Title:The Heart in Sepsis: From Basic Mechanisms to Clinical Management
Volume: 11
Issue: 2
Author(s): Alain Rudiger and Mervyn Singer
Affiliation:
Keywords:
Adrenergic stimulation, beta blocker, early goal directed therapy, esmolol, inflammation, heart, levosimendan, sepsis
Abstract: Septic shock is characterized by circulatory compromise, microcirculatory alterations and mitochondrial damage,
which all reduce cellular energy production. In order to reduce the risk of major cell death and a diminished likelihood
of recovery, adaptive changes appear to be activated. As a result, cells and organs may survive in a non-functioning
hibernation-like condition. Sepsis-induced cardiac dysfunction may represent an example of such functional shutdown.
Sepsis-induced myocardial dysfunction is common, corresponds to the severity of sepsis, and is reversible in survivors. Its
mechanisms include the attenuation of the adrenergic response at the cardiomyocyte level, alterations of intracellular calcium
trafficking and blunted calcium sensitivity of contractile proteins. All these changes are mediated by cytokines.
Treatment includes preload optimization with sufficient fluids. However, excessive volume loading is harmful. The first
line vasopressor recommended at present is norepinephrine, while vasopressin can be started as a salvage therapy for
those not responding to catecholamines. During early sepsis, cardiac output can be increased by dobutamine. While early
administration of catecholamines might be necessary to restore adequate organ perfusion, prolonged administration might
be harmful.
Novel therapies for sepsis-induced cardiac dysfunction are discussed in this article. Cardiac inotropy can be increased by
levosimendan, istaroxime or omecamtiv mecarbil without greatly increasing cellular oxygen demands. Heart rate reduction
with ivabradine reduces myocardial oxygen expenditure and ameliorates diastolic filling. Beta-blockers additionally
reduce local and systemic inflammation. Advances may also come from metabolic interventions such as pyruvate, succinate
or high dose insulin substitutions. All these potentially advantageous concepts require rigorous testing before implementation
in routine clinical practice.
