Optimal Vasopressors and Inotropes in Cardiogenic Shock Angela

Optimal Vasopressors and Inotropes in Cardiogenic Shock Angela M Taylor, MD, MS University of Virginia Associate Professor, Interventional Caridology Medical Director, Coronary Care Unit Medical Director, Cardiometabolic Network

Angela Taylor, MD, MS I have no relevant financial relationships

Pressure End of systole; LVESP; diastole begins with isovolumic relaxation End-systolic pressure-volume relationship; measure of intrinsic contractility C Ea – arterial elastance; measure of afterload Ejection Systolic ejection; pressure builds throughout; volume decreases B Stroke Volume Isovolumic Contraction Isovolumic Relaxation D A End-diastolic pressure volume relationship A. B. C. D. End Diastole – Mitral Valve Closure Aortic Valve Opening End Systole – Aortic Valve Closure Mitral Valve Opening Volume Diastolic filling begins, pressure remains relatively flat due to continued relaxation End of diastole; LVEDP; isovolumic contraction begins

C B SV x Mean Aortic Pressure Stroke Work D A Volume Ventricular Stroke Work = Area of the Pressure-Volume Loop Pressure C B External Work Potential Energy D A Volume Ventricular Wall Tension = Pressure Volume Area

Phenylephrine ↑ventricular wall tension Baseline Pressure Alpha 1 agonist effects – increase in afterload Volume There is no data to support the use of phenylephrine in cardiogenic shock outside of specific indications.

↑ventricular wall tension ↑stroke work Norepinephrine Pressure Baseline A 1 agonist effects – Increase in afterload Add B 1 agonist effects – Increase in contractility Volume

Volume Dopamine 15 mcg/kg/min 5 - Baseline Alpha 1 agonist effects – increase in afterload Beta 1 agonist effects – increase in contractility Volume Dopamine 20 mcg/kg/min Baseline Dopamine Pressure ↑ventricular wall tension ↑stroke work ↑ventricular wall tension

Meta-analysis of Dopamine Versus Norepinephrine in Cardiogenic Shock 28 day mortality DO better DO worse Arrhythmic Events NEJM 2010; 362: 779 -789 Crit Care Med 2012; 40(3): 725 -30 Medicine 2017; 96(43 ): e 8402 Dopamine should not be considered in cardiogenic shock

↑ventricular wall tension ↑stroke work Epinephrine Baseline Pressure Alpha 1 agonist effects – increase in afterload Beta 1 agonist effects – increase in contractility/heart rate Beta 2 agonist effects – decreased afterload Volume Low dose Beta 2 > alpha High dose alpha > beta 2

MAP CI Lactate HR SV Terminated Early Cardiogenic shock after Acute MI, an Analysis of epinephrine vs norepinephrine JACC. 2018: 72(2): 173 -82 Cur Opin Crit Care. 2019 Randomized

Vasopressin increased mean arterial pressure but did not affect other hemodynamic parameters n=36 Vasopressin versus norepinephrine in refractory shock after acute MI 36. 1% n=221 AJC, 2005; 96: 1617 -20 Crit Care Med 2018; 46(1): S 56 n=463

Dobutamine ↑ventricular wall tension ↑stroke work Baseline B 2 agonist effects – Decrease in afterload Pressure Add B 1 agonist effects – Increase in contractility Volume

Milrinone ↑ventricular wall tension ↑stroke work Baseline Pressure Add phosphodiesterase inhibition – Increase in contractility → May also get some peripheral vasodilation → More importantly pulmonary vasodilation Volume

Inotropes in Cardiogenic Shock p=0. 50 p<0. 01 p=0. 32 p=0. 20 n=100, retrospective J Cardio Pharm Ther 2019; 24(2): 130 -8

Levosimendan Increases calcium sensitivity of myocytes (independent of beta receptors) Randominzed, n=60, on beta blokers n=1327, SURVIVE randomized Eur J Heart Fail 2010; 12(4): 404 -10 Eur J Heart Fail 2009; 11(3): 304 -11

Cardiogenic Shock Adequate Perfusion? NO YES NO Congestion? YES Dry and Warm Wet and Warm (Inotropes) (Diurese, Vasodilate) Dry and Cold Wet and Cold (Inotropes, Support) (Diurese, Inotropes, Vasodilate)

Survival in Acute MI and Shock Cardiac Power Output (W) Number of Inotropes 0 1 ≥ 2 ≤ 0. 6 67% 57% 33% 0. 6 to < 0. 8 100% 60% 50% ≥ 0. 8 85% 79% 57% NCSI Registry

Left Ventricular Support ↓ stroke work ↓ ventricular wall tension JACC. 2015; 66(23): 2663 -74

In Conclusion • There are no optimal vasopressors or inotropes in cardiogenic shock • There is limited information about comparative efficacy among agents • Use of vasopressors and inotropes should be a temporary measure as a bridge to a more durable solution • Norepinephrine is preferred based on trial data • If norepinephrine fails to restore perfusion, an inotrope should be considered • Vasopressors and inotropes should be used at lowest doses and shortest time possible