Fluid-limiting treatment strategies among sepsis patients in the ICU: a retrospective causal analysis

ObjectiveIn septic patients, multiple retrospective studies show an association between large volumes of fluids administered in the first 24h and mortality, suggesting a benefit to fluid restrictive strategies. However, these studies do not directly estimate the causal effects of fluid-restrictive strategies, nor do their analyses properly adjust for time-varying confounding by indication. In this study, we used causal inference techniques to estimate mortality outcomes that would result from imposing a range of arbitrary limits ("caps") on fluid volume administration during the first 24h of intensive care unit (ICU) care.DesignRetrospective cohort studySettingICUs at the Beth Israel Deaconess Medical Center, 2008-2012PatientsOne thousand six hundred thirty-nine septic patients (defined by Sepsis-3 criteria) 18years and older, admitted to the ICU from the emergency department (ED), who received less than 4L fluids administered prior to ICU admissionMeasurements and main resultsData were obtained from the Medical Information Mart for Intensive Care III (MIMIC-III). We employed a dynamic Marginal Structural Model fit by inverse probability of treatment weighting to obtain confounding adjusted estimates of mortality rates that would have been observed had fluid resuscitation volume caps between 4L-12L been imposed on the population. The 30-day mortality in our cohort was 17%. We estimated that caps between 6 and 10L on 24h fluid volume would have reduced 30-day mortality by -0.6 to -1.0%, with the greatest reduction at 8L (-1.0% mortality, 95% CI [-1.6%, -0.3%]).ConclusionsWe found that 30-day mortality would have likely decreased relative to observed mortality under current practice if these patients had been subject to "caps" on the total volume of fluid administered between 6 and 10L, with the greatest reduction in mortality rate at 8L.