Midodrine a novel option for PICD prevention in ACLF

Oral midodrine may be a good alternative to intravenous albumin for preventing paracentesis-induced circulatory dysfunction (PICD) in patients with acute-on-chronic liver failure (ACLF) undergoing modest-volume paracentesis for ascites, suggests a new study.

On day 6, the primary endpoint of PICD incidence did not differ significantly between the two groups. Midodrine prevented 84 percent of patients from PICD after paracentesis vs 80 percent  for albumin. “Albumin was associated with a slightly higher incidence of adverse events. It is also an expensive treatment modality,” said presenting author Dr Mithun Sharma from the Department of Hepatology and Liver Transplantation, AIG Hospitals in Hyderabad, India. [AASLD 2022: The Liver Meeting, abstract 117]

“Hence, midodrine may be a safer and cost-effective option for these patients,” added Sharma. “However, the findings should be validated in larger studies.”

The need for a cheaper alternative

PCID is a complication of large volume paracentesis that leads to faster re-accumulation of ascites, hyponatraemia, renal impairment, and shorter survival. Sharma said the incidence of PICD after large-volume paracentesis ranges from 12–20 percent in patients receiving albumin.

Albumin is effective at reducing PCID incidence in those receiving paracentesis. The downside is that albumin requires IV infusion and is comparatively costly, he added.

Midodrine, an alpha-adrenergic agonist, has been used successfully in the treatment of orthostatic hypotension and may also help prevent PICD by maintaining patients’ mean arterial pressure (MAP). The drug works by stimulating the nerve endings in blood vessels, causing them to tighten and for the blood pressure to increase.

In a pilot study, midodrine was not as effective as IV albumin in preventing circulatory dysfunction after large-volume paracentesis (>5 L of ascitic fluid) in patients with cirrhosis and tense ascites. [J Clin Gastroenterol 2014; 48:184 –188]

However, Sharma said patients with ACLF may only need to remove  <5 L of fluid from the peritoneal cavity. Hence, they could be good candidates for midodrine.

Midodrine vs albumin in ACLF

The study included 50 patients with ACLF who were undergoing paracentesis with 3–4 L of fluid volumes. PICD was defined as a 50-percent increase in plasma renin activity (PRA) from baseline on day 6, following paracentesis.

Patients were randomly assigned to receive either midodrine-hydrochloride 7.5 mg thrice daily starting 2 hours prior to paracentesis or IV 20% human albumin infusions toward the end of paracentesis.

MAPs were recorded daily while renal parameters and serum electrolytes were monitored on days 3 and 6. Blood samples were tested for panel-reactive antibody on days 1 and 6. Alcohol-related liver disease was the most common underlying aetiology of cirrhosis.

At day 6, PICD incidence was comparable between groups (4 with albumin and 5 with midodrine). There were no significant differences in absolute change in PRA between groups, nor significant changes in MAP, creatinine, or sodium levels in either group. Fluid overload occurred in one patient in the albumin group. Grade I/II hepatic encephalopathy occurred in three patients on albumin and in two patients on midodrine 2–3 days following paracentesis. There were three cases of acute kidney injury with albumin vs 1 with midodrine.

The mean cost of albumin infusions was about sixfold higher than that of oral midodrine in the cost-effectiveness analysis.

Session moderator Dr Shiv Sarin from the Institute of Liver and Biliary Sciences in New Delhi, India said albumin is mandatory in patients requiring large-volume paracentesis. “It would be unethical not to use it in that situation.”

As for midodrine, he said he would wait for more data in patients who require modest-volume paracentesis.