Tag Archives: cardiac arrest

A Myth Revisited: Epinephrine for Cardiac Arrest

Author: Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

 You receive a radio call from an EMS unit. They are transporting a 61-year-old male who collapsed approximately 5 minutes ago. He is currently in ventricular fibrillation, and the EMS crew is actively doing compressions. They have obtained IV access, defibrillated the patient once, given 1mg epinephrine IV, and are actively bagging the patient. The patient arrives, and you take over the resuscitation. Your partner cleanly intubates the patient while chest compressions are ongoing. The patient receives another defibrillation, and compressions resume. Should the patient receive more epinephrine? What’s the evidence behind its use?

Sudden cardiac arrest accounts for over 450,000 deaths per year in the U.S., with 15% of total deaths due to arrest.1-4 Close to half are out-of-hospital, with poor survival rate (7-9%).1-5

A prior emdocs.net post evaluated epinephrine use in cardiac arrest. Please see this at: http://www.emdocs.net/epinephrine-cardiac-arrest/. Epinephrine is a staple of the AHA Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Updated guidelines were released in 2015, building on a “Chain of Survival”: recognition and activation of emergency response system, immediate high-quality cardiopulmonary resuscitation (CPR), rapid defibrillation, basic and advanced emergency medical services, and advanced life support and post arrest care including advanced cardiac life support (ACLS) for out-of-hospital cardiac arrest (OHCA).7,8 ACLS is considered the standard of care in cardiac arrest, though some argue a lack of evidence.

For more information on the updated guidelines, see http://eccguidelines.heart.org/wp-content/uploads/2015/10/2015-AHA-Guidelines-Highlights-English.pdf, https://emergencymedicinecases.com/acls-guidelines-2015-cardiac-arrest/, https://first10em.com/2015/10/21/acls-2015/, http://rebelem.com/rebel-cast-wee-our-top-5-aha-2015-guideline-updates-for-cpr-and-ecc/.

The Myth: Epinephrine improves patient survival and neurologic outcome in cardiac arrest.

Is this important?

A class IIb recommendation from the AHA states “standard dose epinephrine may be reasonable for patients with cardiac arrest” in the 2015 updates, with doses of 1mg of 1:10,000 epinephrine every 3-5 minutes intravenously.7 Epinephrine has alpha and beta adrenergic effects, which are thought to improve coronary perfusion pressure, though the effect on cerebral perfusion is controversial (and may worsen cerebral perfusion).

The recommendation for epinephrine is based on studies in the 1960s, which found epinephrine given to asphyxiated dogs improved survival.9 The alpha-adrenergic effects improved coronary perfusion in these dogs, with some benefit in survival.

If some is good, is more better? High dose epinephrine was assumed to be better, with several studies finding increased ROSC and survival to hospital admission, but no improvement in survival to hospital discharge or neurologic recovery.10-14 Studies suggest worse survival to hospital discharge and neurologic recovery with higher doses of epinephrine.7,15-20

What about standard dose epinephrine?  Studies suggest improvement in ROSC, but worse neurologic and survival to discharge. Why? The beta agonism provided by epinephrine increases myocardial work, increases tachydysrhythmias, promotes thrombogenesis and platelet activation, and reduces microvascular perfusion (including the brain).7,15

Now down to the nuts and bolts: the evidence on epinephrine…

Table 1 shows the studies on epinephrine. A study in 2011 evaluated over 600 patients with OHCA (one of the few randomized trials).16 Improved likelihood of ROSC, 24% in the epinephrine group versus 8%, with an odds ratio (OR) of 3.4 (95% CI 2.0-5.6) was found. Patients demonstrated no improvement in survival to hospital discharge.16 Ong et al. in 2007 found no difference in survival to discharge, survival to admission, or ROSC with epinephrine versus no epinephrine.17

Nakahara et al. conducted a retrospective study comparing epinephrine versus no epinephrine for patients with ventricular fibrillation, PEA, or asystole.18 Higher overall survival with epinephrine (17.0% vs 13.4%) was found, but not neurologically intact survival.18 Hagihara et al. conducted a prospective non-randomized analysis of over 400,000 patients and found an increase in ROSC with epinephrine (adjusted odds ratio 2.36), but no increase in survival or functional outcome.19 As discussed, ROSC occurred in the epinephrine group at higher rate (18.5% vs. 5.7%), but patients receiving epinephrine had lower survival at one month and worse neurologic outcome.19

One study found those with initially shockable rhythm demonstrated worse outcomes if they receive epinephrine for prehospital ROSC, survival at one month, and neurologic outcome at one month.20 A Swedish study found patients receiving epinephrine experience lower survival, with OR 0.30 (95% CI 0.07-0.82).21

How about BLS compared with ACLS?

