title: Prospectively validated prediction of organ failure and hypotension in patients with septic shock: the Systemic Mediator Associated Response Test (SMART).
abstract: Conventional outcomes research provides only percentage risk categories that are not applicable to individual patients, and it predicts only mortality, utilization of resources and/or broad groupings of multiple organ system dysfunction. The purpose of the present study was to determine whether or not the Systemic Mediator Associated Response Test (SMART) methodology could identify interactions among demographics, physiologic parameters, standard hospital laboratory tests, and circulating cytokine concentrations to predict continuous and dichotomous dependent clinical variables, in advance, in individual patients with septic shock and to integrate these into prospectively validated models. Two hundred forty (240) patients with septic shock who were entered into the placebo arm of a multi-institutional clinical trial were randomly separated into a model building training cohort (n = 154) and a predictive cohort (n = 86), which was used to prospectively validate the prognostic models built upon the training cohort database. From baseline patient demographics; hospital laboratory tests; and plasma levels of interleukin-6, interleukin-8, and granulocyte colony stimulating factor, multiple regression models were developed that predicted clinically important continuous dependent variables quantitatively in individual patients. Multivariate stepwise logistic regression was utilized to develop models that prognosticated dichotomous dependent end points. At the completion of the modeling process, baseline data from individual patients in the predictive cohort was inserted into each multivariate model for each day. Prospective validation was accomplished by simple linear regression of individual predicted versus observed values for continuous dependent variables, and by establishing the Receiver Operator Characteristics Area Under the Curve (ROC AUC) for logistic regression models that predicted dichotomous end points. Through seven days, SMART quantitative predictions of selected physiologic and metabolic parameters were validated at r > 0.500 in 51%. Up to seven days after baseline, 31/49 (63%) SMART models for renal and liver function indicators were validated prospectively at the r > 0.700 level. For hematologic/coagulation models, 37/56 (66%) up to seven days had r > 0.900. Among dichotomous models, ROC AUC > 0.700 was achieved in 30/49 (61%) during the first week. SMART integration of demographics, bedside physiology, hospital laboratory tests, and circulating cytokines predicts organ failure and physiologic function indicators in individual patients with septic shock.
authors.affiliation: Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School-Camden, Cooper Hospital/University Medical Center, 08103, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Slotman
mesh_terms: D019540:Area Under Curve; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D003955:Diagnostic Tests, Routine; D006801:Humans; D007022:Hypotension / Q000453:epidemiology* / Q000209:etiology; D016014:Linear Models; D008954:Models, Biological; D009102:Multiple Organ Failure / Q000453:epidemiology* / Q000209:etiology; D015999:Multivariate Analysis; D017063:Outcome Assessment, Health Care / Q000379:methods*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000150:complications*
chemical_list: D016207:Cytokines