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PLATINUM PARTNERS
facial aesthetics
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www.SRPS.org
Editor-in-Chief Editor Emeritus Contributing Editors Je rey M. Kenkel, MD F. E. Barton, Jr, MD
R. S. Ambay, MD R. G. Anderson, MD S. J. Beran, MD S. M. Bidic, MD G. Broughton II, MD, PhD J. L. Burns, MD J. J. Cheng, MD C. P. Clark III, MD D. L. Gonyon, Jr, MD A. A. Gosman, MD K. A. Gutowski, MD J. R. Gri n, MD R. Y. Ha, MD F. Hackney, MD, DDS L. H. Hollier, MD R. E. Hoxworth, MD J. E. Janis, MD R. K. Khosla, MD J. E. Leedy, MD J. A. Lemmon, MD A. H. Lipschitz, MD R. A. Meade, MD D. L. Mount, MD J. C. OBrien, MD J. K. Potter, MD, DDS R. J. Rohrich, MD M. Saint-Cyr, MD M. Schaverien, MRCS M. C. Snyder, MD M. Swelstad, MD A. P. Trussler, MD R. I. S. Zbar, MD
30 Topics
Grafts and Flaps Wound Healing, Scars, and Burns Skin Tumors: Basal Cell Carcinoma, Squamous Cell Carcinoma, and Melanoma Implantation and Local Anesthetics Head and Neck Tumors and Reconstruction Microsurgery and Lower Extremity Reconstruction Nasal and Eyelid Reconstruction Lip, Cheek, and Scalp Reconstruction Ear Reconstruction and Otoplasty Facial Fractures Blepharoplasty and Brow Lift Rhinoplasty Rhytidectomy Injectables Lasers Facial Nerve Disorders Cleft Lip and Palate and Velopharyngeal Insu ciency Craniofacial I: Cephalometrics and Orthognathic Surgery Craniofacial II: Syndromes and Surgery Vascular Anomalies Breast Augmentation Breast Reduction and Mastopexy Breast Reconstruction Body Contouring and Liposuction Trunk Reconstruction Hand: Soft Tissues Hand: Peripheral Nerves Hand: Flexor Tendons Hand: Extensor Tendons Hand: Wrist, Joints, Congenital Anomalies, and Rheumatoid Arthritis
Selected Readings in Plastic Surgery (ISSN 0739-5523) is a series of monographs published by Selected Readings in Plastic Surgery, Inc. For subscription information, please visit our web site: www.SRPS.org.
INJECTABLES
Alexander T. Nguyen, MD Jeffrey M. Kenkel, MD University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
INTRODUCTION The use and number of injectable agents for cosmetic facial rejuvenation and reshaping continue to increase around the world. According to the 2009 American Society for Aesthetic Plastic Surgery (ASAPS) Cosmetic Surgery National Data Bank Statistics,1 more than 2.5 million botulinum toxin type A (BoNTA) and more than 1.3 million hyaluronic acid (HA) injection procedures were performed in 2009, the top two cosmetic procedures performed that year. These numbers do not include the growing popularity of longer lasting soft-tissue fillers. The use of BoNTA accounted for more than one billion dollars in expenditures in 2009, with a 3824% increase since 1997.1 With increased comprehension of aging and the associated loss of volume of soft tissue and bone, the use of injectables is no longer limited to wrinkles alone. Wrinkles are sometimes a manifestation of volume loss; therefore, injectable agents can be used in several different roles.24 Injectable products and their literature are rapidly expanding and evolving. In this new issue of Selected Readings in Plastic Surgery, we present injectables as a new topic, review the current classifications of products approved by the United States Food and Drug Administration (FDA), and provide an overview of the clinical uses.