ACLS measures include epinephrine, as compared with BLS focusing on optimizing compressions. Stiell et al. in 2004 analyzed 1,400 patients before use of ACLS measures, followed by 4,300 patients after ACLS was implemented.22 Admission rate increased by 3.7% (10.9% to 14.6%), but survival to discharge did not change.  Survivor neurologic status worsened after ACLS implementation (78.3% versus 66.8%).22  Olasveengen et al. evaluated ACLS with and without epinephrine, finding a 40% rate of ROSC in the group receiving epinephrine, versus 25% in the group receiving no epinephrine.23 Survival to discharge and neurologic outcomes were similar, though the epinephrine group had higher hospital admission rates.23  Sanghavi et al. compared BLS and ACLS in an observational cohort study.24 BLS patients had higher survival to hospital discharge (13.1% versus 9.2%), improved survival to 90 days, and better neurologic function.24

Table 1 – Studies evaluating epinephrine16-24

Study Outcome Odds Ratio (95% CI)
Holmberg et al. Survival decrease with epinephrine Survival 0.43 (0.27-.066) for shockable, 0.30 (0.07-0.82) for non-shockable rhythms
Stiell et al. Improved ROSC, no difference in survival to discharge Survival to discharge 1.1 (0.8-1.5)
Ong et al. No difference in ROSC or survival to discharge ROSC 0.9 (0.6-4.5), survival to discharge 1.7 (0.6-4.5)
Olasveengen et al. Improved ROSC, No difference in survival to discharge Survival to discharge 1.15 (0.69-1.91)
Jacobs et al. Improved ROSC, No difference in survival to discharge ROSC 3.4 (2.0-5.6), Survival to discharge 2.2 (0.7-6.3)
Hagihara et al. Improved ROSC, Worse survival and functional outcome ROSC 2.35 (2.22-2.5), Survival 0.46 (0.42-0.51), Functional outcome 0.31-0.32 (0.26-0.38)
Nakahara et al. No difference in neurologic outcome or total survival Neurologic outcome 1.01 (0.78-1.30) for shockable and 1.57 (1.04-2.37) for nonshockable rhythms; Total survival 1.34 (1.12-1.60) for shockable and 1.72 (1.45-2.05) for nonshockable rhythms
Sanghavi et al. No epinephrine associated with improved neurologic outcome, survival to discharge, and total survival Improved neurologic outcome 23.0 (18.6-27.4) for no epinephrine, Survival to discharge 4.0 (2.3-5.7) for no epinephrine, Total survival 2.6 (1.2-4.0) for no epinephrine

The Bottom Line: Epinephrine can increase ROSC, but it does not improve survival to hospital discharge or neurological improvement and may worsen these outcomes.

How does this change practice? Epinephrine is a significant component of the AHA guidelines, despite the controversial literature. A role may exist for epinephrine, though further study is required. Studies suggest three phases (electrical, circulatory, and metabolic) are present in cardiac arrest.25 The electrical phase needs rapid defibrillation and compressions.15,25 The circulatory phase (within 10 minutes of arrest) focuses on perfusion, where epinephrine may improve cardiac perfusion. Epinephrine during the final metabolic phase (greater than 10 minutes after arrest) can impair oxygen utilization, increase oxygen demand and ischemia, cause dysrhythmia, increase clotting, and increase lactate.15,25

The timing and total dose of epinephrine can impact patient outcome.7,15,25-27 A study by Dumas et al. suggests timing of first administration and total epinephrine given impacts survival (with less epinephrine given related to improved outcome).25 This study found that 17% of patients in the group receiving epinephrine demonstrated a good outcome defined by “favorable discharge outcome coded by Cerebral Performance Category,” compared to 63% not receiving epinephrine. However, in this study patients with a shockable rhythm, patients receiving 1mg epinephrine, and patients receiving epinephrine less than 9 minutes after arrest demonstrate the best outcomes, not impacted by the total time of resuscitation. Patients receiving late or multiple doses of epinephrine have decreased neurologic survival.25

