The Unfavorable Result in Plastic Surgery_ Avoidance and Treatment (2018, Thieme)

SECTION III GENERAL PROBLEMS
116
excision is performed by direct removal of necrotic tissue.
For almost all wounds, the lighting and anesthesia afforded
by an operating room are necessary for adequate débride­
ment. Devitalized tissue is removed until healthy, bleeding
tissue is appreciated; depending on the extent of the wound,
removal of nonviable fascia, muscle, and bone may be re­
quired. In fact, amputation is the ultimate form of surgi­
cal débridement, reserved for digits and limbs that are not
functionally salvageable. Determining the margin of healthy
tissues may prove difficult in the normally less vascular sub­
cutaneous tissues, because the presence of punctuate bleed­
ing may not be a reliable indicator of viability. Débridement
should always be followed by thorough irrigation to remove
any remaining debris. This method is relatively nonselective
for devitalized tissue.
Tangential hydrosurgery is a recent innovation that
provides an alternative to the labor-intensive process of
classic surgical excision. A powerful, coherent stream of
saline moves parallel to the wound surface within the tip
of a handheld device and ablates devitalized tissues in the
wound surface. The negative pressure generated by the mov­
ing fluid, a consequence of the Venturi effect, then removes
these tissues.9 This technology provides great control in re­
moving precise layers of tissue. The surgeon can easily rec­
ognize normal tissue when it appears in the field. The hy­
drojet works best in soft tissue but does not débride through
tissues such as fascia or tendons. In addition, it has proved
particularly useful in concavities like those in pressure ul­
cers and joint spaces as well as tight spaces such as breast
capsules.
Low-frequency ultrasound is an interesting new tool for
surgical débridement.15 The tip of the handpiece delivers a
high-intensity, low-frequency, ultrasound that is transmit­
ted by water vapor. The energy implodes necrotic tissue,
bacteria, and biofilm by means of a bubble cavitation ef­
fect. Rapidly oscillating energy waves, 22.5 kilohertz, cause
vacuum bubbles to occur in the low-pressure phase. These
bubbles then collapse in the high-pressure phase, causing
the release of sufficient energy to implode the affected tis­
sue. The end result is a very controlled débridement of all
tissue types.16–18
Biologic débridement uses maggots that have been ir­
radiated to prevent metamorphosis into mature flies. Mag­
gots perform débridement by secreting enzymes that se­
lectively digest necrotic tissue. The process is painless for
the patient, but sensate patients will feel movement of the
larvae. This method is suited for patients who require ag­
gressive débridement but cannot tolerate an operation be­
cause of medical comorbidities. However, partly because of
psychosocial issues among patients and nursing staff, use
of maggots has failed to gain significant popularity in the
United States.9,12
Enzymatic débridement uses preparations of proteo­
lytic enzymes that can be applied to a wound to supple­
ment physiological débridement. Enzymes commonly used
include papain with urea and collagenase. These enzymes
particular, has been noted to cause contact dermatitis and
allergic reactions in periwound skin, reflecting a change
from the normal fluid composition.14
Edge of Wound
Although granulation tissue formation and remodeling
provide a collagen matrix to restore tensile strength and
vascular supply to the skin, complete surface coverage with
epithelium is required to restore the functionality of the
skin barrier. Epithelialization occurs from the wound edges
and skin appendages as part of the proliferative phase of
healing. Consequently, addressing the edge of the wound
promotes successful epithelial coverage. Required for suc­
cessful epithelial migration are a granular tissue base and
a moist environment. Because wound secretion decreases
with granulation tissue formation, moisture may need to
be supplemented with dressings. Often, epithelialization
fails to occur in chronic wounds despite adequate moist­
ening. In such cases, biologically active skin replacement
therapies can promote epithelial coverage of the wound.
Wound Débridement
The most efficient and effective method of preparing a
wound bed for healing is through adequate débridement.
Necrotic tissue provides substrate for proliferating bacteria
that compete with host cells for nutrients and oxygen nec­
essary for healing. The removal of this tissue, therefore, is
essential to promote healing. Several approaches have been
advocated to facilitate débridement: surgical, biologic, en­
zymatic, mechanical, and autolytic (Box 14.2).
Surgical débridement is the standard of care for chronic
wounds and can, when performed properly, move rapidly
and definitively through the TIME sequence.9,11,12 Benefits
of surgical débridement include direct removal of all devi­
talized tissue and reduction of bioburden.
The two general types of surgical débridement include
classic sharp surgical excision and hydrodissection. Surgical
Box 14.2
Surgical
•• Classic sharp surgical excision
•• Hydrodissection
•• Low-frequency ultrasonic débridement
Nonsurgical
•• Biologic
•• Enzymatic
•• Mechanical
•• Autolytic
Types of Wound Débridement

117
Chapter 14 Wound Management
Advanced Dressings and Surgical
Coverage of Wounds
Advanced Dressings
Use of a variety of materials and substances for dressing
wounds has been documented for thousands of years.20 Re­
cently, remarkable progress has been made combining bio­
materials and material science with knowledge of wound
physiology to facilitate the creation of an optimal wound
bed. Modern dressings may be impregnated with antimi­
crobial agents, capable of removing excess exudate, and
providing moisture when needed. In addition, dressings
are now being developed that can differentially respond
to varying wound environments. Choosing an appropriate
dressing for a wound ultimately requires considering the
dressing types that optimize the TIME characteristics, pa­
tient comfort, ease of implementation, and cost (Box 14.3).
Materials
Various dressings and materials have been developed to tar­
get infection and inflammation in the wound bed. A com­
mon feature is the limited application of antibiotic medi­
cations to the dressings. Antibiotics are typically avoided
when treating chronic wounds because of the risk for selec­
tion of resistant pathogen strains, as well as sensitization of
the patient to the antibiotic agent. Antimicrobials that have
demonstrated little to no selection for resistant pathogens
are chlorhexidine, honey, octenidine, polyhexanide, povi­
done iodine, and silver in vitro.13
Ionic silver is a common component of many currently
available antimicrobial dressings. Ionic silver acts by bind­
ing and disrupting protein disulfide bridges and arresting
selectively digest devitalized tissue and halt the develop­
ment of eschar and biofilms, and they are suited to wounds
with minimal necrotic loads. These enzymes require a
moist environment to properly function and therefore may
be combined with dressings that maintain moisture to im­
prove function. Drawbacks to this approach include labor
intensiveness, a protracted process, and possibly pain. Bacte­
rial burden must be controlled when using enzyme prepara­
tions because proteases released by the bacteria can degrade
the enzymes.19 Caution should be exercised, however, when
combining antimicrobial dressings with enzymatic débride­
ment, because compatibility between the enzyme and the
antimicrobial agent is a concern. For example, silver-con­
taining dressings must be avoided when using papain, be­
cause the silver cations inactivate the protease.9
Mechanical débridement is characterized by the physi­
cal removal of necrotic tissue. Methods to accomplish this
include the following:
•• Wet-to-dry dressings
•• Wound irrigation
•• Hydrotherapy
•• Negative-pressure wound therapy
When using wet-to-dry dressings, necrotic tissue is torn
from the wound in a random manner that produces consid­
erable pain for the patient. This method is relatively nonse­
lective for devitalized tissues compared with other options.
In addition, wet-to-dry dressings promote evaporative
cooling of the wound surface, and wound temperatures
around 10ºC cooler than normal body temperatures have
been reported. This local hypothermia has notable negative
effects on wound healing through local vasoconstriction,
hypoxia, diminished phagocytosis, impaired leukocyte
mobility, and increased affinity of hemoglobin for oxygen.
Furthermore, gauze is not a physical obstacle to pathogens,
and it must be changed two to three times daily to maintain
a moist environment.
Autolytic débridement therapies attempt to optimize
the wound environment for the body’s native, physiologi­
cal débridement mechanisms. Débridement, as previously
mentioned, is an essential part of the wound-healing pro­
cess and is normally performed by proteolytic enzymes and
macrophages. Dressings that promote autolytic débride­
ment are occlusive or semiocclusive dressings, hydrocol­
loids, and moisture interactive dressings, which share the
feature of maintaining wound moisture. They may be used
alone, subsequent to surgical débridement, or in conjunction
with other débridement options. This method is nonspe­
cific, uncontrolled, and time and labor intensive. In addition,
open wounds with persistent necrotic tissue are at risk for
development of invasive infection. Autolytic débridement
may therefore benefit patients whose wounds have mini­
mal necrotic load and who cannot tolerate more aggressive
débridement.
Box 14.3
•• Maintains a clean, warm, moist environment
•• Provides hydration if dry or desiccated
•• Removes excess exudates
•• Prevents desiccation and is nontraumatic
•• Protects periwound area
•• Allows gas exchange
•• Impermeable to microorganisms
•• Free of toxic or irritant particles
•• Does not release particles or fibers
•• Conforms to wound shape
•• Minimal pain during application and removal
•• Easy to use
•• Cost-effective
Ideal Characteristics
of Wound Dressings

SECTION III GENERAL PROBLEMS
118
ditional benefits of hemostatic activity, inflammatory pain
analgesia, antitumor activity, and activation of immune and
inflammatory cells. The positive charge allows binding to
negatively charged materials like alginates, and chitosan can
be incorporated into fibers, sponges, hydrogels, and mem­
branes.14
Moisture Regulating Dressings
As previously mentioned, maintenance of a moist wound
bed is one of the most fundamental objectives in promot­
ing wound healing. Numerous dressing types have been de­
veloped that can increase wound moisture or absorb excess
exudates. These dressings often serve as a framework upon
which additional treatments may be added. For example,
many of these dressings are available with antimicrobial
agents, and novel research is attempting to produce ma­
terials that can interact with changes in the local wound
environment.
Alginates
Alginates are a gel-forming material composed of linear
polysaccharides found in marine brown algae. The poly­
saccharides contain varying amounts of mannuronic acid
and glucuronic acid monomers. They form hydrophilic
gels by selective binding of glucuronic acid to divalent
cations like calcium ions.14 Depending on the ratio of gluc­
uronic acid to mannuronic acid monomers, the rigidity of
the gel can be manipulated. Silver and zinc infusions have
been included in some alginate dressings to improve anti­
microbial and clotting activity, respectively. Advantages of
alginates include the ability to remove excess exudate and
associated proteases while maintaining a moist wound
environment. Provided enough exudate is present to sup­
port a homogenous gel, these dressings do not adhere to
the wound. Consequently, new granulation tissue is not
disturbed and patients experience far less discomfort dur­
ing dressing changes.14 Calcium ions in the alginate may
microbial metabolic processes. Silver has a broad spectrum
of activity, covering yeast, viruses, anaerobic and aerobic
bacteria, and gram-positive and gram-negative bacteria.
A number of dressings impregnated with silver are widely
available (Fig. 14.1).
Honey has been used topically in wounds in some coun­
tries continuously for thousands of years, with others re­
cently regaining interest since the introduction of licensed
wound care products containing medical-grade honey.21 The
antimicrobial properties of honey have been demonstrated
in several in vitro studies and are currently understood to be
a consequence of methylglyoxal, which appears to be pres­
ent in highest concentration in manuka honey of New Zea­
land.10 In vitro studies have suggested bactericidal activity
against Pseudomonas aeruginosa, Enterococcus faecium, and
methicillin-resistant Staphylococcus aureus (MRSA).10 Also of
benefit are the high sugar content, acidic nature, and abil­
ity to produce hydrogen peroxide.14 The high sugar content
facilitates reduction of wound odor, because bacteria pre­
fer the sugar to protein and produce lactic acid, which is
not malodorous, can promote autolytic débridement, and
is anti-inflammatory. Recent research has suggested effec­
tiveness as an antibiofilm agent as well. Honey should be
avoided in large wounds of diabetic patients, because it may
lead to large increases in blood glucose.14
Another antimicrobial agent is derived from chitin,
found in arthropod exoskeletons. Chitosan, a partially N-
deacetylated derivative of chitin, has demonstrated excel­
lent antimicrobial activity, targeting both gram-positive and
gram-negative bacteria, including MRSA, with low toxicity
toward mammalian cells. A hypothetical mechanism of ac­
tion suggests that the positively charged amino groups in­
teract with the negatively charged moieties on microbial
outer membranes, causing cell damage and leakage of in­
tracellular contents. Chitooligomers, low-molecular-weight
chitosans, have been developed as well and are reported
to have greater bactericidal activity against Escherichia
coli and inhibit the activation and expression of MMP2 in
primary human dermal fibroblasts. Chitosan has the ad­
Fig. 14.1 (a) A chronic nonhealing wound of the right medial calcaneus secondary to chronic venous insufficiency (CVI). (b) The same wound
covered with a silver-impregnated fabric dressing before placement of a secondary compressive dressing.
a
b

119
Chapter 14 Wound Management
Hydrocolloids
Hydrocolloids are composed of an external layer of poly­
urethane and an internal layer of gelling ingredients like
gelatin, pectin, and sodium carboxy-methyl-cellulose.
These occlusive dressings waterproof the wound and pro­
tect it from bacteria while providing thermal insulation.
The gelling ingredients swell to fill the entire wound cav­
ity and simultaneously bind excess exudate and maintain
wound moisture. As such, suitable wounds for hydrocolloid
dressings must have adequate amounts of exudate or mois­
ture from irrigation solutions. Because these dressings are
opaque, they must be removed for inspection of the wound,
and frequent removal can lower the local wound tempera­
ture. In addition, there is a risk for maceration of the sur­
rounding skin, and the dressings are not highly absorptive.
During dressing removal, residual gel material may re­
main in the wound and resemble purulent material, and a
distinctive malodor may be noted. An inexperienced health
care practitioner may mistake this for infection. Contact
dermatitis has also been associated with hydrocolloids.
Consequently, these dressings are suited for wounds with
light-to-moderate exudate and are not suitable for diabetic
foot ulcers because occlusive dressings may encourage the
growth of anaerobic bacteria. Clinical trials have suggested
that hydrocolloids may be more effective than gauze dress­
ings for pressure ulcers but lack clear advantage over other
low-adherence dressings for ulcer healing when used under
compression.14
Polysaccharide Bead
Another moisture-regulating wound dressing is the poly­
saccharide bead. In this dressing, 0.1- to 0.3-mm–diameter
beads composed of sterile dextranomer, which is hydro­
philic and biodegradable, are mixed with glycol and water
to form a paste contained in a low-adherence nylon bag or
wrapped in foil. As with many of the previously discussed
dressings, the beads can be combined with antiseptic
agents like iodine. Unfortunately, these dressings may cause
discomfort when applied to clean, granulating wounds and
must be used with a secondary dressing to maintain their
positioning, thus reducing cost-effectiveness.
Hydrogels
Hydrogels are polymers of hydrophilic components. They
do not function to absorb excess exudate, but instead pro­
vide moisture for dry, necrotic wounds. Recently, hydrogels
that react to wound conditions have been developed.14
An example of this approach is a gel capable of releasing
wound-healing factors in response to changes in pH.
also be exchanged with the wound bed for sodium ions,
which has been associated with improved coagulation.14
Some patients have noted a burning sensation when the
alginate dressings are applied that is associated with rapid
fluid movement from the soft tissue into the dressing.
Premoistening the wound bed may prevent this, but will
hinder the effectiveness of the dressing. Alginates also
struggle to retain fluid when compressed and therefore
may need supplementation with a secondary absorbent
dressing to prevent complications associated with excess
exudate.
Hydrofibers
Hydrofibers are another polysaccharide-based, gel-forming
dressing. The polysaccharide component of these dressings
is sodium carboxymethylcellulose (CMC), a hydrophilic de­
rivative of cellulose. Soft, nonwoven dressings have been
developed from this material that gel on contact with flu­
ids. These dressings have high fluid absorbency, retaining
15 to 25 g per gram of material, allowing longer periods
between dressing changes. They are believed to bind and
sequester bacteria and may be impregnated with silver.
Unfortunately, CMC filaments are physiologically inert,
serving only to absorb fluid without interacting with the
wound. In addition, hydrofiber dressings are expensive
compared with other dressing types. Hydroconductive
dressings are similar but have a much greater capacity to
acquire and store exudate.
Foams
Foams are another moisture-regulating dressing type and
have been used with increasing frequency in recent years
because of their ease of use compared with gel-forming
dressings. They are composed of polyurethane or silicone
and may have an adhesive dressing, an extra layer to pre­
vent adherence to the wound surface, or an occlusive poly­
meric backing layer to prevent fluid loss and contamina­
tion. In addition, antimicrobial agents can be incorporated.
The foam structure allows the ingrowth of granulation tis­
sue through the pores and an undisturbed gas exchange.
When removed during dressing changes, granulation tissue
that has infiltrated the foam is removed. This process is hy­
pothesized to freshen the wound bed. In addition, foams
provide good thermal insulation for the wound bed. These
dressings can be used as either a wound dressing or wound
tamponade. The native absorptive capacity is relatively low
but can be increased by the addition of acrylates or other
superabsorbers. Dressing change intervals vary with dif­
ferent foam types depending on pore size and granulation
tendency and infection status of the wound; they can be as
long as once per week.

