Controversy Swirls Around Early Goal-Directed Therapy in Sepsis: Pioneer Defends Ground-Breaking Approach to Deadly Disease

Abstract

P lans to re-examine a research finding via a much larger set of clinical trials, a common event in medical research, have provoked an uncommon result: an unusually public airing in the mainstream media of allegations, financial questions and wounded professional pride. The research finding at the center of the dispute is early goal-directed therapy for sepsis, formulated 7 years ago by Emanuel P. Rivers, MD, MPH, vice chairman and director of research in emergency medicine at Henry Ford Hospital in Detroit, MI. Dr. Rivers, who trained in critical care, emergency and internal medicine, proposed applying the “golden hour” to severe sepsis and septic shock. His protocol identified patients and began treating them in the emergency department (ED), before they were admitted to intensive care. It deployed a bundle of conventional measures—early recognition of patients with a high risk of death using blood lactate levels or hypotension and giving antibiotics, fluid therapy titrated to central venous pressure, vasopressors if required to maintain blood pressure, hemoglobin concentration above 10 mg/dl using transfusions if required, and maintaining central venous blood oxygen saturation above 70% using medication (Inotropes) to improve perfusion. And it had dramatic results. Dr. Rivers’ protocol cut the mortality rate in the 130 patients who received it to 30.5%, compared to 46.5% among the 133 patients treated with the hospital’s standard care—a drop in deaths so striking that the study’s data safety monitoring board decided to end it early. That seemed a significant advance for a disease that affects 750,000 Americans each year and costs from $16.7 2 to $24 billion and that had had an intractable mortality rate for 3 decades. Rivers’ protocol was adopted by the Surviving Sepsis Campaign, which is endorsed by the American College of Emergency Physicians and the Society of Critical Care Medicine, and is recommended by the Institute for Healthcare Improvement. Early goal-directed therapy drew some criticism from the start, and EDs were slow to adopt it: 3 years after it was published, a survey of 30 academic medical center EDs, found only 2 using the protocol. (There is no registry of EDs that use early goal-directed therapy, but it has been adopted by several large health systems, and a July 2008 paper surveyed 40 hospitals now using it.) Departments that have adopted it are enthusiastic. In a 2006 article in Chest, describing a yearlong trial at Cooper University Hospital in Camden, NJ, Stephen Trzeciak, MD, MPH, declared that early goal-directed therapy “could reliably be achieved in real-world clinical practice.” And later that year, authors from 9 institutions, including Trzeciak and Rivers, reported the outcomes of implementing early goal-directed therapy in 12 institutions other than Henry Ford; all 12 had comparable declines in sepsis mortality rates.