Trends in estradiol during critical illness are associated with mortality independent of admission estradiol

Background: We have previously demonstrated that elevated serum estradiol (E₂) 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 E₂ during the course of care might signal increasing patient acuity or risk of death. We hypothesized that changes from baseline serum E₂ during the course of critical illness are more strongly associated with mortality than a single E₂ level at admission. Study Design: A prospective cohort of 1,408 critically ill or injured nonpregnant adult patients requiring ICU care for <48 hours with admission and subsequent E₂ levels was studied. Demographics, illness severity, and E₂ levels were examined, and the probability of mortality was modeled with multivariate logistic regression. Changes in E₂ 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 E₂ levels were independently associated with mortality [admission E₂ 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 E₂ 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 E₂ are associated with mortality, changes from baseline E₂ in critically ill or injured adults are independently associated with mortality. Future studies of E₂ dynamics may yield new indicators of patient acuity and illuminate underlying mechanisms for targeted therapy.