EXPERIMENTAL

Hyaluronic Acid Embolism Treated with

Subcutaneous High and Low Hyaluronidase
Doses: Efficacy and Surrounding Tissue Effect

Yolanda Salinas-Alvarez, M.D., Background: The use of hyaluronidase in hyaluronic acid vascular occlusion
M.Sc. has been evaluated; however, the models used do not accurately assimilate the
Esperanza C. Welsh, M.D. facial morphologic characteristics or study the effects on adjacent tissues. The
Adolfo Soto-Dominguez, purpose of this study was to determine an effective concentration of subcuta-
B.C.E., D.Sc. neous hyaluronidase to dissolve a hyaluronic acid embolism and its effect on
Alejandro Quiroga-Garza, surrounding tissue.
M.D., M.Surg., Ph.D. Methods: Fifteen rabbits were divided into six groups. An inguinal incision was
Yenitzeh A. K. Hernandez-Garate performed on the femoral artery to create a hyaluronic acid embolism in the
Oscar De-La-Garza-Castro, control and treatment groups (low-, medium-, and high-hyaluronidase groups).
M.D., Ph.D. Hyaluronidase was injected subcutaneously. Photographic follow-up, histologic
Rodrigo E. Elizondo-Omaña, analysis, and quantification of hyaluronic acid were performed. Kruskal-Wallis
M.D., Ph.D., D.Sc. test and post hoc with Bonferroni correction (p < 0.05) was used to compare
the presence of hyaluronic acid in the arterial lumen between groups.
Santos Guzman-Lopez, M.D.,
Results: Despite the persistence of intravascular hyaluronic acid, macroscopic
Ph.D.
and microscopic differences were found between the embolism control group
Monterrey, Nuevo León, México and embolism hyaluronidase high-dose group. Histologic analysis demonstrated
thrombosis throughout groups. Skeletal muscle was least affected in the embo-
lism hyaluronidase 500 IU group with less lysis and inflammatory infiltrate.
Conclusions: A 500 IU hyaluronidase dose partially prevents the damage caused
by the embolism, and does not affect the surrounding tissue. The use of throm-
bolytic therapy combined with higher doses of hyaluronidase subcutaneously in
this model is proposed.  (Plast. Reconstr. Surg. 148: 1281, 2021.)

T
he application of hyaluronic acid fillers is Subcutaneous hyaluronidase has been
the second most frequent noninvasive aes- described as an emergency treatment in an attempt
thetic procedure.1 It is a simple, outpatient to dissolve the embolism.7,13–16 Several animal mod-
procedure with a low incidence of complications; els have been used to evaluate this, most recently
however, one of the most striking is intravascular a hyaluronic acid injection-induced embolism
embolism. It may be caused by direct intraarterial model in rabbit ear established by Zhuang et al.17
injection, retrograde flow, or extrinsic vascular to assimilate skin necrosis. Although an effective
compression, and cause serious adverse effects.2–6 model, it does not morphologically assimilate the
Several authors have proposed different tech-
niques to avoid this6–11; nonetheless, even with a Disclosure: The authors have no financial interests
broad knowledge of facial anatomy,12 it is a serious and no conflicts of interest to declare. The study was
and unavoidable risk. not supported by any funding source.

From the Human Anatomy and Histology Departments, Related digital media are available in the full-text
Universidad Autonoma de Nuevo Leon, School of Medicine; and version of the article on www.PRSJournal.com.
Department of Dermatology, Universidad Autonoma de Nuevo
Leon, University Hospital.
Received for publication December 16, 2019; accepted June
3, 2021. A “Hot Topic Video” by Editor-in-Chief Rod J.
Poster presented at Experimental Biology 2019, in Orlando, Rohrich, M.D., accompanies this article. Go to
Florida, April 6 through 9, 2019. PRSJournal.com and click on “Plastic Surgery
Copyright © 2021 by the American Society of Plastic Surgeons Hot Topics” in the “Digital Media” tab to watch.
DOI: 10.1097/PRS.0000000000008523

