Impact of loop diuretics on critically ill patients with a positive fluid balance

Abstract

The impact of the use of loop diuretics to prevent cumulative fluid balance in non-oliguric patients is uncertain. This is a retrospective study to estimate the association of time-averaging loop diuretic exposure in a large population of non-cardiac, critically ill patients with a positive fluid balance (> 5% of body weight). The exposure was loop diuretic and the main outcomes were 28-day mortality, severe acute kidney injury and successful mechanical ventilation weaning. Time-fixed and daily time-varying variables were evaluated with a marginal structural Cox model, adjusting bias for time-varying exposure and the presence of time-dependent confounders. A total of 14,896 patients were included. Patients receiving loop diuretics had better survival (unadjusted hazard ratio 0.56, 95%CI 0.39–0.81 and baseline variables adjusted hazard ratio 0.53, 95%CI 0.45–0.62); after full adjusting, loop diuretics had no association with 28-day mortality (full adjusted hazard ratio 1.07, 95%CI 0.74–1.54) or with reducing severe acute kidney injury occurrence during intensive care unit stay – hazard ratio 1.05 (95%CI 0.78–1.42). However, we identified an association with prolonged mechanical ventilation (hazard ratio 1.59, 95%CI 1.35–1.89). The main results were consistent in the sub-group analysis for sepsis, oliguria and the study period (2002–2007 vs. 2008–2012). Also, equivalent doses of up to 80 mg per day of furosemide had no significant association with mortality. After adjusting for time-varying variables, the time average of loop diuretic exposure in non-cardiac, critically ill patients has no association with overall mortality or severe acute kidney injury; however, prolonged mechanical ventilation is a concern.