Sepsis-induced cardiac dysfunction and β-adrenergic blockade therapy for sepsis

Abstract

Despite recent advances in medical care, mortality due to sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, remains high. Fluid resuscitation and vasopressors are the first-line treatment for sepsis in order to optimize hemodynamic instability caused by vasodilation and increased vascular permeability. However, these therapies, aimed at maintaining blood pressure and blood flow to vital organs, could have deleterious cardiac effects, as cardiomyocyte damage occurs in the early stages of sepsis. Recent experimental and clinical studies have demonstrated that a number of factors contribute to sepsis-induced cardiac dysfunction and the degree of cardiac dysfunction is one of the major prognostic factors of sepsis. Therefore, strategies to prevent further cardiomyocyte damage could be of crucial importance in improving the outcome of sepsis.Among many factors causing sepsis-induced cardiac dysfunction, sympathetic nerve overstimulation, due to endogenous elevated catecholamine levels and exogenous catecholamine administration, is thought to play a major role. β-adrenergic blockade therapy is widely used for ischemic heart disease and chronic heart failure and in the prevention of cardiovascular events in high-risk perioperative patients undergoing major surgery. It has also been shown to restore cardiac function in experimental septic animal models. In a single-center randomized controlled trial, esmolol infusion in patients with septic shock with persistent tachycardia reduced the 28-day mortality. Furthermore, it is likely that β-adrenergic blockade therapy may result in further beneficial effects in patients with sepsis, such as the reduction of inflammatory cytokine production, suppression of hypermetabolic status, maintenance of glucose homeostasis, and improvement of coagulation disorders.Recent accumulating evidence suggests that β-adrenergic blockade could be an attractive therapy to improve the prognosis of sepsis. We await a large multicenter randomized clinical trial to confirm the beneficial effects of β-adrenergic blockade therapy in sepsis, of which mortality is still high.

Severe Pneumococcal Pneumonia Causes Acute Cardiac Toxicity and Subsequent Cardiac Remodeling

“…1 Dr Berk Takir et al argue that presence of sepsis or septic shock instead of (or due to) CAP may have influenced our findings by referring to evidence showing that the degree of sepsis-induced cardiac dysfunction is an important prognostic factor in critically ill patients. 2 Our study was conducted in a subset (n = 295) of a cohort of (n = 304) patients hospitalized with CAP in a non-academic teaching hospital. 1 Direct intensive care unit (ICU) admission was an exclusion criterion.…”

Effect of Heart Rate Control on Oxygenation and Vasopressor Need in Sepsis and Septic Shock-A Pilot Randomised Controlled Study

“…β adrenerjik reseptörlerin aktivitesi kendi içerisinde denge oluşturur. β1 aktivitesi ile TNF-a, IL-1β gibi proinflamatuar sitokinlerin salınımı artarken; b2 reseptörlerin çalışması bu salınımı suprese eder (20). Sepsiste ise bir sitokin fırtınası durumu söz konusudur.…”

Review article: Sepsis in the emergency department – Part 3: Treatment

“…Contentious aspects of that trial including liberal levosimendan use and high mortality in the standard care arm have reduced validity of the findings. Nonetheless, evidence of potential beneficial effects of beta‐blockade on microcirculation and cardiac function is accumulating, and results of clinical trials underway are awaited . The novel calcium‐sensitising agent levosimendan is a non‐catecholamine inotropic agent also examined in sepsis.…”

“…Nonetheless, evidence of potential beneficial effects of beta-blockade on microcirculation and cardiac function is accumulating, and results of clinical trials underway are awaited. 59 The novel calcium-sensitising agent levosimendan is a non-catecholamine inotropic agent also examined in sepsis. Despite several small trials and a positive meta-analysis, 60 levosimendan was not found beneficial for patients with septic shock in the LeoPARDS RCT.…”