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 Plastic and Reconstructive Surgery • December 2021

facial region (most frequent site for hyaluronic and 0.5 ml of hyaluronic acid (Belotero Balance,
acid fillers) of a person, because of the lack of sub- Merz Pharmaceuticals, Frankfurt, Germany) was
cutaneous fat tissue and muscle, the presence of injected. Embolus formation was verified by direct
cartilage, and thinner skin. observation. Hemostasis was obtained by direct
The face consists of several layers of tissue, pressure for 30 to 60 seconds, as needed, and veri-
depending on the location: skin, superficial adi- fied before closure.
pose tissue, superficial musculoaponeurotic All animals were treated with ketopro-
system, facial muscles, deep adipose tissue, peri- fen (2  mg/kg subcutaneously every 24 hours),
osteum, and bone.18–20 The rabbits’ ear has thin Tramadol (0.5 mg/ml orally through water intake)
skin and lacks adipose tissue and muscle. It can- for pain-control, and ampicillin (10 to 20 mg/kg
not fully represent the effects of subcutaneous every 12 hours for 5 days) to prevent surgical-site
hyaluronidase administration, or the effects on infection. Animals were supervised and evaluated
surrounding tissues, as it would on a human face. periodically for signs of suffering as elimination
Other authors, such as Baley-Spindel et al., used criteria and indication for euthanasia.
a murine femoral artery embolism model, but
the size proved challenging.21 Unpublished work Control and Treatment Groups
by the authors found similar results using Wistar Fifteen New Zealand rabbits weighing approx-
rats, primarily when administering the hyaluronic imately 3 kg each were randomly assigned into five
acid embolism. However, Chen et al. and Chiang groups: embolism control, embolism hyaluroni-
et al. prove a murine model to be useful, although dase-75 (low dose of 75 IU), embolism hyaluroni-
using an epigastric artery flap.11,22 A model with dase-200 (medium dose of 200 IU), embolism
more morphologic similarity is therefore needed. hyaluronidase-500 (high dose of 500 IU), and sur-
Different subcutaneous doses of hyaluroni- gical control. The contralateral limb (right) of the
dase have been tested to evaluate their effect on surgical control group was designed as the healthy
hyaluronic acid embolism10,21–24; however, few have control group.
been compared to each other in the same model. Embolism hyaluronidase groups were admin-
Studies that include an assessment of the effects istered with their corresponding subcutaneous
of hyaluronidase on the dermis (tissue with a high single dose (75,27 200,28 and 5006 IU) of hyal-
concentration of hyaluronic acid) are also lack- uronidase (x.prof 150 reductonidase; Mesoestetic
ing.25,26 This study tries to evaluate and compare E-Commerce SL, Barcelona, Spain) between
three different single doses (low, medium, and 30 and 60 minutes after the embolism, using a
high) of subcutaneous hyaluronidase in a lower 27-gauge hypodermic needle, injecting distal
extremity intraarterial hyaluronic acid embolism to the incision, along the course of the femoral
rabbit model that would assimilate the morphol- artery; saline solution 0.9% (0.5 ml) was injected
ogy of a person’s face (facial artery) and its effect in the surgical control group. Hyaluronidase at
on surrounding tissue. 75, 200, and 500 IU was also administered as a sub-
cutaneous single dose in the embolism hyaluron-
idase-treated groups in the contralateral limb to
MATERIALS AND METHODS evaluate the effect of hyaluronidase on the skin
The study was previously reviewed and without the embolism; the skin samples from the
approved by institutional review board includ- control groups (embolism, healthy, and surgical)
ing the Institutional Committee for the Care and were obtained from the same limb. The animals
Use of Laboratory Animals of the Universidad were killed on the fifth day (intravenous pento-
Autónoma de Nuevo León, Medical School; con- barbital using a lethal dose of 100 to 150 mg/kg in
forming to the Declaration of Helsinki and the the marginal vein of the rabbit’s ear).
Guide for the Care and Use of Laboratory Animals
(approval number AH17-00014). Evaluation and Statistical Analysis
Photographic tracking was performed every
Rabbit Embolism Model 24 hours until the fourth day after the procedure.
Rabbits were anesthetized with ketamine Perfusion, change in skin color, and mobility of
(25 mg/kg) and xylazine (3.5 mg/kg). The lower the limb were evaluated. Samples of the femoral
abdominal region and lower extremities were region were obtained (skin, subcutaneous tissue,
shaved. An inguinal incision was made dissecting neurovascular bundle, and muscle), and fixed
the left femoral neurovascular bundle, channel- for 24 hours in buffered 10% formalin solution
ing the femoral artery with a 24-gauge catheter, (pH 7.2). At 24 hours, the samples were placed

