Fluid balance correlates with clinical course of multiple organ dysfunction syndrome and mortality in patients with septic shock

Abstract

Introduction: Positive fluid balance is a prognostic factor for mortality in patients with sepsis; however, the association between cumulated fluid balance (CFB) and sepsis-induced multi-organ dysfunction syndrome (MODS) has yet to be elucidated. In this study, we sought to determine whether CFB is correlated with MODS and mortality in cases of septic shock.

Methods: The study retrospectively recruited patients with septic shock from the intensive care unit of a tertiary care hospital. Multiple organ dysfunction syndrome (MODS) was identified as sequential organ failure assessment (SOFA) score ≥ 2 in more than one organ system. The CFB is the sum of all daily intake and output. An independent t-test, single and multivariate logistic regression, the receiver operating characteristic (ROC) curves, and the Pearson correlation coefficient were used to determine whether a relationship exists between CFB and the development of MODS and mortality.

Results: Among the 104 patients enrolled in the study, 58 (55.8%) survived more than 28 days, and 73 (70.2%) developed MODS on day 3. The values of CFB in the first 24 hours and 72 hours after diagnosis of septic shock in patients with MODS were higher than these in patients without MODS (1086.6 ± 176.3 vs. 325.5 ± 205.7 ml, p = 0.013 and 2408 ± 361 vs. 873.1 ± 489 ml, p < 0.0001). In a multivariate logistic regression, the independent factors associated with the development of MODS on day 3 were APACHE II score at ICU admission (27.6 ± 7.6 in patients with MODS vs. 20.5 ± 6.4 in those without; O.R. 1.18; 95% C.1 I. 1.08-1.30; p < 0.001), disseminated intravascular coagulopathy (DIC) (n = 28; 38.4% vs. n = 2; 6.5%; O.R. 23.67; 95% C.I. 3.58-156.5; p = 0.001), and CFB in the first 72 hours (72-hr CFB) > median (1767.50ml) (n = 41; 56.2% vs. n = 11; 35.5%; O.R. 3.67; 95% C.I., 1.18-11.40; p = 0.024). Moreover, a multivariate logistic regression also identified neoplasm (n = 25; 54.3% vs. n = 17; 29.3%; O.R. 3.45; 95% C.I. 1.23-10.0; p = 0.019) and 72-hr CFB > median (n = 30; 65.2% vs. n = 21; 36.2%; O.R. 4.13; 95% C.I. 1.34-12.66; p = 0.013) as independent factors associated with 28-day mortality. 72-hr CFB values were strongly correlated with the SOFA score (r = 0.445, p < 0.0001). The area under the ROC curve revealed that 72-hr CFB has good discriminative power in associating the development of MODS (0.644, p = 0.002) and predicting subsequent 28-day mortality (0.704, p < 0.0001).

Conclusions: 72-hr CFB appears to be correlated with the likelihood of developing MODS and mortality in patients with septic shock. Thus, it appears that 72-hr CFB could perhaps be used as an indicator for MODS and a predictor for mortality in those patients.

Fig 1. Patient flow chart.

Fig 2. Relationship between cumulative fluid balance, MODS, and 28-day survival.

(A) Cumulative fluid balances were significantly higher in non-survivors than in survivors of septic shock on 24 hr (open bar), 48 hr (gray bar), and 72 hr (black bar) (* indicates p<0.05); (B) Cumulative fluid balances were higher in patients with multi-organ dysfunction syndrome (MODS) than patients without MODS only on 24 hr (open bar) and 72 hr (black bar) (p = 0.035) but not on 48 hr (gray bar) of septic shock (* indicates p<0.05) (data expressed as mean ± SEM).

Fig 3. Relationship between 72-hr cumulative fluid balance (CFB) and SOFA score in patients with severe sepsis.

(A) Amount of 72-hr CFB correlated well with SOFA score (r = 0.445, p < 0.0001) (data expressed as Pearson correlation); (B) The higher the SOFA score, the more 72-hr CFB was found (p<0.001 by ANOVA) (data expressed as mean ± SEM).

Fig 4. 72-hr cumulative fluid balance (CFB) in patients with resolved persistent multiple organ dysfunction syndrome (MODS), progressive MODS, or without MODS from 24 hr to 72 hr after onset of septic shock.

Open bars indicate 24-hr CFB; gray bar indicates 48-hr CFB; black bars indicate 72-hr CFB (data expressed as mean ± SEM).

Fig 5. Comparison of 72-hr cumulative fluid balance (CFB) between patients with and without individual organ dysfunction.

No significant difference in 72-hr CFB was observed between patients with and without individual organ failure (p values analyzed using Student t test; data expressed as mean ± SEM).

Fig 6. 72-hr cumulative fluid balance (CFB) between patients with infections of various origin.

Similar 72-hr CFB values were observed in patients with sepsis originating from intra-abdominal infection (4939.4±1256.7 ml), urinary tract infection (2167.4±648.2 ml), pulmonary infection (2086.3±317.3 ml), bloodstream infection (1986.8±645.1ml), and soft tissue infection (1360.9±895.8ml) (p = 0.273 using ANOVA).