April 27, 2017

EJRC Article Review

Fluid administration in severe sepsis and septic shock


Cumulative positive fluid balance among critically ill patients is associated with increased morbidity and mortality. (1) However, the optimal method of fluid administration in the early resuscitation phase of sepsis lacks strong evidence. In the most recent issue of Intensive Care Medicine, Marik et al. report the results of a large retrospective analysis of a ICU database to assess the association between fluid balance and mortality (2).

The 2013 US Premier Hospital Discharge database was used to analyse data from 23,513 patients with severe sepsis and septic shock, who were admitted to an ICU from the emergency department. A retrospective analysis of  the association between the administration of fluids on the first ICU day and mortality. Patients were divided into those receiving “low fluid range” (1–5 L day 1 fluids) or “high fluid range” (5 to ≥9 L day 1 fluids) categories. Analysis was conducted using weighted linear regression controlling for the effects of sample size and variation within the day 1 fluid category.

The mean day 1 fluid administration was 4.4L in the entire cohort. The hospital mortality was 25.8%, with a mean ICU and hospital length of stay of 5.1 and 9.1 days, respectively. Fluid administration was significantly lower in patients not receiving ventilation and without shock (3.6 L) compared to mechanically ventilated patients in shock (5.4 L).

Low volume resuscitation (1-5L) on day 1 was associated with a small but significant reduction in mortality, of −0.7% per litre (95% CI −1.0%, −0.4%; p = 0.02). In patients receiving high volume resuscitation (≥5 L), the mortality increased by 2.3% (95% CI 2.0, 2.5%; p = 0.0003) for each additional litre above 5 L.

Patients with greater illness severity are more likely to require larger volumes of resuscitation fluids and have a higher mortality. Therefore, fluid volumes were adjusted for actual and predicted mortality (based on illness severity). The severity adjusted mortality increased significantly in patients receiving >5L fluids on day 1, suggesting an increased risk of mortality associated with fluid volumes over and above illness severity.

A recent meta-analysis concluded that a conservative approach to fluid administration or deresuscitation (active removal of fluid using diuretics or renal replacement therapy) following haemodynamic stabilisation of critically ill patients with ARDS, sepsis or SIRS was associated with in an increased number of ventilator-free days and a decreased length of ICU stay compared with a liberal strategy or standard care (3).

In a recent RCT, a restrictive approach to fluid therapy after initial resuscitation in sepsis was feasible and safe in ICU patients (4). Although the study was not powered to detect any differences in organ failure or mortality, restrictive approach to fluid therapy may have had a beneficial effect on renal function.

As with all retrospective analyses, it is not possible to draw conclusions about causality. It is only possible to acknowledge the association between increased volume of resuscitation fluid administered and morality, despite adjusting for a number of covariates.
The authors mention that “the mean amount of fluid administered to patients with severe sepsis and septic shock in the USA during the first ICU day is less than that recommended by the Surviving Sepsis Campaign guidelines”. Although this is an interesting observation, it is not possible to draw any conclusions about the standard of care provided by the hospitals nor the recommendation of the Surviving Sepsis Campaign guidelines.

Previous analyses have focused primarily on fluid management strategies after initial resuscitation. The optimal management of fluid management during the resuscitative phase is a relatively uncharted area. This study demonstrates increased risk of mortality associated with initial resuscitative fluid volumes over and above illness severity. These results should be instructional for future prospective clinical studies in initial resuscitative strategies.

Article review submitted by EJRC member Nish Arulkumaran on behalf of the NEXT Committee.


1. Boyd JH, Forbes J, Nakada TA, Walley KR, Russell JA. Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med 2011; 39:259-65
2. Marik PE, Linde-Zwirble WT, Bittner EA, Sahatjian J, Hansell D. Fluid administration in severe sepsis and septic shock, patterns and outcomes: an analysis of a large national database. Intensive Care Med 2017;
3. Silversides JA, Major E, Ferguson AJ, et al. Conservative fluid management or deresuscitation for patients with sepsis or acute respiratory distress syndrome following the resuscitation phase of critical illness: a systematic review and meta-analysis. Intensive Care Med 2017; 43:155-70
4. Hjortrup PB, Haase N, Bundgaard H, et al. Restricting volumes of resuscitation fluid in adults with septic shock after initial management: the CLASSIC randomised, parallel-group, multicentre feasibility trial. Intensive Care Med 2016; 42:1695-705

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