The use of activated protein C (drotrecogin alfa (activated)) in the treatment of severe sepsis

Advances in intensive care have allowed many critically ill patients to survive their initial insult. These patients may later demonstrate multiple organ dysfunction and failure, the genesis of which appears to be the body's reaction to critical illness, manifested by an imbalance and failure of inflammatory and immune system homeostasis. The manifestation of multiple organ dysfunction in the critically ill has been termed multiple organ dysfunction syndrome (MODS). MODS mortality is high and remains a leading cause of death in intensive care units (ICUs).

The understanding of the pathophysiology of severe sepsis and MODS has moved from a focus on inflammation to include an understanding of the associated anti-inflammatory responses. Loss of homeostasis can manifest as malignant inflammation or immune paralysis. Increased emphasis is emerging on the role of loss of immune homeostasis and disordered coagulation as a cause of organ injury and dysfunction. Treatment of severe sepsis is based upon aggressive resuscitation, source control and support for failing organs. Novel therapies directed at the modifying the inflammatory response have, up to now, not proven beneficial. However, a new agent, drotrecogin alfa (activated) has been shown, in a phase III randomised controlled trial, to be of benefit in the treatment of severe sepsis. This new agent affects both the inflammatory and coagulation dimensions of severe sepsis.

The developing concepts of the pathophysiology of sepsis and the emergence of a new therapy increases the complexity of the already complex demands of providing nursing care for the patient with severe sepsis and MODS. This article reviews pathophysiological processes in sepsis, reviews clinical data on activated protein C and illustrates the utility of this therapy in a case study.