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Hyaluronidase Treatment Protocol

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

What are the complications of hyaluronic acid fillers?

Despite their effectiveness, patients may still experience some complications associated with the implantation of hyaluronic acid fillers, such as swelling, bruising, and tenderness at the injection site. These secondary reactions can be managed if the patients are taught basic aftercare methods, such as maintaining the hygiene level of injected sites and keeping the treated area well-protected from extreme temperatures.

However, there are complications that can arise from aesthetic implant treatments which 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 by mistake, the adjacent tissues will not be supplied with enough blood and oxygen, resulting in necrosis – the irreversible death of skin tissues. Besides necrosis, blocked blood 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 experiences accidental skin necrosis following hyaluronic acid filler injections is the nose, especially the tip of the nose. In extreme cases, poor treatment in the nose area can even lead to blindness if the aesthetic implant is administered into the angular vessels around the nose. Dermal fillers that have 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 thereby cause possible visual impairment or even blindness. Hence, it is very important that physicians are trained to quickly identify the possible signs an impending necrosis, in order 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.

What is hyaluronidase?

Hyaluronidases refer to a class of injectable enzymes which act as dispersion agents. These enzymes are also produced naturally in the human body and function to breakdown the natural membranous barriers in tissues. This enzyme has also been used to prematurely dissolve hyaluronic acid-based fillers in the event of any health complications after implantation.  Many factors, including the strength of the hyaluronic acid-based filler, volume of dermal 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 present undesirable side effects, such as unattractive lumps. Those with an unintended “pillow-faced” appearance, whereby substantial volumes of filler appear visible in the mid-face region, can also be treated with hyaluronidase injections. Undesirable treatment after-effects can develop on the corrected facial area(s). Nodules, which are growths of abnormal tissue that develop within two days of filler injection, can be inflammatory and likely to self-resolve, while nodules that occur more longer-term (within two weeks of a treatment) are at a risk to worsen.

In addition, blood clots can also be managed using hyaluronidase injections. Another unintended 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 color 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 occurs when the skin appears mottled or dusky after treatment.  This change in the appearance of the skin is typically accompanied by other symptoms, including pain and a cool sensation in the mottled area. Failure to immediately remedy these signs can cause tissue necrosis to occur.

Since this enzyme improves absorption via hypodermoclysis, which is the process of subcutaneous or interstitial infusion of fluids, it is best that hyaluronidase is not administered when the healthcare practitioner suspects an infection. Instead, an antibiotic should be prescribed. Hyaluronidase should 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, as the efficacy of the enzyme reduces greatly after approximately four hours.

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 is Liporase. This solution for injection is made of 1500 IU of powdered hyaluronidase. This prescription-only-medication appears as white powder that is presented in small vials. Below is the step-by-step process to reconstitute the medication prior to injection.

  • Dissolve the hyaluronidase powder with 1ml of chosen solvent (water or normal saline)
  • Inject the prepared hyaluronidase solution 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 directly into the nodules.
  • When using hyaluronidase to dissolve hyaluronic acid fillers in the superficial dermis layer, inject the solution immediately into and below the injected filler material.
  • When using hyaluronidase to treat vascular comprimise, 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.

Following the administration of hyaluronidase solution, the treated area must be massaged to help with the mechanical breakdown of the filler and to enhance the outcome. 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.

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 agree 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 such as 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 reactions. Besides breaking down the injected hyaluronic acid material, hyaluronidase injection has the potential to also degrade body’s natural hyaluronic acid. In order to lower the risk of this unwanted 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 treatments. Patients should be asked to stay in the clinic for about 30 minutes after being treated with hyaluronidase so 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 fillers may take up to two days to completely disintegrate. Therefore, 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 a valuable medication that  works remarkably well in dissolving inaccurately-placed hyaluronic acid-based fillers and managing the resulting complications. Aesthetic practitioners who perform cosmetic 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 a patch test is optional, physicians may still perform it, especially in non-urgent cases.

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