SECTION III GENERAL PROBLEMS
120
tografts are composed of patient-derived keratinocytes that
are expanded in a laboratory and may or may not be inte­
grated with a carrier material. Like skin grafts, these need a
well-vascularized wound bed. Alternatively, allografts, xe­
nografts, inert membranes (i.e., silicone), and epidermal or
bilayer substitutes that do not include autologous keratino­
cytes may be used for temporary coverage.22
Dermal substitutes are useful for wounds in which the
dermis has been devoid. Using an epidermal substitute
without reformation of the dermis predisposes to blister­
ing, contractures, scarring, and poor cosmetic outcomes.
The dermis is necessary for elasticity and mechanical re­
sistance. In addition, interactions between epithelial and
mesenchymal cells have been shown to impact local tissue
conditions through a mechanism termed double paracrine
signaling. Dermal substitutes are made from synthetic or
biologic three-dimensional matrices. Cells or bioactive mol­
ecules may be incorporated, but many products are acellular
to minimize immunogenic responses. Commonly, neonatal
human foreskin fibroblasts and/or keratinocytes are used,
because neonatal cells are less immunogenic.22
Bilayers present a combination of epidermal and dermal
substitutes and are also fairly expensive. Like the previously
discussed skin substitutes, cellular and acellular products are
available. A commonly used acellular bilayer, Integra (Integra
LifeSciences), features a silicone epidermal replacement
layer and a bovine collagen and shark chondroitin-6-sulfate
dermal matrix. The dermal matrix is degraded and replaced
by host cells with extracellular matrix, particularly collagen.
The silicone may be removed and replaced with an alterna­
tive epidermal replacement such as a split-thickness skin
graft or a skin substitute dressing (Fig. 14.2). Alternatively,
multiple other cellular bilayers are available. Examples in­
clude Permaderm (Regenicin), Tissuetech (Fidia Advanced
Biopolymers), and Apligraf (Organogenesis).18
Surgical Closure
The previously discussed steps and dressings may be ap­
plied to optimize a wound for healing by secondary inten­
tion; however, surgical closure may be in the patient’s best
interests despite the presence of an adequate wound bed.
An open wound may delay further treatments in cases of
malignancy. Wound contraction may also result in unac­
ceptable functional deficit and cosmetic deformity. Ulti­
mately, surgical treatment may still be necessary for the
final treatment of complex wounds.
Following the reconstructive ladder, the next option for
closure after healing by secondary intent is primary clo­
sure. Primary closure is best suited to clean wounds with a
small zone of injury. An indeterminate zone of injury may
preclude primary repair. Tension on the closure should be
avoided, and these wounds are at risk for closed infection.
For wounds poorly suited for primary closure, split-
thickness or full-thickness skin grafting may provide a suit­
Negative-Pressure Wound Therapy
Another moisture-controlling dressing type is the nega­
tive-pressure dressing. Use of these dressings, known as
negative-pressure wound therapy (NPWT), consists of the
application of continuous or intermittent negative pressure
to the wound cavity. These dressings consist of a hydro­
phobic or hydrophilic polyurethane sponge placed in the
wound that is sealed with foil in an airtight manner from
the external environment. Negative pressure is applied to
the wound by means of a negative-pressure pump that is
allowed to communicate with the sealed wound environ­
ment. The manufacturer’s claims, which are only partly
supported by evidence, report adequate drainage of wound
secretion, reduced tissue edema, and increased local tissue
perfusion. However, studies have suggested that the perfu­
sion in immediate tissues may in fact be reduced. In addi­
tion, relatively weak evidence supports the claim of edema
reduction. Despite the lack of a strong evidence base, NPWT
has demonstrated considerable success. A common, prom­
ising use for NPWT that has not been fully investigated is
the temporary management of a wound to prepare for sur­
gical wound closure.10
Future Directions in Wound Dressings
New innovations in wound dressings are pursuing the
development of materials that actively interact with and
effect positive change in the wound environment. Such
dressings may selectively target excess protease activity,
provide important growth factors, or sense the growth
of harmful bacteria and release antimicrobial substances
when necessary.
Ultimately, current data do not demonstrate a clear ad­
vantage to using any certain type of wound dressing. As
such, dressings should be chosen carefully to facilitate a
moist wound environment with a conscious effort to mini­
mize patient discomfort and optimize costs.
Skin Substitutes
Innovations in tissue engineering have pushed forward the
possibility of regenerative healing, facilitating the growth
and development of dermis and epidermis instead of scar.
Skin substitutes attempt to mimic native tissues to promote
sustained healing. Tissue scaffolds, which may be synthetic,
allogenic, or xenogenic, can promote revascularization and
cellular migration and repopulation of a defect. Inclusion of
cells within these scaffolds may provide benefit from the
early release of growth factors and cytokines to stimulate
healing. These treatments may be classified as epidermal
replacements, dermal replacements, or bilayers.22
Epidermal replacements promote reformation of the
epidermis or serve as a temporary replacement to prevent
bacterial colonization and fluid loss. Cultured epithelial au­

121
Chapter 14 Wound Management
multiple stages to expand the skin and underlying soft tissue
and to move the tissue into the defect. Alternative wound
closure methods like skin grafting may be used to provide
coverage until tissue expansion is complete.
The ultimate and more complex method of wound clo­
sure is free tissue transfer. Use of free flaps provides all the
advantages of local flaps, including a rich vascular supply,
bulk of tissue, and customizability without the limitations of
which local flap options may be available. With the greater
understanding of perforating blood vessels and development
of perforator flaps, cutaneous flaps may be elevated, causing
fewer donors site morbidities. Free tissue transfer may be
viewed as a first option in large, complex defects.
Outcomes
Ultimately, wound management outcomes are dependent
on understanding of the wound-healing cascade, ability to
assess a wound, optimizing the patient’s medical status,
wound bed preparation, use of topical therapy, surgical dé­
bridement, and surgical reconstruction or advanced flaps
when indicated (Fig. 14.5, Video 14.1). Wound care is best
performed by a dedicated team of wound experts. There
are many new developments in each product area from ba­
sic wound dressings to advanced therapies. Nevertheless, it
is important to recognize the role of surgery in rapidly ob­
taining a well-prepared wound as well as providing defini­
tive closure. It is evident from the abundant literature with
able alternative. These options allow for simple, quick clo­
sure without the creation of flaps. Because skin grafting
requires a clean, well-vascularized wound bed, meticulous
preparation and hemostasis must precede graft placement.
In addition, skin grafting may lead to poor aesthetic out­
comes with associated contour defects and poor durability
compared with flaps.
Further reconstructive options include local flaps and lo­
cal tissue rearrangement. Random pattern or axial flaps can
be elevated with multiple tissue layers and can be rotated,
advanced, or transposed into the wound. These flaps can be
elevated with or without overlying skin (Fig. 14.3). A skin
graft can be placed if skin is not moved with the flap. This
approach provides well-vascularized tissue, which serves as
a delivery system for leukocytes, oxygen, and antibiotics. The
bulk of the flap can fill large defects, cover vital structures,
and obliterate dead space (Fig. 14.4). Using local tissue also
ensures that the new overlying tissue is similar to both the
surrounding tissue and the original tissue being replaced.
Following this approach requires a more complicated op­
eration and relatively small zone of injury. In addition, local
tissue options may be limited by the location of the wound
and the quality of the surrounding tissue.
One method to overcome limited availability of local flap
options is tissue expansion. Like local tissue rearrangement,
tissue expansion allows wound closure with tissue similar
to the surrounding area. This method is not useful, however,
for closing a wound in the acute setting because it requires
Fig. 14.2 (a) A chronic nonhealing medial malleolus wound. (b) After application of a dermal bilayer skin substitute. (c) Subsequent split-
thickness skin grafting placed over the dermal substitute at 3 weeks after removal of the silicone outer layer. (d) Final healed wound.
a
b
c
d

SECTION III GENERAL PROBLEMS
122
Fig. 14.3 (a) A chronic stage 4 left trochanteric pressure ulcer, which has failed conservative attempts at wound care. (b) Advancement of
a tensor fascia lata (TFL) fasciocutaneous flap to cover the defect, with split-thickness skin grafting to the donor defect.
a
b
Fig. 14.4 (a) A right groin defect with exposed bypass graft. (b) A rectus femoris muscle flap elevated to fill the dead space and cover the
exposed graft with vascularized tissue.
a
b
Fig. 14.5 (a) Preoperative appearance of a chronic right leg wound refractory to conservative treatments. (b) Postoperatively after wound
preparation and débridement using a low-energy ultrasonic device, SonicOne O.R. with SonicVac (Misonix). (These images are provided
courtesy of Mark S. Granick, MD.)
a
b

123
Chapter 14 Wound Management
dustry, with many new products and technologies being
introduced. Each individual wound must be carefully eval­
uated, categorized, and finally treated. Underlying medical
conditions need to be addressed. The importance of under­
standing the wound-healing cascade, identifying the need
for wound bed preparation, level of exudates, and presence
of infection cannot be overstated. With a thorough under­
standing of surgical and nonsurgical options for wound
management, an effective and efficient wound care strat­
egy and plan can be formed by the clinician.
lack of high-quality randomized controlled trials evaluat­
ing the many wound care products that there is no clear
superiority of one material or category over another. The
future of wound healing remains unknown, but the entities
mentioned will likely help shape that future.
Conclusion
An unfavorable result from a wound is the persistence of
the wound. Care of chronic wounds has become a big in­
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14. Sweeney IR, Miraftab M, Collyer G. A critical review of
modern and emerging absorbent dressings used to treat
exuding wounds. Int Wound J 2012;9(6):601–612
15. Tan J, Abisi S, Smith A, Burnand KG. A painless method of
ultrasonically assisted debridement of chronic leg ulcers: a
pilot study. Eur J Vasc Endovasc Surg 2007;33(2):234–238
16. Gibbons GW, Orgill DP, Serena TE, et al. A prospective,
randomized, controlled trial comparing the effects of
noncontact, low-frequency ultrasound to standard care
in healing venous leg ulcers. Ostomy Wound Manage
2015;61(1):16–29
17. Amini S, ShojaeeFard A, Annabestani Z, et al. Low-frequen­
cy ultrasound debridement in patients with diabetic foot
ulcers and osteomyelitis. Wounds 2013;25(7):193–198
18. Butcher G, Pinnuck L. Wound bed preparation: ultrason­
ic-assisted debridement. Br J Nurs 2013;22(6):S36–S43,
S38–S43
19. Shi L, Ermis R, Kiedaisch B, Carson D. The effect of various
wound dressings on the activity of debriding enzymes.
Adv Skin Wound Care 2010;23(10):456–462
20. Broughton G II, Janis JE, Attinger CE. A brief history of
wound care. Plast Reconstr Surg 2006; 117(7, Suppl)
6S–11S
21. Cooper R. Impact of honey as a topical treatment for
wounds remains unclear. Evid Based Med 2014;19(1):11
22. Greaves NS, Iqbal SA, Baguneid M, Bayat A. The role of
skin substitutes in the management of chronic cutaneous
wounds. Wound Repair Regen 2013;21(2):194–210

SECTION III GENERAL PROBLEMS
124
Discussion by Dennis P. Orgill
About 27 million surgical procedures are performed
in the United States each year, two thirds of which are
performed as outpatient procedures.1 Major complica­
tions from surgeries include surgical-site infections and
scarring. These issues are addressed by first discussing
a theory for why these events occur and then providing
recommendations for ideas to minimize complications.
Wound Infections
Estimates for surgical-site infections typically range
from 3 to 4% but vary greatly depending on the type of
surgery being performed. These complications are dev­
astating for patients, costly for the health care system
and are a major source of nosocomial bacteria in health
care institutions. Clearly a preventive strategy would
be a great advance for our society. Surgical wounds
have been classified by the Centers for Disease Control2
(Table 14D.1).
Theory for Wound Infection Prevention
Factors that influence the development of wound in­
fections can be divided into patient factors, surgeon
factors, and system factors (Fig. 14D.1). A surgeon who
can optimize these factors before surgery will signifi­
cantly reduce the risks of surgical-site infections.
Patient Factors
Patient factors become increasingly important as the
population ages and the prevalence of obesity and dia­
betes mellitus grows. Two thirds of adults in the United
States are overweight, and more than 9% have type 2
diabetes. Depending on the operation, diabetics repre­
sent an increasing population of patients; for example,
about 30% of patients who undergo coronary artery
bypass grafting have diabetes.3 It is estimated that dia­
betes increases wound infection rates by a factor of 3;
with proper perioperative glucose control, much of this
risk can be eliminated.4 In our experience, increased
age, diabetes, smoking, obesity, nutritional status, and
behavioral issues are common factors that predispose
patients to an increased risk of surgical-site infections.
It is incumbent on the surgeon to work with the patient
and his or her other providers to modify as many of the
risk factors as possible for elective operations. For el­
derly patients, assessments for frailty and using geri­
atric principles of care can better inform patients and
their families of their risks and improve care. This has
been extensively studied in hip fractures.5
Having frank and candid discussions about how
much intervention elderly patients want in advance of
the surgery can be very helpful in management and may
be assisted by advanced directives, health care proxies,
and living wills. We try to keep the operation as simple
and short as possible and often do procedures under lo­
Table 14D.1 Classification of
wounds
Wound class
Description/example
Class I/clean
Uninfected operative
wound
Class II/
clean-contaminated
Operative wound;
controlled entry of the
respiratory, alimentary, or
urinary tract
Class III/
contaminated
Open, fresh, accidental
wound
Class IV/
dirty-infected
Old traumatic wound
with devitalized tissue,
perforated viscera
Modified from Guideline for Prevention of Surgical Site Infection,
1999.
Accessed April 20, 2016.
Fig. 14D.1 Patient, surgeon, and system factors that influence
wound infections.
Patient Factors
Age
Diabetes
Obesity
Smoking
Malnutrition
Behavioral issues
Surgeon Factors
Short incisions
Minimize cautery
Local anesthesia
Minimize length of surgery
Avoid desiccation
Choice of wound
Technologies
System Factors
Skin preparation
Preoperative antibiotic
Keep patient warm
Keep patient well oxygenated
Sterile environments

