Diuretic resistance and associated mortality outcomes among patients in the cardiac intensive care unit

Abstract Background Diuretic resistance (DR) is the failure to achieve adequate natriuresis despite high diuretic doses, reflecting a state of low diuretic efficiency (DE). In heart failure (HF) and general intensive care cohorts, low DE and the presence of DR have been associated with adverse outcomes, including increased risk of rehospitalization and mortality (1-3). Quantitative data, however, remains limited in patients admitted to the cardiac intensive care unit (CICU) – a population characterized by cardiac critical illnesses and substantial cardiorenal interactions. Purpose The aim of this study is to investigate and characterize the association between DR and associated mortality outcomes in CICU patients. Methods This retrospective cohort study included adult CICU patients (2007-2018) who received loop diuretics on day 1 of admission. Patients with a stay 1 day or oliguria 400mL urine output (UOP) total were excluded. DR was defined as 500mL of UOP per 40mg oral furosemide equivalent (FSE). Acute kidney injury (AKI) was defined per KDIGO guidelines. Primary outcome was all-cause in-hospital mortality (including CICU deaths), and secondary outcome was all-cause 1-year mortality. In-hospital mortality predictors were evaluated using logistic regression and 1-year mortality predictors by Cox proportional-hazards models. 1-year survival was assessed using Kaplan-Meier curves. Multivariable models were adjusted for known confounders. Results 3,229 total patients were included. Median age was 71.2 (61.2, 80.7) years and 41.3% were female. Admission diagnoses included HF exacerbation (79.9%), acute coronary syndrome (34.5%), and respiratory failure (38.9%), among others. 1,098 (34.0%) patients met DR criterion; they had higher severity of illness scores, more comorbidities (including HF, diabetes mellitus, lung disease, and chronic kidney disease, p0.001), and greater laboratory derangements. On admission, 23.6% patients had AKI, of which 54.3% patients met DR criterion. During hospitalization, 56.0% patients had AKI; those with DR had higher prevalence and severity of AKI (unadjusted OR 3.55 3.02-4.17, p0.001). Overall in-hospital mortality was 9.8% (including 5.2% in the CICU). In patients with DR, in-hospital mortality was 17.0% (9.7% in the CICU). Notably, 59.4% of all in-hospital deaths occurred in patients with DR. DR was independently associated with higher in-hospital (adjusted OR 2.00 1.51-2.64, p0.001) and 1-year (adjusted HR 1.64 1.44-1.88, p0.001) mortality. Patients with DR had higher mortality in each AKI stage (Figure 1), and patients with concomitant DR and AKI had the highest risk of 1-year mortality (Figure 2). Conclusion DR, defined by our easily applicable threshold, emerged as a powerful, independent predictor of adverse outcomes and was associated with substantially higher mortality, demonstrating potential as a valuable risk stratifying tool.