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Higher Fluid Balance Increases the Risk of Death From Sepsis: Results From a Large International Audit*

Sakr, Yasser MD, PhD; Rubatto Birri, Paolo Nahuel MD; Kotfis, Katarzyna MD, PhD; Nanchal, Rahul MD; Shah, Bhagyesh MBBS, DA, IDCCM; Kluge, Stefan MD; Schroeder, Mary E. MD; Marshall, John C. MD; Vincent, Jean-Louis MD, PhD, FCCM; on behalf of the Intensive Care Over Nations Investigators

doi: 10.1097/CCM.0000000000002189
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Objectives: Excessive fluid therapy in patients with sepsis may be associated with risks that outweigh any benefit. We investigated the possible influence of early fluid balance on outcome in a large international database of ICU patients with sepsis.

Design: Observational cohort study.

Setting: Seven hundred and thirty ICUs in 84 countries.

Patients: All adult patients admitted between May 8 and May 18, 2012, except admissions for routine postoperative surveillance. For this analysis, we included only the 1,808 patients with an admission diagnosis of sepsis. Patients were stratified according to quartiles of cumulative fluid balance 24 hours and 3 days after ICU admission.

Measurements and Main Results: ICU and hospital mortality rates were 27.6% and 37.3%, respectively. The cumulative fluid balance increased from 1,217 mL (–90 to 2,783 mL) in the first 24 hours after ICU admission to 1,794 mL (–951 to 5,108 mL) on day 3 and decreased thereafter. The cumulative fluid intake was similar in survivors and nonsurvivors, but fluid balance was less positive in survivors because of higher fluid output in these patients. Fluid balances became negative after the third ICU day in survivors but remained positive in nonsurvivors. After adjustment for possible confounders in multivariable analysis, the 24-hour cumulative fluid balance was not associated with an increased hazard of 28-day in-hospital death. However, there was a stepwise increase in the hazard of death with higher quartiles of 3-day cumulative fluid balance in the whole population and after stratification according to the presence of septic shock.

Conclusions: In this large cohort of patients with sepsis, higher cumulative fluid balance at day 3 but not in the first 24 hours after ICU admission was independently associated with an increase in the hazard of death.

1Department of Anesthesiology and Intensive Care, Uniklinikum Jena, Jena, Germany.

2Department of Anaesthesia, Intensive Care and Acute Poisioning, Pomeranian Medical University, Szczecin, Poland.

3Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.

4Department of Critical Care, Care Institute of Medical Sciences, Ahmedabad, India.

5Department of Intensive Care Medicine, University Medical Center, Hamburg Eppendorf, Germany.

6Center for Trauma and Critical Care, George Washington University Hospital, Washington, DC.

7Interdepartmental Division of Critical Care Medicine, Department of Surgery, University of Toronto, St. Michael’s Hospital, Toronto, ON, Canada.

8Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium.

*See also p. 555.

Drs. Sakr and Rubatto Birri designed the study, extracted, and analyzed the data and drafted the article. Drs. Sakr, Kotfis, Nanchal, Shah, Kluge, Schroeder, Marshall, and Vincent participated in the original Intensive Care Over Nations study and reviewed the article for critical content. All authors read and approved the final article.

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 (http://journals.lww.com/ccmjournal).

Additional members of the Care Over Nations Investigators are listed in Appendix 1 (Supplemental Digital Content 1, http://links.lww.com/CCM/C246).

Dr. Marshall has received fees from AKPA Pharma (data safety management board) and Regeneron (consultancy), as well as grant support from the CIHR and Physicians Services Incorporated Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: jlvincent@intensive.org

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