Association between Initial Fluid Choice and Subsequent In-hospital Mortality during the Resuscitation of Adults with Septic Shock.

Abstract

BACKGROUND: Currently, guidelines recommend initial resuscitation with intravenous (IV) crystalloids during severe sepsis/septic shock. Albumin is suggested as an alternative. However, fluid mixtures are often used in practice, and it is unclear whether the specific mixture of IV fluids used impacts outcomes. The objective of this study is to test the hypothesis that the specific mixture of IV fluids used during initial resuscitation, in severe sepsis, is associated with important in-hospital outcomes. METHODS: Retrospective cohort study includes patients with severe sepsis who were resuscitated with at least 2 l of crystalloids and vasopressors by hospital day 2, patients who had not undergone any major surgical procedures, and patients who had a hospital length of stay (LOS) of at least 2 days. Inverse probability weighting, propensity score matching, and hierarchical regression methods were used for risk adjustment. Patients were grouped into four exposure categories: recipients of isotonic saline alone ("Sal" exclusively), saline in combination with balanced crystalloids ("Sal + Bal"), saline in combination with colloids ("Sal + Col"), or saline in combination with balanced crystalloids and colloids ("Sal + Bal + Col"). In-hospital mortality was the primary outcome, and hospital LOS and costs per day (among survivors) were secondary outcomes. RESULTS: In risk-adjusted Inverse Probability Weighting analyses including 60,734 adults admitted to 360 intensive care units across the United States between January 2006 and December 2010, in-hospital mortality was intermediate in the Sal group (20.2%), lower in the Sal + Bal group (17.7%, P < 0.001), higher in the Sal + Col group (24.2%, P < 0.001), and similar in the Sal + Bal + Col group (19.2%, P = 0.401). In pairwise propensity score-matched comparisons, the administration of balanced crystalloids by hospital day 2 was consistently associated with lower mortality, whether colloids were used (relative risk, 0.84; 95% CI, 0.76 to 0.92) or not (relative risk, 0.79; 95% CI, 0.70 to 0.89). The association between colloid use and in-hospital mortality was inconsistent, and survival was not uniformly affected, whereas LOS and costs per day were uniformly increased. Results were robust in sensitivity analyses. CONCLUSIONS: During the initial resuscitation of adults with severe sepsis/septic shock, the types of IV fluids used may impact in-hospital mortality. When compared with the administration of isotonic saline exclusively during resuscitation, the coadministration of balanced crystalloids is associated with lower in-hospital mortality and no difference in LOS or costs per day. When colloids are coadministered, LOS and costs per day are increased without improved survival. A large randomized controlled trial evaluating crystalloid choice is warranted. Meanwhile, the use of balanced crystalloids seems reasonable. (Anesthesiology 2015; 123:1385-93).

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Published Version (Please cite this version)

10.1097/ALN.0000000000000861

Publication Info

Raghunathan, Karthik, Anthony Bonavia, Brian H Nathanson, Christopher A Beadles, Andrew D Shaw, M Alan Brookhart, Timothy E Miller, Peter K Lindenauer, et al. (2015). Association between Initial Fluid Choice and Subsequent In-hospital Mortality during the Resuscitation of Adults with Septic Shock. Anesthesiology, 123(6). pp. 1385–1393. 10.1097/ALN.0000000000000861 Retrieved from https://hdl.handle.net/10161/13930.

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Scholars@Duke

Raghunathan

Karthik Raghunathan

Associate Professor of Anesthesiology

Dr. Karthik Raghunathan is an Associate Professor with Tenure in the Department of Anesthesiology, with a secondary appointment in the Department of Population Health Sciences, at the Duke University School of Medicine and is a Staff Physician at the Durham Veterans Affairs Healthcare System. He is co-director of the Critical care And Perioperative population hEalth Research (CAPER) Program. 

In addition to clinical practice as an anesthesiologist and intensive care physician, Dr. Raghunathan is an epidemiologist and health services researcher with over $2 Million in funding from Federal, Industry, and Non-Profit entities since 2015. He co-directs the Critical care and Perioperative Population Health Research (CAPER) program, generating and disseminating evidence to inform clinical practice guidelines.

His studies focus on: a) the comparative effectiveness and safety of procedures and medications used for acute postoperative pain management, fluid resuscitation during surgery and intensive care; b) the implementation and effectiveness of nonpharmacologic treatments, such as music medicine and peripheral neuromodulation, and c) reducing race, sex, and income-based inequities in treatments and outcomes.

Dr. Raghunathan collaborates with colleagues within Duke, as well as colleagues at Academically affiliated other VA Healthcare Systems. He welcomes collaboration and can be reached at kr118@duke.edu. 

Brookhart

Maurice Alan Brookhart

Professor in Population Health Sciences

M. Alan Brookhart, Ph.D. is a Professor in the Department of Population Health Sciences at Duke University. He is also an Adjunct Professor at UNC Chapel Hill and an Honorary Professor of Clinical Epidemiology at Aarhus University, Denmark. Alan did his doctoral training in biostatistics at UC Berkeley and was on faculty at Harvard Medical School and UNC Chapel Hill prior to joining the faculty at Duke.

Alan has spent his career developing epidemiologic and statistical methods for improving learning from real-world healthcare data. Substantively, his research has focused on understanding the effects of treatments and policies in complex and vulnerable patient populations, such as those with end-stage renal disease. He has taught courses and workshops in pharmacoepidemiology, causal inference, epidemiologic methods, cluster-randomized trials, data visualization, and machine learning. He is a member of many expert panels for industry, academia, not-for-profit organizations, and government.

In addition to his academic work, Alan co-founded two start-up companies: RxAnte, Inc, which uses predictive analytics to target adherence improvement interventions to high-risk patients, and NoviSci, Inc, a healthcare data sciences company that builds tools to facilitate learning and visualization in complex, real-world data.

Areas of Expertise: epidemiology, observational study design, causal inference, predictive models, and data visualization

Miller

Timothy Ellis Miller

Professor of Anesthesiology

Clinical and research interests are Enhanced Recovery and Perioperative Medicine; with particular interests in fluid management, and perioperative optimization of the high-risk non-cardiac surgery patient.


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