Droxidopa in Critical Care: A Systematic Review of an Emerging Off-Label Practice.

Background: Prolonged use of intravenous (IV) vasopressors in critically ill patients is associated with significant complications. Droxidopa, a norepinephrine precursor approved for neurogenic orthostatic hypotension, has gained interest as an off-label agent for facilitating vasopressor weaning in ICU settings. This systematic review aimed to evaluate the efficacy and safety of droxidopa for vasopressor weaning in ICU patients. Methods: A systematic review was conducted following PRISMA guidelines. Databases searched included PubMed, Embase, Cochrane, and Web of Science through April 2025. Eligible studies reporting primary clinical data on droxidopa use in ICU patients were included. Outcomes included time to IV vasopressor discontinuation, duration of droxidopa use, ICU length of stay (LOS), and ICU mortality, and results were narratively synthesized. The risk of bias was assessed using the ROBINS-I and the JBI checklists. Results: Seven studies involving 161 ICU patients were included. Five studies reported time to vasopressor discontinuation, ranging from 29 to 120 h. The duration of droxidopa use ranged from 87 to 192 h. Two studies reported ICU LOS, ranging from 18 to 44 days. ICU mortality was inconsistently reported. These findings are primarily drawn from small, retrospective studies and should be interpreted cautiously. Discussion: Findings suggest that droxidopa may effectively facilitate vasopressor weaning in critically ill patients. However, variations in dosing, patient selection, and outcome reporting limit generalizability. Evidence is drawn primarily from small, retrospective studies, some available only as abstracts. Conclusion: Available evidence on droxidopa for vasopressor weaning in ICU patients remains limited and heterogeneous, with very low certainty. Further research is warranted. No funding was received for this review, and the review was not prospectively registered.