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RESEARCH ARTICLE
Effect of Adding Lidocaine to Hyaluronic Acid Gel for Volume Loss Correction: A Preliminary Observation

  Patrick Micheels1*      Stéphanie Besse2      Badwi Elias3      Joan Vandeputte4   

1Private office, Chemin de la Fontaine, Chêne- Bougeries, Switzerland
2Med Image, RX Institut, Route de Florissant, Geneva, Switzerland
3Private office, Route de Florissant, Geneva, Switzerland
4Private office, Meerspoort, Oudenaerde, Belgium

*Corresponding author: Patrick Micheels, Private office: 8, Chemin de la Fontaine, 1224 Chêne- Bougeries, Switzerland, Tel: + 41 22 347 11 13; E-mail: patrickscab@bluewin.ch


Abstract

Introduction: Although adding a local anesthetic is an effective way to reduce pain during intradermal Hyaluronic Acid (HA) injections, it is not clear if the pain control is as effective when performing injections close to the bone. The primary aim of these preliminary observations was to explore this issue. As a secondary aim, we wanted to assess if the addition of lidocaine alters the behavior of HA gel in the tissues over time.

Subjects: Two women provided informed written consent to participate in the study. Participants were blind to the type of HA gel used for either temporal fossa.

Methods: A cross-linked HA gel was used for the study. One side was injected with the gel with and the other without lidocaine, in no particular order. Photographs from the front, profile and three-quarter left and right and frontal MRI scans were taken before and just after the injections, then every 6 months for 2 years.

Results: The side injected with the gel with lidocaine was significantly less painful than that injected without lidocaine. Both types of gel changed shape on MRI in the first 6 months but stayed stable thereafter till the end of our follow-up at 24 months. Based on MRI, patient reported outcomes and expert assessed aesthetic outcomes, using MAS® and the global aesthetic improvement scale, both types of gel were comparable.

Conclusion: The addition of lidocaine to HA volumiser gels reduces pain to a remarkable degree.

Keywords

Volumiser gel; Lidocaine; Volume loss; IPN-Like; MRI; Temporal; Pain; MRI; MAS; GAIS


Introduction

Ageing process involves loss of fatty tissue, muscle and bone MASs. With the exception of very thin people, a youthful face tends to have a generally convex appearance in women. As they age, the area around the temporal fossa begins to skeletonize. Apart from autologous fat, it is now feasible to use cross-linked hyaluronic acid gels as a filling agent to combat this loss in volume. Since its introduction, nearly 25 years ago, Hyaluronic Acid (HA) gels have become the most commonly used product for smoothing wrinkles [1,2]. Indeed, in the aesthetic industry, HA has become almost indispensable for correcting the loss of facial volume resulting from ageing.

The HA gels that we use come with or without lidocaine, an innovation initially introduced to the European market by Juvéderm® Ultra 3 gel, containing lidocaine, in December 2007, which was later approved by the FDA (Food And Drugs Administration) [3]. It has been clearly demonstrated that adding lidocaine to HA gels significantly reduce patients’ pain perception when their wrinkles are being filled, but without providing any real explanation of the ultrafast efficacy of this addition in the dermis [3,4]. This rapid effect was observed at the time when bovine collagen was being used. It is currently not known if the same pain reduction benefit would also be experienced in the context of age-related volume loss correction, when the gel is injected as a bolus, deep into the muscle close to the bone in the temporal fossa. This issue is particularly relevant because it is possible that the periosteum covering the temporal bone disappears almost completely during a person’s lifetime [5-8].

It is known from studies exploring HA tissue distribution when treating HIV- associated lipodystrophy that HA gel replacement of the lost fat has a lasting effect [9]. However, adding lidocaine can modify the rheological properties of a HA gel, and this in itself can, potentially, modify its persistence over time [10]. The main aim of our preliminary observations was to check whether adding lidocaine to HA volumiser gels reduces the amount of pain experienced when injected deep, intramuscularly, close to the bone. Furthermore, we wanted to assess if the addition of lidocaine had an impact on the behavior and persistence of the gel over time, compared to the same gel without lidocaine.

Methods
Participants

Two white Caucasian women agreed to participate in this observational study in our private aesthetic center. Both subjects were provided with written and oral explanation of the procedure and study and given a 15-day cooling-off period prior to consenting to participate. The study was conducted in full compliance with the Helsinki declaration. Participants also had full rights for their images and were fully aware that they would not be used for any purpose without their prior full consent. The volumiser product was used within the recommended manufacturer and licensing indications and contraindications.