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 Volume 148, Number 6 • Treatment of Hyaluronic Acid Embolism

in inclusion cassettes and submerged again for 24 Hyaluronic acid was present in the arterial
hours more. These were processed by conventional lumen in all embolism hyaluronidase-treated
histologic techniques until their inclusion in paraf- groups; however, a decrease was observed in the
fin. Histologic sections of 5 μm were obtained and high-dose group (Fig. 1). All embolism hyaluroni-
stained with hematoxylin and eosin, Masson tri- dase-treated groups also preserved their thickness
chrome, and orcein, for the skin, vessels, and skel- and normal morphology of the tunics, except
etal muscle tissue analysis; and by a histochemical for hemorrhage in the tunica media between
method of Alcian blue (pH 1), for the identifica- the smooth muscle fibers in the low-dose group
tion of hyaluronic acid. Photomicrographs were (Fig. 1).
taken and blue color of histochemistry with Alcian The surrounding skeletal muscle presented
blue was quantified using Integrated Density with widely separated muscle fibers, lysis, and abun-
ImageJ Software (version 1.51; National Institutes dant inflammatory infiltrate in the embolism con-
of Health, Bethesda, Md.). The ImageJ results were trol group, and progressively less so as the dose
analyzed using IBM SPSS Version 25.0 (IBM Corp., increased in the embolism hyaluronidase-treated
Armonk, N.Y.) with Kruskal-Wallis test and post groups. The high-dose group preserved their
hoc with Bonferroni correction (p < 0.05) to com- muscle fibers’ polygonal morphology (Fig. 2).
pare the presence of hyaluronic acid in the arterial When evaluating the skin of contralateral
lumen between groups. limbs (right) at different hyaluronidase doses
without embolism, and comparing it to the embo-
RESULTS lism, surgical, and healthy control group limb
(left) skin, the epidermis had an increased thick-
Macroscopic Analysis ness in the embolism control group, with abun-
The macroscopic analysis was subjectively eval- dant inflammatory infiltrate in the papillary and
uated by topographic characteristics. [See Figure, reticular dermis, and an increase in the sebaceous
Supplemental Digital Content 1, which shows gland size. The surgical and healthy control and
topographic characteristics of rabbit lower limb. hyaluronidase groups preserved normal skin mor-
Photographic representation of macroscopic phology, adequate organization of the collagen
findings in each experimental group. (Above, left) fibers, and absence of inflammatory infiltrate
Healthy control group. (Above, center) Surgical (Fig. 2).
control group. (Above, right) Embolism control
group. (Below, left) Embolism hyaluronidase-75 Statistical Analysis of Hyaluronic Acid
group (low dose). (Below, center) Embolism hyal- Quantification
uronidase-200 (medium dose). (Below, right) Mean values with standard deviations were
Embolism hyaluronidase-500 (high dose), http:// measured (Table 1). No statistically significant dif-
links.lww.com/PRS/E692.] Hematomas, ecchymo- ference was found in the amount of hyaluronic
sis, and muscular atrophy were observed, primar- acid between the embolism control group with
ily in the embolism control group and in a lower embolism hyaluronidase–treated groups. A statis-
manner in the embolism hyaluronidase low- and tically significant difference was found between
medium-dose groups. The healthy and surgical embolism control and healthy control groups
control groups did not present any of these. Poor (p = 0.043) (Fig. 3).
scarring was most evident in the embolism control
group, with dehiscence of the surgical wound. All
the embolism hyaluronidase-treated groups pre- DISCUSSION
sented adequate wound healing. Even though occlusion caused by an arterial
hyaluronic acid embolism is a rare complication
Microscopic Analysis during hyaluronic acid facial filler application,
Microscopic analysis revealed uneven distri- it is a catastrophic adverse event that can cause
bution of hyaluronic acid throughout the artery blindness or permanent scars in patients if not
with thinning of the tunics, and intraluminal vein treated. In this study, we demonstrate that a high-
obstruction in the embolism control group. Other dose (500 IU) treatment of hyaluronidase was not
segments of the artery presented thrombosis and enough to fully cause degradation of the hyal-
loss of tunics, specially internal tunica endothe- uronic acid embolus, although some changes were
lium and internal elastic lamina, with inflamma- observed in muscle and skin after its application
tory infiltration of macrophages, eosinophils, in this model. Important finding in this study and
neutrophils, and lymphocytes (Fig. 1). the presence of thrombosis (which must also be

