Hyaluronidase: All You Need To Know

Hyaluronidase Protocol

Hyaluronic acid fillers are medical products used to non-invasively correct 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 cheekbones and jawline. One of the best things about dermal fillers is that their results are non-permanent. They either fade away with time or can be eliminated with the help of hyaluronidase whenever the patient wants.

Possible Complications Of Cosmetic Fillers

The basic complications associated with dermal fillers include minor reactions at the injection site, such as:

  1. swelling,
  2. bruising,
  3. redness,
  4. tenderness.

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 temperatures.

However, there are also complications that can be serious and life-threatening. For example, a 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.

Hence, it is very important that physicians are trained to quickly identify the possible signs of 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, which will effectively dissolve the offending hyaluronic acid filler and reverse its effects, both beneficial and adverse.

Health complications are not the only reason for the use of hyaluronidase. Sometimes, patients just don’t get the results they expected or want to get rid of a filler earlier than it dissolves in the body in a natural way.

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 break down 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 or unwanted results.

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 is technically off-label, 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, the volume of filler injected, and degree of cross-linking involved, play a role in determining the sufficient dosage of hyaluronidase.

Hyaluronidase: When To Administer

There are several reasons to use hyaluronidase to dissolve cosmetic fillers. The most popular of them include:

  1. To reverse unexpected or undesired results. Sometimes, patients feel that they look “too different” after filler injection and want to reverse the effects.
  2. To correct using too much filler.
  3. To correct side effects, such as asymmetry, nodules, lumps, granulomas, etc.
  4. To treat adverse side effects and reactions.

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 their severity and 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.

How To Administer Hyaluronidase: The Protocol

Below is the step-by-step instruction on how to administer hyaluronidase to eliminate cosmetic fillers. Remember that the procedure can only be performed by a certified medical professional.

  • Draw 10ml of 0.9% normal saline or water for injection in a syringe.
  • Dissolve the hyaluronidase powder with 1ml of chosen solvent.
  • Rotate the ampoule in order to fully dissolve the powder.
  • Draw up the 1ml of hyaluronidase back into the syringe with the remaining 9ml of chosen solvent.
  • The concentration of the prepared solution is 150 IU/ml, and each 0.01ml of the solution will contain 1.5IU of hyaluronidase.
  • 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.
  • When using hyaluronidase to treat nodules, inject the solution into the nodules.
  • 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.
  • When using hyaluronidase to treat vascular compromise, 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.

Hyaluronidase Injection: Possible Risks

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 the body's 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 complications. Aesthetic practitioners who perform cosmetic filler injections must be trained in 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 tests are optional, physicians may still perform them, especially in non-urgent cases.

Note on articles: These articles are not endorsed by DoctorMedica nor reviewed for medical accuracy. Similarly, views and opinions expressed are those of the author only. Articles are meant for informational purposes only. Ask your doctor for professional medical advice.