Procedure

A 26 mg/ml cross-linked HA gel developed using IPN-Like technology (Vivacy, Archamps, France) was used for the study. Based on the manufacturer’s experiments, the gel is estimated to have cohesive properties ranging between 4.5 and 4.9 on the Sundaram J, et al. scale [11-13]. We used the following gels: Stylage® XL (without lidocaine). Batch: EXI18075F Exp.: 2020-08 and EXH18031F Exp 2020- 07 and Stylage® XL-Lido (with lidocaine). Batch: LXD16362F Exp.: 2019-05.

Not in any particular order, one side of the face was injected with the gel without lidocaine and the contralateral side with the gel with lidocaine. Participants were blind to the type of gel being injected. TSK 27G1/2 (0.4 × 13 mm) needles, included in the packaging provided with the gels, were used for the injections. The needle was inserted perpendicular to the skin surface, 1 cm from the temporal crest and 1 cm above the orbital rim until it touched the bone. The gel was then slowly injected as a bolus into the deep intramuscular area next to the bone in the antero-superior third of the temporal fossa [5-8]. If required, additional injections were given up to a maximum of 1.0 ml per side. The injected HA gel was then gently MASsaged by hand to spread them out uniformly.

MRI

These were performed using an Achievia scanner 1.5 Tesla (Philips SA Health Systems, Gland-Switzerland). Imaging was performed in the medical imaging institute MedImage, Geneva, Switzerland. The lasting effects of both gels were independently and objectively measured using time-lapse MRI over a 24-month period. Prior to any injection a frontal MRI scan was taken in order to evaluate the situation at baseline. A 2nd MRI scan was performed immediately after the injection and MASsage. MRI scans were then carried out at 6, 12, 18 and 24 months. These latter scans were used to assess the behavior of the gels, any spreading into the adjacent tissue over time and monitor gel resorption over the followup period. Evaluations were independently carried by a radiologist who was blind to the type of gel used in the side of the face being assessed. The MRI sequences used were 3DFLAIR, 3DT1, 3DT2. The residual volume was calculated using a tool integrated into the Philips IntelliSpace Portal 7.0 image post-processing software, which can display and measure volumetric data from the captured 2D images.

Photographs

Frontal, profile and three-quarter right and left photographs were taken before each treatment, immediately after, and then at 6 monthly intervals for 2 years. A digital camera was used for the baseline and follow-up photographs (Nikon® DX, lens AF-S DX Nikkor, ED 18-55mm 1: 3.5-5.6 GII).

Patient reported and clinical outcomes

Participants were asked to evaluate the intensity of their pain perception during injection (T0) then immediately after (T1), 5 minutes after injection (T2), 30 minutes after injection (T3) and at home (T4) using a 0 -10 Visual Analog Scale (VAS) where 0=no pain and 10=unbearable pain.

Aided by the digital photographs, participants’ perception of the quality of the aesthetic result were assessed by means of the MAS© visual scale, Merz-Pharma [14] (Figure 1) and the Global Aesthetic Improvement Scale (GAIS), which were self- completed immediately after treatment and at 6, 12, 18 and 24 months post procedure. GAIS is a 5 point scale ranging from 0 - 4 and corresponds to deterioration, no change, visible improvement but requires a 2nd treatment, clear improvement but not optimal and optimum treatment. Additionally, the treating physician and three independent experts used these photographic images to assess aesthetic outcomes at the same time points. The independent experts were blind to the type of gel used in the side of the face being assessed. Similar to participants, the GAIS and MAS© scales were used for the assessments.

Figure 1: Visual analogue assessment for ageing of the temple according to the MAS© Merz- Pharma scale (COURTESY MERZ® Pharma).

Results

The 2 participants were 71 and 58 year old and their skin types were III, III and II, III according to Fitzpatrick’s classification [15] and Glogau scale [16] respectively. The injection side and the participants’ rated VAS pain score for each injection site at the different pre-set time points are presented in table 1 for both participants.

Right Temple Left Temple
Participant 1 Gel Type (Volume) Stylage®XL, (1.0 ml) Stylage®XL-Lido (1.0 ml)
Pain Scores T0 6/10 1/10
T1 5/10 0/10
T2 2/10 0/10
T3 1/10 0/10
T4 0/10 0/10
Participant 2 Gel Type (Volume) Stylage®XL-Lido (0.55 ml) Stylage®XL(0.50 ml)
Pain Scores T0 1/10 6/10
T1 0/10 5/10
T2 0/10 <3/10
T3 0/10 2/10
T4 0/10 0/10

Table 1: Pain scores for different gel types at different time points.
T0: During injection; T1: Immediately after injection; T2: 5 minutes after injection; T3: 30 minutes after injection; T4: At home.

