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Association Between the Choice of IV Crystalloid and In-Hospital Mortality Among Critically Ill Adults With Sepsis*

Raghunathan, Karthik MD, MPH1,2; Shaw, Andrew MB, FRCA, FFICM, FCCM1; Nathanson, Brian PhD3; Stürmer, Til MD, PhD4; Brookhart, Alan PhD4; Stefan, Mihaela S. MD5; Setoguchi, Soko MD, DrPH6; Beadles, Chris MD, PhD2; Lindenauer, Peter K. MD, MSc7

doi: 10.1097/CCM.0000000000000305
Feature Articles

Objective: Isotonic saline is the most commonly used crystalloid in the ICU, but recent evidence suggests that balanced fluids like Lactated Ringer’s solution may be preferable. We examined the association between choice of crystalloids and in-hospital mortality during the resuscitation of critically ill adults with sepsis.

Design: A retrospective cohort study of patients admitted with sepsis, not undergoing any surgical procedures, and treated in an ICU by hospital day 2. We used propensity score matching to control for confounding and compared the following outcomes after resuscitation with balanced versus with no-balanced fluids: in-hospital mortality, acute renal failure with and without dialysis, and hospital and ICU lengths of stay. We also estimated the dose-response relationship between receipt of increasing proportions of balanced fluids and in-hospital mortality.

Setting: Three hundred sixty U.S. hospitals that were members of the Premier Healthcare alliance between November 2005 and December 2010.

Patients: A total of 53,448 patients with sepsis, treated with vasopressors and crystalloids in an ICU by hospital day 2 including 3,396 (6.4%) that received balanced fluids.

Interventions: None.

Measurements and Main Results: Patients treated with balanced fluids were younger and less likely to have heart or chronic renal failure, but they were more likely to receive mechanical ventilation, invasive monitoring, colloids, steroids, and larger crystalloid volumes (median 7 vs 5 L). Among 6,730 patients in a propensity-matched cohort, receipt of balanced fluids was associated with lower in-hospital mortality (19.6% vs 22.8%; relative risk, 0.86; 95% CI, 0.78, 0.94). Mortality was progressively lower among patients receiving larger proportions of balanced fluids. There were no significant differences in the prevalence of acute renal failure (with and without dialysis) or in-hospital and ICU lengths of stay.

Conclusions: Among critically ill adults with sepsis, resuscitation with balanced fluids was associated with a lower risk of in-hospital mortality. If confirmed in randomized trials, this finding could have significant public health implications, as crystalloid resuscitation is nearly universal in sepsis.

Supplemental Digital Content is available in the text.

1Depawwrtment of Anesthesiology, Duke University Medical Center, Durham, NC.

2Durham VA Medical Center, Durham, NC.

3OptiStatim LLC, Longmeadow, MA.

4Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC.

5Department of Medicine, Baystate Medical Center, Springfield, MA.

6Department of Medicine, Duke University School of Medicine, Durham, NC.

7Center for Quality of Care Research and Department of Medicine, Baystate Medical Center and Tufts University School of Medicine, Springfield, MA.

* See also p. 1722.

This study was performed at Duke University, University of North Carolina Chapel Hill, Baystate Medical Center, and OptiStatim LLC.

Drs. Raghunathan, Shaw, Nathanson, and Lindenauer were involved in the conception, hypothesis delineation, design of the study, and acquisition of the data. Dr. Nathanson conducted the data analysis. All authors were involved in the analysis and interpretation of such information and were involved in writing the article or substantially involved in revisions prior to submission. All authors take responsibility for the integrity of the data and the accuracy of the data analysis. No individuals contributing to data collection, analysis, writing or editing assistance, and review of manuscript have been omitted.

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 (

Supported, in part, by departmental funds from the Department of Anesthesiology, Duke University Medical Center.

Dr. Shaw served as board member for Astute Medical, consulted for Baxter Healthcare and Covidien, and has stock options with Thrasos. His institution received grant support from Baxter. Dr. Nathanson’s company, OptiStatim, LLC, was paid a consulting fee by Duke University Medical Center for data analysis and statistical support during this project. Dr. Stürmer consulted for Genentech (CER advisory group). His institution received grant support from Merck (Methods research project and for Center for Pharmacoepidemiology), Amgen (Research project), and Sanofi (Research project). Dr. Brookhart’s institution served as board member for Amgen, Merck, and Pfizer. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Address requests for reprints to: Karthik Raghunathan, MD, MPH, Department of Anesthesiology, Duke University Medical Center/Durham VAMC, DUMC 3094, Durham, NC 27710. E-mail:

© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins