Impact of Fluid Balance on Mortality Is Mediated by Fluid Accumulation Index in Sepsis: A Cohort Study

Abstract

Fluid balance (FB) is associated with poor sepsis outcomes; however, it cannot accurately reflect the dynamic fluid accumulation status. Here, we explored a new index, the FB to fluid intake ratio (FB/FI), for evaluating dynamic fluid accumulation in sepsis. FB/FI values within 48 hours were recorded. Their association with in-hospital mortality was investigated using logistic regression and mediation analyses of data from 7,839 patients. In extended logistic models, a linear association was found between FB and mortality (odds ratio [OR]: 1.05-1.08, p < 0.001). However, this association became non-significant after the adjustment of FB/FI (OR: 1.00, 95% confidence interval [CI]: 0.98-1.02). For FB/FI and mortality, a cut-off value of 0.25 was defined. In the spline function logistic model, FB/FI > 0.25 was significantly associated with increased mortality (OR: 4.46, 95% CI: 2.92-6.80), whereas FB/FI ≤ 0.25 was not. For the FB/FI > 0.25 subgroup, mediation analysis was used to clarify the relationship between FB, FB/FI, and mortality. We observed that the direct effect of FB was non-significant (adjusted coefficient: −0.001, 95% CI: −0.005 to 0.002) while the indirect effect was significant (adjusted coefficient: 0.009, 95% CI: 0.006-0.011). In the FB/FI ≤ 0.25 subgroup, both the FB volume (0.9 ± 0.7 vs. −2.0 ± 1.9, p < 0.001) and the FB/FI ratio (0.14 ± 0.07 vs. −0.77 ± 1.60, p < 0.001) were significantly higher in patients with FB > 0 than those with FB ≤ 0. However, both the crude and adjusted comparisons of hospital mortality were non-significant. Similar associations were observed in septic shock patients. FB/FI > 0.25 is a significant risk factor for mortality in sepsis, while FB/FI ≤ 0.25 is not. The association between FB and mortality is completely mediated by this new fluid accumulation index. More comprehensive indices are required for evaluating dynamic fluid status in sepsis.

Association of Fluid Management With Mortality of Sepsis Patients With Congestive Heart Failure: A Retrospective Cohort Study

“…However, these two variables may be correlated to each other; thus, their separate analysis without adjustment might result in the overestimation of their significance. The definition of FAI was first introduced in the analysis of fluid management by Shen et al, who consequently found that the impact of FB on mortality is mediated by FAI in patients with sepsis ( 9 ). Our pooled FB, FI, and FAI analysis using multivariable logistic regression also showed that FAI, but not FB, was significantly associated with in-hospital mortality, after adjusting for confounding factors.…”

“…This retrospective cohort study aimed to explore the association between fluid management and in-hospital mortality in patients with sepsis and concomitant HF, as well as to find a better indicator to guide fluid management among FB, fluid intake (FI), and the fluid intake ratio (FB/FI), which is called the fluid accumulation index (FAI) and was first introduced by Shen et al ( 9 ). We focused on fluid management within the first 48 h after admission to the ICU and explored the relationship of FI, FB, and FAI with in-hospital mortality in sepsis patients with pre-existing HF.…”

Fluid intake, fluid output or fluid balance, which one matters in ARDS

“…1, with different fluid intake and capillary leak severity, the fluid balance is the same in patients A and B, while the fluid accumulation index is different (0.4 vs. 0.8). In addition, our previous finding [4] also revealed a complete mediation relationship within fluid balance, fluid balance/fluid intake and mortality in sepsis, which suggested that the association between fluid balance and mortality is completely mediated by fluid balance/fluid intake ratio [5]. Therefore, compared to fluid balance, fluid intake or fluid output alone, the fluid accumulation index (fluid balance/fluid intake) can more accurately reflect the ability to excrete excessive fluid under different fluid loads and predict the prognosis.…”

“…Shen et al correctly mention that fluid intake, fluid output and fluid balance have complex interactions, and that a 'fluid accumulation index, ' an index derived from both the fluid balance and the fluid intake, may play a vital role in this association [4].…”

Fluid overload and mortality in critically ill patients with severe heart failure and cardiogenic shock–An observational cohort study

“…This is supported by a recent investigation comparing the fluid accumulation index (FAI) to FB. The FAI consists of the ratio of FB to fluid intake as a measure of the patients’ ability to regulate his body water ( 33 ). A retrospective cohort study in HF patients with septic shock demonstrated an association of the FAI with mortality, while there was no association with FB ( 20 ).…”