Based on the serial MRI images there was a difference between the two types of gels (XL and XL-Lido) with regards to their levels of resorption overtime (Figure 2). The MRI characterization of gel behavior and volume at different time-points is presented in table 1 and 2.

Figure 2: Serial MRI images for both participants.

Right Temple Left Temple
Participant 1 Stylage®XL, withoutlidocaine(1.0 ml) Stylage®XL-Lido (1.0 ml)
AT Gel in the form of a papule with a linear appearance, a dense uniform structure and convex edges located mainly under the aponeurosis, not touching the  bone, (770 mm3). Gel infiltrated underneath the aponeurosis, not touching the bone, no papule  but with a dense uniform structure and concave edges (1,129 mm3)
M6 Gel extended antero-posteriorly, flattening out and infiltrating caudally (1,950  mm3). Gel became narrower and extended caudally (1,226 mm3).
M12 The gel had a stable appearance (1,571 mm3). The gel had a stable appearance (1,458 mm3).
M18 Appearance similar to that observed at 6 and 12 months (2,160 mm3). Gel infiltrated significantly distally in a fan-shaped manner (1,495 mm3).
M24 The shape of the gel remained stable (1,577 mm3). The gel almost completely infiltrated distally, still in a fan-shaped manner  (1,458 mm3).
Participant 2 Stylage®XL-Lido withLidocaine(0.55 ml) Stylage®XL withoutLidocaine(0.50 ml)
AT Gel in the form of a papule with smooth convex edges and uniform structure located very deep in pre- and particularly post-aponeurotic spaces and caudally in the intra-muscular region infiltrating the muscle fibers (1,929 mm3). Gel was cigar-shape with a uniform structure and smooth convex edges  located deep in pre- and post-aponeurotic spaces, but less deeply than on the  right, extending in a fan-shaped manner distally infiltrating the muscle fibers to  a significant extent (2,096 mm3).
M6 Gel still had convex edges and uniform structure extending caudally with an  equal spread in pre- and post-aponeurotic spaces infiltrating the muscle fibers. It extended along the tendons and fibers, which connect the coronoid apophysis (2,936 mm3). Gel still located deeply but moved further in the post- than pre- aponeurotic space. It lost its convex appearance and appeared less uniform in structure  (3,314 mm3).
M12 The gel had a stable appearance (3,221 mm3). The gel had a stable appearance (3,868 mm3).
M18 The gel had a stable appearance (3,647 mm3). The gel had a stable appearance (4,369 mm3).
M24 The gel had a stable appearance and shape but linear edges (4,266 mm3). The gel had a stable appearance (3,953 mm3).

Table 2: MRI characterization of gel behavior and estimated volume at different time points.
AT: After treatment; M6, M12, M18 and M24: 6, 12, 18 and 24-month follow-up time points.

With regards to aesthetic outcomes, participant 1 reported a 2 point improvement on the MAS® scale compared to baseline for both the right and left sides immediately following treatment. This improvement persisted until the 12 months assessment. At 18 months, she considered that there was some deterioration, which was more on the Stylage® XL-Lido side, with 2-points worsening on the MAS® scale compared to 1 point on the right-hand side. Nevertheless, on her self-evaluation using GAIS she rated the left side as 3 (Clear improvement, but not optimal, perhaps a “touch-up” at 3 months) and the right side as 2 (Visible improvement, but requiring a 2nd treatment). However, at 24 months she perceived that there was a significant improvement again, with a 2-point improvement on MAS®, compared to her score at 18 months, for both sides and a score of 3 on GAIS for both sides (Table 3 and Figure 3).

Figure 3: Participant 1: Photographs before treatment (BT) and at 12 months follow-up (M12).

