Midodrine, an α1-adrenergic agonist, has been proposed as a vasoconstrictor therapy to counteract circulatory dysfunction in patients with cirrhosis and ascites. Its potential impact on clinical outcomes, particularly mortality and liver function, remains under active investigation.

A systematic search was conducted for randomized controlled trials comparing midodrine (with or without rifaximin) to standard medical therapy or albumin in cirrhotic patients with ascites. RevMan 5.4 was used to conduct meta-analyses of mortality (binary outcome) and MELD scores (continuous outcome). Heterogeneity was evaluated using I² statistics

Four RCTs, including a total of 729 patients (464 midodrine, 265 control), met the inclusion criteria.Midodrine significantly reduced short-term (12 weeks)mortality compared to SMT (OR: 0.22; 95% CI: 0.11–0.44; p < 0.0001; I² = 29%).Midodrine was also associated with a greater reduction in MELD score (MD: −2.49; 95% CI: −2.74 to −2.25; p < 0.00001; I² = 0%).Heterogeneity was low for both outcomes. No serious adverse effects were reported. Mild symptoms such as thirst and abdominal discomfort were noted in two studies. Midodrine was generally used at 7.5–12.5 mg TID. One study combined midodrine with rifaximin.

Midodrine is associated with significant improvements in both short-term mortality and liver function, as assessed by MELD score, in patients with cirrhosis and ascites. These findings support the consideration of midodrine as a therapeutic adjunct in selected patients. Further large-scale, multicenter trials are warranted to validate these results.