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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

doi: 10.1097/CCM.0000000000000403
Clinical Investigations

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.

Supplemental Digital Content is available in the text.

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.

* See also p. 2138.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

Dr. Wiener received support for article research from the National Institutes of Health (NIH) and disclosed government work. Her institution received grant support from National Cancer Institute (salary support for effort on career development award, K07 CA 138772). Dr. Walkey received royalties from UptoDate and received support for article research from the NIH. His institution received grant support from the NIH National Heart, Lung, and Blood Institute (K01HL116768, R21 grants). The remaining authors have disclosed that they do not have any potential conflicts of interest.

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