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 Plastic and Reconstructive Surgery • December 2021

Fig. 1. Arterial histologic analysis. Microscopic evaluation of transverse section of femoral artery. Control, healthy control group;
Surg, surgical control group; Emb-Tromb, embolism control group with thrombus at arterial lumen; Emb-HA, embolism with hyal-
uronic acid embolus at lumen; Hyal 75, embolism hyaluronidase-75 group (low dose); Hyal 200, embolism hyaluronidase-200
group (medium dose); Hyal 500, embolism hyaluronidase-500 group (high dose); H&E, hematoxylin and eosin stain; AB, Alcian
blue histochemistry; Or, orcein stain; MTr, Masson trichrome stain.

a target in the treatment of this vascular adverse response, and morphologic changes to the skin
event) and the damage that the emboli causes to and surrounding tissues. Hyaluronidase at a low
the arterial tunica. dose of 75 IU was not effective in preventing most
Our study is limited by the number of samples of these. Although the 200- and 500-IU doses did
and the variability in results, the lack of previous not demonstrate a statistical difference in the
in vitro studies, and a subjective interpretation of presence of hyaluronic acid embolism, there was
macroscopic outcomes. However, it is strength- improved preservation of surrounding tissue,
ened by the evaluation of different hyaluronidase without alterations of the dermis and epidermis,
doses that were previously proposed as treatments, and significantly less macroscopic damage, evi-
but in an embolism model that better simulates dencing a clinical benefit.
the facial layers. Compared with other hyaluronic In the embolism model, an irregular distri-
acid embolism models, the results demonstrate bution of hyaluronic acid was observed in the
that a 500-IU dose is safe for the surrounding artery, observing areas without intraluminal hyal-
tissues. uronic acid, similar to that observed by Zhuang
The rabbit hyaluronic acid embolism model et al.17 This may be attributable to the use of a
was effective for testing different doses of hyal- live animal model, adding the blood flow factor,
uronidase; their effect on the embolism, arteries, which causes the fragmentation of hyaluronic
and surrounding tissue; and their dispersion to acid along its path. In addition, we also observed
distal regions. Untreated hyaluronic acid embo- intraluminal hyaluronic acid in the femoral vein,
lism caused necrosis, important inflammatory supporting Zhuang et al.’s hypothesis of the

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 Volume 148, Number 6 • Treatment of Hyaluronic Acid Embolism

Fig. 2. Skeletal muscle fibers and skin layers. Control, healthy control group; Surg, surgical control group; Emb, embolism control
group; Hyal 75, embolism hyaluronidase-75 group (low dose); Hyal 200, embolism hyaluronidase-200 group (medium dose); Hyal
500, embolism hyaluronidase-500 group (high dose). Skin hyaluronidase treatments only represent a single dose without the pres-
ence of embolism. H&E, hematoxylin and eosin stain; MTr, Masson trichrome stain.

migration of hyaluronic acid through the capil- observed in our study, and could be attributed to
laries. Thrombosis was also visualized microscopi- the arterial distention caused by the embolism.
cally with the embolism and treatment groups, Endothelium breakup of tunica intima was
similar to Chiang et al.11 This may be a result of the not observed, nor was the separation of the tunica
turbulence or stasis caused by the hyaluronic acid intima and media in the embolism hyaluroni-
generating endothelial damage, triggering plate- dase high-dose group, unlike that reported by
let aggregation, the formation of a fibrin mesh, Wattanakrai et al.,29 who applied hyaluronidase
and leukocyte adhesion. Therefore, the morpho- intraarterially. Subcutaneous application in this
logic damage is caused not only by total or partial study may be why it was avoided, besides being
obstruction, but also by the acute thrombotic phe- an in vivo model, influenced by blood flow, and
nomenon it causes. different dispersion of the enzyme, among other
Zhuang et al.17 reported thinning of the arte- variables that assimilate a clinical scenario.
rial wall and tunics in sites with abundant intralu- No statistically significant difference was
minal hyaluronic acid, with a breakdown of the observed in the quantification of intraluminal
endothelium and loss of normal fenestration of hyaluronic acid when comparing the embolism
internal and external elastic laminae. This was also control and embolism hyaluronidase-treated
groups, regardless of clinical and microscopic
evidence of improvement. The sample size is a
Table 1.  Mean Values ± SD of Hyaluronic Acid limitation of the statistical analysis of the results
Quantification by Group that could explain this difference; however, a high
Group Integrated Density Value dose of hyaluronidase should provide a benefit
Healthy control 32.8 ± 4.8 against the embolism.
Surgical control 3.4 ± 1.0 None of the subcutaneous hyaluronidase
Embolism control 75.4 ±5.4 doses were enough to fully cause degradation of
Embolism Hyal-75 66.0 ±7.1
Embolism Hyal-200 45.8 ±12.4 the hyaluronic acid embolus; however, the embo-
Embolism Hyal-500 43.7 ±3.4 lism hyaluronidase high-dose group avoided the
Hyal, hyaluronidase. greatest effect on skeletal muscle fibers and had
*Values are the result of the mean integrated density (× 106) which
is the sum of the values of the pixels in the image selection. Results
the least inflammatory infiltrate. This could be
are expressed in pixels. attributed to the partial reduction of the embolus