125
Chapter 14 Wound Management
cal anesthesia. Sometimes this involves staging an op­
eration or not achieving an optimal cosmetic result.
I control diabetes as much as possible through glu­
cose and diet control and will use the hemoglobin A1C
level as a guide to long-term management. I prefer to
perform operations on patients with diabetes in the
morning to minimize the time of fasting and work with
the anesthesiologist to achieve excellent intraopera­
tive glucose control. I continue to monitor glucose lev­
els postoperatively and work with the hospital diabetes
team to optimize postoperative glucose control. We are
able to get almost all of our patients to stop smoking
for at least 30 days before elective surgery. This is par­
ticularly important in facelifts, abdominoplasties, breast
reconstruction procedures, and patients with lower ex­
tremity wounds. When possible, getting patients to lose
weight before surgery can be very helpful. For patients
with a ventral hernia or who are undergoing body con­
touring, I set a goal for a body mass index below 30. The
nutritional state of the patient is critical; severe nutri­
tional deficiencies are common in chronic wound and
burn patients.
Surgical Considerations
Short Incisions
The advent of minimally invasive surgery has come
with a decreased incidence of wound infections. This
risk seems to be associated with shorter incisions.
Since shifting to endoscopic saphenous vein harvests
for cardiac surgery in our institutions, the number of
leg wound infections has decreased dramatically. Simi­
larly, I rarely see surgical-site infections after laparo­
scopic cholecystectomies or appendectomies despite
the contamination common to these operations.
Minimizing Electrocautery
Surgery is, by definition, traumatic and sets off an in­
flammatory cascade. The traditional sharp knife is per­
haps one of the least traumatic devices that we use in
surgery. Electrocautery has been a wonderful invention
to stop bleeding but comes at a price of causing tissue
destruction. Nonviable tissue can be a nidus for infec­
tion, so when possible, particularly in the skin and sub­
cutaneous tissue layers, the cautery should be avoided
or minimized. This obviously comes with a trade-off of
potential blood loss. We have found that by using ad­
junctive measures such as tourniquets and tumescent
solutions blood loss can often be minimized even with
limited use of electrocautery.
Local Anesthesia
Local anesthetics have been a great advance in surgery
and allow surgeons to perform large cases comfortably
without the risks or inconveniences of general anes­
thesia. We use local anesthesia not only as a primary
method of anesthesia but also as an adjunctive mea­
sure. Minimizing the local pain response seems to di­
minish the systemic inflammatory response and speed
recovery. Mixing these agents with vasoconstrictive
agents such as epinephrine minimizes bleeding. Tu­
mescent solutions are very dilute concentrations of lo­
cal anesthetics usually combined with epinephrine and
have been very effective at minimizing blood loss both
in elective procedures such as liposuction and breast
reduction surgery and complex cases such as burn ex­
cisions. Use of regional anesthetic blocks is also quite
helpful.
Avoiding Prolonged Surgery
Surgery should be performed in a manner that is nei­
ther rushed nor leisurely. The various steps of the pro­
cedure should be carefully planned and executed in
a fashion that allows the procedure to be performed
in an efficient and timely fashion. For plastic surgical
procedures there are many opportunities when there
is more than one surgical site being used. This makes
these operations amenable to a team approach to re­
duce operative times. In my practice we very often use
two attending surgeons when performing free tissue
transfer procedures. There are several studies that cor­
relate the risk of postoperative complications with the
duration of the surgery. In our case, we studied breast
reductions and measured the time of surgery and cor­
related this with years of experience. We found that
over about an 11-year period, surgeons significantly
reduced their time doing surgery, with decreased com­
plications and no change in patient satisfaction.6
We noted that as surgeons mature it does not ap­
pear that they are operating faster, just that the case is
completed sooner. Over time, surgeons naturally elimi­
nate excess motions. A medical student applying sutures
often uses large movements involving the elbows and
shoulders, whereas an experienced surgeon does much
more with finger and wrist movements. In addition, an
inexperienced surgeon will go back and forth between
instruments, whereas an experienced surgeon will use
an instrument until the task is complete and then move
onto the next task with the appropriate instrument to
accomplish this. Inexperienced surgeons often require
multiple specialized instruments, creating a complex ar­
ray of instruments on the back table, whereas experi­

SECTION III GENERAL PROBLEMS
126
enced surgeons can often accomplish the same task with
a wide variety of instruments. We have used this to our
advantage by reducing the number of instruments in our
kits. This saves time setting up the room, doing counts
at the end of the case, and taking down and cleaning
the instruments. Experienced surgeons are cognizant
of the importance of an outstanding team and will be
surrounded by individuals (nurses, anesthesiologists,
residents, and technicians) who all contribute to the ef­
ficient pace of an operation. Experienced surgeons an­
ticipate needs and communicate these to nursing and
anesthesia staff well in advance to minimize any waiting
time. An efficient surgeon will also avoid distractions
and interruptions during the course of the operation.
Avoiding Desiccation
George Winter’s landmark paper7 taught us that con­
trary to commonly held beliefs, wound healing is
slowed by allowing wounds to dry out. This is likely to
be true both during and after an operation. Allowing
skin and subcutaneous tissues to desiccate during a
procedure could lead to an inflammatory response and
tissue necrosis.
Choice of Wound Care Technologies
A number of wound care technologies are available to
clinicians to facilitate in the closure of wounds. These
include semisynthetic and decellularized scaffolds,
mechanical devices that facilitate closure, and topical
growth factors. Many of these technologies have been
quite successful in facilitating wound closure. The de­
cision to use these technologies can often be complex
and depends on the particular wound type, the comor­
bidities of the patient, and the constraints of the local
health care system. Use of these technologies should
not excuse the surgeon from doing the other basic
methods to reduce postoperative infections. We have
used mechanical devices such as the vacuum-assisted
closure devices to help us with large open and contami­
nated wounds.8
Preoperative Planning
Skin Preparation
Correct skin preparation can significantly reduce infec­
tion rates. Razors have been generally eliminated from
operating rooms; hair is left alone or clipped. Alcohol-
based prep solutions result in lower rates of infection,
but these solutions have an increased risk of operat­
ing room fires associated with them. Allowing these to
thoroughly dry before surgery will reduce this risk. In
our practice we use alcohol preps below the clavicle,
clip hair, and do not use alcohol preps when there is an
open wound or mucous membrane.
Preoperative Antibiotics
Giving antibiotics before an incision decreases the risk
of infections in many major surgeries. Hospitals have
developed guidelines for specific antibiotics and timing
of administration that are to some degree based on the
local bacteriology of the institution. Much of this has
become a common standard across the United States
as a result of the Surgical Care Improvement Project
(SCIP).9 Prolonged use of prophylactic antibiotics has
been shown in most cases not to make a difference, so
they are typically stopped within 24 hours after the
surgery (48 hours for cardiac surgical cases). This along
with several other measures has substantially contrib­
uted to a reduction in sternal wound infections in our
institution.4
Intraoperative Considerations
Keeping Patients Warm
Hypothermia slows metabolism and can decrease
blood flow. When general anesthesia is induced, there
is peripheral dilation of blood vessels in the skin that
can often result in patients being cooled very quickly.
Maintaining body temperature through the use of
warmed intravenous fluids, passive and active heating
devices, and keeping the room warm are all strategies
to minimize hypothermia.
Keeping Patients Well Oxygenated
Keeping patients well oxygenated is critical for pre­
venting infections and the safe conduct of an operation.
Some have suggested that hyperoxygenation can help
reduce wound infections. In colorectal surgery, using
high levels of oxygen during the surgery (80%) followed
by several hours of high oxygen postoperatively has
produced mixed results. Additional studies are neces­
sary to better define whether there is a specific role for
elevated oxygen levels in the perioperative period.10
Keeping a Sterile Environment
The importance of maintaining a sterile environment
is well appreciated, particularly in a hospital setting
where there are patients who carry resistant organ­
isms. Also, many patients have a depressed immune

127
Chapter 14 Wound Management
system and are more susceptible to infections. Treating
airflow within operating rooms with laminar air flow
filters, wiping down surfaces with antiseptic solutions,
and having adequate sterilization protocols for instru­
ments are all key factors that can lead to a sterile envi­
ronment. Having an active surveillance and monitoring
system to study clusters of infections can be critical to
identifying and modifying policies and procedures that
may be related to infections. This can be particularly
challenging when operating on chronically infected
pressure sores. My preferred technique of excision and
flap closure of an ischial pressure sore is shown in Fig.
14D.2 (Video 14D.1).
Scarring
Scarring is a complication of surgery that adversely
affects patients, yet we still have much to learn about
the process and the optimal way to treat scars. In lower
vertebrate animals such as amphibians, injury results
in a regenerative response. Removing a limb, even in
an adult, will result in a regenerated limb over time.
In mammals, it appears that much of this regenera­
tive response has been lost and replaced by the paired
mechanisms of scarring and wound contraction. For
the surgeon, understanding how these mechanisms
work and intervening when possible can minimize but
not eliminate scarring.
Fig. 14D.2 This patient’s left ischial pressure ulcer was stained with methylene blue, injected with local anesthesia, and excised
(Video 14D.1). (a) Incision. (b) A cavity is raised out of the wound. (c) Additional stain material is removed. (d) Just before removal
of the ulcer. (e–h) After excision the bone is shaved down with an osteotome and a deep bone biopsy is obtained for microbiol­
ogy. The gluteus maximus muscle is mobilized to cover the bone. (e) Before removal. (f) Removed specimen with small stained
specimens on the left.
a
b
c
d
e
f
Continued

SECTION III GENERAL PROBLEMS
128
g
h
i
Fig. 14D.2, cont’d (g) Ostectomy of the ischium with an osteotome. (h) Mobilization of the gluteus maximus muscle to cover the
bone. (i–l) A rotation flap is designed and advanced to close the skin over a drain. (i) Inspection for bleeding (j) Drain placement.
(k) Advancement and preliminary inset of the flap. (l) Final flap inset.
j
k
l
When injured the skin forms a tissue known as a
scar. Actually, scar tissue is in many ways quite similar
in chemical composition to normal dermis; however,
the collagenous bundles in scar tissue are shorter, more
compact, and oriented differently from normal dermis.
The scar tends to change over time. Initially, the scar is
hyperemic with many blood vessels coursing through it.
Later, these vessels seem to go away, and the scar loses
its red appearance. A number of physical, pharmaco­
logic, and energy-based methods have been proposed
to treat scars. This discussion focuses on what surgeons
can do to minimize scarring in elective surgical cases.
Minimizing Tension
Tension is a key driver of scar formation. There are ar­
eas of the body such as the anterior chest and shoul­
ders that have a high propensity for heavy scarring and
other areas such as the scalp and anterior tibia that
rarely form problematic scars. I routinely use slowly
absorbing subcuticular and deep sutures that keep the
tension off of wounds for long periods of time. I use
Steri-Strips (3M Nexcare) and tissue glues to reinforce
the closure and reduce tension. Devices that precisely
apply compression to wounds are currently being mar­
keted and may provide a nice advance in the scar pre­
vention area.
The Role of the Dermis
Heavy scarring seems to have its origin in the deep or
reticular dermis. Superficial burns, laser treatment,
and superficial lacerations all appear to heal with no
scarring. Dunkin et al11 performed experiments in nor­
mal humans and found that in the upper third of the
dermis, healing occurred without scarring. The deeper
reticular dermis with its unique wavy orientation of
extracellular matrix may be key to scar formation.
Orientation of Scars
Langer12 showed that there are natural lines of tension
in the skin. There are also natural wrinkle lines and ar­
eas of movement that surgeons need to consider when
planning scars. Scars should be oriented considering
that when healing occurs they will often decrease in

129
Chapter 14 Wound Management
length. I have learned from burn scar contractures that
when tension is taken off of scars using local tissue re­
arrangement techniques such as z-plasties, scars will
flatten over time.
High-Risk Areas
High-risk areas for scarring include the anterior chest,
back, and shoulders. This may be a combination of the
thickness of the dermis, mechanical stresses in these
areas, and the application kinetics of these external
forces. Care should be taken when closing these areas
of the body to minimize tension and follow high-risk
patients postoperatively to allow for early intervention.
I have found that intralesional triamcinolone injec­
tions are a powerful tool in reducing scarring. I gener­
ally start the injections about 3 months after surgery
and give up to 3 injections spaced 4 to 8 weeks apart.
Silicone sheeting has some efficacy, and I use this se­
lectively in patients who are concerned about scarring.
There are some exciting data on laser scar treatments,
particularly for burns, but this treatment has not been
well proven in high-level clinical trials. Antineoplas­
tic agents are also used by many surgeons, but we
use these rarely in our practice. Combining radiation
therapy with scar excision has been quite successful for
very difficult scars. I work with radiation therapists to
do one radiation therapy session immediately after ex­
cision and closure of scars. I generally apply this tech­
nique only after other scar management techniques
have failed.
Treatment of Hypertrophic Scars
Hypertrophic scars are common after cutaneous burns
but can also occur after injury and elective surgery.
Common to hypertrophic scarring is increased inflam­
mation and tissue that is raised and stiff. There have
been several theories on how to both treat and prevent
hypertrophic scarring. Several scar scales have been
developed to quantify scarring that look at factors such
has height, redness, pigmentation, and irregularity as
indications of the degree of hypertrophic scarring. An­
giogenesis is a central theory for why these develop as
evidenced by the color of the scar and the rich network
of capillaries that are present within the scar tissue.
Methods to quell the angiogenic response, including a
variety of drugs, pressure, laser, and pulsed light, have
been attempted and are often used today. Although
there are some small case series and anecdotal evi­
dence to support many of these methods, robust data
for the best methods are lacking. More data is needed
on these techniques so that clinicians can better choose
from methods to treat these difficult problems.
Treatment of Keloids
Keloids are in many ways similar to hypertrophic scars
but seem to grow past the original edges and can be
substantially more challenging to treat than hypertro­
phic scars. Tension seems to be a major contributing
factor. Keloids tend to be more common in certain areas
of the body and are relatively rare on areas where there
is little movement, such as the scalp and the anterior
tibia. I have had reasonable success treating keloids
with intralesional steroid injection either alone or in
combination with surgery. I have also found immediate
postoperative radiation can be effective for recalcitrant
keloids. There is some concern with using radiation to
treat a benign disease process, but it does appear to be
quite effective. I have also seen some minor pigmenta­
tion changes with radiation therapy. Nevertheless, for
patients with difficult keloids, excision with closure
and immediate postoperative radiation can be quite ef­
fective.
Conclusion
There has been great growth in elective surgery over
the last several years, but this has not totally eliminated
postoperative complications. Two of the most common
wound complications are wound infections and heavy
scarring. The theory and principles in this discussion
are based on the available literature and my practice
and aim to minimize these complications in elective
surgery.
References
1. Halzack NM, Miller TR. Surgical Procedure Volume in
the United States, 2011 and 2013. ASA Newsl. 2015
Apr 1; 79(4). Retrieved from:
resources/publications/newsletter-articles/2015/
april-2015/policy-matters. Accessed February 27,
2016
2. Guideline for Prevention of Surgical Site Infection
1999. Available at
table7-8-9-10-SSI.html. Accessed May 1, 2016
3.
Leavitt BJ, Sheppard L, Maloney C, et al; Northern New
England Cardiovascular Disease Study Group. Effect
of diabetes and associated conditions on long-term

SECTION III GENERAL PROBLEMS
130
survival after coronary artery bypass graft surgery. Cir­
culation 2004;110(11 Suppl 1):II41–II44
4. Matros E, Aranki SF, Bayer LR, McGurk S, Neuwalder
J, Orgill DP. Reduction in incidence of deep sternal
wound infections: random or real? J Thorac Cardio­
vasc Surg 2010;139(3):680–685
5. Thingstad P, Taraldsen K, Saltvedt I, et al. The long-
term effect of comprehensive geriatric care on gait
after hip fracture: the Trondheim Hip Fracture Tri­
al—a randomised controlled trial. Osteoporos Int
2016;27(3):933–942
6. Carty MJ, Chan R, Huckman R, Snow D, Orgill DP. A de­
tailed analysis of the reduction mammaplasty learning
curve: a statistical process model for approaching surgi­
cal performance improvement. Plast Reconstr Surg 2009;
124(3):706–714
7. Winter GD. Formation of the scab and the rate of epi­
thelization of superficial wounds in the skin of the
young domestic pig. Nature 1962;193:293–294
8. Chen YE, Gerstle T, Verma K, Treiser MD, Kimball AB,
Orgill DP. Management of hidradenitis suppurativa
wounds with an internal vacuum-assisted closure
device. Plast Reconstr Surg 2014;133(3):370e–377e
9. Surgical Care Improvement Project 2006. Available at

provement_project
10. Sohn VY, Steele SR. Temperature control and the role
of supplemental oxygen. Clin Colon Rectal Surg 2009;
22(1):21–27
11. Dunkin CS, Pleat JM, Gillespie PH, Tyler MP, Rob­
erts AH, McGrouther DA. Scarring occurs at a criti­
cal depth of skin injury: precise measurement in a
graduated dermal scratch in human volunteers. Plast
Reconstr Surg 2007;119(6):1722–1732, discussion
1733–1734
12. Langer K. On the anatomy and physiology of the
skin. I. The cleavability of the cutis. (Translated from
Langer, K. (1861). Zur Anatomie und Physiologie der
Haut. I. Uber die Spaltbarkeit der Cutis. Sitzungsb­
ericht der Mathematisch-naturwissenschaftlichen
Classe der Kaiserlichen Academie der Wissen­
schaften, 44, 19.). Br J Plast Surg 1978;31(1):3–8

131
Complications in microsurgery have similarities with
complications in any area of surgery; they can affect the
outcome of the patient’s condition and discourage the sur­
geon and the medical team. Microsurgery is a technique,
however, and no greater auras should be bestowed upon
it. Thus all of the details and principles of surgery should
be followed as they are for any surgical procedure. Perhaps
one of the significant differences, though, in microsurgical
complications is that there is a greater time investment and
potential morbidity associated with the complications. Mi­
crosurgical complications can be grouped into very specific
instances in which complications are more likely to occur
(Box 15.1).
Avoiding Unfavorable
Results and Complications in
Microsurgery
Indications
Perhaps one of the greatest faults of any microsurgeon is
that they perceive microsurgery as a hammer with every
case presentation being a nail. A microsurgical reconstruc­
tive procedure may not be the most appropriate for a given
patient or case scenario. Understanding that the anatomy,
previous history of radiation, or comorbidities may signifi­
Microsurgery
Abigail M. Cochran and Michael W. Neumeister
CHAPTER
15
Summary Box
Complications Associated with Microsurgery
•• Complications of prolonged operations in microsurgery:
○
○Anesthesia-related risks:
–
– Myocardial infarction
–
– Embolic event (deep venous thrombosis/
pulmonary embolism)
–
– Aspiration pneumonitis
–
– Hypoxic brain injury
–
– Death
○
○Nerve injury
○
○Pressure sore development
○
○Postoperative delirium
○
○Respiratory failure and ventilator dependence
•• Complications related to poor flap design:
○
○Bulk of flap
○
○Incomplete coverage of defect
○
○Vessel tension or kinking (leading to
intraluminal clots and flap compromise)
○
○Inset under tension
○
○Donor site–related complications

