Hyaluronidase Protocol



Last Updated On: 2024-01-25

Hyaluronic acid fillers are medical devices that are used to correct and non-surgically augment various aesthetic deformities, such as dehydration, dullness, fine lines, and wrinkles. Read more!

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Hyaluronic acid fillers are medical devices that are used to correct and non-surgically augment various aesthetic deformities, such as dehydration, dullness, fine lines, and wrinkles. These injectable implants are also perfect for enhancing various facial features, such as thin and shapeless lips, and for defining facial contours, like the cheekbones and jawline.

What are the complications of hyaluronic acid fillers?

Despite their effectiveness, patients may still experience some health complications associated with the implantation of hyaluronic acid fillers, such as mild swelling, bruising, and tenderness at the injection site. These secondary reactions can be adequately managed if the patients are taught basic aftercare methods, such as maintaining the hygiene level of injected sites and keeping the treated area(s) well-protected from places with extreme temperature. However, there are complications that can arise from aesthetic implant treatments that can be serious and life-threatening. For example, filler that is accidentally injected into a vein or artery can occlude normal blood circulation. If a significant blood-supplying vessel is blocked, the adjacent tissues will not be supplied with enough blood and oxygen, resulting in necrosis — the irreversible death of skin tissues. Besides necrosis, blocked vessels can also cause the backflow of blood into the tissues, thereby increasing pressure to the point that low grade ischemia occurs. One facial region that frequently succumbs to skin necrosis following hyaluronic acid filler injections is the nose, especially the tip of the nose. In extreme cases, poor treatment in this area can even lead to blindness if the aesthetic implant is administered into the angular vessels around the nose. Dermal fillers that had been accidentally injected into the facial artery can travel proximally to the internal carotid system. With the release of pressure, the filler material can then travel into the central retinal artery and cause possible visual impairment or even blindness. Hence, it is very important that the physicians are trained to quickly identify the possible signs an impending necrosis, so as to be able to administer immediate corrective actions in order to reduce the risk of adverse health reactions. One such medical intervention is the administration of hyaluronidase that will effectively dissolve the offending hyaluronic acid filler and reverse its effects, both beneficial and adverse.

What is hyaluronidase?

Hyaluronidases refer to a class of injectable enzymes that act as dispersion agents. These enzymes are actually produced naturally in the body and function to breakdown the natural membranous barriers in tissues. These enzymes are then manufactured synthetically in order to promote the breakdown of hyaluronic acid through hydrolysis. Once the membranous barriers are broken down, there will be an enhanced tissue permeability, so injected solutions, like medications, subcutaneous fluids, and infusions, can be absorbed into the targeted sites in an improved manner. Besides the approved therapeutic indications, this enzyme has also been used to prematurely dissolve hyaluronic acid-based fillers in the event of any health complications. Estheticians can only administer this enzyme when it is absolutely necessary and after they have obtained full consent from their patients. While such a use of hyaluronidase technically an off-label use, this does not mean that it is unsafe to use; instead, it simply means that physicians need to seek guidance from other professionals and rely on their own expertise in order to determine the accurate reconstitution process and the adequate dosage required for best results. Many factors, including the strength of the hyaluronic acid-based filler, volume of filler injected, and degree of cross-linking involved, play a role in determining the sufficient dosage of hyaluronidase.

When should hyaluronidase be administered?

Hyaluronidase can be injected when patients who are treated with hyaluronic acid-based implants display undesirable side effects, such as unattractive lumps. Those with a “Pillow face” appearance, whereby substantial volumes of filler appear visible in the mid-face region, can also be treated with hyaluronidase injections. Treatment aftereffects, like nodules, can develop on the corrected facial area. Nodules, which are growths of abnormal tissue that develop within two days of filler injection, can be inflammatory, while nodules that occur sub-acutely (within two weeks of a filler injection) or late (after two weeks of a filler injection) are at a higher risk to worsen into an infection. Besides that, large hematomas (blood clots) can also be managed using hyaluronidase injections. Another frustrating side effect of cosmetic filler injection that can be managed using hyaluronidase is the Tyndall effect. This condition is used to describe the unsightly bluish discoloration of the skin that occurs when the filler is injected too superficially in the skin. Another indication that requires the administration of hyaluronidase is skin blanching, which is when the skin appears mottled or dusky.  This change in the appearance of the skin is usually accompanied by other symptoms, including pain and a cool sensation in the mottled area. Failure to immediately remedy these signs will only cause tissue necrosis to occur. Since this enzyme improves absorption via hypodermoclysis, which is the process of subcutaneous or interstitial infusion of fluids into the body, it is best that hyaluronidase is not administered when the healthcare practitioner suspects an infection. Instead, an antibiotic should be prescribed. Hyaluronidase must be injected the moment complications occur, so as to reduce the severity of complication or prevent the manifestation of tissue necrosis. Early administration of the enzyme also ensures its effectiveness in dissolving hyaluronic acid filler since the efficacy of the enzyme dwindles greatly after approximately four hours. Physicians must educate their patients on the risks associated with the administration of hyaluronic acid-based implants and the off-label use of hyaluronidase. Their informed consent must be obtained before the aesthetic procedure can even begin.

What is the protocol to administer hyaluronidase?

While there are a few brands of hyaluronidase available on the market, a common preparation of the enzyme that is widely used in the UK is Hyalase. This solution for injection is made of 1500 IU of freeze-dried hyaluronidase. This prescription-only-medication appears as white powder that is presented in small glass ampoules. Below is the step-by-step process to reconstitute the medication prior to injection.

