Hyaluronidase Protocol

BY LEE ROWE / 01 JUL 2015

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Aesthetic nurse Lee Rowe outlines the protocol for administering hyaluronidase and highlights
the importance of understanding its use in aesthetics
Introduction
The aesthetic community is expanding, with non-surgical treatments now contributing to 75% of the
market, making the industry worth an estimated £3.6 billion in 2015, in the UK alone.1Numerous
training days are held across the UK, qualifying delegates to obtain and use hyaluronic acid (HA)
dermal fillers for their patients’ anti-ageing concerns. However, as we know, the art of injecting is just
one aspect of this treatment; other aspects include knowledge and understanding of anatomy and
physiology, consenting issues, aftercare and, more importantly, complication management. I find
practitioners are frequently raising the issue of how to treat complications on support forums,
networking groups and during study days. It is a worrying sight to see how many practitioners do not
feel confident nor hold the experience to deal with the adverse reactions that can be so detrimental to a
patient. The aim of this article is to give the reader a valuable insight into the use of hyaluronidase; how
it works and, crucially, when to administer it.
What is hyaluronidase?
Hyaluronidases are a family of injectable enzymes that act as dispersion agents. These help speed up the
natural breakdown of hyaluronic acid through hydrolysis.2 Licensed for therapeutic indications, such as
increasing tissue permeability to enhance the delivery of drugs or to increase the uptake of
subcutaneous fluids, in aesthetics, it is widely used ‘off license’.3Off license does not necessarily mean it
is unsafe to use, but that it is being prescribed and administered in a way that is different to its licensed
use. The license is obtained from the Medicines and Healthcare products Regulatory Agency4 (MHRA)
and will state what the drug can be used for, how much to give and the age of patients suitable to be
treated with it. As long as the practitioner is acting in the patient’s best interests, their autonomy is
respected and the patient has fully consented, then hyaluronidase can be administered in the event of an
adverse reaction.5 Due to this ‘off license’ use of hyaluronidase, practitioners can only seek guidance
from other professionals (as well as use their own expertise) in order to judge how much hyaluronidase
to use and how to reconstitute it, which can be limiting if one has little experience of using it. Various
factors will influence the administration and dosage – for example, the concentration of HA filler, level of
cross-linking and amount of HA deposit.
Recognising complications with HA fillers
There are, of course, several complications associated with having a HA dermal filler treatment, such as
bruising, mild swelling and tenderness at the injection site6, which can be easily managed through
observation and support on the patient’s behalf. It is the more serious complications, such as when filler
is injected into a vein or an artery, that will require medical intervention and the administration of
hyaluronidase as part of its management. If HA is injected into an artery this can cause a clot formation
around the filler, or the filler itself may cause the blockage. If the vessel is significant in supplying blood
to the skin, this can lead to necrosis, an irreversible complication that results in the death of the skin
tissue.7,8 This occurs when the skin region cannot access enough blood and oxygen.8 When injected into a
vein, HA can also cause a blockage, resulting in blood flowing back into the tissues and therefore
increasing pressure and causing low grade ischaemia.8
The nose is one of the most feared sites for necrosis following HA procedures, with the tip being the
most affected.9 To give an example of how serious a vascular complication can be, injecting dermal filler
into the angular vessels around the nose can potentially lead to blockage and skin necrosis or, in
extremely rare cases, blindness.10 Fillers injected into an artery in the face can travel proximally to the
internal carotid system whereby, on release of pressure, the product travels into the central retinal
artery resulting in possible visual loss or blindness.11 It is therefore imperative that practitioners are
able recognise the signs of an impending necrosis and have the skills to be able to act quickly, thus
lowering the risk of harm to the patient. Not only must a policy be in place which allows the practitioner
to deal with the situation, but they must also be fully competent and confident in what to do.
When should it be used?
Over injection can be a potential risk when injecting HA fillers, leaving the patient with unsightly
lumpiness or looking ‘pillow-faced’, with large volumes of filler visible in the mid face.11Nodules can also
occur following HA anywhere on the face, and those that start within 48 hours of injection may be
inflammatory – however, those occurring sub-acutely (up to two weeks post-treatment) or late (after
two weeks) are more likely to involve infection.12 Large haematomas can also be treated with
hyaluronidase.6 The use of hyaluronidase can improve absorption via hypodermoclysis, the process of
interstitial infusion or subcutaneous infusion of fluids into the body.13 It is important to stress that if the
practitioner suspects infection then hyaluronidase shouldn’t be used14 and antibiotics should be
prescribed. However, another side effect that can be resolved with hyaluronidase is when the Tyndall
effect presents itself. This is when the HA is too superficially placed and creates a bluish discoloration of
the skin.8
Throughout the procedure the practitioner must observe for signs of blanching of the skin, a change in
appearance that may appear dusky or mottled.6 In this instance, the patient may complain of pain and
the area might begin to feel cool to touch. If these signs are ignored then the area may turn blue and
tissue necrosis can occur.8 Hyaluronidase should be administered as soon as this complication occurs,
and there is good evidence that tissue necrosis can be prevented or be less severe the sooner the
hyaluronidase is injected.8 Hyaluronidase must be used early, as its effectiveness in dissolving HA fillers
is reduced after approximately four hours.8 Whether the situation is an emergency or not, it is
imperative that the patient fully understands the implications of why it is being prescribed, how it will
be administered and a consent form should be signed. Patients must also be made aware of the
impending risks involved with the use of hyaluronidase and that it is being used off license.
 How to use hyaluronidase
A common preparation of hyaluronidase in the UK is made up of 1500 IU of hyaluronidase in a
powder for Solution for Injection / Infusion.14 This comes as a freeze-dried white powder in small
glass vials or ampoules. As a prescription only medication (POM), it should only be administered
following a face-to-face consultation with the prescriber. Below is my technique for preparing
hyaluronidase 1500IU:
1. Draw up 10ml of water for injection or 0.9%normalsalinein a syringe
2. Reconstitute the hyaluronidase 1500IU with 1ml of the 10ml of normal saline or water for injection
3. Rotate the vial to ensure the powder is fully dissolved
4. Draw up the 1ml of hyaluronidase back into the syringe with the remaining 9ml saline or water for
injection thus giving a concentration of 150IU/ml. Each 0.01ml will then be 1.5IU of hyaluronidase.
Once the solution is prepared, using a clean non-touch procedure, inject the hyaluronidase into the
affected area in small aliquots using a 30 gauge needle for superficial injections and 27 gauge for
deeper deposits. Administration should be extremely accurate and limited to the affected area. In the
case of nodules, they should be injected directly, and for product that has been injected into the
superficial dermis, injections should be placed immediately into and below the product.10 For vascular
compromise, serial puncture should be used to inject hyaluronidase along the course of the vessel.
The needle should be perpendicular to the skin and several injections are often necessary. During and
after the procedure, I recommend massaging the treated area quite vigorously to optimise the result
and aid mechanical breakdown.