SECTION III GENERAL PROBLEMS
132
those for which the microsurgical procedure may be associ­
ated with a higher morbidity or even mortality in certain pa­
tients. Such conditions do not necessarily preclude free flap
reconstruction, but these patients should be given thought­
ful consideration and counseling about their potential in­
creased risks of flap failure and potential complications.1–5
These conditions are included in Box 15.3.
Local or regional flaps may or may not prove better
than the microsurgical free tissue transfer counterparts in
some situations of complex reconstruction. The surgeon
must evaluate what is best for the patient in terms of goals
of the surgery, functional outcome, and, finally, aesthetic
results. In a palliative surgery in which patient longevity
is already determined by the cancer staging, local or re­
gional flaps may actually suffice to provide the objectives
of surgery that include wound closure and some element of
functional recovery. Complex microsurgical procedures that
prolong the patient’s time in the operating room may lead
to increased blood loss, hypothermia, and morbidity and
may not be indicated in these palliative circumstances.1,6,7
This does not mean that reconstructive microsurgery is not
part of the algorithm of palliative surgery, but the surgeon
must be aware of the increased risk of complications with
microsurgery.
Microsurgery is a technique used in the treatment of
patients for various reconstructive procedures. Microsur­
gery should not be considered the only technique that pa­
tients are offered to best suit their needs. Complications of
prolonged operations are addressed in the Summary Box.
Execution
Design
Every defect and every wound that is evaluated by the mi­
crosurgeon is unique in many ways. It is unique in the size,
in the depth, in the location, in the composite structures
that are involved, and in the functional loss that has ensued
cantly affect the overall outcome should play an important
role in the decision-making regarding microsurgical recon­
struction of any part of the body. Contraindications to re­
constructive microsurgery are included in Box 15.2.
Patient Selection
Every patient is unique. The reconstructive needs of indi­
vidual patients demand a variety of reconstructive options
and procedures. This is similar to other areas of medicine
in which different patients are treated with different mo­
dalities to meet similar ends. As a physician treats hyper­
tension, one patient may be prescribed one medication
while another receives something different. Treatment in
microsurgery is similar, with a given flap chosen specifi­
cally for a given patient to fit form and function. One of the
challenges, however, is selecting patients who will not be
subject to complications of the surgery.
What may be more important for microsurgeons to un­
derstand are the factors that are not the absolute contrain­
dications to performing microsurgery procedures but rather
Box 15.3
•• Smoking
•• Obesity
•• Diabetes
•• History of hypercoagulability
•• Collagen vascular disorders
•• Use of medications that increase
thromboembolic events (e.g., tamoxifen)
•• History of radiation
•• Steroid use/immunosuppression
•• Severe atherosclerotic disease
•• Renal disease
•• American Society of Anesthesiologists class (>3)
Patient Factors Contributing
to Increased Complications
in Microsurgery
Box 15.1
•• Indications
•• Selection
•• Execution
○
○Design
○
○Pedicle selection
○
○Flap elevation
○
○Recipient vessel procurement
○
○Flap inset
○
○Anastomosis
○
○Clamp release
○
○Pedicle resting position
○
○Final wound closure
○
○Body positioning
•• Flap monitoring
•• Anticoagulants
•• Rehabilitation
Categories for Microsurgery
Complications
Box 15.2
•• Concomitant life-threatening injuries
•• Patient instability
•• Patients in hospice or receiving end-of-life care
•• Patients better served by an amputation or
prosthesis
•• Patient noncompliance
Contraindications to
Microsurgery Reconstruction

133
Chapter 15 Microsurgery
design may arise from a number of different approaches
to the reconstructive problem (see Summary Box). The
design of the flap needs to meet the overreaching goals of
the reconstructive surgery such that all required composite
tissues are incorporated in the flap, the pedicle will reach
the appropriate recipient vessels, the donor site morbidity
is minimized, and flap surveillance is optimized11,12 (Figs.
15.1 and 15.2).
as a result of the preceding trauma or cancer resection. Flap
design, therefore, is often rather innovative and must take
into consideration all aspects of form and function. The
goal is to restore normalcy. Over the last 30 years, the num­
ber of available donor sites has blossomed to allow the sur­
geon to choose the most appropriate compatible tissue that
fulfills the goals of reconstruction yet minimizes the donor
defects and optimizes patient satisfaction.8–11 Failures in
Fig. 15.1 Flap design and selection. (a,b) A muscular flap with a skin graft, such as the free rectus shown in this patient, offers stable and
well-vascularized coverage of the defect. (c,d) However, the bulk of this flap prevents the patient from wearing a shoe. Better options, such
as a free fasciocutaneous or fascial flap with skin graft, not only provides similar successful coverage, but also results in a more functional
final contour for the patient.
a
b
c
d
Fig. 15.2 Flap design and selection. (a,b) This lower extremity wound was covered with a thin fascial flap and skin graft. (c,d) The outcome
is stable coverage and a nicely contoured flap, which allows excellent range of motion. Furthermore, the flap bulk is reduced and allows
the patient to wear a shoe.
a
c
b
d

SECTION III GENERAL PROBLEMS
134
formed flawlessly. Struggling in a poor recipient site with
poor quality vessels will lead to poor outcomes!
There are many situations that may create a challenge
to identifying the appropriate vessels for free tissue transfer.
Such situations may include previous radiation, recurrent
dissection, history of local infection, and location within the
zone of trauma.1,14 Inflammation, fibrosis, and atheroscle­
rosis change the native characteristics of the arteries espe­
cially. The arteries become more friable, are susceptible to
intimal wall separation, and invite clot formation.
Avoiding Clot Formation
Uninjured, disease-free vessels are devoid of any foreign
material within the lumen. This is how the microsur­
geon should want to see the lumen when performing the
anastomosis. Lumen adulterants promote clot formation.
With a little saline irrigation, the lumen should appear pa-
tent with white intima. Any haziness, red spots (clot frag­
ments), webbing, free suture material, or gauze lint within
the lumen needs to be removed before the anastomosis is
complete or platelets will aggregate, form a clot, and result
in vascular occlusion and, ultimately, flap compromise. Ad­
ventitial stripping is less important in clot formation and
vessel preparation than suture placement. Thus loose ends
of adventitia near the lumen edge may invert into the lu­
men during suturing. Adventitia within the lumen will be a
nidus for platelet aggregation and clot formation. That does
not mean the surgeon needs to strip a vessel 2 to 3 cm away
from the anastomosis site.
Other circumstances that lead to clot formation include
intimal tears, retained long ends of tied sutures within the
lumen, vascular clamp trauma, and injury to the vessel dur­
ing vessel dissection. It is important for the surgeon to real­
ize that both the surgeon and the assistant can cause intimal
tears and vessel damage during early dissection. A dissec­
tion that is too aggressive may result in instrument trauma
to the vessels. Similarly, having the assistant hold and pro­
vide some tension to vessel branch ends or suture ends at
the anastomosis site may cause intimal tearing if too much
tension is applied. The vessel end will need to be freshened
again if a tied suture is pulled out or a tear is noticed at
the suture site (Box 15.4). Whenever intimal damage is ob­
served, it is prudent for the surgeon to cut the vessel back
to an area proximal to the damaged vessel. This will set the
stage for the best chances for patency.16,17
Pedicle Selection
Microsurgical procedures rely on adequate donor and re­
cipient vessels that are coapted without tension in a non­
hostile environment. There are many principles involved in
this aspect of reconstructive microsurgery. The recipient
vessels should be nontraumatized, be easily accessible, and
have significant caliber to provide inflow and outflow.13
Vessels identified within an area of inflammation or trauma
or that is at risk of secondary contamination are inappro­
priate as recipient vessels.14 In 1992 Dr. Ian Taylor15 pro­
vided a total body overview of perforator anatomy where
blood vessels arise from deeper main vessels to supply
overlying angiosomes of skin. Each of those angiosomes or
skin paddles could be transferred as a separate free tissue
transfer based on one perforator.4
Microsurgeons, however, must use the most appropri­
ate flap based on the most appropriate vessel that is per­
haps based on the most appropriate perforator to achieve
the most appropriate reconstructive result. Picking the right
length of a pedicle is a “Goldilocks” phenomenon. If it is too
long, it will kink. Kinking results in vascular obstruction and
secondary clotting with flap compromise. If the vessel is too
short and the anastomosis is performed under tension, the
lumen size is diminished and flow dynamics change, which
may lead to intraluminal clots and flap compromise.4 There­
fore the “just right” pedicle length is imperative to secure
adequate blood flow (Fig. 15.3).
Recipient Vessel
Identifying the best recipient artery and vein for the free
tissue transfer is arguably one of the most important con­
siderations in microsurgery. Recipient vessels must be eas­
ily accessible and in an easy site of surgery for the anas­
tomosis. The vessels need to be accessible to the primary
surgeon and the assistant for the anastomosis to be per­
Box 15.4
•• Incomplete removal of adventitia
•• Intimal tears
•• Instrument trauma
•• Incomplete removal of existing clot in lumen
•• Existing trauma to the vessel wall
Intraoperative Factors
Leading to Clot Formation
Fig. 15.3 Pedical position. This scalp replant demonstrates a nice
resting curve of the vessels. The pedicle must lie in a smooth curve
without too much tension, and similarly without too much redun­
dancy, which may lead to kinking.

135
Chapter 15 Microsurgery
erative swelling adds to the compression of the vessels. This
complication is avoided by harvesting flaps slightly larger
than a given defect. The opposite is true, however, for flaps
inset into cavities, such as deep inferior epigastric perfora­
tor (DIEP) flaps in a skin-sparing mastectomy (Fig. 15.4).
Anastomosis
All of the principles that apply to avoiding clot formation
also apply to avoiding complications when performing the
vascular anastomosis. In addition, a number of technical
points should be emphasized that minimize the chance
of platelet aggregation and thrombus formation18 (Table
15.1).
Flap Inset
The main caution with flap inset is the position of the vas­
cular pedicle. Kinking of the artery or vein is a complication
that leads to vascular occlusion and clot formation within
the vessels.
Although it is preferred to have a pedicle lie in a straight
line after the anastomosis is complete, dramatic curves can
be tolerated as long as the pedicle is not bent at the anas­
tomosis site. The anastomosis is a point of weakness in the
normal elastic properties of the blood vessel. A native vessel
curves as a unit, whereas at the site of the anastomosis, the
vessel caves in on the concave side of the bending vessel to
form a 90-degree or smaller angle, which impedes flow, in­
creases resistance and turbulence, and forms a thrombosis.
The pedicle should be trimmed to an appropriate length so
the vessels are not forced to kink when the flap is inset or
when body position is altered postoperatively. Alternatively,
the surgeon must be sure a long pedicle has a gentle curve
that will not fold upon itself. If the pedicle is too long and
the surgeon does not feel comfortable resecting some vessel
and redoing the anastomosis, an easy fix is to place a piece
of fat or muscle on the inner aspect of the curving vessel,
preventing it from kinking at that site.19,20
Flaps that are closed under tension are also prone to
vascular compromise as the pedicle is compressed. Postop­
Table 15.1 Technical anastomotic
suture tips to prevent patency
failure
Technical tip
Rationale: clot producers
Do not grasp the edge of
the lumen.
Trauma exposes collagen.
Remove all lumen debris.
Platelets will adhere.
Do not use side branches
as handles.
Intimal tears lead to
collagen exposure.
Use atraumatic dilators
in the lumen.
Trauma causes intimal
tears and collagen
exposure.
Clean suture of adherent
blood.
Blood drags a clot into the
lumen.
Use the curve of the
needle while suturing.
Lifting the needle may tear
the lumen.
Suture from inside out in
lumens with intimal peel.
Intimal flaps will capture
platelets or clots.
Limit compression of
vascular clamps.
Intimal damage leads to
collagen exposure.
Fig. 15.4 Flap inset. This patient underwent deep inferior epigastric perforator (DIEP)
flap reconstruction. Although her flap was successful, the compromise and impend­
ing necrosis of the mastectomy skin flaps were not recognized at the time of the initial
operation. The de-epithelialized DIEP flap became exposed, and this ultimately led
to flap loss. Inset without complete de-epithelialization in this scenario would have
preserved the healthy abdominal skin for final inset once the mastectomy flaps had
proven nonviable.

SECTION III GENERAL PROBLEMS
136
Flap Salvage
If a problem with a flap is identified early in the postop­
erative period, emergent return to the operating room for
exploration is paramount. The window of opportunity for
flap salvage is narrow, with the highest salvage rates being
within the first 24 hours postoperatively.23–25
Upon exploration of a compromised flap, vessel patency
is assessed. The artery and/or vein may be compromised with
intravascular clot, which is the most common reason for flap
reexploration.4 The anastomosis is either opened on one side
to minimize suture disruption or excised to have full view of
the proximal and distal lumens. The clot is gently removed,
ensuring that the micro–jeweler forceps do not traumatize
the intima, which would act as another nidus for platelet ag­
gregation.26 The lumen must be pristinely clean after clot re­
moval or another clot will form. If a clot has propagated fur­
ther into the vessel, a 2-mm Fogarty catheter can be inserted
into the vessel to drag the clot out. Tissue plasminogen acti­
vator may also be used as an intravascular means of throm­
bolysis. Streptokinase and urokinase are no longer available
for use for thrombolysis. After successful thrombolysis with
restoration of blood flow, the patient will be heparinized to
prevent repeat vascular thrombosis27,28 (Fig. 15.5).
Anticoagulants
Many agents have been used to prevent clot formation or
thrombus propagation. Currently, clinical prospective ran­
domized trials do not exist to identify a need for any type of
anticoagulant in microsurgery. One might say that the best
anticoagulant is good technique. With that in mind, some
Postoperative Complications
Flap Monitoring
Vascular patency can be monitored in many ways, with
the ultimate goal to identify intravascular clot forma­
tion as soon as it happens. Although most microsurgeons
use some form of flap monitoring, there is no one proven
method that rises above others with superior sensitivity or
specificity. Clinical evaluation is the most commonly used
flap monitor amongst seasoned microsurgeons. Flap ex­
amination for turgor, color, temperature, and capillary refill
offers the most valuable information on the health of the
flap and the patency of the artery and vein.21,22 No matter
what monitoring protocol is used, the key to preventing
flap complications is to act on changes. Blue engorged flaps
have a venous outflow problem. White, cool flaps with poor
turgor have an arterial inflow problem. Occasionally, the
position of the patient may have kinked a vessel, and simple
repositioning solves the problem. This is rare, however. In
most cases the vessels require exploration and anastomotic
revision. If the flap is severely congested, bedside suture re­
moval or vein incisions can prevent further tissue damage
or clot formation by allowing the blood to drain from the
flap. This will result in significant blood loss mandating im­
mediate return to the operating room for vein repair.
Early detection of vascular compromise is the goal of all
flap-monitoring methods. Temperature monitors, tissue pH
indicators, oximeters, and indwelling catheters may iden­
tify early vascular compromise, but the surgeon should be
aware that each monitoring method has its own inherent
errors.21,22
Fig. 15.5 Flap inset. (a–c) This scapular flap to the dorsum of the hand demonstrates
anatomic inset with normal color and capillary refill. (d) Postoperative venous occlusion
resulted in color change, brisk capillary refill, and obvious swelling, indicating venous
compromise and impending flap failure. Immediate surgical intervention of the venous
compromise is warranted. The clot was lysed with tissue plasminogen activator for sal­
vage.
d
a
b
c

