A Higher Fluid Balance in the Days After Septic Shock Reversal Is Associated With Increased Mortality: An Observational Cohort Study

Abstract

Objectives: Previous studies demonstrated that extensive fluid loading and consequently positive fluid balances during sepsis resuscitation are associated with adverse outcome. Yet, the association between fluid balance and mortality after reversal of shock, that is, during deresuscitation, is largely unappreciated. Our objective was to investigate the effects of fluid balance on mortality in the days after septic shock reversal. Design: Retrospective observational cohort study. Setting: ICUs of two university-affiliated hospitals in The Netherlands. Patients: Adult patients admitted with septic shock followed by shock reversal. Reversal of septic shock was defined based on Sepsis-3 criteria as the first day that serum lactate was less than or equal to 2 mmol/L without vasopressor requirement. Interventions: None. Measurements and Main Results: Reversal of septic shock occurred in 636 patients, of whom 20% died in the ICU. Mixed-effects logistic regression modeling, adjusted for possible confounders, showed that fluid balance in the days after reversal of septic shock (until discharge or death) was an independent predictor of ICU mortality: odds ratio 3.18 (1.90-5.32) per 10 mL/kg increase in daily fluid balance. Similar results were found for 30-day, 90-day, hospital, and 1-year mortality: odds ratios 2.09 (1.64-2.67); 1.79 (1.38-2.32); 1.70 (1.40-2.07); and 1.53 (1.17-2.01), respectively. Positive cumulative fluid balances vs. neutral or negative fluid balances on the final day in the ICU were associated with increased ICU, hospital, 30-day, and 90-day mortality: odds ratios 3.46 (2.29-5.23); 3.39 (2.35-4.9); 5.33 (3.51-8.08); and 3.57 (2.49-5.12), respectively. Using restricted cubic splines, we found a dose-response relationship between cumulative fluid balance after shock reversal and ICU mortality. Conclusions: A higher fluid balance in the days after septic shock reversal was associated with increased mortality. This stresses the importance of implementing restrictive and deresuscitative fluid management strategies after initial hemodynamic resuscitation. Prospective interventional studies are needed to confirm our results.