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 Plastic and Reconstructive Surgery • December 2021

Fig. 3. Statistical groups comparison of hyaluronic acid quantification. Quantification was objectively
obtained by the mean integrated density for hyaluronic acid, using ImageJ software. *A value of p < 0.05
for statistical difference between groups was obtained using SPSS software with Kruskal-Wallis test and
post hoc with Bonferroni correction.

in the smaller collateral arteries that give irriga- rabbit ear embolism model treated with 750 IU of
tion to the muscle. hyaluronidase subcutaneously.23 This is similar to
Skin evaluation demonstrated inflammatory what was observed by Loh et al. and Chauhan and
infiltrate in the papillary and reticular dermis Singh, using the “DeLorenzi high-dose pulsed
and thickened epidermis in the embolism control hyaluronidase” technique,31,32 or Wibowo et al.
group, similar to that reported by Maruyama.30 who, based on their case report, concluded that
However, we did not observe differences between a high dose of hyaluronidase could help in man-
the healthy control and surgical control groups aging postfiller vision loss and impending skin
compared with the hyaluronidase. This proves necrosis.33
that a high dose of 500 IU does not affect the der- Our microscopic analysis demonstrated intra-
mis or epidermis. luminal thrombosis, similar to that reported
Further animal experimental studies are by Chen et al.22 This leads us to hypothesize an
necessary to evaluate higher doses of subcutane- improved outcome with the application of high
ous hyaluronidase. Although Baley et al., Chen doses of hyaluronidase subcutaneously and
et al., and Chiang et al. established a functional according to the findings of Lee et al. that a
hyaluronic acid rat embolism model,7,21,22 unpub- higher dose should be distributed at several appli-
lished work performed by our group resulted in cations.34 The effect may also be improved when
methodologic difficulties because of the artery combined with thrombolytic therapy, as Chiang
size (<1  mm), which was easily perforated by an et al.11 reported a better flap survival rate when
expert microvascular surgeon during canaliza- applying intravenous hyaluronidase with uroki-
tion, or bursted during intraarterial injection nase in a hyaluronic acid embolism rat model, or
because of the high viscosity of hyaluronic acid what was observed with patients in the study by
and lack of injection-pressure control. Because of Zhang et al.35 However, further studies are needed
mixed results, a femoral artery rabbit embolism to confirm efficacy.
model was designed. Our macroscopic and microscopic results
The most satisfactory macroscopic recov- demonstrate that a low dose is ineffective in treat-
ery was observed in the embolism hyaluroni- ing hyaluronic acid embolisms, and should not be
dase-500 (high-dose) group, a dose proposed by considered for treatment in a clinical scenario or
DeLorenzi6 according to his clinical experience. animal models, different from what was reported
Similar results were presented by Kim et al., where by Lambros.27 Although there was no statistically
a macroscopic improvement was observed in a significant difference between the embolism

