Efficacy and Safety of Sequential Nephron Blockade Compared to Standard Loop Diuretic for Fluid De-resuscitation in the ICU

Diuretics are integral in fluid de-resuscitation of ICU patients following initial stabilization. While loop diuretics are commonly used, sequential nephron blockade (SNB) is an alternative diuretic strategy that combines a loop diuretic with at least one diuretic from another pharmacologic class to increase efficacy and limit adverse effects. The objective of this study was to compare the safety and efficacy of SNB to loop diuretics alone for de-resuscitation of critically ill patients. This retrospective study included adult ICU patients who received either a loop diuretic alone or combined with an aldosterone antagonist, carbonic anhydrase inhibitor, and/or thiazide diuretic on two consecutive days. The primary outcome was comparison of diuretic efficacy, assessed by urine output, on diuresis day 1. Secondary outcomes included comparison of diuretic efficacy on diuresis days 2-5 and incidence of acute kidney injury and electrolyte abnormalities on diuresis day 1. A total of 100 patients were included (SNB = 15, Loop = 85). At baseline, SNB patients had more hypernatremia (20% vs 2.4%, P = 0.023) and hyperchloremia (20% vs 2.4%, P = 0.023). Patients in the SNB group had increased urine output on diuresis day 1 (4725 vs 2215 mL, P = 0.0004). AKI did not occur in SNB patients on diuresis day 1 vs 15.5% of loop patients ( P = 0.208). Hypernatremia (26.7% vs 2.4%, P = 0.004) and hyperchloremia (13.3% vs 3.5%, P = 0.161), persisted in the SNB group on diuretic day 2. In conclusion, among ICU patients requiring de-resuscitation, SNB may be associated with improved diuresis and similar safety concerns compared to loop diuretics alone.