  1. Draw 10ml of 0.9% normal saline or water for injection in a syringe.
  2. Dissolve the hyaluronidase powder with 1ml of chosen solvent.
  3. Rotate the ampoule in order to fully dissolve the powder.
  4. Next, draw up the 1ml of hyaluronidase back into the syringe with the remaining 9ml of chosen solvent.
  5. The concentration of the prepared solution is 150 IU/ml and each 0.01ml of the solution will contain 1.5IU of hyaluronidase.
  6. Inject the prepared hyaluronidase solution in small aliquots into the affected areas. Use a 30G needle for superficial injections and a 27G needle for treating deeper skin layers.
  7. When using hyaluronidase to treat nodules, inject the solution into the nodules.
  8. When using hyaluronidase to dissolve hyaluronic acid fillers in the superficial dermis layer of the skin, inject the solution immediately into and below the filler material.
  9. When using hyaluronidase to treat vascular comprise, inject the solution using the serial puncture technique along the length of the vessel. The needle must be positioned perpendicular to the skin. Several injections may be required for best results.

Following the administration of hyaluronidase solution, the treated area must be massaged vigorously to help with the mechanical breakdown of the filler and to enhance the outcome(s). The procedure listed above must be performed by a certified and experienced physician in accordance with strict aseptic medical standards, so as to reduce the risk of infections and/or cross-contamination.  

What are the risks associated with hyaluronidase injections?

Clinical studies have found that one major complication of hyaluronidase injection is allergic reactions, with a frequency of occurrence in approximately 0.05% to 0.69% of cases. Though there is conflicting evidence on whether or not a patch test should be conducted to rule out an allergic reaction, many practitioners believe that a patch test may help to minimize the risk of allergic responses. The patch test should be done intradermally (between the skin). Physicians should then observe for signs like erythema, persistent itching, and inflammation. Patients who develop signs of a vascular compromise must be treated using hyaluronidase injection instantly to lower the risk of any life-threatening adverse reactions. Besides breaking down the injected hyaluronic acid implant, hyaluronidase injection has the potential to also degrade bodys natural hyaluronic acid. In order to lower the risk of this undesirable side effect, aestheticians are recommended to administer the enzyme slowly instead of administering the full dosage. If small dosages are inadequate, patients can always return for additional treatment sessions. Patients should be asked to stay in the clinic for about 30 minutes after being treated with hyaluronidase injection so that they can be observed in a controlled clinical environment for any side effects. Though the effects of hyaluronidase injection occur almost immediately, highly cross-linked and denser fillers may take up to two days to completely disintegrate. So, physicians should book a follow-up appointment with their patients about two to three weeks after the initial treatment session so that further corrective actions can be administered if necessary.


Hyaluronidase is an important medication that not only helps to enhance the permeability and absorption of injected solutions but also works remarkably well in dissolving inaccurately-placed hyaluronic acid-based fillers and managing the resulting complications. Aesthetic practitioners who perform cosmetic filler injections must be trained at preparing and administering hyaluronidase without delay or doubt should an emergency situation arise. Aesthetic clinics should prepare and regularly review a policy regarding the correct handling of hyaluronidase. Though patch test is optional, physicians may still perform it, especially in non-urgent cases.   


[1] American Board of Cosmetic Surgery, Injectable Fillers Guide

[2] U.S. Food and drug Administration (FDA), Dermal Fillers (Soft Tissue Fillers)

[3] P Lafaille, A Benedotto, Fillers: Contraindications, Side Effects and Precautions, Journal of Cutan Aesthetic Surgery 3(1) (2010), 16-19.

[4] Necrosis, (US: National Library of Medicine, 2013)

[5] Inglefield C, Collins F, Duckett M, Goldie K, Huss G, Paun S, Williams S, Expert consensus of Botulinum Toxin and Dermal Filler Treatment second edition (UK: Aesthetic Medical Expert Group, 2014)

[6] Dr Lisa Danielle Grunebaum, Dr. Inja Bogdan Allemann, Dr. Steven Dayan, Dr. Stephen Mandy and Dr. Lesley Baumann, The Risk of Alar Necrosis Associated with Dermal Filler Injection, (US: Denova Research, 2009)

[7] Berthold Rzany, Petra Becker-Wegerich, Frank Bachmann, Ricardo Erdmann and Uwe Wollina, Hyaluronidase in the correction of hyaluronic acid-based fillers: a review and a recommendation for use, Journal of Cosmetic Dermatology, 8 (2009), 317-32

[8] David Funt and Tatjana Pavicic, Dermal fillers in aesthetics: an overview of adverse events and treatment approaches, Journal of Clinical, Cosmetic and investigational Dermatology, 6 (2013), 295-316

[9] Hyaluronidase, (US:, 2015)

[10] Hyaluronidase Enzyme (UK: Clinica London, 2013)

[11] Jessica A. Savas ,Steven Yang ,Katlein Franca, Ivan Camacho, Keyvan Nouri, Inflammatory Nodules Following Soft Tissue Filler Use: A Review of Causative Agents Pathology and Treatment Options, American Journal of Clinical Dermatology, 14(5) (2013), 401-411.

[12] 13. Dr Menahem Sasson and Dr Pesach Shvartzman, Hypodermoclysis: An Alternative Infusion Technique, (US: American Academy of Family Physicians, 2001)

[13] Package Leaflet: Information for the User,(,2014)

[14] Dr Maurizio Cavallini, Dr Riccardo Gazzola, Dr Marco Metalla, and Dr Luca Vaienti, The Role of Hyaluronidase in the Treatment of Complications From Hyaluronic Acid Dermal Fillers, Aesthetic Surgery Journal 33(8) (2013), 1167–1174

[15] Claudio De Lorenzi,‘ Complications of Injectable Fillers, PartI, Aesthetic Surgery Journal, 33 (2013), 561.

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