Higher Fluid Balance Increases the Risk of Death From Sepsis
Fluid administration is one of the most common interventions in the acutely ill patients, both prior to and after admission to a critical care unit. It also remains an important principle of the management of the septic patient, with the most recent guidelines recommending at least 30 mL/kg crystalloid be given within the first three hours (1). However, there is a large body of evidence that a positive fluid balance is at least a predictor of (2, 3) and may actually increase mortality in the critically ill patients (4,5).
The article by Sakr and colleagues (6) presents the results of a very important substudy of the large Intensive Care Over Nations audit (7) of >10,000 patients admitted to participating centres around the world between May 8 – May 28 2011. A subset of 1800 patients were selected for the this analysis – all with sepsis or septic shock – and followed to hospital discharge, 60 days or death, whichever occurred first.
The authors looked at the fluid balance at 24 hours, 3 days and 7 days of admission to an ICU. The overall balance was calculated as measured output subtracted form measured input, insensible losses not accounted for.
In order to determine the relative risk of hospital death according to quartiles of cumulative fluid balance at 24 and 72 hours following admission to ICU the authors developed a multivariable Cox proportional hazard model. This model was applied both to the overall population and to the patients stratified into the presence or absence of septic shock. Of note, patients with highest SOFA and SAPS II scores, as well as those with abdominal sepsis fell into the higher fluid balance quartiles (p <0.001). The authors adjusted for differences in the renal function by including the renal scores in SOFA in the multivariable analysis.
The survivors have a clearly negative fluid balance at day 3 and 7 of their ICU admission, both in the septic shock and in the non-shock groups. Cumulative fluid input was similar in survivors and nonsurvivors; however, fluid output was lower in nonsurvivors. The authors speculate various pathophysiological mechanisms to explain this difference. Mainly, their reasoning is that by increasing tissue oedema and interstitial pressure, especially in encapsulated organs like the kidney and the liver, impairs the function of the tissues.
There are some limitations of this study, some acknowledged by the authors themselves. The fact that the study took place across continents and medical cultures meant that there could have been no way of standardising fluid management; where some centres would have had a lower threshold for renal replacement therapy as a means of controlling fluid overload, others will have used diuretics or nothing at all. The same applies to management of perfusion pressure and renal blood flow. It is clear, though, from the data that survivors had a lower vasoactive medication score, which can be interpreted either way – better controlled blood pressure and/or they were less sick.
All in all, this remains a beautifully conceived and conducted study, with sound statistical analysis, and one which will be one of the reference articles in the future.
Article review prepared by EJRC member Dr Oana Cole.
1. Rhodes A, Evans LE, Alhazzani W et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Crit Care Med 2017; 45 (3): 486 – 552;
2. Kelm DJ, Perrin JT, Cartin – Ceba R et al. Fluid overload in patients with severe sepsis and septic shock treated with early-goal directed therapy is associated with increased acute need for fluid-related medical interventions and hospital death. Shock 2015; 43: 68 – 73;
3. Sirvent JM, Ferri C, Baró A, et al: Fluid balance in sepsis and septic shock as a determining factor of mortality. Am J Emerg Med 2015; 33:186–189;
4. Acheampong A, Vincent JL. A positive fluid balance is an independent prognostic factor in patients with sepsis. Crit Care 2015; 19: 251 – 257;
5. Boyd JH, Forbes J, Nakada T et al. 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 - 265;
6. Sakr Y, Birri PNR, Kotfis K et al. Higher fluid balance increases the risk of death from sepsis: results from a large international audit. Crit Care Medicine 2017; 45: 386 – 394;
7. Vincent JL, Marshall JC, Namendys-Silva SA et al. Assessment of the worldwide burden of critical illness: the Intensive Care Over Nations (ICON) audit. Lancet Respir Med 2014; 2: 380 – 386.