137
Chapter 15 Microsurgery
area of microsurgery (Fig. 15.6). Avoiding complications
in the rehabilitation period requires good communication
among all individuals involved in the care of the patient.
This includes the treating surgeons, residents, students,
nurses, therapists, and the patient. Limitations in position­
ing and activity need to be specifically defined to prevent
flap compromise.31–33
Conclusion
There are many steps involved in performing microsurgery.
The more steps and points of treatment for any given sur­
gery, the more opportunity there is for potential complica­
tions. Adherence to sound principles of microsurgery and
to diligent postoperative surveillance will keep complica­
tion rates low. Microsurgical flap loss is not common, so
this procedure should be more than 95% successful. When
complications do occur, early management and identifica­
tion of the complicating stimulus will usually result in sal­
vage of the flap.
surgeons will use one or more of a variety of pharmaco­
logic therapeutics available.29 Intraoperative clot formation
in vessels is more common with replants than with elective
free tissue transfer. The trauma of amputations may lead to
multiple levels of vessel damage, each fostering platelet ag­
gregation and clot formation. Postoperative heparinization
may be warranted in these situations.15,23,29 Enoxaparin has
been associated with greater complication rates compared
with heparin. The most common complication is hema­
toma formation, which compromises vessel patency by
direct pressure or skin viability through pressure necrosis
or capillary bed compression.23,30 This complication is pre­
vented by avoiding the use of enoxaparin in microsurgery.
Rehabilitation
Postoperative complications may arise during the rehabili­
tation phase of the patient’s treatment. The rehabilitation
is dependent on the location and function of the free tissue
transfer. Complications may or may not be specific to the
Fig. 15.6 Postoperative body positioning/rehabilitation. (a,b) This patient underwent a free gracilis muscle flap with skin graft to the lower
extremity. (c,d) Because of a lack of postoperative patient counseling, the patient was resting with his leg in a dependent position, which
lead to decreased venous return and significant flap edema and congestion. Establishing a plan for patient positioning and, in the case of
lower extremity flaps, a dangling protocol, is paramount to flap success.
a
b
c
d
References
1. Ishimaru M, Ono S, Suzuki S, Matsui H, Fushimi K, Yasu­
naga H. Risk factors for free flap failure in 2,846 patients
with head and neck cancer: a national database study in
Japan. J Oral Maxillofac Surg 2016;74(6):1265–1270
2. Klein HJ, Fuchs N, Mehra T, et al. Extending the limits of
reconstructive microsurgery in elderly patients. J Plast
Reconstr Aesthet Surg 2016;69(8):1017–1023
3. O’Neill AC, Haykal S, Bagher S, Zhong T, Hofer S. Predictors
and consequences of intraoperative microvascular prob­
lems in autologous breast reconstruction. J Plast Reconstr
Aesthet Surg 2016;69(10):1349–1355
4. Demir A, Kucuker I, Keles MK, Demirtas Y. The effect of
learning curve on flap selection, re-exploration, and sal­
vage rates in free flaps; A retrospective analysis of 155
cases. Microsurgery 2013;33(7):519–526
5. De Pinho Pessoa BB, Menezes Cavalcante BB, Maia MP, et
al. Effect of tamoxifen on arterial microvascular anasto­
mosis. Microsurgery 2007;27(4):286–288
6. Kwok AC, Agarwal JP. An analysis of free flap failure using
the ACS NSQIP database. Does flap site and flap type mat­
ter? Microsurgery 2016:1–8
7. Wong AK, Joanna Nguyen T, Peric M, et al. Analysis of
risk factors associated with microvascular free flap fail­
ure using a multi-institutional database. Microsurgery
2015;35(1):6–12

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cle in microvascular free tissue transfer. Microsurgery
2016;36(7):613–614
21. Han ZF, Guo LL, Liu LB, et al. A comparison of the Cook-
Swartz Doppler with conventional clinical methods for
free flap monitoring: a systematic review and a meta-
analysis. Int J Surg 2016;32:109–115
22. Moubayed SP, Mourad M, Urken ML. What are the opti­
mal monitoring techniques in head and neck microvas­
cular reconstruction? ORL J Otorhinolaryngol Relat Spec
2016;78(5):241–244
23. Glass GE, Nanchahal J. Why haematomas cause flap fail­
ure: an evidence-based paradigm. J Plast Reconstr Aesthet
Surg 2012;65(7):903–910
24. Novakovic D, Patel RS, Goldstein DP, Gullane PJ. Salvage
of failed free flaps used in head and neck reconstruction.
Head Neck Oncol 2009;1:33
25. Davies A, O’Neill JK, Wilson SM. Microvascular lifeboats:
a stepwise approach to intraoperative venous congestion
in DIEP flap breast reconstruction. Plast Reconstr Surg
2015;135(3):638e–639e
26. Hong KY, Chang LS, Chang H, Minn KW, Jin US. Direct
thrombectomy as a salvage technique in free flap breast
reconstruction. Microsurgery 2016
27. Chang EI, Mehrara BJ, Festekjian JH, Da Lio AL, Crisera CA.
Vascular complications and microvascular free flap sal­
vage: the role of thrombolytic agents. Microsurgery 2011;
31(7):505–509
28. Panchapakesan V, Addison P, Beausang E, Lipa JE, Gilbert
RW, Neligan PC. Role of thrombolysis in free-flap salvage. J
Reconstr Microsurg 2003;19(8):523–530
29. Chien W, Varvares MA, Hadlock T, Cheney M, Deschler
DG. Effects of aspirin and low-dose heparin in head and
neck reconstruction using microvascular free flaps. La­
ryngoscope 2005;115(6):973–976
30. Reiter M, Kapsreiter M, Betz CS, Harréus U. Perioperative
management of antithrombotic medication in head and
neck reconstruction—a retrospective analysis of 137 pa­
tients. Am J Otolaryngol 2012;33(6):693–696
31. Kolbenschlag J, Bredenbroeker P, Daigeler A, et al. Changes
of oxygenation and hemoglobin-concentration in lower
extremity free flaps during dangling. J Reconstr Micro­
surg 2014;30(5):319–328
32. Ridgway EB, Kutz RH, Cooper JS, Guo L. New insight into
an old paradigm: wrapping and dangling with lower-ex­
tremity free flaps. J Reconstr Microsurg 2010;26(8):559–
566
33. Rohde C, Howell BW, Buncke GM, et al. A recommended
protocol for the immediate postoperative care of lower
extremity free-flap reconstructions. J Reconstr Microsurg
2009;25(1):15–19
8. Harry LE, Sandison A, Pearse MF, Paleolog EM, Nanchahal
J. Comparison of the vascularity of fasciocutaneous tissue
and muscle for coverage of open tibial fractures. Plast Re­
constr Surg 2009;124(4):1211–1219
9. Kroll SS, Schusterman MA, Reece GP, et al. Choice of flap
and incidence of free flap success. Plast Reconstr Surg
1996;98(3):459–463
10. Yazar S, Lin CH, Lin YT, Ulusal AE, Wei FC. Outcome com­
parison between free muscle and free fasciocutaneous
flaps for reconstruction of distal third and ankle trau­
matic open tibial fractures. Plast Reconstr Surg 2006;
117(7):2468–2475, discussion 2476–2477
11. Ragbir M, Brown JS, Mehanna H. Reconstructive consider­
ations in head and neck surgical oncology: United King­
dom National Multidisciplinary Guidelines. J Laryngol
Otol 2016;130(S2):S191–S197
12. Dornseifer U, Kleeberger C, Kimelman M, et al. Less is
more? Impact of single venous anastomosis on the in­
trinsic transit time of free flaps. J Reconstr Microsurg
2017;33(2):137–142
13. Saint-Cyr M, Youssef A, Bae HW, Robb GL, Chang DW.
Changing trends in recipient vessel selection for micro­
vascular autologous breast reconstruction: an analysis of
1483 consecutive cases. Plast Reconstr Surg 2007;119(7):
1993–2000
14. Spector JA, Levine S, Levine JP. Free tissue transfer to the
lower extremity distal to the zone of injury: indications
and outcomes over a 25-year experience. Plast Reconstr
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15. Taylor GI, Palmer JH. ‘Angiosome theory’. Br J Plast Surg
1992;45(4):327–328
16. Seo MH, Kim SM, Huan F, Myoung H, Lee JH, Lee SK. Anal­
ysis of Microvascular Free Flap Failure Focusing on the
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17. Mücke T, Wolff C, von Düring M, Mitchell DA, Ritschl
LM, Fichter AM. Form and size matter: increased risk of
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thelial lesions. J Reconstr Microsurg 2017;33(1):40–44
18. Kim E, Singh M, Akelina Y, Shurey S, Myers SR, Ghanem
AM. Effect of microvascular anastomosis technique on
end product outcome in simulated training: a prospective
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2016;32(7):556–561
19. Nelson JA, Fischer JP, Grover R, et al. Vein grafting your
way out of trouble: examining the utility and efficacy of
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20. Scaglioni MF, Kuo YR, Chen YC. A simple and effec­
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139
Chapter 15 Microsurgery
Discussion by Milomir Ninkovic
Reconstructive microsurgery surgery has progressed
from its initial ability to achieve wound coverage us­
ing free tissue transfer to a new level of sophistica­
tion in regard to restoration of function and aesthetics
when dealing with acquired or congenital problems in
all body regions. The ability to select the optimal re­
constructive procedure based on suitable donor tissue
and to transfer these directly to the site of the defects
has permanently altered many reconstructive methods
and has expanded the indications for microsurgery.
Advances in the understanding of vascular and nerve
supply have established the unique role of free tissue
transfer in reconstructive surgery. As the success rate
of free flaps has improved to surpass 95%, their indica­
tions have changed from serving as the last reconstruc­
tive option to one that achieves the best reconstruction
possible.
Personal Approach
My goal for reconstructive microsurgery is to obtain
the best possible functional and aesthetic result with
minimal donor site morbidity. Surgical planning is cru­
cial to achieve this; as Napoleon said, “A battle should
be won before the first shot.”
First, the plan must be developed based on the indi­
vidual patient’s reconstructive requirements (including
appropriate assessment of damaged or missing struc­
tures in relation to anatomic, functional, and aesthetic
requirements) (Fig. 15D.1).
The most important part of preoperative decision-
making is determining these reconstructive require­
ments. The guidelines presented in Box 15D.1 must also
be taken into consideration.
Flap characteristics can be adapted based on the
reconstructive requirements. I routinely enlarge the
Box 15D.1
•• Definition of the anatomic, functional,
and aesthetic reconstructive requirements
(assessment of damaged or missing
structures)
•• Evaluation of the flap characteristics: size,
bulk, sensibility, pliability, durability, motor
units, etc.
•• Determination of the cause of the defect,
whether acquired (trauma, tumor resection)
or congenital (vascular malformation,
aplasia)
•• Determination of timing of flap closure:
primary, delayed, or secondary
•• Assessment of donor site morbidity, which
is crucial in free flap selection
•• Understanding of the possible needs for a
secondary procedure, such as tendon, nerve,
or bone grafting
•• Assessment of age-related factors (there is
no age limit, but the general condition of the
patient is essential)
•• Evaluation of the capability and experience
of the surgical team
•• Assessment of the equipment available in
the hospital
Guidelines for Planning
Reconstructive
Microsurgical Procedures
Fig. 15D.1 Guidelines for optimal
choice of reconstructive microsur­
gical procedure.
Anatomic Requirements
Localization
Extent of soft tissue and bone loss
(size and depth)
Extent of nerve injury
Quality of vascular supply
Presenting infection
Quality of neighboring tissue
Functional Requirements
Restoration of mobility and sensibility
Effective wound closure
Reconstructive Requirements
Assessment of damaged structures
Aesthetic Requirements
Based on the body region

SECTION III GENERAL PROBLEMS
140
gracilis muscle flap through microscopically aided in­
tramuscular dissection. It is possible to achieve a very
flat and thin flap with extension to three to four times
the muscle surface with excellent muscle blood supply.1
Preexpansion of fasciocutaneous donor site of po­
tential free flaps, primarily groin, scapular, and antero­
lateral perforator skin flaps, is easily feasible and pro­
vides enough tissue for aesthetic unit reconstruction,
especially in burn patients, resulting in less scarring and
morbidity at the donor site.2 Furthermore, preexpansion
results in thinning of the flap through fat tissue atrophy,
with increased pliability, vascularity, and elasticity for
reconstruction of aesthetic units at the neck and face.
However, this method is a two-stage procedure and is
not without risk.2
The management of complex injuries of the extrem­
ities or other parts of the body has changed with the
development of reconstructive microsurgery. Micro­
surgical techniques, including free tissue transfer, have
enabled surgeons to reconstruct or salvage injured or
amputated limbs. The timing of soft tissue reconstruc­
tion using flap techniques is extremely important but
still controversial. Since the mid-1980s there has been
increasing enthusiasm for early flap coverage of severe
extremity injury. Byrd and colleagues3,4 pointed out the
importance of early aggressive wound management and
soft tissue coverage with a flap within 5 days in severe
injuries of the lower extremity. Godina5 emphasized the
importance of early coverage within the first 72 hours
and the advantages of free flap reconstruction versus a
local flap technique. Lister and Scheker6 first defined the
emergency free flap as “a flap transfer performed either
at the end of primary débridement or within 24 hours
after the injury.” To standardize nomenclature in free
flap wound closure, Ninkovic and associates7–9 presented
three categories: “primary free flap closure” (within 24
hours), “delayed primary free flap closure” (2 to 7 days),
and “secondary free flap closure” (after 7 days). This sys­
tem is analogous to the standard terms “primary,” “de­
layed primary,” and “secondary simple wound closure.”
It is consistent with known biologic and microbiologic
principles of wound closure in general and provides
a simple basis for classifying free flap wound closure.
Negative-pressure wound therapy (NPWT) extends the
time for definitive coverage using free flaps. However,
the principles of wound closure using free flaps are the
same, and long-term NPWT causes significant scarring
and delayed wound closure, which are significant dis­
advantages.
My preferred treatment for an isolated complex ex­
tremity injury with a soft tissue defect is primary free
flap closure, which provides improved functional and
aesthetic results and psychological benefits through
lowered patient morbidity, decreased invalidity, and sig­
nificantly lower costs. However, early radical débride­
ment is the most important aspect of wound manage­
ment, because the bacterial count doubles every 6 to 8
hours and produces clinical infection when it reaches
more than 105 organisms per gram of tissue. Radical dé­
bridement is always done under tourniquet control. All
dead and devitalized tissue is removed, including small
devascularized bone fragments. Débridement is per­
formed through healthy tissue, similar to malignancy
radical resection, to ensure that all nonviable tissue is
removed. Important neurovascular structures and ten­
dons are preserved and débrided if they are damaged
but structurally intact. The use of well-vascularized free
flaps as primary free flaps provides adequate healthy tis­
sue to allow generous radical débridement of traumatic
wounds. Moreover, primarily soft tissue cover preserves
bone fragments; obviates bone resection; and permits
primary nerve repair or nerve grafting and tendon re­
pair, transposition of muscles and tendons, and bone
grafting if necessary.5–9
An important factor in preventing problems in post­
operative blood supply is avoiding compression and
tension at the point of vascular anastomosis. The best
way to achieve this is to plan a perforator-pedicled skin
island flap for coverage of microvascular anastomoses
in myocutaneous flaps to extended fasciocutaneous flap
for coverage of vascular anastomosis10 (Figs. 15D.2 and
15D.3).
Thus the vascular anastomoses can be placed be­
neath healthy tissue outside the zone of injury, which
should be a main principle in microvascular reconstruc­
tion.5–10 Dissection of the myocutaneous perforators to
the skin island does not lead to a prolonged operating
time, which is of practical relevance because the ves­
sels can be easily identified and localized with modern
Doppler systems and the perforator does not need to be
isolated—it can be moved together with the surrounding
fat and muscle tissue (see Fig. 15D.2).
In addition, the skin island of myocutaneous flaps
not only serves as an ideal flap-monitoring system but
can also be used as a pedicled fasciocutaneous or cuta­
neous flap conjoined with the transferred muscle flap.
By moving the pedicled skin island or a part of it sup­
plied by the myocutaneous perforators in any desired
direction, a tension-free wound closure not only above
the vascular pedicle but everywhere can be obtained.
Breaking a possible contractual ring and lengthening of
the scar may best be achieved by rotating or transpos­
ing the skin island of a myocutaneous free flap, as men­
tioned previously.
The skin island of a myocutaneous flap can also be
used for coverage of parts of the presenting defect that
are not covered by the muscle. This may reduce the to­
tal amount of muscle that must be harvested for total
defect coverage or may allow the coverage of large de­
fects that cannot be reached by the muscle surface alone

141
Chapter 15 Microsurgery
without increasing donor site morbidity. A large skin is­
land increases the blood supply of the distal part of the
muscle flap. A bulky skin island above the muscle can be
avoided by resecting excess fat tissue to improve pliabil­
ity of the skin island flap. At the periphery of the skin
island, an oblique subcutaneous fat resection should be
performed before it is fixated in its new position on the
muscle to avoid creating a step deformity at the border
between the skin island and the muscle and surround­
ing tissue. This technique may provide a better contour
of the reconstructed area and thus a better aesthetic ap­
pearance (see Figs. 15D.2 and 15D.3).10,11
The major role of free flaps remains coverage of dif­
ficult wounds caused by severe injury, burns, tumor re­
section, or other trauma. However, after the first suc­
cessful functioning neurovascular muscle transfer on
experimental animals in 1970, work in this area has led
to exciting concepts regarding the capability of using
functioning muscle to restore facial expression, for lower
lip reconstruction,12 to improve extremity flexion or ex­
tension, to augment cardiac compression, or to replace
a paralyzed bladder detrusor.13
As the success rate of free flaps has improved, they
are increasingly recognized as a method to achieve the
best functional and aesthetic reconstruction possible.14 
Conclusion
Successful microsurgical reconstruction provides op­
timal functional and aesthetic results with minimal
donor site morbidity. It can be achieved by develop­
ing an individualized approach; performing appropri­
ate evaluation of all reconstructive requirements; and
adequate free flap selection, design, tailoring and use.
In addition, the surgeon must take into consideration
possible causes of the defect (acquired or congenital),
the timing of flap closure (primary, delayed, or sec­
ondary), donor site morbidity, needs for a potential
secondary procedure, age and general condition of the
patient, and the capability and experience of the surgi­
cal team and equipment available in the hospital. This
way of approaching different microsurgical indications
can guarantee superior results and very happy patients
and surgeons.
Fig. 15D.2 (a) Perforator-pedicled skin island flap for coverage of microvascular anastomoses in a myocutaneous gracilis muscle
flap. (b) Appropriate insertion of flap. (c) Final result 1 year after the reconstruction.
a
b
c
Fig. 15D.3 Extended fasciocutaneous flap
(extended lateral arm flap) for coverage of a
vascular anastomosis.

