Inotropic Support in the Treatment of Septic Myocardial Dysfunction: Pathophysiological Implications Supporting the Use of Levosimendan

Myocardial dysfunction is a frequent organ manifestation during septic shock and the subsequent impairment in cardiac output may result in organ hypoperfusion, requiring prompt and adequate treatment to restore cardiovascular function and reverse shock [1]. Current sepsis guidelines recommend resuscitation with intravascular fluid administration in association with inotropes and vasopressors to maintain organ perfusion [2]. Dobutamine is recommended as first-line inotropic agent and should be administered when low cardiac output or signs of hypoperfusion persist after adequate fluid resuscitation and perfusion pressure have been achieved [2]. However, the efficacy of dobutamine in patients with heart failure has not been fully demonstrated and concerns on its use are still present [3]. Although dobutamine improves perfusion and increases oxygen delivery (DO(2)), its impact on survival in septic shock patients is limited, with guideline recommendations based mainly on the landmark study by Rivers et al. [4]. Recently, Wilkman et al. [5] reported that the use of inotropes, particularly dobutamine, in septic shock was associated with increased 90-day mortality. In explaining the lack of outcome benefit [3, 5], several aspects need to be taken into account. First, the need of inotropic support may simply represent an expression of disease severity rather than the cause of a poor outcome. Second, whereas the treatment of impaired cardiac output should be tailored based on the etiological mechanism of the cardiovascular dysfunction, the current guidelines recommend the use of inotropes without differentiating the underlying causes of impaired left ventricular (LV) stroke volume [2, 6]. In addition, the majority of cardiovascular monitoring instruments provide data almost exclusively on cardiac output and pressures. This approach may potentially increase the number of patients who may be harmed by inotrope administration (Fig. 1). Finally, the beneficial short-term effect of enhanced contractility by cAMP-increasing drugs (e. g., dobutamine, milrinone) is, at least partly, abolished by the increased energy consumption, the worsening of ventricular relaxation and the direct cardiomyocyte toxicity [1, 7–10].