Sepsis-induced myocardial dysfunction: pathophysiology and management

Abstract

Sepsis is aggravated by an inappropriate immune response to invading microorganisms, which occasionally leads to multiple organ failure. Several lines of evidence suggest that the ventricular myocardium is depressed during sepsis with features of diastolic dysfunction. Potential candidates responsible for septic cardiomyopathy include pathogen-associated molecular patterns (PAMPs), cytokines, and nitric oxide. Extracellular histones and high-mobility group box 1 that function as endogenous damage-associated molecular patterns (DAMPs) also contribute to the myocardial dysfunction associated with sepsis. If untreated, persistent shock causes cellular injury and the liberation of further DAMPs. Like PAMPs, DAMPs have the potential to activate inflammation, creating a vicious circle. Early infection control with adequate antibiotic care is important during septic shock to decrease PAMPs arising from invasive microorganisms. Early aggressive fluid resuscitation as well as the administration of vasopressors and inotropes is also important to reduce DAMPs generated by damaged cells although excessive volume loading, and prolonged administration of catecholamines might be harmful. This review delineates some features of septic myocardial dysfunction, assesses its most common underlying mechanisms, and briefly outlines current therapeutic strategies and potential future approaches.

Keywords: Damage-associated molecular patterns; Immune system; Infection; Septic shock; Systemic inflammatory response syndrome.

Fig. 1

Pathophysiology of septic shock and secondary myocardial dysfunction. (a) In the normal condition, cardiac output is adequate to meet the oxygen demand in peripheral tissues. (b) At the very early phase of sepsis, LV ejection fraction (EF) is not impaired (typically LVEF >55 %), but stroke volume (SV) is low because of insufficient cardiac preload due to a high vascular permeability and vasodilation. The compensatory increase in heart rate (HR) is often insufficient to maintain adequate cardiac output. (c) After fluid loading, SV can be recovered especially in the case of survivors while LVEF is temporarily decreased (typically <45 %) in part due to high LVEDV. This indicates that low LVEF may represent preload optimization and good adaptation. (d) During the later phase of sepsis, non-survivors are given more fluid than survivors but, nevertheless, have lower LVEDV suggesting a persistent vascular hyperpermeability and preload deficiency. In these cases, LVEF can be retained in part due to low LVEDV and/or ongoing harmful adrenergic over-stimulation

Fig. 2

Direct myocardial depression in sepsis. A major mechanism of direct cardiac depression in sepsis is cardiomyocyte hyporesponsiveness due to down-regulation of β-adrenergic receptors and depression of post-receptor signaling pathways. These changes seem to be mediated by many substances, including cytokines and nitric oxide. Another mechanism of direct cardiac depression is cardiomyocyte injury or death, which can be induced by toxins, complements, damage-associated molecular patterns (DAMPs), neutrophil extracellular traps (NETs), and as-yet-unidentified myocardial depressant factors (MDFs). MOF multiple organ failure, PAMPs pathogen-associated molecular patterns, PRRs pattern recognition receptors

Fig. 3

Management of myocardial dysfunction in septic shock. Prompt and adequate antibiotic therapy, accompanied by surgical removal of the infectious focus if indicated and feasible, is important to decrease PAMPs arising from invasive microorganisms. Early goal-directed therapy (EGDT), including fluid resuscitation, vasopressor and inotropic therapy, and red blood cell transfusion, is important to re-establish organ perfusion pressure, which helps maintain blood flow to tissues and reduces the release of damage-associated molecular patterns (DAMPs) in patients with septic shock. Sepsis bundle is a selected set of elements of care distilled from Surviving Sepsis Campaign guidelines. PAMPs pathogen-associated molecular patterns, PRRs pattern recognition receptors, SIRS systemic inflammatory response syndrome