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Higher Fluid Balance Increases the Risk of Death from Sepsis: Results from a Large International Audit
Sakr T, Rubatto Birri PN, Kotfis K, et al. Crit Care Med. 2017;45:386-94.
Study Question: Does a positive fluid balance influence the outcomes of patients with sepsis?
Study Description: This was a multicenter, observational study including a subset patients with sepsis from a European intensive care database (Intensive Care Over Nations). Patients were included if they were admitted between May 8 and May 18, 2012. Fluid balance was calculated using daily fluid intake and output documentation. Cumulative fluid balances in the first 24 hours, 3 and 7 days were calculated. Patients were stratified according to quartiles of cumulative fluid balance at 24 and 72 hours, with a primary outcome of hospital mortality at 28 days.
Results: A total of 1808 patients were included. Total fluid intake was similar between groups (survivors and non-survivors) across all times periods. There was a difference between fluid balance quartiles in the number of patients with heart failure (p=0.024), with the least numerically in the highest quartile. There was no difference between quartiles in the number of patients with chronic renal failure (p=0.154). Fluid output was significantly lower and total fluid balance was significantly higher in non-survivors versus survivors over all time periods (p<0.05). Fluid balance remained positive over time in non-survivors while survivors were noted to have a negative fluid balance by day 3. There was a significantly decreased cumulative fluid balance in the ICU in the survivors compared to the non-survivors (+354 mL, 95% CI -3016-[+4224] vs. 3972 mL, 95% CI +667-[+8276], p<0.001). Non-survivors also received more synthetic colloids than survivors, including hydroxyethyl starches (22.8% vs. 17.8%; p=0.015). The need for renal replacement therapy and vasoactive support as well as SOFA scores all increased with increasing quartiles of 24 hour cumulative fluid balance (p<0.001). After adjusting for cofounders, cumulative fluid balance at 24 hours was not associated with an increased hazard ratio of death in the whole cohort or in patients with septic shock. However, at 72 hours, there was a stepwise increase in the HR for death between each quartile (2nd: 1.36, 95% CI 1.03-1.80, p=0.035; 3rd: 1.47, 95% CI 1.12-1.92, p=0.005; 4th: 1.63, 95% CI 1.25-2.12, p<0.001).
Conclusion: In this large cohort of patients with severe sepsis and septic shock, higher quartiles of total cumulative fluid balance at 72 hours after ICU admission was associated with a significant increase in the risk of death.
Perspective: The most appropriate strategy for managing fluids in patients with sepsis remains unclear. Given the pathophysiology of sepsis, initial large volume fluid resuscitation is often necessary. This study suggests that impaired elimination of resuscitation fluid and the subsequent increase in fluid balance is associated with worse outcomes. Renal function was included as a potential confounder in the multivariable analysis but may not fully illustrate the associations found in this study. The authors speculate that excess fluid administration may lead to tissue edema and worsening organ function. Further investigations could help identify the time point in therapy in which clinicians should begin to focus on volume elimination strategies.