Vasodilation by Verapamil‐Nitroglycerin Solution in Microvascular Surgery

Abstract

<jats:sec><jats:title>Objective</jats:title><jats:p> Papaverine is a topical vasodilator commonly used during microvascular surgery to inhibit undesired vasoconstriction. A previous national shortage of papaverine prompted evaluation of an alternative, effective vasodilator. This study aims to assess the experience of a solution of verapamil and nitroglycerin (VG) as a potential alternative pharmacologic vasodilator. </jats:p></jats:sec><jats:sec><jats:title>Study Design</jats:title><jats:p> Retrospective case series. </jats:p></jats:sec><jats:sec><jats:title>Setting</jats:title><jats:p> Two tertiary academic medical centers. </jats:p></jats:sec><jats:sec><jats:title>Subjects and Methods</jats:title><jats:p> Among 298 patients, 306 consecutive free tissue transfers performed between 2014 and 2017 for head and neck defect reconstruction utilized a VG solution. Patient and flap characteristics, intraoperative patient and flap complications, and postoperative complications were reviewed. Diameter of the cervical recipient artery was measured intraoperatively before and after topical application of the VG solution in a subset of 43 patients (44 flaps). </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Flaps included fibula, radial forearm, subscapular system, and anterolateral thigh. In total, 3 (0.98%) flaps failed with varied etiology unrelated to the VG solution (venous thrombosis, arterial anastomosis thrombosis, physical damage to the perforator). Specific to topical application of the VG solution, the mean recipient artery diameter increased from 2.1 to 3.1 mm, a 48% increase ( P &lt; .01). There were no intraoperative cardiac events or complications attributable to the VG solution. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> We describe the use of a VG solution for pharmacologic vasodilation during microvascular free tissue transfer. Its use was associated with an acceptable incidence of adverse events, none of which were directly attributable to the VG solution. Apparent and sustained vasodilation was demonstrated. The VG solution represents a safe and efficacious alternative to papaverine in microvascular surgery. </jats:p></jats:sec>

Designing an evidence‐based free‐flap pathway in head and neck reconstruction

“…Yu et al 25 found that 94% of microvascular surgeons implement topical vasodilators with the most common agents being papaverine, verapamil, and lidocaine. Papaverine is a phosphodiesterase inhibitor and acts as a smooth muscle relaxant via an incompletely known mechanism involving direct action on calcium channels along with increases in cyclic guanosine monophosphate (cGMP) 23,26 . In vitro studies have demonstrated up to 60% increase in vessel caliber with papaverine treatment 27 .…”

“…At low concentrations (2%) lidocaine may induce norepinephrine‐mediated vasoconstriction while vasodilatory effects are seen at higher concentrations (20%) 28 . However, its use is limited by the risk of systemic toxicity with high dose lidocaine and thus it is less regularly implemented than papaverine or verapamil 23 . Lastly, topical nitroglycerin has been implemented at some centers in the setting of recent papaverine national shortages 23,26 .…”

“…21,22 Other factors that may contribute to vascular spasm are perioperative use of vasoactive medications, low core body temperature, and surgical catecholamine surge. 21,23,24 The microvascular surgeon must recognize the above factors and attempt to mitigate their effects.…”

“…27 Drawbacks to papaverine include short duration of action (<2 h), dose-dependent endothelial toxicity, and acidic solution. 21,23,26 Verapamil works via selective inhibition of the L-type voltage-gated calcium channels on smooth muscle thus inducing vasodilation. While the onset of action is slower than papaverine, verapamil has a half-life of 4.8 h. 21 Lidocaine is an amide local anesthetic with activity against voltage-gated sodium channels.…”

“…23,26 Nitroglycerin induces nitric oxide formation in smooth muscle cells and increases intracellular cGMP inhibiting downstream calcium release and resulting in vasodilation. 21,23,26 However, the half-life is short and its isolated dilatory effect may be less than that of papaverine or verapamil alone. 21 The authors use a similar mixture to that recently published by Seth et al which is presented in Table 2.…”