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Levy B, et al. "Epinephrine Versus Norepinephrine for Cardiogenic Shock After Acute Myocardial Infarction". J Am Coll Cardiol. 2018. 72(2):173-182.
PubMedFull text

Clinical Question

In adult patients with cardiogenic shock following acute myocardial infarction and percutaneous coronary intervention, what is the comparitive efficacy and safety of epinephrine as compared to norpeinephrine

Bottom Line

In patients with acute myocardial infarction, as compared to norepinepherine, epinepherine led to more refractory shock.

Major Points

In patients that develop cariogenic shock after experiencing an acute myocardial infarction and receiving the benefit of revascularization via percutaneous coronary intervention, mortality remains high. [1] As demonstrated by the SOAP II trial, norepinepheine was demonstrated to be superior to dopamine in cardiogenic shock.

In this trial, Epinephrine Versus Norepinephrine for Cardiogenic Shock After Acute Myocardial Infarction (OptimaCC), a multicentred, randomized control trial conducted in nine French ICU's. They randomized 57 patients following percutaneous intervention for acute mycardial infarction to either norepinepherine or epinepherine. Refractory shock was seen in those patients receiving epinepherine (37%) as compared to norepinepherine (7%, ARI 30%, NNH 3) and the trial was stopped early.


Contemporary Management of Cardiogenic Shock: A Scientific Statement From the American Heart Association 2017, adapted[2]

  • Classic wet and cold: Norepinephrine or dopamine + Inotropic agent
  • Euvolemic cold and dry: Norepinephrine or dopamine + Inotropic agent + Small fluid boluses
  • Vasodilatory warm and wet or mixed cardiogenic and vasodilatory: Norepinephrine + Consider hemodynamics-guided therapy
  • RV Shock: Fluid boluses + Norepinephrine, dopamine, or vasopressin + Inotropic agents + Inhaled pulmonary vasodilators
  • Normotensive shock: Inotropic agent or vasopressor
  • Aortic regurgitation: Dopamine + temporary pacing
  • Mitral stenosis: Phenylephrine or vasopressin + Esmolol or amiodarone
  • Mitral regurgitation: Norepinephrine or dopamine + Inotropic agents + Temporary MCS, including IABP
  • Dynamic LVOT obstruction: Fluid boluses + Phenylephrine or vasopressin + Avoid inotropic agents + Avoid vasodilating agents + Esmolol or amiodarone + RV pacing
  • Bradycardia: Chronotropic agents or Temporary pacing
  • Pericardial tamponade: Fluid bolus + Norepinephrine


  • Multicenter, double-blind, randomized, controlled trial
  • N=57
    • Epinephrine (n=27)
    • Norpeinephrine (n=30)
  • Setting: 9 French ICUs
  • Enrollment: September 2011 to August 2016
  • Analysis: Intention-to-treat
  • Primary Outcome: change in cardiac index


Inclusion Criteria

  • >18 years of age
  • cardiogenic shock due to acute mycardial infarction successfully revascularized by using percutaneous intervention
  • systolic arterial pressure <90 mm Hg or mean arterial pressure (MAP) <65 mm Hg without a vasopressor agent or need for vasopressor therapy to correct hypotension
  • cardiac index <2.2 l/min/m2 in the absence of vasopressor or inotrope therapy
  • pulmonary artery occlusion pressure >15 mm Hg or echocardiographic evidence of high pressure
  • echocardiographic ejection fraction <40% without inotrope support (this criterion was not taken into account in instances of treatment with dopamine, norepinephrine, epinephrine, dobutamine, or milrinone)
  • at least one evidence of tissue hypoperfusion (e.g., skin mottling, oliguria, elevated lactate level, altered consciousness); and
  • an inserted pulmonary artery catheter.
  • vasopressor therapy no more than 6 hours before randomization

Exclusion Criteria

  • shock of other origin
  • immediate indication for extracorporeal life support (ECLS)
  • cardiac arrest with early signs of cerebral anoxia
  • septic, toxic, and obstructive cardiomyopathy
  • patient without medical insurance
  • adult patient under legal protection, and
  • patients considered moribund by the attending physician.
    • Moribund status was defined according to a state of imminent death with no medical therapeutic option.

Baseline Characteristics

Epinepherine Group displayed

  • Demographics: 68(55-79) years old, 48% female
  • Physiologic parameters: HR 11(70-118), MAP 72(69-79) mmHg, SAPS2 score 59(45-74), SOFA score 10(9-12), ST-segment elevation 96%, LVEF 34%,lactate 5 mmol/L
  • Anthropomorphics: BMI 25.2(22.3-27.4)
  • Past Medical History: Hypertension 30%, Diabetes 7%, Stroke 7%, Myocardial infarction 7%
  • Supports: hours of shock before randomization 6.1(4.5-8.0), Mechanical ventilation 96%


  • blinded epinephrine or norepinephrine increased by 0.02 mcg/kg/min to reach and maintain a target MAP 65-70 mm Hg


Comparisons are Epinephrine therapy vs. Norpeinephrine therapy.

Primary Outcomes

Mean arterial pressure over 72 hours, mmHg
overall p = 0.25

Secondary Outcomes

Cardiac Index over 72 hours, ml/min/m^2
overall p = 0.43
Hour 2 = epinephrine higher than norepinephrine, p = 0.011
Hour 4 = epinephrine higher than norepinephrine, p = 0.011
Heart Rate over 72 hours, beats/min
overall 0.031
Stroke Volume Index over 72 hours, ml/beats/min
overall p = 0.25

Adverse Events

Refractory shock
37% vs. 7% (ARI 30%, P-value 0.008, OR 8.24[95% CI1.61-42.18] NNH 4)
41% vs. 33% (ARI 8%, P-value 0.59, OR 1.37[95% CI0.47-4.05])
Extracorporeal life support
11% vs. 3% (ARI 8%, P-value 0.34, OR 3.62[95% CI0.35-37.14])
52% vs. 37% (ARI 15%, P-value 0.29, OR 1.86[95% CI00.65-5.36])


  • Excluded patients without medical insurance
  • Patients had to have a PA Catheter inserted, a practice not common in all areas
  • Potential failure in randomization as epinephrine included 48% female but noreinephrine included 20%


  • not reported

Further Reading

  1. Thiele H et al. PCI Strategies in Patients with Acute Myocardial Infarction and Cardiogenic Shock. N. Engl. J. Med. 2017. 377:2419-2432.
  2. Diepen et al. Contemporary Management of Cardiogenic Shock: A Scientific Statement From the American Heart Association 2017