SECTION III GENERAL PROBLEMS
142
References
1. Huemer GM, Dunst KM, Maurer H, Ninkovic M. Area
enlargement of the gracilis muscle flap through mi­
croscopically aided intramuscular dissection: ideas
and innovations. Microsurgery 2004;24(5):369–373
2. Ninkovic M, Moser-Rumer A, Ninkovic M, Spanio S,
Rainer C, Gurunluoglu R. Anterior neck reconstruc­
tion with pre-expanded free groin and scapular flaps.
Plast Reconstr Surg 2004;113(1):61–68
3. Byrd HS, Cierny G III, Tebbetts JB. The management of
open tibial fractures with associated soft-tissue loss:
external pin fixation with early flap coverage. Plast
Reconstr Surg 1981;68(1):73–82
4. Byrd HS, Spicer TE, Cierney G III. Management of open
tibial fractures. Plast Reconstr Surg 1985;76(5):719–
730
5. Godina M. Early microsurgical reconstruction of
complex trauma of the extremities. Plast Reconstr
Surg 1986;78(3):285–292
6. Lister G, Scheker L. Emergency free flaps to the upper
extremity. J Hand Surg Am 1988;13(1):22–28
7. Ninkovic M, Deetjen H, Ohler K, Anderl H. Emergency
free tissue transfer for severe upper extremity inju­
ries. J Hand Surg [Br] 1995;20(1):53–58
8. Ninkovic M, Schoeller T, Wechselberger G, Otto A,
Sperner G, Anderl H. Primary flap closure in complex
limb injuries. J Reconstr Microsurg 1997;13(8):575–
583
9. Ninkovic M, Mooney EK, Ninkovic M, Kleistil T, An­
derl H. A new classification for the standardization
of nomenclature in free flap wound closure. Plast Re­
constr Surg 1999;103(3):903–914, discussion 915–
917
10. Rainer C, Meirer R, Gardetto A, Schwabegger AH,
Ninkovic MM. Perforator-pedicled skin island flap for
coverage of microvascular anastomoses in myocu­
taneous flaps in the lower extremity. Plast Reconstr
Surg 2003;112(5):1362–1367
11. Rainer C, Schwabegger AH, Gardetto A, Schoeller T,
Hussl H, Ninkovic MM. Aesthetic refinements in re­
constructive microsurgery of the lower leg. J Reconstr
Microsurg 2004;20(2):123–131
12. Ninkovic M, Spanio di Spilimbergo S, Ninkovic M.
Lower lip reconstruction: introduction of a new pro­
cedure using a functioning gracilis muscle free flap.
Plast Reconstr Surg 2007;119(5):1472–1480
13. Stenzl A, Ninkovic M, Kölle D, Knapp R, Anderl H,
Bartsch G. Restoration of voluntary emptying of the
bladder by transplantation of innervated free skeletal
muscle. Lancet 1998;351(9114):1483–1485
14. Ninkovic M, Buerger H, Ehrl D, Dornseifer U. One-
stage reconstruction of tracheal defects with the me­
dial femoral condyle corticoperiosteal-cutaneous free
flap. Head Neck 2016;38(12):1870–1873

Aesthetic
Surgery
S E C T I O N I V

Detail of Kore, ACR 684. (Acropolis Museum Athens, Greece. Photo: Socrates Mavromatis.)

145
CHAPTER
16

Dermal Fillers and Neurotoxins
David Kenneth Funt
Public awareness and demand for injectable dermal fillers
and botulinum neurotoxin treatments continue to grow as
more people opt for noninvasive aesthetic rejuvenation and
enhancement. This trend is illustrated by recent data from
the American Society of Aesthetic Plastic Surgery (ASAPS),
which show that dermal filler and neurotoxin treatments
have increased by 35 and 39%, respectively, in the past
5 years.1 Along with neurotoxin injections, dermal fill­
ers are the mainstay of most medical aesthetic practices.
Recently, the FDA also approved deoxycholic acid, a non­
invasive method for removing submental fat, which now
joins intense pulse light (IPL) therapy, laser, ultrasonic, and
radiofrequency devices to further expand the aesthetic
provider’s growing armamentarium. When performed by
experienced, well-trained practitioners, adverse events oc­
cur in less than 1% of patients, and most of these are minor
and short lived.2 However, as treatment indications expand
and the number of treatments performed increases, so to
do the number and spectrum of adverse events. Although
most adverse reactions are mild and transient, more seri­
ous complications do occur, leaving patients with long-
lasting or permanent functional and aesthetic deficits. It
is essential that a practitioner be aware of the spectrum
of complications that can occur and be able to recognize,
diagnose, and treat these adverse events. Any provider
performing injectable treatments should have a compre­
hensive understanding of the injectate characteristics and
capabilities, available injection techniques, and the injec­
tion site anatomy, because these are the triad that reduce
the risk of an adverse event. This requires expert familiarity
with the properties and potential complications of a vari­
ety of products, including those that are not available in the
injector’s country of practice, because patients may present
with adverse reactions to fillers injected abroad.
I have had the privilege to serve as a medical director for
Merz USA and as a medical advisor to Allergan Corporation
assisting practitioners with adverse events and their man­
agement. I have extensive personal injection experience and
have taught anatomy, technique, and adverse event treat­
ment avoidance for over a decade. To prepare this chapter, I
reviewed reports in the literature regarding complications
with dermal fillers, botulinum neurotoxin, and deoxycholic
acid injection and combined this data with my wide-ranging
experience to develop recommendations for avoiding and
managing complications.
Categories of Dermal Filler
Dermal fillers may be classified as biodegradable (moder­
ate and long duration) or nonbiodegradable fillers. Hyal­
uronic acid (HA) fillers are the most widely used biode­
gradable fillers in both Europe and the United States and
generally have effects lasting 6 to 24 months. HAs are linear
polymeric dimers of N-acetylglucosamine and glucuronic
acid, which differ in the proprietary methods used to cross-
link their dimers, their degree of chain cross-linking, the
uniformity and size of their particles, and their concentra­
tion. These characteristics all have a significant impact on
the clinical effect of these products. Increased cross-link­
ing, concentration, and particle size increase the viscosity
and elasticity and the time necessary for degradation by
native hyaluronidase. The hydrophilic nature of HA means
that the more concentrated and/or large-particle products
will tend to absorb more water and thus cause more tis­
sue swelling after injection. HA fillers may be biphasic or
monophasic (Table 16.1).
Each type of HA has a predictable histologic behavior in
the skin affecting its suitability for different indications.3 The
different HAs have varying degrees of hardness (G′), which
also influence their suitability for a particular procedure.
In general, the greater the G′ of the product, the deeper it
should be injected. It should be noted that although more
concentrated products with a greater degree of cross-linking
have a longer duration of effect, they also increase reactivity

SECTION IV AESTHETIC SURGERY
146
Avoiding and Managing
Complications Associated with
Dermal Fillers
Bruising
Any injection procedure has the potential to cause bruising.
Bruising is related to several factors:
•• Filler used
•• Site of injection
•• Depth of injection
•• Size of the needle used to inject the filler
•• Amount of tissue trauma during injection
•• Patient’s propensity to bleed
Bruising is observed more often after injection into the
deep dermal and immediate subdermal planes using fan­
ning and threading techniques, and less often when ma­
terials are injected using the depot technique at the pre­
periosteal level (Fig. 16.1). Larger-bore needles cause more
trauma and more bruising. Cannulas are believed to pro­
duce less bruising than do sharp needles. Transcutaneous
puncture sites should be limited, because each is a poten­
tial site of bruising, and tissue trauma should be minimized
while “massaging and molding” the filler.
Bruising can be further reduced by having patients avoid
all anticoagulant medications for 5 to 7 days before the pro­
cedure (Box 16.1). The surgeon should contact the prescrib­
ing physician before instructing a patient to discontinue pre­
scription anticoagulants and aspirin.
The area to be treated can be cooled with ice packs and
pretreated with local infiltration of lidocaine with epineph­
rine (using small volumes that will not distort the patient’s
anatomy) for patients who have had problems with bruising
after previous treatments. If local anesthetic is mixed with
the filler, 2% lidocaine with epinephrine should be used.
in the body and thus the risk of inflammation and granu­
loma formation.
Fillers with biodegradable particles that stimulate the
body to produce its own collagen have a longer duration of
effect and include calcium hydroxylapatite (CaHA; Radiesse
[Merz Aesthetics]) and poly-L-lactic acid (PLLA; Sculptra
[Galderma]). Radiesse consists of synthetic CaHA micro­
spheres (25 to 40 microns) suspended in a carrier gel. Injec­
tion provides immediate correction with long-term deposi­
tion of new collagen surrounding the microspheres, which
contributes to an average duration of effect of 15 months.4
PLLA is a synthetic polymer that provides soft tissue aug­
mentation through stimulation of an inflammatory tissue
­response resulting in collagen deposition.5 Each injection
session with PLLA builds on the volumization achieved
with the previous treatment. Once the final correction is
achieved, it can persist for longer than 1 year, requiring a
single treatment session for maintenance.
The nonbiodegradable fillers provoke a foreign body re­
action that stimulates a fibroblastic deposition of collagen
around the nonabsorbable microspheres. Products in this
category include polymethylmethacrylate (PMMA; Bellafill
[Suneva Medical]); the polyacrylamide hydrogel Acquamid;
and Silikon 1000, a medical-grade pure form of silicone. Bel­
lafill (previously marketed as Artefill) consists of 80% bovine
dermal collagen plus 20% PMMA microspheres. The collagen
vehicle is degraded within 1 to 3 months, leaving the micro­
spheres encapsulated by a fine fibrous capsule. Acquamid is
a hydrophilic polyacrylamide gel composed of 97.5% ster­
ile water bound to 2.5% cross-linked acrylamide polymer. A
continuous exchange of fluid occurs between the hydrogel
and surrounding tissue, which becomes integrated in the
soft tissue.6 Silikon 1000 is injected in very small quantities
using a microdroplet technique. Similar to the other per­
manent fillers, the body forms collagen around the silicone
particles. The permanent nature of the nonbiodegradable
fillers make their complications more long-lasting and dif­
ficult to treat.
Table 16.1 Categories of dermal filler
Biphasic
Monophasic monodensified
Monophasic polydensified
Selectively sized particles of cross-
linked HA suspended within
non–cross-linked HA
Variable amounts of high- and low-
molecular-weight HAs mixed and
cross-linked in single step
Two cross-linking steps
Restylane,a Perlane,a Macrolanea
Juvéderm,b Teosyal,c Prevelle Silk,d
Varioderme
Beloterof
aGalderma.
bAllergan.
cTeoxane.
dMentor Worldwide.
eAdoderm.
fMerz Aesthetics.

147
Chapter 16 Dermal Fillers and Neurotoxins
­After the procedure, the application of cold compresses will
limit bruising and swelling. The patient should sleep with
the head elevated, and strenuous exercise should be avoided
that day.
If bruising occurs, the patient should avoid unprotected
sun exposure as long as the bruising is present. Vitamin K
cream has been shown to speed the resolution of ecchymo­
sis, and persistent staining can be treated with pulsed-dye
laser or potassium titanyl phosphate (KTP) laser and IPL.7
Skin Erythema and Discoloration
Erythema
Immediately after injection some skin redness is normal.
If erythema persists for more than a few days, the surgeon
should consider hypersensitivity, other tissue reaction, or
infection. A medium-strength topical steroid is advocated
for persistent erythema. Long-term use of high-potency
steroids should be avoided, because they may cause atrophy
and telangiectasias. Treatments for rosacea may be effec­
tive, including oral tetracycline, metronidazole, and azelaic
acid. Lasers and IPL can be effective for the treatment of tel­
angiectasias and erythema (see later discussion). Vitamin K
cream is useful in accelerating resolution of erythema and
facial bruising.8 Patients with rosacea have a higher risk of
developing postinjection erythema and should be warned
of this before beginning the procedure.
Neovascularization
New capillaries, arterioles, and venules may occur at the
site of dermal filler injection. These tiny vessels can ap­
pear days or weeks after the procedure but should fade
Box 16.1
•• Aspirin
•• Warfarin
•• Dipyridamole
•• Clopidogrel
•• All nonsteroidal anti-inflammatory drugs
•• Fish oil
•• Vitamin E
•• St. John’s Wort
•• Garlic tablets
•• Gingko biloba
•• Ginseng
Medications and Herbal
Supplements to Avoid Before
a Filler Procedure
Summary Box
Treatment
Complications
Dermal filler
Injection site trauma (bruising, erythema, edema)

Noninflammatory nodules

Inflammatory nodules

Skin discoloration

Infection

Malar edema
Botulinum toxin
Injection site trauma (bruising, erythema, edema)

Eyelid ptosis

Eyebrow ptosis

Lip asymmetry
Deoxycholic acid
Injection site trauma (bruising, erythema, edema, induration, pain)

Injection site numbness
Most Common Problems with Dermal Fillers, Botulinum Toxins, and Deoxycholic Acid
Fig. 16.1 Bruising.

