title: Do-not-resuscitate status and observational comparative effectiveness research in patients with septic shock*.
abstract: OBJECTIVE
  To assess the importance of including do-not-resuscitate status in critical care observational comparative effectiveness research.
  
  
  METHODS
  Retrospective analysis.
  
  
  METHODS
  All California hospitals participating in the 2007 California State Inpatient Database, which provides do-not-resuscitate status within the first 24 hours of admission.
  
  
  METHODS
  Septic shock present at admission.
  
  
  METHODS
  None.
  
  
  RESULTS
  We investigated the association of early do-not-resuscitate status with in-hospital mortality among patients with septic shock. We also examined the strength of confounding of do-not-resuscitate status on the association between activated protein C therapy and mortality, an association with conflicting results between observational and randomized studies. We identified 24,408 patients with septic shock; 19.6% had a do-not-resuscitate order. Compared with patients without a do-not-resuscitate order, those with a do-not-resuscitate order were significantly more likely to be older (75 ± 14 vs 67 ± 16 yr) and white (62% vs 53%), with more acute organ failures (1.44 ± 1.15 vs 1.38 ± 1.15), but fewer inpatient interventions (1.0 ± 1.0 vs 1.4 ± 1.1). Adding do-not-resuscitate status to a model with 47 covariates improved mortality discrimination (c-statistic, 0.73-0.76; p < 0.001). Addition of do-not-resuscitate status to a multivariable model assessing the association between activated protein C and mortality resulted in a 9% shift in the activated protein C effect estimate toward the null (odds ratio from 0.78 [95% CI, 0.62-0.99], p = 0.04, to 0.85 [0.67-1.08], p = 0.18).
  
  
  CONCLUSIONS
  Among patients with septic shock, do-not-resuscitate status acts as a strong confounder that may inform past discrepancies between observational and randomized studies of activated protein C. Inclusion of early do-not-resuscitate status into more administrative databases may improve observational comparative effectiveness methodology.
authors.affiliation: 1Pulmonary Center and the Section of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA. 2Center for Quality of Care Research, Baystate Medical Center, Springfield, MA. 3Division of General Internal Medicine, Baystate Medical Center, Springfield, MA. 4Department of Medicine, Tufts University School of Medicine, Boston, MA. 5Center for Healthcare Organization and Implementation Research, ENRM VA Hospital, Bedford, MA. 6The Dartmouth Institute for Healthcare Policy and Clinical Practice, Hanover, NH.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Bradford
authors.forename: Peter K
authors.initials: PK
authors.lastname: Lindenauer
authors.forename: Renda Soylemez
authors.initials: RS
authors.lastname: Wiener
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Walkey
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002140:California; D057186:Comparative Effectiveness Research; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage; D006305:Health Status Indicators; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units / Q000458:organization & administration / Q000706:statistics & numerical data*; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000008:administration & dosage; D044469:Racial Groups; D016414:Resuscitation Orders; D012189:Retrospective Studies; D012772:Shock, Septic / Q000401:mortality* / Q000628:therapy
chemical_list: D005343:Fibrinolytic Agents; D011486:Protein C