Current real-life use of vasopressors and inotropes in cardiogenic shock - adrenaline use is associated with excess organ injury and mortality

Abstract

BackgroundVasopressors and inotropes remain a cornerstone in stabilization of the severely impaired hemodynamics and cardiac output in cardiogenic shock (CS). The aim of this study was to analyze current real-life use of these medications, and their impact on outcome and on changes in cardiac and renal biomarkers over time in CS.MethodsThe multinational CardShock study prospectively enrolled 219 patients with CS. The use of vasopressors and inotropes was analyzed in relation to the primary outcome, i.e., 90-day mortality, with propensity score methods in 216 patients with follow-up data available. Changes in cardiac and renal biomarkers over time until 96 hours from baseline were analyzed with linear mixed modeling.ResultsPatients were 67 (SD 12) years old, 26 % were women, and 28 % had been resuscitated from cardiac arrest prior to inclusion. On average, systolic blood pressure was 78 (14) and mean arterial pressure 57 (11) mmHg at detection of shock. 90-day mortality was 41 %. Vasopressors and/or inotropes were administered to 94 % of patients and initiated principally within the first 24 hours. Noradrenaline and adrenaline were given to 75 % and 21 % of patients, and 30 % received several vasopressors. In multivariable logistic regression, only adrenaline (21 %) was independently associated with increased 90-day mortality (OR 5.2, 95 % CI 1.88, 14.7, p = 0.002). The result was independent of prior cardiac arrest (39 % of patients treated with adrenaline), and the association remained in propensity-score-adjusted analysis among vasopressor-treated patients (OR 3.0, 95 % CI 1.3, 7.2, p = 0.013); this was further confirmed by propensity-score-matched analysis. Adrenaline was also associated, independent of prior cardiac arrest, with marked worsening of cardiac and renal biomarkers during the first days. Dobutamine and levosimendan were the most commonly used inotropes (49 % and 24 %). There were no differences in mortality, whether noradrenaline was combined with dobutamine or levosimendan.ConclusionAmong vasopressors and inotropes, adrenaline was independently associated with 90-day mortality in CS. Moreover, adrenaline use was associated with marked worsening in cardiac and renal biomarkers. The combined use of noradrenaline with either dobutamine or levosimendan appeared prognostically similar.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1387-1) contains supplementary material, which is available to authorized users.

Organ dysfunction, injury and failure in acute heart failure: from pathophysiology to diagnosis and management. A review on behalf of the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

“…levosimendan, milrinone) and vasopressors (norepinephrine is preferred over dopamine based on a subgroup analysis that suggested fewer side effects and lower mortality with norepinephrine, as noted in heart failure guidelines) should only be used when cardiac output is severely reduced, vital organ perfusion is compromised, filling pressures are normal or high, and patients cannot be stabilized by other means because of their associations with increased mortality . Recent evidence suggests that epinephrine should be avoided in cardiogenic shock …”

Long‐term safety of intravenous cardiovascular agents in acute heart failure: results from the European Society of Cardiology Heart Failure Long‐Term Registry

“…The CardShock study recently demonstrated the association between the use of adrenaline in cardiogenic shock and a striking myocardial injury as well as increased 90-day mortality, thus raising questions about the safety of this treatment. 20 The increasing safety concerns for the use of catecholamines are reflected in current clinical practice guidelines. The recent ESC guidelines for the diagnosis and treatment of acute and chronic HF further restrict the use of inotropic agents to AHF patients only with symptomatic hypotension and hypoperfusion.…”

Cardiogenic Shock

“…Based on the results of a multicenter cohort observational study on 1058 shock patients, following the German-Austrian guideline recommendations, the use of dopamine is an independent risk factor for mortality (p = 003), while this is not the case for dobutamine and norepinephrine [34]. Based on prospectively collected real-life data, epinephrine should be used only for resuscitation because it produces advanced organ damage and it is associated with higher mortality compared to dobutamine, levosimendan, and norepinephrine [35]. The European Association of Cardiology guidelines recommended the combination of levosimendan with a vasopressor agent in CSMI patients refractory to catecholamines or using it with a phosphodiesterase III inhibitor such as enoximone or milrinone, with or without dobutamine in intractable CS (ICS) patients [33].…”