Critical Care Medicine

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Critical Care Medicine:
doi: 10.1097/CCM.0000000000000403
Clinical Investigations

Do-Not-Resuscitate Status and Observational Comparative Effectiveness Research in Patients With Septic Shock*

Bradford, Mark A. MD; Lindenauer, Peter K. MD, MSc; Wiener, Renda Soylemez MD, MPH; Walkey, Allan J. MD, MSc

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Objectives: To assess the importance of including do-not-resuscitate status in critical care observational comparative effectiveness research.

Design: Retrospective analysis.

Setting: All California hospitals participating in the 2007 California State Inpatient Database, which provides do-not-resuscitate status within the first 24 hours of admission.

Patients: Septic shock present at admission.

Interventions: None.

Measurements and Main 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.

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