In:
American Journal of Physiology-Gastrointestinal and Liver Physiology, American Physiological Society, Vol. 318, No. 2 ( 2020-02-01), p. G313-G321
Abstract:
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): group A received terlipressin followed by the addition of dobutamine; group B received dobutamine and terlipressin as monotherapies; and group C 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, P 〈 0.01) but had no significant effects on GFR. Renin ( P 〈 0.05), angiotensin II ( P 〈 0.005), and aldosterone ( P 〈 0.05) increased after dobutamine infusion. Terlipressin as a monotherapy improved GFR (18.9 mL·min −1 ·m −2 , P = 0.005) and mean arterial pressure (MAP) (14 mmHg, P = 0.001) but reduced CO (−0.92 L/min, P 〈 0.005) and renin ( P 〈 .005). A combined treatment of dobutamine and terlipressin had a positive effect on CO (1.19 L/min, P 〈 0.05) and increased renin ( P 〈 0.005), angiotensin II ( P 〈 0.005), and aldosterone ( P 〈 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. NEW & NOTEWORTHY 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.
Type of Medium:
Online Resource
ISSN:
0193-1857
,
1522-1547
DOI:
10.1152/ajpgi.00328.2019
Language:
English
Publisher:
American Physiological Society
Publication Date:
2020
detail.hit.zdb_id:
1477329-6
SSG:
12
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