What are the risks of administrating hyaluronidase?

One complication following the administration of hyaluronidase is allergic reactions,11 and, according to
clinical studies, occur at a frequency of approximately 0.05% to 0.69%.1 There appears to be conflicting
evidence as to whether a patch test of hyaluronidase should be carried out to rule out evidence of
allergic reaction, with several practitioners suggesting that when it is used for elective treatments a
patch test should be carried to minimise the risk.8 The patch test should be done intradermally (within
or between the skin) and I would advise the practitioner to look for signs of inflammation, erythma and
persistent itching. However, if the patient is showing signs of a vascular compromise then it could be
justifiable to use the hyaluronidase as soon as possible to lower the risk of further harm.
Another possible side effect of hyaluronidase is its potential to degrade the body’s natural hyaluronic
acid in preference to the foreign hyaluronic acid filler that has been injected.15 I would therefore
recommend treating the effect rather than absolute dosage, to go slow and to bring the patient back for
additional treatments. Following the use of hyaluronidase, I would suggest observing the patient for 30
minutes in a clinical environment and making sure they have appropriate aftercare information. Results
are often seen almost immediately, although I have found for denser, more cross-linked products it may
take 48 hours for the effects to be seen. A review appointment at two to three weeks should be booked
and further treatment offered at this point if needed.
Conclusion
Hyaluronidase plays an important role in the management of treating complications with HA dermal
fillers, however, it should not be a substitute for good technique. Practitioners who deem themselves
qualified to inject and treat patients with HA fillers must also be capable and confident to treat and
manage complications. Having some knowledge into the use hyaluronidase is not enough to keep and
patients safe, and so it is imperative that a policy is in place that all injectors can follow, justify and
administer hyaluronidase without delay in an emergency situation. The policy must provide a set of
guiding principles to help with decision-making. This doesn’t have to be complicated but understood by
all injectors and reviewed regularly. The need for patch testing doesn’t appear mandatory yet but is
often recommended, especially if the situation is not urgent.

https://aestheticsjournal.com/feature/hyaluronidase-protocol