Dobutamine Reverses the Cardio-suppressive Effects of Terlipressin Without Improving Renal Function in Cirrhosis and Ascites: a Randomized Controlled Trial

Acute kidney injury and hepatorenal syndrome (HRS) are frequent complications in patients with cirrhosis and ascites. First-line treatment is terlipressin, which reverses HRS in ~40% of patients but also lowers cardiac output (CO). We aimed to investigate whether reversing the cardio-suppressive effect of terlipressin with the β-adrenoceptor agonist dobutamine would increase CO and thereby increase the glomerular filtration rate (GFR). We randomized 25 patients with cirrhosis, ascites, and impaired renal function (2:2:1): received terlipressin followed by the addition of dobutamine; received dobutamine and terlipressin as monotherapies; and received placebo. Renal and cardiac functions were assessed during 8 clearance periods of 30 min, and concentrations of vasoactive hormones were measured. Dobutamine as a monotherapy increased CO (1.03 L/min, < 0.01) but had no significant effects on GFR. Renin ( < 0.05), angiotensin II ( < 0.005), and aldosterone ( < 0.05) increased after dobutamine infusion. Terlipressin as a monotherapy improved GFR (18.9 mL·min·m, = 0.005) and mean arterial pressure (MAP) (14 mmHg, = 0.001) but reduced CO (-0.92 L/min, < 0.005) and renin ( < .005). A combined treatment of dobutamine and terlipressin had a positive effect on CO (1.19 L/min, < 0.05) and increased renin ( < 0.005), angiotensin II ( < 0.005), and aldosterone ( < 0.05), but it had no significant effects on MAP or GFR. Dobutamine reversed the cardio-suppressive effect of terlipressin in cirrhosis, ascites, and impaired renal function. However, dobutamine reduced peripheral vascular resistance, activated renin-angiotensin-aldosterone system, and did not improve GFR compared with terlipressin as a monotherapy. Therefore, dobutamine cannot be recommended in cirrhosis and ascites. This study shows that the cardio-suppressive effects of the vasopressin receptor agonist terlipressin can be reversed by dobutamine. This is a novel observation in patients with decompensated cirrhosis. Furthermore, we show that dobutamine reduced the peripheral vascular resistance and activated the renin-angiotensin system, whereas renal function was not further improved by terlipressin alone.