Independent nurse prescriber Alex Henderson outlines techniques for a safe and effective outcome when opting for elective and emergency use of hyaluronidase
Hyaluronidases are endogenous enzymes (endoglycosidases) that can depolymerise hyaluronic acid (HA), leading to its degradation. These reduce viscosity of HA which improves tissue diffusion by hydrolysing the disaccharides at hexosaminidic b-1 through b-4 linkages.1,2,3 In the UK, hyaluronidase is licensed for enhancing permeation of subcutaneous and intramuscular injections ranging from local anaesthetics to infusions.3 The use of hyaluronidase has many factors that need to be considered when prescribing for the correction of dermal filler injections. Practitioners require sufficient understanding of the drug and its uses when applying it to aesthetic practice, for both elective and emergency situations.
Prior to treatment
Hyaluronidase (Hyalase) is available in 1500u of dry power in a glass vial. It is recommended by the Aesthetic Complications Expert (ACE) Group World that should be stored between 2-80C in the package container in which it is dispensed.4 However, if it is stored at room temperature (250C), the stability is only guaranteed for 12 months, and not the three years shelf-life as stated on the SmPC.4
The ACE Group World recommends the use of a test patch (except when the indication is for vascular compromise, as a delay could result in further harm to the patient).11 An intradermal injection of 15-20 units of hyaluronidase in the forearm is advised, observing the results after 20-30 minutes.11
In the event of elective reversal of HA-based dermal filler, guidelines combine studies of hyularonidase dosing relevant to HA dosing, and suggest the following algorithm for effective use of the drug in elective cases:4 Volume to inject (mls) = number of units required (units) X volume of diluent (mls) total number of units (1,500 units).4
Different brands of HA filler have differing physical properties that influence their degradation.3 Products which have a higher G-prime and more cross linking or HA concentration will require stronger doses, and HAs of the opposite rheology would require less. The Complications in Medical Aesthetics Collaborative (CMAC) suggests ‘treat to effect’ with concentrations no less than 1500u in 5ml.5
Ultrasound examination is a rapid technique for the detection of dermal filler and its position beneath the skin.6 With the correct training and experience, it can be an effective method because it provides the practitioner with a visual, while also reducing the likelihood of ‘guess work’ and unnecessary injury to the skin and tissue. In aesthetic practice, it is common for practitioners to have patients presenting with complications from another clinic or injector. In instances when records are not clear, or the patient’s previous clinician doesn’t provide medical records, techniques such as multilayering may be required to dilute dermal filler.7 For example, to correct the volume loss which affects the deep fat pads, a dermal filler with a high G-prime and HA concentrations is used deep on the periosteum which in turn requires deep placement of hyularonidase.8 For effective dissolution of HA product in this compartment, 3D anatomical knowledge is required as is knowledge in the reconstitution of hyularonidase, explained in the aforementioned ACE Group World guidelines algorithm.4
Some evidence suggests that mimetic muscles may displace or shift HA filler over time, in particular if products have been injected to modulate specific muscles for the improvement of their movement.9,10 To minimise trauma, a 25 gauge x 50mm cannula is recommended as a viable alternative to needles due to its association with fewer adverse effects.7 Gliding through soft tissue with ease, the cannula will achieve more precise placement and allow the practitioner to treat several different plains with minimal trauma.4
Impending necrosis is a possible complication of all injectable HA. According to ACE Group World, vascular compromise as a result of HA filler injection should be treated immediately.4
Onset of immediate pain with a vascular occlusion can be possible even with small bolus injections of 0.1ml, so management and knowledge of this is essential in the patient journey to recovery.11 Lidocaine 2% is recommended as an adjunctive pain relief with additional properties of vasodilation.5,4 Because hyaluronidase is a dispersing agent, lidocaine will also perfuse nearby tissue, increasing the likelihood of good pain management and the uptake of hyaluronidase into nearby vessels.
Both ACE Group World and CMAC guidance on emergency administration of hyaluronidase states that 1500u should be diluted in 1ml and infiltrated over the entire area including the course of the vessel.4,5
Multiple puncture technique refers to repeated injections at the site of compromise in emergency reversal. Serial punctures should be used to inject hyaluronidase along the course of the vessel, and the needle should be perpendicular to the skin.4 Whilst a cannula is recommended in elective use of hyularonidase, this device is blunt and therefore the likelihood of intra-arterial placement is highly unlikely.12 In this instance, I instead use a 31 gauge needle with the aim of reducing tissue trauma and pain where possible. The clinician should aim for soft tissue and intra-arterial placement with a needle. As mentioned, ultrasound can help to guide a practitioner to the location of any embolism or compression and so should be considered as a potential aid.6
When considering hyaluronidase injection, the practitioner should take a full medical history to understand any allergies and medications that the patient might be on. A history of allergy to wasp or bee stings can indicate a contraindication to hyaluronidase as the venom of any of the hymenopteran order may contain hyaluronidase.13 In this case it is important to establish the allergy type and whether or not the patient has a history of anaphylaxis as intradermal patch testing would then be considered a risk and not advised. Instead, the patient would require a confirmed diagnosis from a specialist allergy testing centre.14 If the patient is considering dermal filler and has such a history, the practitioner would have to balance the decision making of treatment based on risk vs benefit. Considering the potential side effects of dermal filler with possible delayed onset of complications, the clinician would not be able to safely reverse the HA filler, resulting in potential long-term issues for the patient.14
Hyaluronidase is also known to commonly react with benzodiazepines, phenytoin, dopamine and furosemide. Whilst these interactions are mildly significant, it’s always best to avoid if possible.7,4,15 The practitioner should also be aware of the antagonist effects of non-steroidal anti-inflammatory drugs, anti-histamines and mast cell stabilisers which include vitamin C.13 I would recommend discontinuing the use of any relevant medications for approximately 48-72 hours and taking into account the half-life of the medication.
If the corrective treatment is not related to the clinician’s practice, then they should obtain a clear and concise history of the patient’s treatment journey by contacting the original clinic/practitioner.6
Topilase is a new topical treatment to adjust skin irregularities associated with dermal filler injections. It is suggested to be an effective way of safely shaping and reducing undesirable outcomes associated with injection. Whilst Topilase does not have to be prescribed as it is a natural formula, the clinician should still obtain the skill and knowledge to enable a skin diagnosis and justify their decision in the patient’s best interest.16
Hyaluronidase is a diverse drug universally used in medicine as a dispersing agent. Its ability to permeate membranes, tissue and vessel walls makes for an effective reversal in emergency and elective presentations. Clinicians should treat safely by understanding the drug and how to effectively inject when reversing dermal filler.
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