Continuing Medical Education Article

Early changes in organ function predict eventual survival in severe sepsis* Mitchell M. Levy, MD, FCCM; William L. Macias, MD, PhD; Jean-Louis Vincent, MD, PhD, FCCM; James A. Russell, MD; Eliezer Silva, MD, PhD; Benjamin Trzaskoma, MS; Mark D. Williams, MD

LEARNING OBJECTIVES

On completion of this article, the reader should be able to: 1. Explain organ function abnormalities associated with poor patient outcomes from sepsis. 2. Describe the significant time periods to predict outcome. 3. Use this information in a clinical setting. Dr. Levy has disclosed that he is/was the recipient of direct grant/research funds from Eli Lilly & Co., Chiron, Moguel, Phillips, and Edwards; is a consultant for Chiron and Phillips; and is/was on the speakers bureau of Eli Lilly & Co., Edwards, Phillips, and Ortho. Dr. Macias has disclosed that he is/was an employee and a current stock shareholder of Eli Lilly & Co. Dr. Vincent has disclosed that he is/was the recipient of direct grant/research funds from, a consultant for, and on the speakers bureau of Eli Lilly & Co. Mr. Trzaskoma and Dr. Williams have disclosed that they were/are employees and stock shareholders of Eli Lilly & Co. Dr. Silva has disclosed that he is/was a consultant for and was on the speakers bureau of Eli Lilly & Co. Dr. Russell has disclosed that he has no financial relationships with or interests in any commercial companies pertaining to this educational activity. Wolters Kluwer Health has identified and resolved all faculty conflicts of interests regarding this educational activity. Visit the Critical Care Medicine Web site (www.ccmjournal.org) for information on obtaining continuing medical education credit. Objective: Early identification and treatment of severe sepsis can significantly reduce mortality rate. We hypothesized that a risk prediction model based on early (baseline to day 1 of study) response to standard care should be significantly related to 28-day survival. Design: Analysis of organ dysfunction data from two placebocontrolled severe sepsis trials (PROWESS and secretory phospholipase A2 inhibitor trials). Setting: Research laboratory. Patients: The placebo arms of two randomized, double-blind sepsis trials were combined (n ⴝ 1036). These patients met criteria for severe sepsis and received supportive standard intensive care and fluid resuscitation. Interventions: None. Measurements and Main Results: Sequential Organ Failure Assessment (SOFA) scores were calculated daily using the most aberrant physiologic or laboratory variables. Baseline and postbaseline SOFA scores categorized as improved, unchanged, or worsened were used in regression analyses correlating organ dysfunction changes with 28-day mortality. Improvement in cardiovascular (p ⴝ .0010),

*See also p. 2412. Professor of Medicine, Director Medical ICU, Brown University School of Medicine, Rhode Island Hospital, Providence, RI (MML); Senior Medical Director, Cardiovascular and Acute Care Platform (WLM), Statistician (BT), Eli Lilly & Co., Indianapolis, IN; Head, Department of Intensive Care, Erasme University Hospital, Brussels, Belgium (J-LV); Professor of Medicine, Division of Crit-

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renal (p < .0001), or respiratory (p ⴝ .0469) function from baseline to day 1 was significantly related to survival. Odds ratios (95% confidence intervals) associated with improved vs. worsened respiratory, cardiovascular, or renal function before start of day 1 were 0.56 (0.35– 0.91), 0.33 (0.18 – 0.59), and 0.30 (0.17– 0.52), respectively. Continued improvement in cardiovascular function before start of day 2 and start of day 3 was associated with further improvement in survival (p