Moderate IV Fluid Resuscitation Is Associated With Decreased Sepsis Mortality

Abstract

Objectives: Significant practice variation exists in the amount of resuscitative IV fluid given to patients with sepsis. Current research suggests equipoise between a tightly restrictive or more liberal strategy but data is lacking on a wider range of resuscitation practices. We sought to examine the relationship between a wide range of fluid resuscitation practices and sepsis mortality and then identify the primary driver of this practice variation.

Design: Retrospective analysis of the Premier Healthcare Database.

Setting: Six hundred twelve U.S. hospitals.

Patients: Patients with sepsis and septic shock admitted from the emergency department to the ICU from January 1, 2016, to December 31, 2019.

Interventions: The volume of resuscitative IV fluid administered before the end of hospital day- 1 and mortality.

Measurements and main results: In total, 190,682 patients with sepsis and septic shock were included in the analysis. Based upon patient characteristics and illness severity, we predicted that physicians should prescribe patients with sepsis a narrow mean range of IV fluid (95% range, 3.6-4.5 L). Instead, we observed wide variation in the mean IV fluids administered (95% range, 1.7-7.4 L). After splitting the patients into five groups based upon attending physician practice, we observed patients in the moderate group (4.0 L; interquartile range [IQR], 2.4-5.1 L) experienced a 2.5% reduction in risk-adjusted mortality compared with either the very low (1.6 L; IQR, 1.0-2.5 L) or very high (6.1 L; IQR, 4.0-9.0 L) fluid groups p < 0.01). An analysis of within- and between-hospital IV fluid resuscitation practices showed that physician variation within hospitals instead of practice differences between hospitals accounts for the observed variation.

Conclusions: Individual physician practice drives excess variation in the amount of IV fluid given to patients with sepsis. A moderate approach to IV fluid resuscitation is associated with decreased sepsis mortality and should be tested in future randomized controlled trials.

Figure 1.

Variation in resuscitative IV fluid administered within the first day. A, Observed and mean predicted volume of IV fluid administered before the end of hospital day-1 (IVFD₁) based upon baseline patient characteristics. Patient demographic and illness severity variables included in the IVFD₁ prediction model are displayed in Table S3 (http://links.lww.com/CCM/H573). B, Cumulative number of patients within attending fluid groups by increasing amounts of IVFD₁. Table S5 (http://links.lww.com/CCM/H573) further describes IVFD₁ volumes by attending fluid group.

Figure 2.

Risk-adjusted hospital mortality, mechanical ventilation, and vasopressor use by attending fluid group. Hospital mortality, mechanical ventilation, and vasopressor use were adjusted by the covariates listed in the Text. Resuscitative IV fluid administered before the end of hospital day-1 (IVFD₁).

Figure 3.

Risk-adjusted mortality controlling for variations in care between hospitals. This figure’s results were based upon a fixed-effects logistic regression, in which the 612 hospitals were entered into the model with the covariates used in the primary analysis. A result in which the observed differences in adjusted mortality between fluid groups were entirely a result of between-hospital differences would be represented by a horizontal fixed-effects line.