    Right temple Left Temple
Participant 1 Gel Stylage®XL, (1.0 ml) Stylage®XL-Lido (1.0 ml)
Assessor Participant’sscore Average expert’ score Participant’srating Average expert’ rating
Scale MAS ΔMAS GAIS MAS ΔMAS GAIS MAS ΔMAS GAIS MAS ΔMAS GAIS
MAS BT 4 - - 3.75 - - 3 - - 3.75 - -
AT 2 2 3 1.75 1.75 3 1 2 3 2 1.75 3
M6 2 2 3 2 1.5 2.75 1 2 4 2 1.75 2.5
M12 2 2 3 2 1.5 2.5 1 2 2 2.25 1.5 2.5
M18 3 1 2 2.25 1.25 2.5 3 0 3 2 1.75 2.5
M24 1 3 3 2.5 1.0 2 1 2 3 1.4 2.35 2.5
Participant 2 Gel Stylage®XL-Lido (0.55 ml) Stylage®XL(0.50 ml)
Assessor Participant’sscore Average expert’ score Participant’srating Average expert’ rating
Scale MAS
score
ΔMAS GAIS MAS
score
ΔMAS GAIS MAS
score
ΔMAS GAIS MAS
score
ΔMAS GAIS
MAS BT 2 - - 1.75 -   2 - - 1.25 -  
AT 1 1 4 0.75 1 2.75
1
1 1 4 0.75 0.5 2.75
  M6 0 2 4 1 0.75 2.75 0 2 4 1 0.25 2.5
M12 0 2 4 0.75 1 2.5 0 2 4 0.75 0.5 2.5
M18 0 2 4 0.75 1 2.75 0 2 4 0.75 0.5 2.5
M24 1 1 4 1.25 0.5 2 1 1 4 1.25 0 2.25

Table 3: MAS© and GAIS scores as evaluated by participants and experts at the different time point.
ΔMAS: Points of improvement compared to before treatment; BT: Before treatment; AT: After treatment; M6, M12, M18 and M24: 6, 12, 18 and 24 month follow-up time points.

Participant 2 reported a 1-point improvement on the MAS® scale for each side immediately after treatment. At the 6, 12 and 18 months follow-up she considered the improvement to be better where she scored a 2-point improvement compared to baseline. By 24 months the participant still considered there was an improvement in her volume loss but rated this as a 1-point improvement on the MAS® scale in comparison to before treatment. Nevertheless, she rated her aesthetic improvement as perfect on GAIS throughout (Table 3 and Figure 4).

Figure 4: Participant 2: Photographs before treatment (BT) and at follow-up.

Using the same scales and time points, individual and average experts’ assessments of photographic images for both participants are presented in table 4.

Expert BT AT M6 M12 M18 M24
Participant 1 R L R XL L
XL-Lido
R XL L
XL-Lido
R XL L
XL-Lido
R XL L
XL-Lido
R XL L
XL-Lido
MAS® 1 4 4 2 3 3 2 2 3 2 2 3 2
2 3 4 2 2 2 2 3 2 3 2 2 1
3 2 3 0 1 0 2 0 2 0 2 1 2
4* 4 4 3 2 3 2 3 2 4 2 4 2
Participant 2 GAIS
1 3 3 3 2 3 3 3 3 2 2
2 2 2 2 2 1 1 1 1 1 2
3 4 3 4 2 4 2 4 2 3 2
4* 3 4 2 4 2 4 2 4 2 4
Participant 1 R L R
XL-Lido
L XL R
XL-Lido
L XL R
XL-Lido
L XL R
XL-Lido
L XL R
XL-Lido
L XL
MAS® 1 2 2 1 1 1 1 1 2 0 1 1 1
2 1 1 1 1 1 1 0 0 1 1 1 2
3 2 2 1 1 1 1 1 1 1 1 2 2
4* 2 0 0 0 0 1 1 0 1 0 1 2
Participant 2 GAIS
1 4 4 4 3 3 3 4 3 3 3
2 1 1 1 1 1 1 1 1 1 1
3 2 2 2 2 2 2 2 2 1 1
4* 4 4 4 4 4 4 4 4 3 4

Table 4: Evaluation of the efficacy of "IPN-Like" HA gel Stylage® XL and XL-Lido injections in the temporal fossa according to the MAS® and GAIS scale by experts.
*Physician who performed the injections. XL: Stylage® XL without lidocaine; XL-Lido: Stylage® XL with lidocaine; R: Right; L: Left; BT: Before treatment; AT: After treatment; M6, M12, M18 and M24: 6, 12, 18 and 24 month follow-up time points.

Discussion

We observed that adding lidocaine to a cross-linked HA gel developed using IPN-Like technology and intended for correcting facial skeletonization reduced the pain experienced by patients at the time of injection despite its depth. Indeed, both participants felt almost no sensation during the Stylage® XL-Lido compared to XL injections (1/10 on the VAS scale, compared to 6/10 at T0). Furthermore, both participants reported no pain by 5 minutes in the XL-Lido injection sides.

