Controversies in the Treatment of Sepsis

Christian E. Sandrock, M.D., M.P.H.; Timothy E. Albertson, M.D., M.P.H., Ph.D.

Disclosures

Semin Respir Crit Care Med. 2010;31(1):66-78. 

In This Article

Abstract and Introduction

Abstract

Sepsis is a common illness of intensive care unit patients that carries a high morbidity, mortality, and increases hospital cost. Although mortality from sepsis remains high when compared with other critical illnesses, it has declined over the last few decades due to several adjunctive therapies and focused care programs or guidelines. Many interventions, such as early appropriate antibiotic therapy and lung protective, low tidal volume ventilation are commonplace and carry little controversy in their benefit. However, other therapies still have an unclear benefit and remain controversial. This article discusses the controversial roles of intensive insulin therapy, corticosteroids, and activated protein C in the treatment of sepsis.

Introduction

In the intensive care unit (ICU), severe sepsis and septic shock are common conditions that are associated with significant morbidity, mortality, and health care expense. With ~700,000 cases of severe sepsis annually in the United States (US), it is estimated that the annual cost exceeds $16.7 billion/year.[1] Despite the use of large amounts of health care resources, the mortality rate for severe sepsis still ranges from 20% to 50% and that of septic shock ranges from 30% to 87%.[1,2]

Recently revised international guidelines—the Surviving Sepsis Campaign—have been published that review and recommend many potential primary and adjunctive therapies for the treatment and management of sepsis.[3] In an analysis of the mortality data from control arms of sepsis trials conducted between 1990 and 2000, van Ruler and colleagues[4] showed a decline in mortality from 44 to 35%. Several newer therapeutic strategies for managing the patient with sepsis were also evaluated during this time of improved outcomes, including hemodynamic, endocrine, antiinflammatory/anticoagulant, nutritional, and airway management/mechanical ventilation strategies and the use of intensivists to manage the sepsis patient. This group concluded that basic care of the sepsis patient has improved with modernization of ICU care and that newer therapeutic strategies such as early appropriate antibiotics, early goal-directed therapy, the use of activated protein C (APC), and intensive insulin therapy were in order the most effective strategies.[4] Others have noted that the history of sepsis research has seen more failures than successes, and to date, no intervention has been shown to be efficacious in multiple, large, well-designed, multicenter, randomized clinical trials.[5]

This article reviews three of the more controversial adjunctive treatments for the severe sepsis patient, including the use of intensive insulin therapy for glycemic control, corticosteroids, and APC

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