Early changes in organ function predict eventual survival in severe sepsis

• Published in: Critical care medicine Vol. 33; no. 10; pp. 2194 - 2201
• Main Authors: Levy, Mitchell M, Macias, William L, Vincent, Jean-Louis, Russell, James A, Silva, Eliezer, Trzaskoma, Benjamin, Williams, Mark D
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD by the Society of Critical Care Medicine and Lippincott Williams & Wilkins 01-10-2005; Lippincott
• Subjects: Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Cardiovascular System - physiopathology; Emergency and intensive cardiocirculatory care. Cardiogenic shock. Coronary intensive care; Emergency and intensive care: infection, septic shock; Female; Hematopoietic System - physiopathology; Humans; Intensive care medicine; Kidney - physiopathology; Liver - physiopathology; Logistic Models; Male; Medical sciences; Middle Aged; Predictive Value of Tests; Respiratory System - physiopathology; Sepsis - complications; Sepsis - mortality; Sepsis - physiopathology; Survival Rate; Infection; Sepsis syndrome; Intensive care; sequential organ failure assessment; Prognosis; Mortality; clinical prediction; Survival; Resuscitation; outcome; sepsis; organ dysfunction
• ISSN: 0090-3493; 1530-0293
• DOI: 10.1097/01.CCM.0000182798.39709.84

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 placebo-controlled 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 = 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 = .0010), renal (p < .0001), or respiratory (p = .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 <. 0001), with odds ratios of 0.15 (0.06–0.39) and 0.11 (0.04–0.31) for patients who improved compared with those who worsened. No other organ system was retained in the model, and improvement beyond day 1 in any other organ function did not add to the modelʼs predictive power.
CONCLUSIONS:These analyses suggest that outcomes for patients with severe sepsis are closely related to early (baseline to day 1 here) improvement, or lack thereof, in organ function. Also, clinical improvement on subsequent days may have little additional impact on the likelihood of survival.
LEARNING OBJECTIVESOn completion of this article, the reader should be able to: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.