During the follow-up we demonstrated that the aesthetic results of Stylage® XL and Stylage® XL-Lido gels for the correcting age-related volume loss were comparable. For participant 1 and based on the MAS® scores from the participant’s and experts’ evaluations over 24 months there was a change in score “from very severe” to “moderate” and from “severe” to “low” loss of volume after the use of Stylage® XL and XL-Lido respectively. All evaluators observed slow resorption by comparing the visual appearance in the photographic records, but this resorption was less marked for the XL- Lido gel after 24 months. Nevertheless, it is important to take into account the slight difference in the MAS® score at baseline for both sides. For participant 2, there was an improvement in the MAS® score at 24 months compared to baseline based on the participant’s assessment. Nonetheless, the improvement based on experts’ average score was only achieved for Stylage® XL-Lido. These improvements were also demonstrated on the participants’ and experts’ GAIS scores in both women. However, these were slightly better in the Stylage® XL-Lido side for participant 1 only.

Adding lidocaine to gels during manufacture can affect the rheological characteristics ofthe gel [10]. These variations can possibly lead to a difference in the stability of the gel over time when compared to the same gel without lidocaine [4]. In our study, both gels appeared stable over time. Although there was a perceived reduction in volume between 12 and 18 months, there was no apparent difference between the gels at 24 months, except perhaps in the participant with the most skeletonization (participant 1). Similarly, on MRI, the gels appearance, both for XL and XL-Lido, did not change between the 6 and the 24-month follow-up periods. Hence, it is plausible that, just as for the Non-Animal Stabilised Hyaluronic Acid (NASHA) technology, the resorption of the gel occurs iso-volumetrically. It is suggested that shear forces could have caused the change in gel shape over the first 6 months. However, it is important to stress that although we have undertaken multiple objective and validated subjective measures, these observations involve only 2 participants and such information should be interpreted with caution till further evidence is available.

Conclusion

Adding lidocaine to hyaluronic acid gels, especially when intended for correcting volume loss with deep intramuscular injections close to the bone, is an advantage based on patient reported level of pain perception. There were some variations in the reported scores by patients and experts on the MAS® and GAIS scales at different time-points. However, both types of HA preparations seemed to behave fairly similarly and achieved comparable results. Nevertheless, we observed an advantage with Stylage® XL-Lido in that it was more stable over time on the GAIS scale. It would be prudent to confirm our observations in larger studies involving more patients, multiple centers and longer follow-up duration before drawing final conclusions.

Acknowledgement

The authors would like to sincerely thank the two study participants for their involvement. We also want to thank Dr O Jordan, MD-PhD, for his expert observation about the shear forces. Dr D Sarazin, Institut Viollier, Geneva (Switzerland), for their help with researching the anatomy of the periosteum in the temporal fossa, Mrs Maria Ferros, secretary to P Micheels, for her valuable work, laboratoire VivacyArchamps, France for supplying the HA gels used for this study and The radiology institute MedImage, Geneva, Switzerland, for allowing us to use their equipment. We would also like to acknowledge Superviseme LTD-medical writing services-(http://www.superviseme.eu) for their support with the medical writing and editing of the manuscript, which was funded by LABORATOIRES VIVACY.

Declarations of Interest

The syringes were supplied by the Laboratoire Vivacy, Archamps, France. Dr S Besse was remunerated for the radiology work she performed. The other authors declared no conflict of interest, having received no financial compensation in return for the work carried out. Dr P Micheels is a consultant and/or trainer for Allergan, IBSA, Galderma Q-Med Switzerland, KioMed, Kylane, Merz, Sinclair, Teoxane and Vivacy. Dr J Vandeputte is a consultant and trainer for Merz and Advanced Aesthetic Technologies.


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Article Information

Aritcle Type: RESEARCH ARTICLE

Citation: Micheels P, Besse S, Elias B, Vandeputte J (2022) Effect of Adding Lidocaine to Hyaluronic Acid Gel for Volume Loss Correction: A Preliminary Observation. J Clin Cosmet Dermatol 6(2): dx.doi.org/10.16966/2576-2826.173

Copyright: © 2022 Micheels P, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication history: 

  • Received date: 26 Apr, 2022

  • Accepted date: 20 May, 2022

  • Published date: 27 May, 2022

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