Heart Rate Control in sepsis and septic shock

Transcription

1 Heart Rate Control in sepsis and septic shock Antonia Koutsoukou Associate Professor of Intensive Care Medicine University of Athens/ Sotiria General Chest Diseases Hospital

2 Introduction Sepsis, is a clinical syndrome that arises from an inappropriate and excessive inflammatory response against infection It is the leading cause of death among critically ill patients, predominantly as a consequence of multiple organ failure Hotchkiss and Karl. N Engl J Med 2003;348:138 Annane et al. Lancet 2005;365:63

3 Current understanding of sepsis-induced cardiovascular alterations heart under filling cardiac output O2 supply demand imbalance At this point, it seems odd that a β-blocking agent might have neutral or positive clinical impact So, why make a case in favor of β blockers? Hotchkiss and Karl. N Engl J Med 2003;348:138

4 Previous β-blocker use protects against sepsis-related mortality β-blocker use non β-blocker use Patients who receive chronic β-blocker prescription may have a survival advantage if they subsequently develop sepsis and are admitted to ICU Macchia et al. Crit Care Med 2012;40:2768

5 β blockers are safe in human sepsis Morelli et al. JAMA 2013;310:1683

6 β blockers are safe in human sepsis The authors concluded that administration of esmolol in septic shock patients was associated with a reduction in heart rate without adverse effects, while they noted a statistically significant difference in the secondary outcome of survival Heart Rate MAP Survival SVI CI MAP: Mean Arterial Pressure; SVI: Stroke Volume Index; CI: Cardiac Index Morelli et al. JAMA 2013;310:1683

7 Why this might have happened?

8 Severe Sepsis is characterized by excessive adrenergic stimulation Annane et al. Am J Resp Crit Care Med 1999;160:458

9 Adrenergic effects on heart Sympathetic effects on the heart are positive Inotropic ( contractility)* Chronotropic ( Heart Rate)* Dromotropic ( atrio-ventricular conduction) Lusitropic ( relaxation) * to meet increased requirements Annane et al. Am J Resp Crit Care Med 1999;160:458

10 Consequences of β1 adrenergic stimulation Activation of β1 adrenergic receptors contractility myocardial O2 demand tachycardia restricted diastolic filling and risk of decreased stroke volume O 2 requirements

11 Adrenergic storm! Exogenous catecholamine therapy Catecholamine toxicity Elevated heart rate after fluid resuscitation (and control of anemia, pain and agitation) may indicate an inappropriate degree of sympathetic activation and/or represent an adverse effect of catecholamine therapy

12 Cardiomyocyte-level adaptation during persistent adrenergic stimulation Down-regulation of β adrenergic receptors Internalization Desensitization Decreased Density Suzuki et al. Crit Care Med 2005;33:2294

13 Keep the sick from harm Hippocrates To prevent further damage, the cells have to reduce their energy requirements Iatrogenically, mimicking this with the use of β-blockers may protect the heart from sympathetic overstimulation Using β-blockers during severe sepsis might attenuate excessive tachycardia

14 What will be the effect on Cardiac Output? What will be the effect on Cardiac Efficiency? What will be the effect on Ventricular-Arterial Coupling? What will be the effect on microcirculation?

15 Our fears regarding β blockade effect on Cardiac Output Cardiac Output = Stroke Volume x Heart Rate Giving a combined negative inotropic and chronotropic agent might worsen cardiac output in septic shock

16 Our fears are partially true Heart Rate SV or SV Cardiac Output SV SV Cardiac Output Cardiac Output

17 Let s go back to physiology Kunada et al. Jpn J Physiol 1967;17:538

18 Lowering the heart rate Effect on Cardiac Output If the increase of heart rate is obtained by sympathetic stimulation, the increase of CO with increasing heart rate is greater than with pacing, because sympathetic stimulation has inotropic and lusitropic effects, that is it increases the contractility and increases the speed of relaxation of the myocardium during diastole.

19 Insignificant effect of heart rate reduction on Cardiac Output at the population level Morelli et al. JAMA 2013;310:1683

20 Lowering the heart rate Effect on Cardiac efficiency Heart Rate can limit the increased myocardial O 2 demand and its inherent risks The efficiency is the ratio between the external work and the energy which has been consumed to do that external work. Kunada et al. Jpn J Physiol 1967;17:538

21 β blockers in experimental sepsis Infusion of the β adrenergic blocker esmolol attenuates myocardial dysfunction in septic rats β blocker treated animals developed higher Stroke Volume and Cardiac Output Suzuki et al. Crit Care Med 2005;33:2294

22 Ventricular-arterial (un)coupling What would be the effect of β-blockers on Ventricular-arterial uncoupling? Ea: Arterial Elastance; Ees: Endsystolic Elastance Suga et al. Am J Physiol 1983;244:H206 Guarracino et al. Crit Care 2014;18:R80

23 What about the microcirculation? Prospective observational study with specific focus on macrocirculation (Swan-Ganz) and microcirculation (Sidestream dark-field imaging) 25 septic patients who received a titrated esmolol infusion to a Heart Rate< 95 bpm Morelli et al. Crit Care Med 2013;41:2162

24 What about the microcirculation? Jacquet-Lagrèze et al. Crit Care 2015;19:241

25 Conclusions There is some evidence that β blocker use is safe in clinical sepsis and weak evidence of efficacy This challenges our current understanding of cardiovascular alterations leading to multi-organ failure This action might be mediated by alterations In cardiac output In cardiac efficiency In ventriculo-arterial uncoupling In the microcirculation More data are needed