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

Mads Israelsen, Emilie Kristine Dahl, Bjørn Stæhr Madsen, Signe Wiese, Flemming Bendtsen, Søren Møller, Annette Dam Fialla, Boye L Jensen, Aleksander Krag

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11 Citations (Scopus)

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.

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

Keywords

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

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