HISTORY The history of tissue augmentation began when Neuber5 used autologous free fat from arms to reconstruct depressed facial defects in 1893 (Fig. 1). The first cosmetic injection was performed by Gersuny6 in 1899. He injected paraffin into a scrotum as a testicular prosthesis to correct the cosmetic deformity after testicular resection for advanced tuberculosis. Injectable paraffin and mineral oil were popular in the United States and Europe until about 1920. Miller,7 in his 1926 book, Cannula Implants and Review of Implantation Technics in Esthetic Surgery, described the use of various materials, including bits of braided silk, bits of silk floss, particles of celluloid, gutta percha, vegetable ivory, and several other insoluble foreign materials, injected into the facial tissues to correct depressions, pits, and lines.8 Liquid silicone became popular in the 1940s and has been associated with numerous complications.9,10 Modern autologous fat transplantation emerged with the evolution of liposuction. In 1986, Illouz11 presented a report on the reinjection of fat from liposuction. Klein and Elson12 detailed the history of soft-tissue augmentation in 2000. THE IDEAL INJECTABLE The ideal injectable should have a safe composition, easy delivery, excellent outcomes, and appropriate 1
Characteristics
Composition
Delivery
Outcomes
Sensibility
Table 2 Classification of Soft-tissue Injectables Longevity Temporary 06 months Injectable Botulinum toxin Collagen Hyaluronic acid Poly-l-lactic acid Calcium hydroxylapatite Autologous fat Silicone Polymethylmethacrylate
BoNTA-ONA (Botox/Botox Cosmetic) OnabotulinumtoxinA, known as BoNTA-ONA and previously known as BoNTA, is marketed as Botox and Botox Cosmetic (Allergan, Irvine, CA). When first studied, it was named Oculinum. Botox is FDA-approved for cervical dystonia, severe primary axillary hyperhidrosis, strabismus, and blepharospasm. In 2002, it received FDA approval for temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugators and/or procerus muscle activity in adult patients younger than 65 years.
According to the full prescribing information, Botox is contraindicated in the presence of infection at the proposed injection site(s) and in persons with known hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation. Caution is advised for patients with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis, or neuromuscular junctional disorders (e.g., myasthenia gravis or Lambert-Eaton syndrome). Patients with neuromuscular disorders might be at increased risk for clinically significant effects, including severe dysphagia and respiratory 3
Figure 2. Botulinum toxin mechanism of action. A, Release of acetylcholine at neuromuscular junction is mediated by assembly of synaptic fusion complex. B, Botulinum toxin binds to neuronal cell membrane at nerve terminus and enters neuron by endocytosis. (Reprinted with permission from Arnon et al.19)
compromise. Aminoglycoside co-administration can also potentiate the clinical effects.28 Botox is not recommended for use in children but has shown significant benefit as an adjunct to treatment in children with cerebral palsy spasticity.29 Application of Botox is not recommended during pregnancy, and without adequate studies, it is considered to be in pregnancy category C. It is not known whether it is excreted in human milk.30 Botulinum toxin type A precautions are as follows: Infection at injection site Known hypersensitivity Neuromuscular disorders Aminoglycosides Children Pregnancy Lactation 4
Table 3 Dysport versus Botox Dysport Vial size Composition Total protein Albumin Other Type A strain Complex weight Preparation Clinical generalizations Conversion Onset Spread Duration Price 2.5 U 3 days More Same Less 1U 4 days Less Same More 4.35 ng 125 mg 2.5 mg of lactose NCTC 2916 5 ng 500 mg 0.9 mg of NaCl Hall 300 U Botox 100 U
300 kDa
Freeze-dried
900 kDa
Vacuum-dried
Treatment Recommendations Considering the significant variation in techniques, guidelines in the literature, and personal experiences, Carruthers et al.41,62 convened in 2004 to develop consensus guidelines for best practices, which were updated in 2008. The recommendations were briefly summarized in the resulting articles, which should be reviewed for further detail and are recapitulated in Table 4 and Figure 4. After intramuscular treatment, most areas should not be manipulated for several hours.41 The duration of activity should be expected to last approximately 3 to 4 months. Fagien63 and Carruthers and Carruthers64 presented a report of pretreatment with Botox 1 to 2 weeks before laser resurfacing, which might improve results by eliminating the hyperfunctional component during healing.