Table 2 – Epinephrine Dosing Outcomes25

Treatment Adjusted OR (95% CI)
Time to Epinephrine Dose

< 9 min

10-15 min

16-22 min

> 22 min


0.54 (0.32-0.91)

0.33 (0.20-0.56)

0.23 (0.12-0.43)

0.17 (0.09-0.34)

Total Epinephrine Dose

1 mg

2-5 mg

> 5 mg


0.48 (0.27-0.84)

0.30 (0.20-0.47)

0.23 (0.14-0.37)

Epinephrine within 10 minutes of arrest may provide the most benefit. Koscik et al. found earlier provision of epinephrine improved ROSC, from 21.5% to 48.6% (OR 3.45).26 Nakahara et al. compared early epinephrine in OHCA (within 10 minutes of arrest), finding early epinephrine was associated with survival (OR 1.73, 95% CI 1.46-2.04) and improved neurologic outcome (OR 1.39, 95% CI 1.08-1.78).27 However, there is potential harm with epinephrine within the first two minutes of arrest.27 Anderson et al. compared epinephrine before or after the second defibrillation attempt.28 Patients receiving epinephrine before the second defibrillation demonstrated decreased survival (OR 0.70), decreased functional outcome (OR 0.69), and decreased ROSC (OR 0.71). This study suggests epinephrine within the first two minutes after arrest can be harmful, and they recommend epinephrine should be given after the second defibrillation.27

Some support targeting coronary perfusion pressure (CPP), or the aortic to right atrial pressure gradient during the relaxation phase of CPR. Targeting coronary perfusion pressure is supported by several animal studies.29,30 CPP levels > 15 mm Hg demonstrate greater likelihood of ROSC.31 Epinephrine is most commonly used to maintain CPP levels with compressions. However, this needs further study and requires the use of invasive monitoring.25,31

What improves outcomes?

Components that improve outcomes include witnessed arrest, witnessed by EMS, bystander CPR, shockable rhythm (VF/VT), early defibrillation, minimal interruptions to CPR, automated external AED use, and therapeutic hypothermia in comatose cardiac arrest patients.7,15,32 Optimal chest compressions and early defibrillation if warranted are essential.7 Emergency PCI is recommended for all patients with STEMI and for hemodynamically unstable patients without ST elevation infarction if a cardiovascular lesion is suspected. Targeted temperature management between 32oC and 36oC is acceptable for comatose patients with ROSC.7 The 2015 recommendations for BLS measures are shown below. 7,32

2015 Guideline Recommendations for Compressions
-Perform compressions at rate 100-120 per minute

-Perform compressions at depth of 5-6 cm (at least 2 inches), but not more than 6 cm (2.4 in)

-Rescuers should allow full chest wall recoil and avoid leaning on the chest between compressions

-Rescuers should minimize the frequency and duration of intervals between compressions

-Audiovisual devices and compression depth analyzers can be used to optimize CPR quality

Bottom Line: The most important aspect of care in cardiac arrest is basic life support measures with compressions and early defibrillation.



– 2015 AHA Guidelines state epinephrine is reasonable to give for patients in cardiac arrest.

– Recommendations are based on studies with asphyxiated dogs in the 1960s.

High dose epinephrine is harmful and is not advised.

– Epinephrine can increase ROSC, but it may worsen neurologic outcome and survival upon discharge.

– Epinephrine may provide the greatest benefit if given within 10 minutes of arrest (though it may be harmful if given before 2 minutes).

BLS measures with optimal compressions and early defibrillation are essential!


