Abstract and Introduction
Abstract
Sepsis accounts for more than 210,000 deaths per year. Despite adequate fluid resuscitation the associated maldistribution of blood flow may cause an imbalance between oxygen delivery and demand, leading to global tissue hypoxia, shock, and, if not reversed, death. Vasoactive therapies including catecholamine and noncatecholamine vasopressors, ionotropes, and vasodilating agents aimed at restoring perfusion and normalizing oxygen consumption have improved outcomes in patients with persistent shock despite crystalloid resuscitation. In this review we discuss the mechanisms, clinical use, and commonly observed pitfalls of the most common and a few uncommon vasodilator agents used in the management of sepsis and septic shock.
Introduction
Sepsis develops in ~750,000 people annually and accounts for more than 210,000 deaths per year. Evolving definitions of sepsis including predisposing factors, host response, and end-organ damage have emerged in recent years leading to our improved understanding of the pathophysiology of the disorder and targeted treatments. Severe sepsis and septic shock develop when infectious agents or infection-induced inflammatory mediators lead to circulatory abnormalities including peripheral vasodilatation, reduced mean arterial pressure, myocardial depression, and intravascular volume depletion. Despite adequate fluid resuscitation, maldistribution of blood flow may cause an imbalance between oxygen delivery and demand, leading to global tissue hypoxia, shock, and, if not reversed, death. Support of circulatory abnormalities with both catecholamine (and noncatecholamine) vasopressors or ionotropes after adequate fluid resuscitation is a common therapeutic intervention and may lead to improved survival in critically ill patients with sepsis. In addition nontraditional vasoactive agents such as direct or indirect nitric oxide donors have been used with some hemodynamic profile improvements in patients with sepsis. This review discusses the mechanisms and effectiveness of several commonly used vasoactive agents and a few novel uncommonly used agents with potential for the treatment of patients with severe sepsis and septic shock.