Comparative Effectiveness of Different Interventions of Perivascular Hyaluronidase

Background: Soft-tissue necrosis caused by vascular compromise is a frequent and troublesome complication of hyaluronic acid filler injection. Hyaluronidase has been proposed as a treatment for this condition. This study aimed to determine the effective dose and administration interval of hyaluronidase injection in a skin necrosis animal model. Methods: New Zealand rabbits were used to simulate the hyaluronic acid–associated vascular occlusion model. Hyaluronic acid filler (0.1 ml) was injected into the central auricular artery to create an occlusion. Three rabbit auricular flaps were injected with 500 IU of hyaluronidase once (group A) and three flaps each were injected at 15-minute intervals with 250 IU of hyaluronidase twice (group B), 125 IU of hyaluronidase four times (group C), 100 IU of hyaluronidase five times (group D), and 75 IU of hyaluronidase seven times (group E), all at 24 hours after occlusion. No intervention was administered after occlusion in the control group. Flap fluorescence angiography was performed immediately after hyaluronidase injection and on postoperative days 2, 4, and 7. Flap necrotic areas were analyzed. Results: All control and experimental flaps demonstrated total occlusion after hyaluronic acid injection. The average total survival rate (positive area/total area ×100 percent) of control flaps was 37.61 percent. For experimental groups, the average total survival rates were 74.83 percent, 81.49 percent, 88.26 percent, 56.48 percent, and 60.69 percent in groups A through E, respectively. Conclusion: A better prognosis can be obtained by administering repeated doses rather than a single high dose of hyaluronidase.