Addition of a Loop Diuretic to Norepinephrine During Treatment of Hepatorenal Syndrome Type 1

Diuretics are commonly discontinued in patients with cirrhosis with acute kidney injury (AKI) because they are presumed to trigger hepatorenal syndrome type 1 (HRS-1). We hypothesized that if HRS-1 is adequately treated with a vasoconstrictor (mean arterial pressure [MAP] effectively increased), diuretics are safe and effective.

Records of hospitalized patients with cirrhosis who received i.v. furosemide while receiving i.v. norepinephrine as a vasoconstrictor to treat HRS-1 were examined. We assessed change in urine output (UOP), trajectory of serum creatinine (sCr), and impact of portopulmonary hypertension (PoPHTN) on the therapeutic response.

Twenty-six patients with HRS-1 received i.v. furosemide (median: 2 days, 160 mg boluses every 6-24 hours) added to i.v. norepinephrine. Median age was 51 years; 91% were of White race, 36% were women, and median model for end-stage liver disease score was 32. The median initial sCr was 4.0 mg/dl. Before treatment, median UOP was 358 ml/d. Norepinephrine alone led to a median increase in UOP to 850 ml/d. Addition of furosemide to norepinephrine induced a subsequent increase in median UOP to 2072 ml/d (P < 0.0001), which was not observed in a control group (n = 22) who did not receive furosemide. Nineteen patients (73%) treated with norepinephrine plus furosemide (median MAP increase, 16 mm Hg) either maintained or improved their sCr trajectory. The magnitude of norepinephrine-induced increase in MAP correlated with the norepinephrine plus furosemide-induced UOP (r = 0.67, P = 0.0002), and the correlation coefficient was numerically stronger among those with PoPHTN.

In patients with HRS-1 who are adequately treated with norepinephrine and achieved an optimal MAP increment, addition of i.v. furosemide enhances diuresis without negatively affecting renal recovery.