A multibiomarker-based outcome risk stratification model for adult septic shock*.

TitleA multibiomarker-based outcome risk stratification model for adult septic shock*.
Publication TypeJournal Article
Year of Publication2014
AuthorsWong, HR, Lindsell, CJ, Pettilä, V, Meyer, NJ, Thair, SA, Karlsson, S, Russell, JA, Fjell, CD, Boyd, JH, Ruokonen, E, Shashaty, MGS, Christie, JD, Hart, KW, Lahni, P, Walley, KR
JournalCrit Care Med
Volume42
Issue4
Pagination781-9
Date Published2014 Apr
ISSN1530-0293
KeywordsAdult, Age Factors, Aged, APACHE, Biological Markers, Chronic Disease, Decision Support Systems, Clinical, DNA Probes, Hospital Mortality, Humans, Intensive Care Units, Middle Aged, Prognosis, Risk Assessment, ROC Curve, Sensitivity and Specificity, Shock, Septic
Abstract

OBJECTIVES: Clinical trials in septic shock continue to fail due, in part, to inequitable and sometimes unknown distribution of baseline mortality risk between study arms. Investigators advocate that interventional trials in septic shock require effective outcome risk stratification. We derived and tested a multibiomarker-based approach to estimate mortality risk in adults with septic shock.DESIGN: Previous genome-wide expression studies identified 12 plasma proteins as candidates for biomarker-based risk stratification. The current analysis used banked plasma samples and clinical data from existing studies. Biomarkers were assayed in plasma samples obtained from 341 subjects with septic shock within 24 hours of admission to the ICU. Classification and regression tree analysis was used to generate a decision tree predicting 28-day mortality based on a combination of both biomarkers and clinical variables. The derived tree was first tested in an independent cohort of 331 subjects, then calibrated using all subjects (n = 672), and subsequently validated in another independent cohort (n = 209).SETTING: Multiple ICUs in Canada, Finland, and the United States.SUBJECTS: Eight hundred eighty-one adults with septic shock or severe sepsis.INTERVENTION: None.MEASUREMENTS AND MAIN RESULTS: The derived decision tree included five candidate biomarkers, admission lactate concentration, age, and chronic disease burden. In the derivation cohort, sensitivity for mortality was 94% (95% CI, 87-97), specificity was 56% (50-63), positive predictive value was 50% (43-57), and negative predictive value was 95% (89-98). Performance was comparable in the test cohort. The calibrated decision tree had the following test characteristics in the validation cohort: sensitivity 85% (76-92), specificity 60% (51-69), positive predictive value 61% (52-70), and negative predictive value 85% (75-91).CONCLUSIONS: We have derived, tested, calibrated, and validated a risk stratification tool and found that it reliably estimates the probability of mortality in adults with septic shock.

DOI10.1097/CCM.0000000000000106
Alternate JournalCrit. Care Med.
PubMed ID24335447
Grant List8UL1 TR000077 / TR / NCATS NIH HHS / United States
HL081619 / HL / NHLBI NIH HHS / United States
HL087115 / HL / NHLBI NIH HHS / United States
HL102254 / HL / NHLBI NIH HHS / United States
NIH HL115354 / HL / NHLBI NIH HHS / United States
R01GM064619 / GM / NIGMS NIH HHS / United States
R01GM099773 / GM / NIGMS NIH HHS / United States
RC1HL100474 / HL / NHLBI NIH HHS / United States
/ / Canadian Institutes of Health Research / Canada