References / Further Reading

  1. Zheng ZJ, Croft JB, Giles WH, Mensah GA. Sudden cardiac death in the United States, 1989 to 1998. Circulation 2001; 104:2158.
  2. Rea TD, Pearce RM, Raghunathan TE, et al. Incidence of out-of-hospital cardiac arrest. Am J Cardiol 2004; 93:1455.
  3. Centers for Disease Control and Prevention (CDC). State-specific mortality from sudden cardiac death–United States, 1999. MMWR Morb Mortal Wkly Rep 2002; 51:123.
  4. Chugh SS, Jui J, Gunson K, et al. Current burden of sudden cardiac death: multiple source surveillance versus retrospective death certificate-based review in a large U.S. community. J Am Coll Cardio 2004;44:1268.
  5. Kuller LH. Sudden death–definition and epidemiologic considerations. Prog Cardiovasc Dis 1980; 23:1.
  6. Gillum RF. Sudden coronary death in the United States: 1980-1985. Circulation 1989; 79:756.
  7. Link MS, Berkow LC, Kudenchuk PJ, et al. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132:S444-S464.
  8. Neumar RW, Otto CW, Link MS, et al. Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122(Suppl 3):S729-67.
  9. Callaham M. Evidence in support of a back-to-basics approach in out-of-hospital cardiopulmonary resuscitation vs. “advanced treatment.” JAMA Intern Med. 2015;175:205-206.
  10. Stiell IG, Hebert PC, Weitzman BN, et al. High-dose epinephrine in adult cardiac arrest. N Engl J Med. 1992;327:1045-1050.
  11. Brown CG, Martin DR, Pepe PE, et al. A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital. The Multicenter High-Dose Epinephrine Study Group. N Engl J Med. 1992;327:1051-1055.
  12. Rivers EP, Wortsman J, Rady MY, et al. The effect of total cumulative epinephrine dose administered during human CPR on hemodynamic, oxygen transport, and utilization variables in the postresuscitation period. Chest. 1994;106:1499-1507.
  13. Behringer W, Kittler H, Sterz F, et al. Cumulative epinephrine dose during cardiopulmonary resuscitation and neurologic outcome. Ann Intern Med. 1998;129:450-456.
  14. Guegniaud PY, Mols P, Goldstein P, et al. A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital. N Engl J Med. 1998;339:1595-1601.
  15. Callaway CW. Questioning the use of epinephrine to treat cardiac arrest. JAMA. 2012;307:1198-1199.
  16. 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 Sep;82(9):1138-43.
  17. Ong ME, Tan EH, Ng FS, Panchalingham A, Lim SH, Manning PG, et al. Survival outcomes with the introduction of intravenous epinephrine in the management of out-of-hospital cardiac arrest. Ann Emerg Med. 2007 Dec;50(6):635-42.
  18. Nakahara S, Tomio J, Takahashi H, et al. Evaluation of pre-hospital administration of adrenaline (epinephrine) by emergency medical services for patients with out of hospital cardiac arrest in Japan: controlled propensity matched retrospective cohort study. The BMJ. 2013;347:f6829. doi:10.1136/bmj.f6829.
  19. 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 Mar 21;307(11):1161-8. doi: 10.1001/jama.2012.294.
  20. Goto Y, Maeda T, Goto YN. Effects of prehospital epinephrine during out-of-hospital cardiac arrest with initial non-shockable rhythm: an observational cohort study. Critical Care. 2013;17(5):R188. doi:10.1186/cc12872.
  21. Holmberg M, Holmberg S, Herlitz J. Low chance of survival among patients requiring adrenaline (epinephrine) or intubation after out-of-hospital cardiac arrest in Sweden. Resuscitation. 2002 Jul;54(1):37-45.
  22. 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. Advanced cardiac life support in out-of-hospital cardiac arrest. N Engl J Med. 2004 Aug 12;351(7):647-56.
  23. Olasveengen TM, Sunde K, Brunborg C, Thowsen J, Steen PA, Wik L. Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial. JAMA. 2009 Nov 25;302(20):2222-9.
  24. Sanghavi P, Jena AB, Newhouse JP, Zaslavsky AM. Outcomes After Out-of-Hospital Cardiac Arrest Treated by Basic vs Advanced Life Support. JAMA Intern Med 2015;175(2):196-204.
  25. Dumas F, Bougouin W, Geri G, Lamhaut L, Bougle A, Daviaud F, et al. Is epinephrine during cardiac arrest associated with worse outcomes in resuscitated patients? J Am Coll Cardiol. 2014; 64(22):2360–7.
  26. Koscik C, Pinawin A, McGovern H, Allen D, Media DE, Ferguson T, Hopkins W, Sawyer KN, Boura J, Swor R. Rapid epinephrine administration improves early outcomes in out-of-hospital cardiac arrest. Resuscitation. 2013 Jul;84(7):915-20.
  27. Nakahara S, Tomio J, Nishida M, Morimura N, Ichikawa M, Sakamoto T. Association between timing of epinephrine administration and intact neurologic survival following out-of-hospital cardiac arrest in Japan: a population-based prospective observational study. Acad Emerg Med. 2012 Jul;19(7):782-92.
  28. Andersen LW, Kurth T, Chase M, et al. Early administration of epinephrine (adrenaline) in patients with cardiac arrest with initial shockable rhythm in hospital: propensity score matched analysis. BMJ 2016; 353:i1577.
  29. Friess SH, Sutton RM, French B, et al. Hemodynamic Directed CPR Improves Cerebral Perfusion Pressure and Brain Tissue Oxygenation. Resuscitation. 2014;85(9):1298-1303.
  30. Sutton RM, Friess SH, Naim MY, et al. Patient-centric Blood Pressure–targeted Cardiopulmonary Resuscitation Improves Survival from Cardiac Arrest. American Journal of Respiratory and Critical Care Medicine. 2014;190(11):1255-1262.
  31. Paradis NA, Martin GB, Rivers EP, et al. Coronary Perfusion Pressure and the Return of Spontaneous Circulation in Human Cardiopulmonary Resuscitation. JAMA. 1990;263(8):1106-1113.
  32. Sasson C, Rogers MA, Dahl J, Kellermann AL. Predictors of survival from out-of-hospital cardiac arrest: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2010 Jan;3(1):63-81.