Upper FaceThe upper face is the most common site to receive neuromodulator injections. The literature about treatment to the upper face, particularly the glabellar complex, is extensive. The Botox Cosmetic package insert30 recommends five injection sites for the glabellar complex and vertical frown lines. Men, in general, might require more injection sites and more product, considering the male muscle mass is larger, on average. For horizontal forehead lines, the goal should be to weaken but not completely paralyze the frontalis muscle. Usually, four to eight injection points are used. Overtreatment of the frontalis will result in brow ptosis or asymmetry and can be avoided by keeping injections no closer than 1 to 2 cm above the bony orbital rim at the 7
Region/Target Muscle(s)
Upper face Vertical frown lines, glabellar complex (procerus, depressor supercilii, corrugator supercilii) 5-7; men might require more sites Women: 10-30 U Men: 20-40 U 40-80 U
Horizontal forehead lines (frontalis, but consider interactions with procerus, corrugators, and orbicularis oculi in overall facial shape)
4-8; more or fewer might be required based on anatomic and aesthetic evaluations
30-60 U
40-60 U
Nasal tip (depressor septi nasi, levator labii superioris alaeque nasi)
2-4
10-15 U
Lower face Perioral area, orbicularis oris 2-6; 4 sites, 1 site per lip quadrant 4-5 U 10-20 U
1-2
2-3 U
6-10 U
4-10 U
10-20 U
<10 U/band
Masseteric hypertrophy
12 sites in muscle
25-30 U/side
Figure 5. Injection techniques: serial puncture (above, left), linear threading (above, right), fanning (below, left) and cross-hatching or radial (below, right). (Reprinted with permission from Rohrich et al.118)
pushing blood vessels out of the way. This technique might be useful for enhancing the nasolabial folds and the vermiliocutaneous border by finding the potential spaces with limited needle movement. Retrograde injection might avoid intravascular injection, as in the glabellar region, and does not create additional tracks or dissection planes.62,95 Fanning involves multiple passes in different directions without withdrawing the needle. The needle can also be passed several times, superimposing deep and superficial layers of fillers, which is thought to achieve superior results for the nasolabial fold. Cross-hatching involves linear injection in an evenly spaced grid pattern. This is effective for large areas, three-dimensional filling, and the oral
commissures.118 Glogau and Kane119 conducted a prospective, blinded, controlled study of injection techniques. They found that techniques that increase the dissection of the subepidermal plane (fanlike needle use, rapid injection, rapid flow rates, and higher volumes) increase the incidence of local adverse events whereas injection techniques that increase epidermal damage (multiple punctures, deep subcutaneous injection) have no effect on adverse events. Post-procedure management can include cold compresses or ice to help reduce swelling and tenderness. Reduced facial expression for the first 48 hours might minimize migration.95
15
Late
14 days1 year
Granuloma formation
Delayed
>1 year
Biofilms
Treat one side at a time. Pinch or tent the skin to provide more space. Occlude the vessels at their origins.136,139 Early intervention when encountering vascular compromise might prevent necrosis, with the goal of increasing blood flow. The procedure should immediately be aborted and the area massaged to disperse the material. Warm gauze and nitroglycerin paste will promote vasodilation. Hyaluronidase injection can be used to decompress the vessels.140 Hyperbaric oxygen can be considered. Essential products to have available when using injectables include ice, heat, nitroglycerin, and hyaluronidase. Hyaluronidase might result in sensitivity, especially in patients with bee venom allergies. The Tyndall effect refers to the blue discoloration seen when soft-tissue fillers are injected too superficially. This occurs because of light scattering differently depending on the diameter of particles encountered.141 Visible blanching and immediate appearance of lumps and bumps are technical errors of product placement, such as filler placement that is too superficial, which can be avoided by slowing down the injection and using finer-gauge needles. This will avoid inflammatory nodules or hypertrophic scarring. Currently, no products should be placed superficially. Immediate massage of products might minimize nodules or irregularities. Angry red bumps, with and without tenderness, describe delayed erythema at the sites
