Myocardial dysfunction in sepsis: mechanisms and therapeutic implications

Sepsis and its related syndromes represent potentially devastating illnesses, estimated to account for 1% of all hospital admissions and for 100 000 deaths per annum in the U.S.A. alone. Although sepsis is defined as the systemic response to infection, an infective organism is found in fewer than 50% of cases. It is therefore increasingly recognised that sepsis represents only one example of a systemic inflammatory response that can be triggered not only by infection, but also by noninfectious disorders such as trauma and pancreatitis. The clinical features of these conditions are thought to be attributable to the triggering of a cascade of inflammatory mediators, the overproduction of which result in organ dysfunction. This spectrum of diseases shares a common, overlapping clinical end-point, termed the systemic inflammatory response syndrome. The definitions of sepsis, the systemic inflammatory response syndrome and related syndromes are shown in Table 1. The systemic inflammatory response syndrome is associated with considerable morbidity and is the leading cause of death in the intensive care unit, attributable to refractory hypotension, cardiac dysfunction and multi-organ failure. In the 40% of patients with sepsis who develop cardiovascular impairment, mortality rises from 20% to 70–90%, a figure that has changed little in recent years, despite considerable advances in supportive techniques. This review describes the changes in cardiac function in sepsis, outlines the underlying mechanisms by which they are thought to occur, and discusses the current