Use of Midodrine for Intraoperative Hemostasis in Cutaneous and Percutaneous Surgery

Owing to the increasingly high volume of cutaneous and percutaneous procedures performed annually, the demand for local anesthesia has steadily risen. The gold-standard formulations for local anesthesia contain epinephrine at a concentration of 1:100,000 added to lidocaine to aid in hemostasis. Epinephrine, an α-agonist, also exhibits off-target β-adrenergic effects that carry risk of adverse events with these injections. Furthermore, the ongoing global shortage of epinephrine highlights the need for a safer and viable alternative. Midodrine, a targeted a₁-adrenergic receptor agonist, is utilized as a vasopressor to induce arterial and venous vasoconstriction. We developed a formulation of 2% lidocaine combined with 1:2,000,000 epinephrine and 50 μM midodrine (midodrine/lidocaine/epinephrine formulation), hypothesizing that this combination would exhibit synergism on hemostasis. In a porcine model of blood loss after punch biopsies, our formulation was compared with 2% lidocaine; 2% lidocaine with 1:100,000 epinephrine; 2% lidocaine with 1:2,000,000 epinephrine; and 2% lidocaine with 50 μM midodrine. Our results indicate that 2% lidocaine with 1:100,000 epinephrine and our midodrine/lidocaine/epinephrine formulation were statistically comparable, with both significantly reducing bleeding when compared with the 2% lidocaine (P < .05). The 2% lidocaine with midodrine alone also showed additional promise as an effective hemostatic formulation. Thus, combination of low-concentration epinephrine and midodrine with lidocaine may exhibit synergistic hemostatic effect in cutaneous surgical settings while reducing potential off-target effects of either vasoconstrictor alone at higher concentrations as adjunct monotherapies.