Associations Between Volume of Early Intravenous Fluid and Hospital Outcomes in Septic Patients With and Without Heart Failure: A Retrospective Cohort Study

Abstract

Objectives: To evaluate the relationship between early IV fluid volume and hospital outcomes, including death in-hospital or discharge to hospice, in septic patients with and without heart failure (HF).

Design: A retrospective cohort study using logistic regression with restricted cubic splines to assess for nonlinear relationships between fluid volume and outcomes, stratified by HF status and adjusted for propensity to receive a given fluid volume in the first 6 hours. An ICU subgroup analysis was performed. Secondary outcomes of vasopressor use, mechanical ventilation, and length of stay in survivors were assessed.

Setting: An urban university-based hospital.

Patients: A total of 9613 adult patients were admitted from the emergency department from 2012 to 2021 that met electronic health record-based Sepsis-3 criteria. Preexisting HF diagnosis was identified by the International Classification of Diseases codes.

Interventions: None.

Measurements and main results: There were 1449 admissions from patients with HF. The relationship between fluid volume and death or discharge to hospice was nonlinear in patients without HF, and approximately linear in patients with HF. Receiving 0-15 mL/kg in the first 6 hours was associated with lower likelihood of death or discharge to hospice compared with 30-45 mL/kg (odds ratio = 0.61; 95% CI, 0.41-0.90; p = 0.01) in HF patients, but no significant difference for non-HF patients. A similar pattern was identified in ICU admissions and some secondary outcomes. Volumes larger than 15-30 mL/kg for non-HF patients and 30-45 mL/kg for ICU-admitted non-HF patients were not associated with improved outcomes.

Conclusions: Early fluid resuscitation showed distinct patterns of potential harm and benefit between patients with and without HF who met Sepsis-3 criteria. Restricted cubic splines analysis highlighted the importance of considering nonlinear fluid outcomes relationships and identified potential points of diminishing returns (15-30 mL/kg across all patients without HF and 30-45 mL/kg when admitted to the ICU). Receiving less than 15 mL/kg was associated with better outcomes in HF patients, suggesting small volumes may be appropriate in select patients. Future studies may benefit from investigating nonlinear fluid-outcome associations and a focus on other conditions like HF.

Keywords: fluid therapy; heart failure; intensive care units; regression analysis; sepsis.

Figure 1.

Cohort selection flow diagram. All patients in the initial population were adults (≥ 18 yr) presenting to the emergency department (ED) of an urban academic medical center between June 2012 and June 2021. Suspected infection was defined as having blood cultures ordered and IV antibiotics administered within 24 hours of presentation. End-stage renal disease patients were dependent on dialysis before admission. Volume overload was defined as receiving IV diuretics in the first 6 hours from ED presentation. SOFA = Sequential Organ Failure Assessment.

Figure 2.

Death or discharge to hospice versus volume of early IV fluid in 9602 hospitalized patients with or without heart failure (HF) meeting Sepsis-3 criteria. A, Estimated probability of death in-hospital or hospice discharge as a function of IV fluid volume received in the first 6 hours after presenting to the emergency department. Logistic regressions included all 9602 patients who were not missing gender or limited English proficiency data for propensity score estimation. Fluid volume is the independent variable and was transformed using restricted cubic splines with three knots. The line represents the estimate, and the shaded area is the 95% CI for the estimate. B, Figure 2A adjusted for propensity to receive a given volume of fluid. C, Figure 2A stratified by HF status without adjustment. HF patients are shown in red, and patients without HF in black. D, Figure 2C adjusted for propensity to receive a given volume of IV fluid.

Figure 3.

Death or discharge to hospice versus volume of early IV fluid in 2349 ICU patients with or without heart failure (HF) meeting Sepsis-3 criteria. A, Estimated probability of death in-hospital or hospice discharge as a function of IV fluid volume received in the first 6 hours after presenting to the emergency department among patients in the subgroup of patients whose first admission level of care was ICU. Logistic regression including 2349 patients who were not missing gender or limited English proficiency data for propensity score estimation. Fluid volume is the independent variable and was transformed using restricted cubic splines with three knots. The line represents the estimate, and the shaded area is the 95% CI for the estimate. B, Adjusted for propensity to receive a given volume of IV fluid.