed by epinephrine.

If this evidence is eventually found, it is something that should have been insisted on decades ago. We should not use wishful thinking and surrogate endpoints to justify interventions that harm patients.

We used to stop compressions to let the medic/nurse/doctor intubate, or start an IV (IntraVenous) line.

We knew that the tube was more important.

We knew that the drugs given through the IV line were more important.

The 2005 guidelines told us to continue compressions during intubation and during IV attempts and to improve the quality of the compressions.

That focus on high quality compressions is the only time we have improved outcomes that matter.

CONCLUSIONS: Compared with controls, patients with out-of-hospital cardiac arrest treated with a renewed emphasis on improved circulation during CPR had significantly higher neurologically intact hospital discharge rates.[3]


33 1/3% vs 60% increased survival without severe brain damage.

In 2004, we began a statewide program to advocate chest compression-only CPR for bystanders of witnessed primary OHCA. Over the next five years, we found that survival of patients with a shockable rhythm was 17.7% in those treated with standard bystander CPR (mouth-to-mouth ventilations plus chest compression) compared to 33.7% for those who received bystander chest-compression-only CPR.[4]


18% vs 34% increased survival only – not increased survival without severe brain damage.

In the analysis of MICR [Minimally Interrupted Cardiac Resuscitation] protocol compliance involving 2460 patients with cardiac arrest, survival was significantly better among patients who received MICR than those who did not (9.1% [60/661] vs 3.8% [69/1799]; OR, 2.7; 95% CI, 1.9-4.1), as well as patients with witnessed ventricular fibrillation (28.4% [40/141] vs 11.9% [46/387]; OR, 3.4; 95% CI, 2.0-5.8).[5]


9% vs 4% increased survival only – not increased survival without severe brain damage.

Neurologic outcomes were also better in the patients who received CCR (OR=6.64, 95% CI=1.31 to 32.8).[6]


6 2/3 more likely to have increased survival without severe brain damage. The range is 1 1/3 to almost 33 times, because of the small numbers, but unlike epinephrine, this is statistically significant and supported by other research.

We are still making excuses for using a drug that causes harm and does not appear to provide a benefit that is greater than the harm. If there is more benefit, it is too small to be measured, even in a study with over 9,000 patients. We do not know which patients benefit and which patients are harmed, so we do not know how to minimize the harm that we cause.

Our patients deserve better.


[1] Vasopressors in Adult Cardiac Arrest
Time left for commenting: 11 days 15:49:49
ILCOR staff
Created: March 21, 2019 · Updated: March 21, 2019
Draft for public comment
Consensus on Science with Treatment Recommendations (CoSTR)
Vasopressors in Adult Cardiac Arrest page for comments until April 04, 2019 at 06:00 Eastern Time

[2] A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest.
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.
N Engl J Med. 2018 Aug 23;379(8):711-721. doi: 10.1056/NEJMoa1806842. Epub 2018 Jul 18.
PMID: 30021076

Free Full Text from N Engl J Med.

[3] Implementing the 2005 American Heart Association Guidelines improves outcomes after out-of-hospital cardiac arrest.
Aufderheide TP, Yannopoulos D, Lick CJ, Myers B, Romig LA, Stothert JC, Barnard J, Vartanian L, Pilgrim AJ, Benditt DG.
Heart Rhythm. 2010 Oct;7(10):1357-62. doi: 10.1016/j.hrthm.2010.04.022. Epub 2010 Apr 24.
PMID: 20420938

Free Full Text from Heart Rhythm.

[4] The cardiocerebral resuscitation protocol for treatment of out-of-hospital primary cardiac arrest.
Ewy GA.
Scand J Trauma Resusc Emerg Med. 2012 Sep 15;20:65. doi: 10.1186/1757-7241-20-65. Review.
PMID: 22980487

Free Full Text from PubMed Central.

[5] Minimally interrupted cardiac resuscitation by emergency medical services for out-of-hospital cardiac arrest.
Bobrow BJ, Clark LL, Ewy GA, Chikani V, Sanders AB, Berg RA, Richman PB, Kern KB.
JAMA. 2008 Mar 12;299(10):1158-65. doi: 10.1001/jama.299.10.1158.
PMID: 18334691

Free Full Text from JAMA.

[6] Cardiocerebral resuscitation is associated with improved survival and neurologic outcome from out-of-hospital cardiac arrest in elders.
Mosier J, Itty A, Sanders A, Mohler J, Wendel C, Poulsen J, Shellenberger J, Clark L, Bobrow B.
Acad Emerg Med. 2010 Mar;17(3):269-75. doi: 10.1111/j.1553-2712.2010.00689.x.
PMID: 20370759

Free Full Text from Acad Emerg Med.