Treatment of Hyaluronic Acid Filler–Induced Impending Necrosis With Hyaluronidase: Consensus Recommendations

Abstract

Injection-induced necrosis is a rare but dreaded consequence of soft tissue augmentation with filler agents. It usually occurs as a result of injection of filler directly into an artery, but can also result from compression or injury. We provide recommendations on the use of hyaluronidase when vascular compromise is suspected. Consensus recommendations were developed by thorough discussion and debate amongst the authors at a roundtable meeting on Wednesday June 18, 2014 in Las Vegas, NV as well as significant ongoing written and verbal communications amongst the authors in the months prior to journal submission. All authors are experienced tertiary care providers. A prompt diagnosis and immediate treatment with high doses of hyaluronidase (at least 200 U) are critically important. It is not felt necessary to do a skin test in cases of impending necrosis. Some experts recommend dilution with saline to increase dispersion or lidocaine to aid vasodilation. Additional hyaluronidase should be injected if improvement is not seen within 60 minutes. A warm compress also aids vasodilation, and massage has been shown to help. Some experts advocate the use of nitroglycerin paste, although this area is controversial. Introducing an oral aspirin regimen should help prevent further clot formation due to vascular compromise. In our experience, patients who are diagnosed promptly and treated within 24 hours will usually have the best outcomes.

An Islanded Rabbit Auricular Skin Flap Model of Hyaluronic Acid Injection-Induced Embolism

“…Ischemia with subsequent skin necrosis mainly occurs in the glabella [6,7], nose [7][8][9][10][11][12], forehead [7,8], nasolabial fold [10], and cheek [13]. Moreover, intracranial artery embolism can lead to blindness caused by retinal artery occlusion and [10,11,13] has been sporadically reported to treat HA embolism-induced skin necrosis [14][15][16][17], however, well-designed case-control studies are required to verify the efficacy and safety of hyaluronidase before it can be used routinely in humans. Because HA injection-induced embolism is a rare complication, creation of an animal model is necessary for thorough study of its pathophysiological progress and potential treatment.…”

Ischemical Problems after Filler Injections: Anatomical Details and Practical Guide Lines to Avoid Disasters

“…An extra volume of hyaluronidase can be injected (up to 4 cycles) if there is no clinical improvement after 60 min [31]  If ophthalmic artery necrosis is suspected, the authors recommend immediately contacting oculoplastic surgeon for urgent retrobulbar injection of hyaluronidase which can dissolve intravascular as well as extravascular hyaluronic acid [32]  To prevent the further clot formation it is recommended to start treatment with 2 pills of 325 mg of aspirin daily for a week in association with gastroprotective (as pantoprazol 20 mg) to prevent gastritis [33]  In severe cases, low-molecular-weight heparin and systemic anticoagulation may be helpful. Prostaglandin E1 (PGE1) can also be used to promote vasodilation.…”

“…When potent vasoactive drugs are used, the patient shoul be carefully monitored in the hospital [15]. Even if patient presentation is delayed, treatment is still recommended because it may restore normal circulation and speed the healing process [34][35]  Oral prednisone, 20 to 40mg daily, for three to fi ve days is recommended because it helps to decrease the infl ammatory component of the injury and prevent further vascular compromise [27][28]  If necrosis is progressive and not responsive to the above treatments, hyperbaric oxygen therapy should be considered [36]  Of note, topical oxygen therapy, low molecular weight heparin, systemic steroids, sildenafi l, plateletrich plasma, fi ller removal through puncture and intravenous prostaglandin are reported to be benefi cial [15-35-37-38]  Localized skin breakdown should be treated with topical (with or without systemic) antibiotics, and antivirals should be used especially if necrosis is around the mouth [8][9]  Also adipose-derived stem cell injection to boost the healing process and tissue regeneration promoting angiogenic processes. However, exact mechanisms are not yet come out into the open [39]  Keeping the wound covered with ointment to prevent crusting and keeping out bacteria until healing is complete is important.…”

“…Less than 0.1% of patients injected with hyaluronidase develop urticaria and angioedema. More caution has to be taken in patients with a history of bee allergy because hyaluronidase is considered to be one of the active components in bee venom [27][28][29][30][31][32][33][34][35][36][37][38][39][40]. There are no reported anaphylactic reactions after subepidermal injections [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44].…”

Experience and Management of Intravascular Injection with Facial Fillers: Results of a Multinational Survey of Experienced Injectors

“…The most serious adverse event is inadvertent intravascular injection of material with filling antegrade into the larger branches and subsequent smaller branches of this vessel, or initial retrograde flow upon injection followed by antegrade flow upon injection pressure release into more proximal branched vessels and their distribution which can lead to skin necrosis or blindness. [15][16][17][18][19] The incidence of vascular occlusion following intravascular injection has been estimated at 3 per 1000 for calcium hydroxyl apatite and 3-9 per 10,000 for hyaluronic acid products, [20] but the true incidence of this complication is unknown because of underreporting by clinicians [16,19]. The eventual cutaneous outcome appears unclear in the literature with fillers, but reactions and outcomes seem to be more severe with non-hyaluronic acid fillers such as calcium hydroxyl apatite and poly(methyl methacrylate) [16,19].…”