(1431) Efficacy and Safety of Sequential Nephron Blockade vs Loop Diuretic for De-Resuscitation in the ICU

Introduction: Diuretics are integral in de-resuscitation of intensive care unit (ICU) patients following initial fluid resuscitation and stabilization. While use of loop diuretics is common, sequential nephron blockade (SNB) is an alternative diuretic strategy that combines a loop diuretic with at least one diuretic from another pharmacologic class to potentially increase efficacy and limit adverse effects. The purpose of this study is to compare efficacy and safety of SNB compared to loop diuretics alone for de-resuscitation of critically ill patients.

Methods: This retrospective study was performed at an academic medical center and included adult patients admitted to the medical critical care service that received either a loop diuretic alone or in combination with a thiazide, carbonic anhydrase inhibitor, and/or aldosterone antagonist on two consecutive days. Select exclusion criteria were admission for acute decompensated heart failure and unmeasured urine volume 24-hours post-diuretic administration. 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 (AKI) and electrolyte abnormalities on diuresis day 1.

Results: A total of 100 patients were included (SNB = 15, Loop = 85). At baseline, patients in the SNB group were more likely to have hypernatremia (Na >150 mmol/L, 20% vs 2.4%, p = 0.0232) and hyperchloremia (Cl > 115mmol/L, 20% vs 2.4%, p = 0.0232). Patients in the SNB group experienced increased urine output on diuresis day 1 (4725 vs 2215 mL, p=0.0004) and day 2 (4240 vs 2830 mL, p=0.0364). AKI occurred in 15.5% of loop patients versus no SNB patients on diuresis day 1 (p=0.2077). Clinically significant hypernatremia (26.7% vs 2.4%, p=0.0043) and hyperchloremia (13.3% vs 3.5%, p=0.1609) persisted for the SNB group on diuresis day 1. Incidence of hypokalemia (K ≤ 3.3mEq/L) and elevated serum bicarbonate (HCO3 > 35mmol/L) was similar between groups following diuresis.

Conclusions: Among ICU patients requiring de-resuscitation, SNB may be associated with improved diuresis with similar safety concerns compared to loop diuretics alone.