Addition of midodrine to albumin reduces the incidence of complications of large-volume paracentesis: an RCT comparing midodrine, terlipressin, and albumin.

Background and aims: Large-volume paracentesis (LVP), a therapeutic procedure for cirrhosis patients with refractory ascites, is associated with paracentesis-induced circulatory dysfunction (PICD). While albumin infusion is known to prevent PICD, it is unknown whether the addition of vasoconstrictors to albumin reduces complications of LVP.

Methods: Cirrhosis patients undergoing LVP for refractory ascites were randomized to receive albumin alone (Gr. I), terlipressin with albumin (Gr.II), or midodrine with albumin (Gr. III). The primary endpoint was the incidence of PICD, and the secondary endpoints were the incidence of new-onset complications (hyponatremia, acute kidney injury, and encephalopathy), 28-day survival and adverse events to therapy.

Results: One hundred and sixty-fifty cirrhosis patients with refractory ascites undergoing LVP were equally randomized to 3 groups. The incidence of PICD in Gr. I (14%), II (7%), and III (11%) was similar (p = 0.46). Mean arterial pressure (MAP) reduced in Gr.I and II compared to the rise in Gr. III on day 3 (ΔMAP: Gr.I = - 8.2 ± 5.01; Gr.II = - 4.34 ± 5.82; Gr. III = 9.16 ± 5.14 mmHg; p < 0.001), with a statistically significant rise in PRA (ng/ml/hour) at day 6 in Gr. I and II than in Gr. III. The incidence of new-onset complications was significantly higher in Gr.I (52.72%) and Gr.II (45.46%) than Gr.III (23.63%) (p = 0.005). Overall mortality on day 28 was not different between the groups.

Conclusions: PICD remains a challenge even in hospitalized settings. The addition of oral midodrine to albumin prevents hypotensive response on day 3, thereby reducing the incidence of new-onset complications following LVP.