The Young Cardiac Arrest Patient

Author: Joshua Bucher, MD (Assistant Professor of Emergency Medicine, Rutgers-RWJMS) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)


A 43-year-old male arrives in cardiac arrest. According to EMS, he was playing basketball when he suddenly clutched his chest. On EMS arrival, he was ashen, in severe respiratory distress and cardiogenic shock. A 12-lead EKG showed an anterior wall STEMI. On the way to the hospital, he went into cardiac arrest. After 10 minutes of chest compressions, intubation, defibrillations, and epinephrine administration, he is still in ventricular fibrillation.


The young cardiac arrest patient presents a difficult situation for the emergency provider. In general, younger patients are healthier than their geriatric counterparts. There are differences in physiology which may contribute to different prognosis and care.

Andersen et al. evaluated out-of-hospital cardiac arrest patients and found that there was no age in which resuscitation was futile; however, there was a progressive decline in good neurologic outcome after the age range of 45 – 64 years. The best age of survival with good neurologic outcome was 25 – 29 (46%).1

Unfortunately, sudden cardiac death (SCD) is possible at any age. Roberts et al. investigated the incidence of SCD in a Minnesota High School athlete population, and found 4 cardiac arrests out of 1,666,509 athletes, calculated to equal 0.24 deaths/100,000 athlete-years.2 They did not discuss the individual cases, but highlighted that sport-related SCD was uncommon, but present, in the high school athletic population.

Chugh et al. reviewed pre-hospital cardiac arrests and found that the proportion of arrests < the age of 65 in their community was only 25%. 50% of their cases over the age of 35 had the cause of death identified as coronary artery disease, on autopsy, of the non-survivors. Coronary artery disease was observed in 76% of all patients greater than the age of 35. The two patients less than 35 years of age suffered from WPW and congenital aortic disease. Unusually, 74% of the sudden cardiac arrests under the age of 35 had no discernible cause of death identified.3

One area of focus is the setting of exercise induced cardiac arrest. Berdowski et al. collected prospective data on their out of hospital cardiac arrest population. They found that exercise-related cardiac arrest was more likely in a younger patient population, male gender, in public, and with higher rates of bystander CPR and AED utilization. They were also more likely to present with shockable rhythms and demonstrated higher survival. They calculated an incidence of 0.3 exercise related SCD per 100,000 patient years in the less than 35 age group and 2.8 per 100,000 in non-exercise related SCD. Interestingly, all of their survivors of exercise related SCD were neurologically intact, regardless of age. Furthermore, they found that survival was higher in the group of 36 – 50-year-old men compared to less than or equal to 35 and greater than or equal to 51, when the arrest occurred in a public location, had bystander CPR, a public AED was used, shorter response time, and a shockable rhythm on EMS arrival. Overall, survival from exercise related SCD was maintained even when controlling for other variables.4