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 Volume 148, Number 6 • Treatment of Hyaluronic Acid Embolism

control and embolism hyaluronidase-treated wp-content/uploads/2019/12/ISAPS-Global-Survey-2018-

groups, a high dose is recommended because of Press-Release-English.pdf. Accessed May 22, 2020.
2. Rohrich RJ, Ghavami A, Crosby MA. The role of hyal-
the effects on surrounding muscle tissue and mac- uronic acid fillers (Restylane) in facial cosmetic surgery:
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4. DeLorenzi C. Complications of injectable fillers, Part 1.
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assimilates a more realistic scenario and provides pressure. J Am Acad Dermatol. 2016;75:243–262.
a base for future subcutaneous hyaluronidase 6. DeLorenzi C. New high dose pulsed hyaluronidase protocol
for hyaluronic acid filler vascular adverse events. Aesthet Surg
application. Therefore, we recommend the use J. 2017;37:814–825.
of higher doses of hyaluronidase, subcutaneously, 7. Park KY, Kim HK, Kim BJ. Comparative study of hyaluronic
along the occluded artery pathway immediately acid fillers by in vitro and in vivo testing. J Eur Acad Dermatol
after the identification of the vascular occlusion, Venereol. 2014;28:565–568.
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Souza J, Brum C. Double-blind, randomized, controlled
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CONCLUSIONS cannula versus a standard needle for soft tissue augmen-
A high dose (500 IU) of subcutaneous hyal- tation of the nasolabial folds. J Am Acad Dermatol. 2011;38:
207–214.
uronidase partially limits the damage caused by 10. Urdiales-Gálvez F, Delgado NE, Figueiredo V, et al. Treatment
a hyaluronic acid intraarterial embolism on the of soft tissue filler complications: Expert consensus recom-
artery wall and its adjacent tissues, providing the mendations. Aesthetic Plast Surg. 2018;42:498–510.
best macroscopic outcomes, comparable to what 11. Chiang C, Zhou S, Liu K. Intravenous hyaluronidase with
is pursued in a clinical scenario; higher doses urokinase as treatment for arterial hyaluronic acid embo-
lism. Plast Reconstr Surg. 2016;137:114–121.
should be studied. A thrombolytic therapeutic 12. Scheuer JF, Sieber DA, Pezeshk RA, Campbell CF, Gassman
must be evaluated because of the thrombosis AA, Rohrich RJ. Anatomy of the facial danger zones:
caused by the hyaluronic acid emboli, to prevent Maximizing safety during soft-tissue filler injections. Plast
arterial and surrounding tissue damage. Reconstr Surg. 2017;139:50e–58e.
13. Beleznay K, Humphrey S, Carruthers JD, Carruthers A.

Alejandro Quiroga-Garza, M.D., M.Surg., Ph.D. Vascular compromise from soft tissue augmentation:
Avenida Francisco I. Madero S/N y Dr. Eduardo Experience with 12 cases and recommendations for optimal
Aguirre Pequeño outcomes. J Clin Aesthet Dermatol. 2014;7:37–43.
Colonia Mitras Centro 14. Abduljabbar MH, Basendwh MA. Complications of hyal-

Monterrey, Nuevo León, México 64460 uronic acid fillers and their managements. J Dermatology
dr.aquirogag@gmail.com Dermatologic Surg. 2016;20:100–106.
Facebook: DrAlejandroQuiroga 15. DeLorenzi C. Transarterial degradation of hyaluronic acid
Twitter: @DrAlejandroQui1 filler by hyaluronidase. Dermatol Surg. 2014;40:832–841.
16. Wang M, Li W, Zhang Y, Tian W, Wang H. Comparison of
intra-arterial and subcutaneous testicular hyaluronidase
ACKNOWLEDGMENTS injection treatments and the vascular complications of hyal-
uronic acid filler. Dermatol Surg. 2017;43:246–254.
The authors would like to thank Gilberto Arevalo- 17. Zhuang Y, Yang M, Liu C. An islanded rabbit auricular skin
Martinez, D.V.M., and Brayan Javier Carranza- flap model of hyaluronic acid injection-induced embolism.
Martinez, D.V.M., for help in the care and handling of Aesthetic Plast Surg. 2016;40:421–427.
laboratory animals. The first author, Yolanda Salinas- 18. Sykes JM, Cotofana S, Trevidic P, et al. Upper face: Clinical
Alvarez, M.D., M.Sc., would like to thank Juan Antonio anatomy and regional approaches with injectable fillers.
Plast Reconstr Surg. 2015;136(Suppl):204S–218S.
Rivera-Perez, M.D., for help and support during the 19. Cotofana S, Schenck TL, Trevidic P, et al. Midface: Clinical
experimental process. anatomy and regional approaches with injectable fillers.
Plast Reconstr Surg. 2015;136(Suppl):219S–234S.
20. Cotofana S, Fratila AA, Schenck TL, Redka-Swoboda W,
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