Abstract

Autologous free-flap reconstruction has transformed reconstructive surgery by restoring form and function in complex head, neck, breast, and limb defects; however, maintaining stable perfusion intraoperatively remains critical, and the optimal choice of vasopressor is still debated due to concerns about α-adrenergic vasoconstriction and microcirculation. This systematic review and meta-analysis, conducted according to PRISMA guidelines and registered in PROSPERO, included randomized controlled trials and observational cohort studies comparing perioperative phenylephrine (pure α-agonist) with mixed α/β-agonists (norepinephrine or ephedrine) in adult free-flap surgery, with primary outcomes of flap failure and surgical revision for microvascular compromise, and secondary outcomes including thrombosis, analyzed using random-effects models. Nine studies (two RCTs and seven cohorts) comprising 7,181 patients and 8,626 flaps were included; overall flap failure was low (3%), but higher with norepinephrine (6%) compared to phenylephrine (2%) and ephedrine (2%). Surgical revision occurred in 12% overall, again higher with norepinephrine (15%) versus phenylephrine (2%), while thrombosis occurred in 7% overall and was most frequent with norepinephrine (11%). Sensitivity analyses confirmed the robustness of these findings despite high heterogeneity and possible publication bias. Overall, vasopressors are not uniformly harmful in free-flap surgery; however, phenylephrine and ephedrine were associated with fewer surgical revisions and thrombotic events compared to norepinephrine, suggesting that vasopressor choice may influence outcomes and should be individualized, with further randomized trials needed to optimize perioperative hemodynamic management in microvascular reconstruction.