SECTION IV AESTHETIC SURGERY
148
ficially placed particulate HA filler, it is reflected back with
blue becoming the prominent reflected color. The more su­
perficial the placement of any filler, the more visible it will
be. Hyaluronidase should be the initial approach to treat­
ment of HA visibility. For HAs that are less susceptible to
hyaluronidase because of a high degree of cross-linking or
large particle size, multiple treatments may be necessary
(dosage is increased until material is dissolved). CaHA filler
placed too superficially can be visible as white streaks or
pustules or as salmon-colored discoloration of lower eyelid
skin (Fig. 16.2). CaHA or HA can be treated by nicking the
skin with a small-gauge needle (30 gauge) or surgical scal­
pel (no. 11 blade) and expressing the superficial unwanted
dermal filler.11,12 This procedure can be performed imme­
diately or as long as 12 months or more after placement.12
I have found this is only effective in the first 48 hours after
injection with CaHA.
Infection
As with any procedure that breaks the surface of the skin,
dermal filler injections are associated with a risk of infec­
tion. This is exacerbated by the presence of the filler im­
plant, which significantly reduces the threshold concentra­
tion at which contaminating bacteria can cause infection.
To minimize this risk the injection site must be cleansed
with an effective topical disinfectant (alcohol, povidine
iodine, or preferably 2% chlorohexidine gluconate in 70%
alcohol), the needle and syringe should be safely removed
from the sterilized individual packaging, gloves should be
worn throughout the procedure, and care should be taken
that the needle is not contaminated during the procedure.13
Excess filler material should not be wiped from the needle
tip with nonsterile gauze; residual amounts of material
should be flicked off the needle. Injection sites should be
cleansed again after manipulation with nonsterile gloves.
Care must be taken to use strict aseptic technique when
mixing or reformulating a product. Although rare, postfiller
infections do occur and may be bacterial, fungal, polymi­
crobial, or viral. Virulent late infections (biofilms) can also
within 3 to 12 months without further treatment. They are
caused by tissue trauma as a result of tissue expansion by
the product or by excessive molding and massage of the
product. Lasers shown to be effective in the treatment of
telangiectasias include 532-nm KTP, 532-nm diode copper
vapor, 585-nm pulsed-dye lasers, and IPL.
Hyperpigmentation
Darker skin has a tendency to hyperpigment after trauma.9
Dermal filler procedures are a common cause of postin­
flammatory hyperpigmentation in individuals with Fitz­
patrick skin types IV through VI,10 although postinjection
hyperpigmentation can also be seen in other skin types. If
persistent hyperpigmentation develops after dermal filler
injection, first-line treatment should be with a bleaching
agent such as topical hydroquinone (2 to 8%) and tretinoin
combined with daily full-spectrum sunscreen application.
If this is unsuccessful, the next step is treatment with IPL,
a pulsed-dye laser, or fractional laser; the low fluence Q-
switched neodymium-doped: yttrium aluminum garnet
(Nd:YAG) 1064-nm laser is also effective. Current lasers
have limited use in the treatment of Fitzpatrick skin types
IV to VI, but the long wavelength Nd:YAG laser allows
darker skin to be treated without disrupting natural skin
color, and IPL systems can treat Fitzpatrick skin types I to IV.
Limiting the number of skin punctures during the injection
process by using the linear threading or fanning technique
or injecting at the preperiosteal level (“walking” the needle
from depot to depot) may reduce injection trauma and re­
sultant postinflammatory hyperpigmentation.
Dyspigmentation
When particulate HA fillers are inappropriately implanted
into the superficial dermis or epidermis a bluish hue may
occur as a result of the Tyndall effect (scattering of light by
particles in suspension). Blue light waves have a higher fre­
quency than red and are more easily scattered, so when a
ray of light hits the skin’s surface and reflects off the super­
Fig. 16.2 (a) Superficially placed Radiesse that resulted in contour irregularity and dyschromia. (b) Irregular placement of Radiesse with visible
material causing irregular contours. (c) Salmon-colored discoloration after Radiesse injection into the infraorbital hollow and tear trough.
a
b
c

149
Chapter 16 Dermal Fillers and Neurotoxins
­injected with filler, after systemic infection or local infec­
tion, or after a procedure that causes a bacteremia (e.g., a
dental cleaning).
Biofilms are widespread in nature and consist of densely
packed communities of bacteria that surround themselves
with secreted polymers and are irreversibly adherent to a
living structure or an inert surface. When a material is in­
jected into the skin or subcutaneous tissue, it can become
coated with bacteria and a biofilm can form. These complex
collections of bacteria are very difficult to treat, so the focus
should be on prevention. Initially, free swimming organisms
attach to a surface. They achieve a permanent chemical at­
tachment and secrete a protective and adhesive matrix of
extracellular polymeric substance (EPS). Biofilm EPS, which
is also referred to as slime, is a polymeric conglomeration
generally composed of extracellular deoxyribonucleic acid
(DNA), proteins, and polysaccharides. The microbial cells
growing in a biofilm are physiologically distinct from plank­
tonic cells of the same organism, which, by contrast, are sin­
gle cells that may float or swim in a liquid medium. Over
time the single layer becomes thicker, and vertical towers
and horizontal channels develop. Once mature, a biofilm
gives rise to a low-grade chronic infection that is resistant
to antibiotics and difficult to culture.16,17 The matrix encases
the cells within it and facilitates communication among
them through biochemical signals and gene exchange.
Bacteria in a biofilm may require higher antibiotic con­
centrations and transfer antibiotic resistance by sharing ge­
netic material via plasmids. Bacteria within a biofilm shift
between an active and dormant state, the former generating
little host response and resulting in negative cultures. More
sophisticated examination of biopsied tissue (fluorescence
in situ hybridization using peptide nucleic acid probes) may
be required for diagnosis.
A mature biofilm will release individual free swimming
bacteria in the tissues. Many bacterial species are capable of
forming a biofilm. The most common organisms are S. au­
reus and Staphylococcus epidermidis, but Pseudomonas aeru­
ginosa, Enterococcus species, and yeast and fungi (e.g., Can­
dida) can also form biofilms. When activated, for example
by trauma from a subsequent dermal filler procedure, the
biofilm can cause a local infection, a systemic infection, or a
granulomatous or inflammatory response.
Distinguishing inflammation caused by a bacterial bio­
film from a low-grade hypersensitivity reaction is difficult. If
an erythematous and/or indurated area appears at any time
after treatment, regardless of duration, a biofilm should be
suspected.18,19 Persistent inflammatory conditions not show­
ing improvement with other therapy and inflammatory nod­
ules that recur after resolution may also indicate a biofilm.
The signs of inflammation may be no more than edema with
or without erythema and induration, or nodularity at the
treated site (or a site that has been treated with filler before
the most recent treatment).
occur. I believe that many filler adverse events, including
nodules and persistent, fluctuating edema and erythema,
are at least in part caused by bacterial contamination.
Erysipelas, Cellulitis, and Abscess
Erysipelas and phlegmon are a diffuse inflammation of the
skin or connective tissue caused by infection. As is the case
with cellulitis and abscess, responsible organisms are usu­
ally Staphylococcus aureus or Streptococcus pyogenes, but
gram-negative, anaerobic, and atypical infections have been
reported.14 If untreated the conditions may lead to sepsis,
particularly in elderly people and those with diabetes or
other illnesses that alter the immune system. Mild forms
may be treated with oral antibiotics, but more serious cases
require intravenous antibiotics and hospitalization. Antibi­
otics with activity against S. aureus are necessary, such as
cephalexin, dicloxacillin, doxycycline, or nafcillin. To avoid
spreading infection, hyaluronidase should not be used in
the primary phase, and the area should not be massaged. If
the injectate was HA and a recurrence occurs after antibi­
otic treatment, hyaluronidase should be considered to elim­
inate any persistent nidus of infection. Abscesses should be
treated with incision and drainage and antibiotics. Cultures
should be obtained, if possible, before initiating antibiotic
therapy. Treatment should then be tailored to the obtained
sensitivity reports.15 Midfacial and periorbital infection can
in rare cases result in intracerebral complications.
Herpetic Outbreak
Dermal filler injections can lead to reactivation of herpes
virus infections. If the treatment is targeting the lips or
mouth area and the individual has a history of cold sores,
prophylactic treatment with valacyclovir (500 mg twice
daily) immediately before and for 1 to 2 days after injec­
tion should be considered. If the patient has not received
prophylactic treatment but infection is recognized early,
valacyclovir at a dose of 2 g twice daily for 1 day should
be given.
If suprainfection occurs, the patient should be treated
with appropriate antibiotics. Most herpetic recurrences oc­
cur in the perioral area, nasal mucosa, and mucosa of the
hard palate. Shingles (herpes zoster) after injection is very
rare. When a blistering reaction occurs outside of the ar­
eas of recurrent herpes simplex virus infection (lip skin and
vermilion, nasal mucosa, and mucosa of the hard palate),
a diagnosis of vascular compromise should be considered.
Biofilms
Biofilms occur when injected filler material becomes con­
taminated with bacteria or yeast. This can take place at
the time of injection, after injecting a patient previously

SECTION IV AESTHETIC SURGERY
150
heating has been used in the same fashion. These minimally
invasive techniques could be an intermediate step before at­
tempting surgical excision of an inflammatory nodule.
The incidence of biofilms as a result of filler injections
is not known, and diagnosis is difficult. Fortunately biofilms
are very rare with most filler products, but it is important
to take precautions to prevent infection when injecting fill­
ers (Box 16.2).
Edema
Short-Term Posttraumatic Edema
Some transient swelling in the immediate postprocedural
period is normal and occurs with all dermal fillers. This
type of edema occurs very shortly after injection and is re­
lated to the volume and technique used. It also appears to
be idiosyncratic, because it occurs in some patients but not
in others who have been treated using the same technique
and filler. Methods for avoidance are the same as those for
bruising (i.e., smaller needles, atraumatic technique, and
avoiding overly vigorous massage of the treated area). Most
cases of postinjection, trauma-related edema resolve with­
out treatment within 7 days. Most require no treatment
other than elevation of the treated site. In severe cases pa­
tients can be treated with a steroid dose pack, but the injec­
tor must be vigilant not to miss an infective cause.
There are also some cases of edema that do not resolve
within the first week after injection. These occur within
hours to several days or weeks after the injection, may per­
sist for months, and may or may not be confined to the site
of injection. I group these cases by probable etiology based
on temporal occurrence of the edema, the clinical appear­
ance, and retrospectively what treatment the patient re­
sponded to.
Antibody-Mediated Edema (Angioedema)
Acute hypersensitivity reactions to dermal fillers are very rare.
Dermal fillers are essentially foreign bodies, and some patients
Because they are usually culture negative, these nod­
ules were previously believed to be a result of an allergic or
foreign body reaction to the filler substance. However, the
technique of fluorescence in situ hybridization confirmed
an infective cause in a series of polyacrylamide gel-related,
culture-negative, inflammatory nodules.20 The use of scin­
tigraphy with radiolabeled autologous white blood cells is
also an accurate method for diagnosing infection in patients
with long-term dermal filler complications.21 Most inflam­
matory nodules that are resected and sent for pathology are
reported as foreign body granulomas, so the importance of
biofilm as a cause of inflammatory nodules is still not quan­
tifiable. A clinician’s index of suspicion for biofilm formation
should be high, and biofilm should be at the top of the dif­
ferential diagnosis when signs of inflammation occur weeks
to months after a previously uncomplicated injection pro­
cedure.
Antibiotic treatment is the first step in treating a pa­
tient with a suspected biofilm, even if the culture is nega­
tive, and should be initiated with a broad-spectrum agent
(quinolone) such as ciprofloxacin 500 mg twice daily and
a macrolide such as clarithromycin XL 500 mg twice daily
for 3 to 6 weeks (see Fig. 16.6 later in the chapter). Com­
bination amoxicillin and clavulanic acid, a cephalosporin,
or doxycycline can be substituted for the macrolide. Single
antibiotic therapy can be started if the index of suspicion is
lower. I have patients continue antibiotics for 2 weeks after
all signs and symptoms have resolved. If there is a suspicion
of biofilm, intralesional steroids should not be used until
antibiotic therapy has been initiated, because they can ex­
acerbate the problem.
With any biofilm, whether a result of a biodegradable or
nonbiodegradable product, removal of the filler will reduce
the inflammatory potential of the biofilm, because it is irre­
versibly adherent to it. Hyaluronidase should be used if the
patient was injected with an HA. Because the biofilm EPS
contains HA, hyaluronidase may be useful in the treatment
of all biofilms. I also believe that in addition to antibiotics
repeated injections of hyaluronidase should be performed
when treating a biofilm where an HA filler was used before
administering oral or intralesional steroids. The exact dos­
age necessary to dissolve the highly cross-linked HA fillers in
use today has not been quantified (particularly because the
exact location of the injected subcutaneous material cannot
be accurately determined). Hyaluronidase must be in direct
physical contact with its substrate to work. One or more in­
tralesional steroid injections and/or courses of oral steroids
may result in reduction of inflammation but make it difficult
to make appropriate therapeutic decisions because the clini­
cian cannot gauge the patient’s true response.
Laser technology has been reported to have beneficial
effects in the treatment of infectious filler complications.22
The intralesional subcutaneous introduction of an optic la­
ser microfiber and the subsequent heat production result in
a theoretical decrease of bacterial counts of the biofilm and
in liquefaction of the filler microparticles. Radiofrequency
Box 16.2
•• Thoroughly cleanse the area before injection
•• Reprep after contaminating the site
•• Avoid contaminating the filler or needle
•• Avoid injecting through oral or nasal mucosa
•• Avoid hydrophilic permanent materials
•• Avoid injecting over previous filler or into
traumatized or infected tissue
•• Promptly and aggressively treat any postfiller
infection
Strategies to Reduce the Risk
of Biofilm

151
Chapter 16 Dermal Fillers and Neurotoxins
is ­obtained. Edema should be controlled with the smallest
dose of oral steroids that is effective. I have had success in
reducing the steroid dose with concurrent use of the leu­
kotriene receptor antagonist montelukast, 10 mg per day.
Non–Antibody-Mediated (Delayed) Edema
Delayed hypersensitivity reactions are characterized by
induration, erythema, and edema and are mediated by
macrophages and T lymphocytes (rather than antibodies)
and may lead in many cases to the development of granu­
lomatous inflammation. They typically occur 48 to72 hours
after injection but may be seen as late as several weeks
after injection and may persist for many months.25,26 De­
layed hypersensitivity reactions are nonresponsive to an­
tihistamines. The allergen should be removed (see Fig.
16.4). In the case of HA this will involve treatment with
hyaluronidase. For other fillers this may involve treatment
with steroids until the filler resorbs, laser treatment, and/
or extrusion.22 Excision is a last resort. Symptoms should
be controlled with the lowest possible dose of oral steroids
(prednisone).
Nodular Masses
Nodule development is a common adverse event after the
use of fillers for soft tissue augmentation. They are com­
monly categorized as inflammatory or noninflammatory.
Noninflammatory nodules are typically seen immediately
or shortly after implantation and are usually secondary to
improper placement of the filler. Inflammatory nodules can
occur from days to years after filler placement and vary as
to their cause.
Noninflammatory Nodules
When too much material accumulates in an area as a result
of poor technique (overcorrection, too superficial place­
ment of a filler, or inappropriate placement into a structure,
such as intramuscular placement in a sphincteric muscle)
(Fig. 16.5), a noninflammatory nodule may result that is
palpable and may be visible. Such implant nodules do not
may manifest hypersensitivity reactions to injected products
because of an antibody-mediated (usually immunoglobulin E
[IgE]) immune response (type I hypersensitivity reaction). This
may occur after initial or repeated exposure. IgE stimulates
mast cells to degranulate, releasing proteases, heparin, hista­
mine, cytokines, prostaglandins, leukotrienes, and platelet-
activating factor, which result in the edema, erythema, pain,
and itching characteristic of an urticarial or angioedemic al­
lergic response. One mechanism proposed for hypersensitivity
associated with HA is its interaction with tissue resident mast
cells through the CD44 receptor.23 Angioedema occurs within
hours of exposure. Reactions can be severe and last for several
weeks.24 Edema may be confined to the injection sites but may
also be more generalized. An acute idiopathic allergic response
can also occur in which no allergen can be identified. The reac­
tion may be localized, or there may be acute generalized facial
edema (Fig. 16.3).
Treatment of angioedema, whether of known cause or
idiopathic, depends on the severity of the condition. In many
cases the swelling resolves spontaneously after a few hours
or days. If mast-cell mediated, the swelling is short lived
and responsive to antihistamines (both H1 and H2, sedating
and nonsedating). I have found that the most patients with
filler-related edema do not respond to antihistamines and
therefore are not demonstrating classic type I hypersensitiv­
ity reactions. For edema not responsive to antihistamines,
oral prednisone is the mainstay of treatment (Fig. 16.4). The
patient should be closely monitored to ensure the edema
is not a result of an infectious process. Rapidly progressing
angioedema is treated as a medical emergency because of
the risk of airway obstruction and is treated with subcuta­
neous administration of epinephrine, antihistamines, and
oral steroids.
Chronic urticaria or angioedema refers to episodes that
last more than 6 weeks. These cases are often difficult to
treat and have a variable response to medication. When
treating chronic urticaria from other causes, immunomod­
ulators (cyclosporine, dapsone, methotrexate, mycopheno­
late, mofetil, cyclophosphamide, hydroxychloroquine, and
sulfasalazine) have been used. The algorithm featured in
Fig. 16.4 highlights the treatment steps recommended. Each
step is added to the previous one if an inadequate response
Fig. 16.3 (a) Acute generalized edema after Radiesse injection. (b) Delayed generalized edema occurring 7 days after injection of Voluma (Al­
lergan) to the cheeks. (c) At 6 months after injection, the patient in (b) has persistent edema and moon face from oral steroid administration.
a
b
c

SECTION IV AESTHETIC SURGERY
152
­occurring after treatment with a non-HA filler may respond
to vigorous massage; the material can also be extruded
(Fig.  16.6). Nodules may also be hydrodisrupted with li­
docaine or saline followed by vigorous massage.28 The pa­
tient should maintain the disruption with home massage.
­Nodules that do not resolve may respond to intralesional
steroids (keep intralesional and limit dose to avoid skin
atrophy). Additional treatment options are a series of in­
jections of 5-fluorouracil (5-FU), triamcinolone and lido­
caine, or 5-FU and lidocaine. These can be repeated as long
grow and are well delineated. They appear early after the
procedure and should be differentiated from hypersen­
sitivity reactions, foreign body granulomas, or biofilms,
which are a result of an inflammatory reaction around the
product or site of infection and usually occur later. Poor
technique and filler placement and the use of particulate
fillers (e.g., PMMA, CaHA) in highly mobile areas such as the
lips can cause delayed-onset noninflammatory nodules.27
If nodules occur after treatment with an HA filler they
will resolve with hyaluronidase treatment. Early nodules
Difficult to predict. Sometimes patients
have had filler reactions in the past. Proper
­placement using appropriate sterile technique.
Avoidance
Difficult to predict. Take careful patient history.
Do not treat patients with known allergy to
avian or bacterial proteins, allergic history, or
patient with known angioedema.
Infection
Biofilm reaction
Differential diagnosis
Acute (< 6 weeks
duration)
Chronic (≥ 6 weeks
duration)
Mild
Severe
Dissolve HA filler
with hy­al­uron­i­dase
HA filler
Non-HA filler
Antibody-mediated angioedema, type I
hypersensitivity or other direct effect of the
filler on the immune system
Rapid swelling of skin and subcutaneous tissue
early after injection; localized or generalized
facial edema within hours of injection
Non­–antibody-mediated (delayed type IV
hypersensitivity)
Persistent facial edema occurring several days
to months after injection; not responsive to
antihistamines; difficult to treat and distinguish
from biofilm and direct filler–tissue interaction
(also see inflammatory nodules)
Presentation
Persistent
edema
Remove allergen
with hy­al­uron­i­dase;
repeat treat­ments,
especially if im­
prove­ment
Control symptoms
with lowest possible
dose of oral steroids
Ice or cold
compress
Dissolve HA
filler with
hy­al­uron­i­
dase
Non­se­da­t­
ing an­ti­his­
ta­mines
If persistent, treat
with lowest possible
dose of oral cortico­
steroids/Singulair
Remove allergen by
extrusion, dispersion
or breakdown with
laser therapy, or
excision
Oral or
injected an­
ti­his­ta­mines
Sedating
an­ti­his­ta­
mines
Treatment
If need for long-term treatment con­
sider nonsteroidal immune modulator
Oral or
intravenous
cor­ti­co­ste­
roids
Oral cor­ti­co­ster­oids;
if need for long-term
treat­ment consider
non­ste­roidal im­mune
mod­u­la­tor
Fig. 16.4 Immune-mediated edema. HA, Hyaluronic acid; LMW, low molecular weight.