Marijon et al. also investigated sports and exercise related SCD in the out of hospital environment in France. 95% were male with a mean age of 46. Not surprisingly, bystander CPR and use of an AED were the strongest predictors of survival to discharge. Interestingly, 86.5% of the patients with sports-related SCD were reported to regularly exercise, highlighting that routine exercise does not eliminate the possibility of ACS causing SCD in a healthy population. SCD during team-related sports activities occurred at a significantly younger age than patients performing individual activities such as cycling or running (33 v 51, p <0.0001).  There was no correlation between age and survival.5

They also reported on the causes of cardiac arrest. In the young, competitive athlete population, 98% of the causes were related to a cardiac origin. 75% of the patients suffered from acute coronary syndrome. Other causes included hypertrophic cardiomyopathy, congenital cardiac diseases, dilated cardiomyopathy, myocarditis, arrhythmogenic right ventricular dysplasia, commotio cordis, prolonged QT syndrome, mitral valve prolapse, and WPW. There were 4 non cardiac causes identified – epilepsy, cerebral aneurysm rupture, stroke, and ruptured aortic aneurysm. The most common cause was idiopathic.

Marijon et al. investigated a second group of prospective SCD patients in the out of hospital environment in Portland over a 10-year period. They found similar results to the prior study; SCD due to exercise is rare, but an important cause in the younger population. They also found similar causes to the prior study.6

The CASPER study attempted to determine the cause of unexplained cardiac arrest survivors with preserved ejection fraction (with the assumption being that they did not suffer ACS as a cause of the arrest). After adequate testing and follow up, the most common causes were primary electrical disease (65% – Brugada, catecholaminergic ventricular tachycardia, early repolarization, long QT syndrome) and underlying structural issues (35% – ARVD, coronary spasm, dilated cardiomyopathy, myocarditis). The average age of the patients was 48.6; their average age at cardiac arrest was 41.5.7

Farioli et al. investigated SCD rates and causes in firefighters from several available databases. They found that, outside of coronary artery disease, common causes of arrest were hypertrophic cardiomyopathy, dilated cardiomyopathy, left ventricular hypertrophy, myocarditis, and valvular disorders.8

While this is mainly focused on medical causes of death, take care to consider other causes. According to the CDC, unintentional injury is the #1 cause of death in patients aged birth to 44. Suicide is the 2nd most common cause from ages 10 – 34. Homicide is the 3rd most common in ages 15 – 34. Other common causes are malignant neoplasms, and in younger children, congenital anomalies (although this article is focusing on adults). Overall, heart disease is the most common cause of death.9


Case resolution

The patient is defibrillated into sinus tachycardia. He is transferred to the catheterization lab, stented, undergoes therapeutic hypothermia, and walks out of the hospital 5 days later neurologically intact.

Table 1 – Etiologies of young cardiac arrest
Coronary artery disease

Hypertrophic cardiomyopathy

Dilated cardiomyopathy

Electrical conduction disorders (Brugada, catecholaminergic ventricular tachycardia, long QT syndrome, ARVD, WPW)

Congenital aortic disease

Coronary spasm



Screen Shot 2016-08-09 at 11.24.44 PM

Take Home Points

  1. Younger cardiac arrest patients often have different causes than older patients.
  2. Pay strong consideration to congenital abnormalities, conduction disorders, or other cardiac causes outside of coronary artery disease.
  3. Younger patients generally have better prognosis than their older counterparts.

