• Mark A Bradford, Peter K Lindenauer, Renda Soylemez Wiener, and Allan J Walkey.
• 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.
• Crit. Care Med. 2014 Sep 1; 42 (9): 2042-7.

ObjectivesTo assess the importance of including do-not-resuscitate status in critical care observational comparative effectiveness research.DesignRetrospective analysis.SettingAll California hospitals participating in the 2007 California State Inpatient Database, which provides do-not-resuscitate status within the first 24 hours of admission.PatientsSeptic shock present at admission.InterventionsNone.Measurements And Main ResultsWe 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).ConclusionsAmong 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.

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