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Dobutamine reverses the cardio-suppressive effects of terlipressin without improving renal function in cirrhosis and ascites: A randomized controlled trial

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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 cardiosuppressive 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.

Original languageEnglish
JournalAmerican Journal of Physiology: Gastrointestinal and Liver Physiology
Volume318
Issue number2
Pages (from-to)G313-G321
Number of pages9
ISSN0193-1857
DOIs
Publication statusPublished - 1 Feb 2020

    Research areas

  • AKI, Acute kidney injury, HRS, Hepatorenal, Portal hypertension, Humans, Middle Aged, Arterial Pressure/drug effects, Male, Kidney Function Tests, Young Adult, Terlipressin/adverse effects, Adult, Female, Kidney Diseases/prevention & control, Adrenergic beta-Agonists/therapeutic use, Ascites/metabolism, Liver Cirrhosis/metabolism, Glaucoma Drainage Implants, Acute Kidney Injury/drug therapy, Dobutamine/therapeutic use, Hepatorenal Syndrome/drug therapy, Renin/urine, Cardiac Output/drug effects, Adolescent, Aged

ID: 58720105