References / Further Reading

  1. Andersen LW, Bivens MJ, Giberson T, et al. The relationship between age and outcome in out-of-hospital cardiac arrest patients. Resuscitation. 2015;94:49-54.
  2. Roberts WO, Stovitz SD. Incidence of sudden cardiac death in Minnesota high school athletes 1993-2012 screened with a standardized pre-participation evaluation. J Am Coll Cardiol. 2013;62(14):1298-1301.
  3. Chugh SS, Jui J, Gunson K, et al. Current burden of sudden cardiac death: multiple source surveillance versus retrospective death certificate-based review in a large U.S. community. J Am Coll Cardiol. 2004;44(6):1268-1275.
  4. Berdowski J, de Beus MF, Blom M, et al. Exercise-related out-of-hospital cardiac arrest in the general population: incidence and prognosis. European heart journal. 2013;34(47):3616-3623.
  5. Marijon E, Tafflet M, Celermajer DS, et al. Sports-related sudden death in the general population. Circulation. 2011;124(6):672-681.
  6. Marijon E, Uy-Evanado A, Reinier K, et al. Sudden cardiac arrest during sports activity in middle age. Circulation. 2015;131(16):1384-1391.
  7. Herman AR, Cheung C, Gerull B, et al. Outcome of Apparently Unexplained Cardiac Arrest: Results From Investigation and Follow-Up of the Prospective Cardiac Arrest Survivors With Preserved Ejection Fraction Registry. Circ Arrhythm Electrophysiol. 2016;9(1):e003619.
  8. Farioli A, Christophi CA, Quarta CC, Kales SN. Incidence of sudden cardiac death in a young active population. Journal of the American Heart Association. 2015;4(6):e001818.
  9. CDC. Ten Leading Causes of Death and Injury. 2016; http://www.cdc.gov/injury/wisqars/leadingcauses.html. Accessed 5/31, 2016.

Epinephrine in Cardiac Arrest

Anand Swaminathan, MD, MPH (@EMSwami) is an assistant professor and assistant program director at the NYU/Bellevue Department of Emergency Medicine in New York City.

Clinical Question

Does epinephrine increase the rate of survival with good neurologic outcome in patients with out-of-hospital cardiac arrest (OHCA)?


Sudden cardiac arrest is common and, obviously, very bad. In the US, there are about 500,000 cardiac arrests each year. About half of these cardiac arrests are OHCA and the survival rate is pretty poor. The most recent survival estimates put it at 7 – 9.5% in most communities. About 10-12 years ago, the American Heart Association built the 4-step “chain-of-survival.”

  • Step One – Early access to emergency care
  • Step Two – Early CPR
  • Step Three – Early defibrillation

In fact, in communities with high layperson BLS training and AEDs in the community, the rate of survival after OHCA is higher.

The 4th step in the chain, however is slightly more controversial; early advanced care. This basically means rapid access to ACLS type resuscitation skills.

The ACLS package of therapies has minimal evidence to defend it and yet, it is the standard care patients receive. The real question, though is does it improve outcomes? Specifically, does the application of ACLS decrease mortality and increase the rate of good neurologic outcomes after OHCA?

As always, we also have to ask if we are doing harm. Does the ACLS algorithm harm patients by bringing back more people with severe neurologic disabilities?

This question was answered 10 years ago in the Ottawa Prehospital Advanced Life Support (OPALS) Study. Follow this link to the Skeptics Guide to Emergency Medicine blog/podcast for a detailed review of this study with Ken Milne (@TheSGEM). Here’s a quick review:

OPALS was a prospective before and after study. They collected data on OHCA for 12 months before adoption of ACLS (paramedics did CPR and defibrillation only) and for 36 months after adoption of ACLS. They found a significant increase in ROSC and admission to hospital but no significant increase in survival to discharge. Additionally, neurologic outcomes of the survivors to discharge were worse in the ACLS group. Overall, this study demonstrated harm from incorporation of ACLS.

Can we separate out parts of the ACLS bundle that would be helpful? Doing a study like this is difficult as ACLS is the accepted standard care but there are some studies delving into the utility of epinephrine in OHCA.

The pathophysiologic basis behind epinephrine being beneficial comes mainly from animal models. Here are three of those efforts (courtesy of Bryan Hayes – @PharmERToxGuy):

  1. ‘Beneficial’ effects come primarily from alpha-adrenergic stimulation induced vasoconstriction [dog study, Yakaitis RW, Crit Care Med 1979]
  2. This effect increases CPP and myocardial perfusion during CPR [dog study, Michael JR, Circulation 1984]
  3. The potential problem is that the beta-agonist effects may increase myocardial work and reduce subendocardial perfusion [dog study, Ditchey RV, Circulation 1988]

What about the argument against epinephrine?

  1. Beta-adrenergic effects are undesirable in arrest patients – tachycardia, tachydysrhythmias, and increased myocardial oxygen
  2. Can promote thrombogenesis and platelet activation
  3. Impairs myocardial function in spite of increased coronary perfusion pressure (in animal studies)
  4. Reduces microvascular perfusion – particularly brain perfusion. What good is saving the heart if the brain is dead?

