Optimal vasopressor use in cardiogenic shock. Pr Levy Bruno Réanimation Médicale Nancy Institut du Cœur et des Vaisseaux Groupe Choc, Inserm France

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1 Optimal vasopressor use in cardiogenic shock Pr Levy Bruno Réanimation Médicale Nancy Institut du Cœur et des Vaisseaux Groupe Choc, Inserm France

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3 Cardiogenic shock Low cardiac output Decrease in left/right ventricular function Increase in preload (liver failure) Low arterial pressure Decrease in vascular responsiveness to vasopressor Decrease in organ perfusion pressure Myocardial ischemia Low coronary perfusion pressure Compensatory tachycardia

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5 Potential problems with vasopressor Excessive increase in afterload Further decrease in flow Excessive increase in peripheral resistances Further decrease in perfusion pressure at the organ level Risk of ischemia exacerbation Excessive tachycardia Increase in MVO 2 Decrease in diastolic time Cellular increase in calcium arrhythmias

6 Visible/invisible effects of catecholamines Pre/post load and frequency dependant parameters Increase in heart rate. Increase in arterial pressure/afterload Variable effects on cardiac index/svo2 Variable effects on pulmonary pressure Less visible parameters Intrinsic cardiac function MVO 2 Calcium load Heart structure Immunologic

7 Catecholamine induced cardiomyopathy Pheochromocytoma, acute emotional stress, intracranial bleeding, head trauma, ischemic stoke. Acute medical illness including sepsis. Exogenous catecholergic agents inhaled beta-agonist, epinephrine, amphetamines, cocaine

8 Mechanisms Stimulation of adrenoreceptor in the myocardium Local release of NE by sympathic nerve terminal directly innervating the myocardium +++ Diffusion of circulating catecholamine from the coronary circulation Differential effects of NE and E NE is inotropic and lusitropic at low and high concentrations E increases inotropism at low concentration and decreases it at high concentration Explained by a different action on beta-2 receptor Both Gs and Gi Pathways are stimulated by E and only Gs by NE

9 Not only adrenoreceptor binding Catecholamine induced deleterious effects through oxidative mechanisms Oxydation leads to aminochromes and free radical production Intracellular calcium overload Myocardial cell damage (contraction band necrosis)

10 " obvious e.g. tachyarrhythmias, digital ischaemia " stimulation of bacterial growth + virulence " immunosuppression " metabolic modulation " thrombogenic " decreased bioenergetic efficiency " increased cardiac work " ventricular remodelling " myocardial damage Singer M. Lancet 2007; 370: 636-7

11 The questions? Which vasopressor? Alone or in combination with inotropes? Mean arterial pressure level? Cardiac index/svo 2 level? Monitoring? Timing and indication : vasopressor versus ECMO?

12 Cardiogenic shock Heart and vessels : a difficult coupling

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15 Epinephrine versus norepinephrine

16 ravens

17 Norepinephrine is an inotrope

18 Norepinephrine as an inotrope MAP 65 mmhg MAP 85 mmhg p= Heart rate (bpm) 102 +/ /- 7 p > 0,05 CI (l/min/m 2 ) 2,3 +/- 0,4 2,8 +/- 0,3 p < 0,05 CPI (watt/m 2 ) 0,38 +/- 0,03 0,58 +/- 0,04 p < 0,01 SVO 2 (%) 73 +/ /- 2 p < 0,05

19 Study Comparing the Efficacy and Tolerability of Epinephrine and Norepinephrine in Cardiogenic Shock (OptimaCC) " NCT " Prospective, double blind, randomized, multicenter study " Cardiogenic shock due to myocardial infarction treated by angioplasty and needing a vasopressor support " Epinephrine or norepinephrine titrated to MAP : 70 mmhg " Monitoring with a Swan-Ganz catheter. " 60 patients, end of the study in December " Evaluation : composite score including CI, SVO 2, lactate, heart rate, cardiac power index, side effects, number of refractory shock. " More refractory cardiogenic shock in the epinephrine group. " 39% in the epinephrine groupe versus 13 % in the Nor-epi group (p< 0.05) " Survival rate : 47 % in the epinephrine group versus 64 % in the Norepi

20 Il est recommandé d atteindre par le traitement inotrope et/ou vasopresseur un objectif de pression artérielle moyenne (PAM) d au moins 65 mmhg et davantage en cas d antécédents d HTA ou de pression veineuse centrale (PVC) élevée. La constatation d'une PAD basse doit faire envisager l utilisation d un vasopresseur si la PAM est < 65 mmhg. Il est recommandé d utiliser la noradrénaline pour restaurer une pression de perfusion au cours du choc cardiogénique. L adrénaline peut s avérer une alternative thérapeutique à l association dobutamine et noradrénaline mais est associée à un risque plus important d arythmie, de tachycardie et d hyperlactatémie.

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22 The new paradigm

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26 The french recommandations Norepinephrine is the vasopressor of choice Epinephrine is a therapeutic alternative but is associated with tachycardia, hyperlactaemia and arythmia. Continuous monitoring of cardiac output and SVO 2 are mandatory Use of Swan-Ganz catheter or transpulmonary thermodilution MAP between mmhg (more might be discussed) NE could be associated to dobutamine Always discussed an increase in vasopressor versus an increase in pure inotrope Always discuss to switch for ECMO