title: Trends in estradiol during critical illness are associated with mortality independent of admission estradiol.
abstract: BACKGROUND
  We have previously demonstrated that elevated serum estradiol (E(2)) at intensive care unit (ICU) admission is associated with death in the critically ill, regardless of sex. However, little is known about how changes in initial E(2) during the course of care might signal increasing patient acuity or risk of death. We hypothesized that changes from baseline serum E(2) during the course of critical illness are more strongly associated with mortality than a single E(2) level at admission.
  
  
  METHODS
  A prospective cohort of 1,408 critically ill or injured nonpregnant adult patients requiring ICU care for ≥48 hours with admission and subsequent E(2) levels was studied. Demographics, illness severity, and E(2) levels were examined, and the probability of mortality was modeled with multivariate logistic regression. Changes in E(2) were examined by both analysis of variance and logistic regression.
  
  
  RESULTS
  Overall mortality was 14.1% [95% confidence interval (CI) 12.3% to 16%]. Both admission and subsequent E(2) levels were independently associated with mortality [admission E(2) odds ratio 1.1 (CI 1.0 to 1.2); repeat estradiol odds ratio 1.3 (CI 1.2 to1.4)], with subsequent values being stronger. Changes in E(2) were independently associated with mortality [odds ratio 1.1 (CI 1.0 to 1.16)] and improved regression model performance. The regression model produced an area under the receiver operating characteristic curve of 0.80 (CI 0.77 to 0.83).
  
  
  CONCLUSIONS
  Although high admission levels of E(2) are associated with mortality, changes from baseline E(2) in critically ill or injured adults are independently associated with mortality. Future studies of E(2) dynamics may yield new indicators of patient acuity and illuminate underlying mechanisms for targeted therapy.
authors.affiliation: Division of Trauma and Surgical Critical Care, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37212, USA.
authors.forename: Rondi M
authors.initials: RM
authors.lastname: Kauffmann
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Norris
authors.forename: Judith M
authors.initials: JM
authors.lastname: Jenkins
authors.forename: William D
authors.initials: WD
authors.lastname: Dupont
authors.forename: Renee E
authors.initials: RE
authors.lastname: Torres
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Blume
authors.forename: Lesly A
authors.initials: LA
authors.lastname: Dossett
authors.forename: Tjasa
authors.initials: T
authors.lastname: Hranjec
authors.forename: Robert G
authors.initials: RG
authors.lastname: Sawyer
authors.forename: Addison K
authors.initials: AK
authors.lastname: May
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003422:Critical Care; D016638:Critical Illness / Q000401:mortality* / Q000628:therapy; D003955:Diagnostic Tests, Routine; D004958:Estradiol / Q000097:blood*; D005260:Female; D006801:Humans; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D010343:Patient Admission; D011237:Predictive Value of Tests; D012372:ROC Curve; D012189:Retrospective Studies
chemical_list: D004958:Estradiol