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Literature Review

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

Sakr Y, Rubatto Birri PN, Kotfis K, et al. Crit Care Med. 2017; 45(3):386–394.

Reviewers: Jacob Gutsche, MD1; Sunberri Murphy, MD1; Jared Feinman, MD1

  1. University of Pennsylvania, Philadelphia, PA

Sepsis is a common problem in intensive care unit (ICU) patients and is associated with a high level of mortality. Adequate fluid resuscitation is crucial to reduce mortality in patients with sepsis, particularly patients with septic shock. Although fluid resuscitation is important, too much fluid may be harmful. Modern methods to assess volume status have significant limitations, and it can be challenging to assess the position the patient occupies on the Frank-Starling curve. Further, the duration of active resuscitation necessary to improve outcome is unclear. Sakr et al sought to assess the impact of a positive fluid balance by analyzing prospectively collected patient data as a planned substudy of the Intensive Care Over Nations (ICON), a multicenter, worldwide audit.


A multicenter international, observational cohort study prospectively collected patient data from 730 ICUs in 84 countries. The study collected data only on patients with an admission diagnosis of sepsis admitted between May 8 and 12, 2012. Patients were followed until death, hospital discharge, or for 60 days. Patient fluid balance was recorded and patients were divided into quartiles based on cumulative fluid balance at 24 hours and 3 days post–ICU admission to investigate the influence of early fluid balance on outcome.


The cumulative fluid intake was similar in survivors and nonsurvivors, but nonsurvivors had less fluid output leading to a more positive fluid balance. The comparison of day-3 quartiles demonstrated a twofold increase in ICU and hospital mortality from the lowest to highest quartiles.


This study demonstrated that a higher positive fluid balance at 3 days, but not 24 days, correlated with an increase in the hazard of death. The authors were unable to discern the reason for this association, and it is entirely possible that patients with the increased fluid balance had poor source control and sustained persistent sepsis. The authors found that after adjustment for confounders there was no difference in mortality, with increasing quartiles of fluid balance at 24 hours.

The Surviving Sepsis guidelines recommend administering 30 mL/kg of intravenous crystalloid within 3 hours of the diagnosis of sepsis, which appears safe and reasonable based on the results of this and other supporting studies.1 Earlier recommendations endorsed using protocol-based resuscitation, which may promote more liberal fluid administration.2 Based on the results of this study, clinicians may need to use caution in continuing high-volume crystalloid resuscitation in patients with sepsis. Of course, source control is the paramount concern, which, if aggressively pursued, may diminish the need for ongoing resuscitation.

  1. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43(3):304–377.
  2. Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165–228.

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