of injection of various products that are associated with visible or palpable nodules. These occur more often with permanent fillers or collagen. The causes have been thought to vary from hypersensitivity to infections to foreign body reactions.135 If infectious, the majority of contaminating bacteria are nonpathogenic species, such as Propionibacterium acnes, Streptococcus oralis/mirabilis, Staphylococci epidermidis, and mycobacteria, and antibiotic coverage should be considered early.131 Late complications include migration, discoloration, scarring, atrophy, and foreign body granulomas, which is the bodys attempt to remove unfamiliar material. Histologically, the granulomas consist of inflammatory lymphocytes, neutrophils, eosinophils, multinucleated giant cells, and plasma cells. Causes of granuloma formation include the volume of injected material, size of the filler particles used, impurities, and biofilms. The diagnosis of filler foreign body granuloma should be based on clinical findings.105,128,129,131,142 Steroid injections are proven treatments of granulomas.112 We refer the reader to the extensive reviews by Lemperle et al.128 and Lemperle and GauthierHazan129 of the complexity of granuloma formation. Delayed complications associated with injectables potentially occur from biofilms, as reviewed by Rohrich et al.132 Biofilms are defined as a structured community of microorganisms encapsulated within a self-developed polymeric matrix and irreversibly adherent to a living or 17
Figure 6. Management algorithm of late and delayed complications of soft-tissue injectables (Reprinted with permission from Rohrich et al.132)
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1. American Society for Aesthetic Plastic Surgery. Cosmetic Surgery National Data Bank Statistics. http://www.surgery. org/media/statistics. Last accessed June 30, 2010. 2. Donath AS, Glasgold RA, Glasgold MJ. Volume loss versus gravity: New concepts in facial aging. Curr Opin Otolaryngol Head Neck Surg 2007;15:238243. 3. Rohrich RJ, Pessa JE, Ristow B. The youthful cheek and the deep medial fat compartment. Plast Reconstr Surg 2008;121:21072112. 4. Gonzalez-Ulloa M, Flores ES. Senility of the face: Basic study to understand its causes and effects. Plast Reconstr Surg 1965;36:239246. 5. Neuber F. Fettransplantation [in German]. Chir Kongr Verhandl Dsch Gesellch Chir 1893;22:66. 6. Gersuny R. Ueber eine subcutane prothese [in German]. Ztschr Heilkunde 1900;199204. 7. Miller C. Cannula Implants and Review of Implantation Technics in Esthetic Surgery. Chicago: The Oak Press; 1926. 8. Rogers BO. A brief history of cosmetic surgery. Surg Clin North Am 1971;51:265288. 9. Ellenbogen R, Rubin L. Injectable fluid silicone therapy: Human morbidity and mortality. JAMA 1975;234:308309. 10. Achauer BM. A serious complication following medical-grade silicone injection of the face. Plast Reconstr Surg 1983;71:251254. 11. Illouz YG. The fat cell graft: A new technique to fill depressions. Plast Reconstr Surg 1986;78:122123. 12. Klein AW, Elson ML. The history of substances for soft tissue augmentation. Dermatol Surg 2000;26:10961105. 13. Broder KW, Cohen SR. An overview of permanent and semipermanent fillers. Plast Reconstr Surg 2006;118 [suppl 3]:7S14S. 14. Matarasso SL. Injectable collagens: Lost but not forgotten: A review of products, indications, and injection techniques. Plast Reconstr Surg 2007;120[suppl 6]:17S26S. 15. Rohrich R J, Nguyen AT, Kenkel JM. Lexicon for soft tissue implants. Dermatol Surg 2009;35[suppl 2]:16051611. 16. Huang W, Foster JA, Rogachefsky AS. Pharmacology of botulinum toxin. J Am Acad Dermatol 2000;43:249259. 17. Simpson LL. The origin, structure, and pharmacological activity of botulinum toxin. Pharmacol Rev 1981;33:155188. 18. Wortzman MS, Pickett A. The science and manufacturing behind botulinum neurotoxin type A-ABO in clinical use. Aesthet Surg J 2009;29[suppl 6]:S34S42.
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We thank the Aesthetic Surgery Journal and Plastic and Reconstructive Surgery for their support.
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