Let’s look at some studies. There are a number of observational studies (usually before and after) that show increased ROSC without increased good neurologic survival.

Hagihara A et al. Prehospital Epinephrine Use and Survival among Patients with OHCA. JAMA 2012; 307(11): 1161-68

  • Observational study. Database of all cardiac arrests over 4 years (415,000). 15,000 got epinephrine and the rest did not.
  • Higher rate of ROSC (OR = 3.75)
  • Higher rate of survival at 1 month 5.4% vs. 4.7% (OR 1.15)
  • Good neuro outcome was significantly less 1.4% vs. 2.2%
    Of note, differences in groups favored epi (more witnessed arrest, more initial VF)

Nakahara S et al. Evaluation of pre-hospital administration of adrenaline (epinephrine) by emergency medical services for patients with out of hospital cardiac arrest in Japan: controlled propensity matched retrospective cohort study. BMJ December 2013

  • VF/VT Arrest
    • Overall survival: 17% vs. 13.4% (favored epinephrine group)
    • Neurologically intact survival: 6.6% vs. 6.6%
  • Non-VF/VT Arrest
    • Overall survival: 4.0% vs. 2.4% (favored epinephrine group)
    • Neurologically intact survival: 0.7% vs. 0.4%

Olasveengen TM, Sunde K, Brunborg C, et al. Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial. JAMA 2009;302:2222–2229.

This was an RCT (not blinded) looking at whether giving epinephrine improved outcomes in OHCA. Basically, they either did ACLS without drugs or ACLS with drugs.

  • ROSC 40% (IV drugs) vs 25%
  • ROSC and Admission 32% (IV drugs) vs. 21% (p<.001)
  • Survival to discharge 10.5% (IV drugs) vs. 9.2% (no IV drugs) (p = .61)
  • Survival with good neurologic outcome 10% vs. 8% (p = .53)

Jacobs IG, Finn JC, Jelinek GA, et al. Effect of adrenaline on survival in out-of hospital cardiac arrest: a randomised double-blind placebo-controlled trial. Resuscitation 2011; 82:1138–1143.

This was an RDCT with placebo that unfortunately lost funding before full enrollment. They were able to randomize 600 patients and had complete data on 534.

  • ROSC 23.5% (epinephrine) vs. 8.4% OR = 3.4
  • Survival to hospital discharge: 4.0% (epinephrine) vs. 1.9% – not statistically different

Bottom line

Epinephrine and other ACLS drugs lead to more patients with ROSC but no increase in the number of patients with good neurologic outcomes after OHCA.

Something that’s very interesting is the actual ACLS recommendation for epinephrine. It reads, “it is reasonable to consider administering a 1 mg dose of IV/IO epinephrine every 3 to 5 minutes during adult cardiac arrest.” This actually leaves room to not give the medication if the physician thinks it should be withheld.

OPALS was a pretty robust study and little has changed in the last 10 years. The literature that has come out has been quite clear, thus it’s time to re-examine this recommendation.

Further Reading / Resources

  1. Hagihara A et al. Prehospital Epinephrine Use and Survival Among Patients with OHCA. JAMA 2012; 307(11): 1161-68.
  2. Olasveengen TM, Sunde K, Brunborg C, et al. Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial. JAMA 2009; 302:2222–2229.
  3. Jacobs IG, Finn JC, Jelinek GA, et al. Effect of adrenaline on survival in out-of hospital cardiac arrest: a randomised double-blind placebo-controlled trial. Resuscitation 2011; 82:1138–1143.
  4. Nakahara S et al. Evaluation of pre-hospital administration of adrenaline (epinephrine) by emergency medical services for patients with out of hospital cardiac arrest in Japan: controlled propensity matched retrospective cohort study. BMJ December 2013.
  5. Callaway CW. Epinephrine for Cardiac Arrest. Curr Opin Cardiol 2013; 28: 36-42.
  6. Stiell IG et al. ACLS in OHCA. NEJM 2004; 351: 647-56.
  7. Callaway CW. Questioning the use of epinephrine to treat cardiac arrest. JAMA 2012; 307(11): 1198-1200.
  8. http://www.ncbi.nlm.nih.gov/pubmed/24252225
Edited by Alex Koyfman, MD