153
Chapter 16 Dermal Fillers and Neurotoxins
Activated ­macrophages secrete a variety of cytokines and
other inflammatory products that attract additional mac­
rophages and blood monocytes. Individual macrophages
may become larger (epithelioid histiocytes) or fuse to form
multinucleated foreign body giant cells. These cells are
characteristic of granulomas, and if a biopsy is obtained,
a true granulomatous reaction can be confirmed histologi­
cally. Particle shape, surface charge, and hydrophilicity also
affect phagocytosis. In the case of HA and collagen fillers,
cross-linking also inhibits phagocytosis. There are three
potential causes for inflammatory nodules32:
1. Immune-mediated reactions (classic or direct)
2. Foreign body responses
3. Infectious processes
Regardless of the cause, when a biopsy of an inflammatory
nodule is performed histologic examination invariably con­
firms a diagnosis of a foreign body granulomatous response.
Immune-Mediated Delayed Nodules
Fillers have been suggested to act as T-cell–specific acti­
vators and adjuvants (rather than antigens) in individu­
als with predisposed genetic backgrounds.33 They may do
so directly or in association with a biofilm. Inflammatory
filler-related adverse events have also been linked to trig­
gering factors such as local trauma, infections, or vaccine
administration (potentially because of increased interferon
levels).
Another potential cause of inflammatory responses to
Voluma and other HA fillers may be direct effects of HA
as ­improvement is noted. Fractional lasers, which are used
after the carrier gel has been absorbed, have been reported
to improve visible material in the lower eyelids and the lips
after Radiesse injections.29,30 Excision of implanted material
is only used as a last resort. Chronic, intractable nodules that
persist for months despite disruption and become increas­
ingly fibrotic are foreign body granulomas and should be
treated as described in that section.
Implant nodules are one of the most common adverse
events after dermal filler procedures,31 but their incidence
can be reduced by taking care to maintain strict aseptic
technique and to avoid too superficial placement of filler,
selecting the appropriate filler for the tissue site, molding
after injection to ensure even distribution and smoothness,
avoiding intramuscular injection, and avoiding injection and
particularly into sphincteric muscles (orbicularis oris and
oculi) that may cause clumping of fillers.
Inflammatory Nodules
Inflammation around an implant particle is normal and al­
ways occurs and leads eventually to its resorption in the
case of biodegradable fillers. Ideally such fillers should
be immunologically inert and stimulate collagen neogen­
esis to allow persistence of the product and not initiate a
granulomatous reaction. Phagocytosis by macrophages
is an initial tissue reaction to any foreign body and is the
most important factor in determining filler longevity. Cir­
culating granulocytes are attracted to the site. Monocytes
differentiate into macrophages that phagocytize particles
that the polymorphonuclear cells cannot. Particle sizes
greater than 5 μm resist degradation by macrophages.
Fig. 16.5 Noninflammatory nodules. (a) Juvéderm nodule in upper lip. (b) Juvéderm nodule in the lower lip. (c) Superficially injected Radiesse
visible as a nodule in the lower eyelid. (d) Radiesse in the labial-gingival sulcus from mental crease injection.
a
b
c
d

SECTION IV AESTHETIC SURGERY
154
antigenicity of the filler, but rather its structural composi­
tion.35,36 High-molecular-weight fragments of HA (HMW-
HA) are primarily anti-inflammatory, whereas low-molec­
ular-weight fragments (LMW-HA) are proinflammatory and
trigger the immune system. LMW-HA has been shown to
inhibit fibrocyte differentiation via the CD44 receptor.35 An
interaction with CD44 is also involved in LMW-HA–induced
proinflammatory cytokine interleukin 6 (IL-6) and chemo­
kines IL-8, CXCL1, CXCL2, CXCL6, and CCL8 gene expres­
sion in normal human dermal fibroblasts.36 LMW-HA can
also activate macrophages, dendritic cells, and signal T cells
(CD44 and TLR4). LMW-HA is present in Voluma and may
increase in concentration as the product is metabolized after
injection. This effect, alone or in combination with a trigger­
ing event, may produce a vigorous inflammatory response.
This recent link to the nonantigenic immune stimulatory
properties of HA is further evidence of our lack of under­
standing of the mechanisms of inflammatory ­dermal filler
reactions. There may be other physical or chemical proper­
ties distinct to a particular filler or group of fillers, or their
breakdown products that interact with the body to cause
adverse ­reactions.
fragments at the site of injection. HA is generally thought
not to be immunostimulatory because it is found in the ex­
tracellular matrix of human and animal dermis and has no
species specificity. However, a recent report documents a
number of cases of delayed-onset nodules after treatment
with Voluma, a volumizing HA filler.34 Delayed nodules
were identified in 23 out of 2,342 (0.5%) patients treated
over 68 months. The median time to onset of nodules was
4 months (range, 1 to 13 months), and the median time
to resolution of the nodules was 6 weeks (range, 1 to 36
weeks). A seasonal variation in onset of nodules was also
observed, with most occurring in the fall and winter. Nine
of the patients (39%) had an immunologic stimulus such as
a flulike illness or dental procedure immediately preced­
ing the reaction.
Initially, immune responses to HA fillers were proposed
to be caused by impurities such as DNA fragments, endo­
toxins, and proteins in the filler left after their manufacture.
Since these impurities have been reduced with improve­
ments in the manufacturing process, the incidence of hy­
persensitivity reactions has diminished, but they still occur.
Recent literature suggests that this may not be a ­result of the
Avoidance
Avoid overcorrection and/or too superficial placement of filler.
Avoid large volume bolus injections.
Avoid intramuscular injection.
Select appropriate filler for tissue site.
Massage for even distribution.
*The exact dosage is 0.4 mL of 50 mg/mL 5-FU, 0.3 mL of 10 mg/mL tri­am­cin­o­lone (or 40 mg/mL tri­am­cin­o­lone depending on the site and
degree of inflammation), and 0.3 mL 2% lidocaine with adrenalin. Hy­al­uron­i­dase may also be added (30 units). The injection amount is
between 0.1 mL (e.g., tear trough or lips) and 0.5 mL (e.g., in the cheeks) per nodule; because the injection should be intralesional, volume
is that which will remain within the nodule.
Foreign body granuloma (persistent nonresolving nodules that become more fibrotic over
time).
Differential diagnosis
Implant nodules
Relatively common, palpable, sometimes visible, noninflammatory nodules generally
appearing 2–4 weeks after injection.
Presentation
HA filler
Non-HA filler
Hy­al­uron­i­dase
Vigorous massage.
Disrupt with
lidocaine/saline.
Extrusion.
Treatment
Treat persistent nodules with small
amounts of intralesional steroids.
For stubborn nodules begin series of injec­
tions of 5-FU, triamcinolone and lidocaine,
or 5-FU and lidocaine.*
Fractional lasers for eyelids and lips.
Surgical excision is last resort.
Fig. 16.6 Noninflammatory nodules.

155
Chapter 16 Dermal Fillers and Neurotoxins
acrylate microspheres and polyacrylamide. The structural
changes that some nonbiodegradable fillers undergo dur­
ing years in situ in human tissue may be one reason why
adverse reactions to these permanent fillers occur clini­
cally with a delay of several years.42 The mechanism of late
inflammation or granuloma formation is still unknown. In
some patients who have been previously injected with long-
lasting or permanent filler and who have been asymptom­
atic (sometimes for many years), the injection of a second
filler material at the same site triggers an inflammatory re­
action against both fillers.
Prevention of Inflammatory Nodules
Because the role of bacterial contamination and biofilms
cannot as yet be quantified and they are responsible for at
least some of these adverse events, the use of sterile tech­
nique for all stages of the procedure cannot be overempha­
sized. The skin should be cleansed of all makeup using an
effective antiseptic (i.e., alcohol and chlorhexidine), and
needle and skin contamination should be avoided when
injecting. The same technique recommendations described
previously for noninflammatory nodules apply to inflam­
matory nodules.
Treatment of Inflammatory Nodules
Inflammatory reactions to HA fillers should be treated with
hyaluronidase.43 It should be injected intralesionally, or for
a more diffuse process throughout the site of filler injec­
tion. There are no specific dose guidelines, but an initial
dose of 10 units per 0.1 mL of HA has been suggested.33,34 If
inflammation improves but does not resolve, I have found
­repeated treatments with or without increasing the ­number
Foreign Body Granulomas
The failure of effective phagocytosis leads to foreign body
granuloma formation. The result is epithelioid histio­
cytes, foreign body giant cells, and a surrounding infiltrate
of T  lymphocytes that secrete cytokines such as tumor
­necrosis factor (TNF) alpha, interferon gamma, and IL-12,
responsible for ongoing macrophage activation.33 Clinically,
foreign body granulomas appear as red papules, nodules, or
plaques (with or without ulceration) (Fig. 16.7). The center
of the lesion may be necrotic, but any material expressed
is usually culture negative. The lesions become firmer over
time because of fibrosis.
True foreign body granulomas are rare, with an esti­
mated incidence between 0.01 and 1%. They can occur with
all injectable dermal fillers and usually appear after a latent
period, which can be several months to years after injection,
as compared with 2 to 4 weeks for early noninflammatory
nodules.37–40 Factors that influence increased foreign body
granuloma development include the chemical composition
of the filler, its hydrophilicity, surface charge, hyaluronic acid
cross-linking, large injection volumes, intramuscular injec­
tion, and postinjection infections or facial trauma. The shape
of the microspheres appears to be an important factor, with
granulomatous reactions occurring less commonly after im­
plantation of microspheres with smooth surfaces. Irregular
and sharp-edged particles may induce more severe granu­
lomatous reactions.41
Nonbiodegradable fillers are not characterized by a
higher rate of foreign body granulomas than temporary fill­
ers, but their clinical appearance is more pronounced and
they persist longer if not treated appropriately. The develop­
ment of foreign body granuloma can be delayed, coming as
late as 1 to 2 years after treatment with polymethylmeth­
Fig. 16.7 Inflammatory nodules that formed after use of fillers. All were confirmed as foreign body granulomas on biopsy.

SECTION IV AESTHETIC SURGERY
156
Nonbiofilm inflammatory response.
Biofilm reaction.
*The exact dosage is 0.4 mL of 50 mg/mL 5-fluorouracil (5-FU), 0.3 mL of 10 mg/mL triamcinolone (or 40 mg/mL triamcinolone depending on the site and degree of
inflammation), and 0.3 mL 2% lidocaine with adrenalin. Hyaluronidase may also be added (30 units). The injection amount is between 0.1 mL (e.g., tear trough or
lips) and a maximum of 0.5 mL (e.g., in the cheeks) per nodule.
Note: Material injected should remain intralesional. Always consider an infectious cause and begin antibiotics any time there is a new inflammatory response after an
asymp­tom­at­ic period.
Differential diagnosis
Avoidance
Cleanse face thoroughly before injection.
Avoid injecting through oral or nasal mucosa or injured
or infected tissue; maintain sterile technique through­
out treatment; avoid large-volume bolus injections.
Avoid large-volume bolus injections. Avoid intramus­
cular injection. Inject filler material in the appropriate
plane using careful sterile technique.
Initial treatment is with antibiotics and intralesional (or zonal) hy­al­uron­i­dase whether or not an HA was injected.
Positive, but incomplete response
to above, particularly if there is
erythema, induration, and edema,
treat for:
No response. Discrete nodule
without edema and induration.
If HA, always inject with hyal­
uronidase. Multiple treatments
may be necessary to dissolve a
cross-linked HA filler.
Edema/induration without ery­
thema, persists despite adequate
course of antibiotics. May wax and
wane. No discrete nodules: direct
filler interaction with tissue, not
classic immune response.
Biofilm
Erythematous, indurated area that
may occur after an asymptomatic
period.
Usually culture negative, fluores­
cence in situ hy­brid­iz­a­tion can
confirm infective etiology.
Foreign body granuloma
(Multiple etiologies— infectious
process, immune-mediated,
foreign body reaction.)
Discrete nodule that does not
resolve and becomes increasingly
fibrotic without ulceration, may be
multiple nodules.
Presentation
Repeat injections of hyaluronlidase and use
of broad-spectrum antibiotics (cip­ro­flox­a­cin,
clarithromycin) for 4–6 weeks (continue
antibiotics 2–3 weeks after resolution of
signs and symptoms.)
If feasible, extract material with 16-gauge
needle and syringe or 3-mm punch biopsy
and negative pressure for diagnosis.
If discrete nodule persists, treat as FBG.
5-FU intralesional injection every 3–4 weeks.
Intralesional antibiotics.
Intra­le­sional ste­roid (con­tro­ver­sial).
Treat nodules with intra­
lesional tri­am­cin­olone
10 mg/mL
*Add 5-FU to corticoste­
roid for discrete lesions
unresponsive to steroid
alone.
Laser lysis.
Surgical excision should
be performed for symp­
tomatic or visible lesions
that are not responsive
to treatment.
Repeat hy­al­uron­i­dase injections
into all areas where any HA filler
is known or suspected to be
present.
Initiate oral steroids as Medrol
dose pack
If edema recurs, begin tapering
course of corticosteroids for
2­–3 weeks. Steroid dose may be
reduced with concurrent use of
the leukotriene receptor antago­
nist (Singulair 10 mg per day.)
If after taper, edema persists
then control with lowest possible
dose of prednisone and consider
switching patient to a nonsteroi­
dal anti-inflammatory/immune
modulator to avoid steroid side
effects.
If induration persists consider laser lysis,
incision, and washing out cavity with
antibiotics.
Surgical excision should be performed for
symptomatic or visible lesions that are not
responsive to treatment.
Treatment
Fig. 16.8 Inflammatory nodules.

157
Chapter 16 Dermal Fillers and Neurotoxins
activity causing fibrosis through its antimetabolite function
and its direct antibacterial effect. Furthermore, this combi­
nation has the added advantage of reducing the amount of
steroid injected and thereby the risk of steroid-related ad­
verse events such as tissue atrophy and telangiectasia.42 In
case of the failure of other therapies, surgical excision is the
treatment of choice.37
Malar Edema
Malar edema is a serious complication that has been re­
ported with all fillers when injected into the infraorbital
hollow and tear troughs44 (Fig. 16.9). In a retrospective
study of 51 patients who received placement of an HA gel
to the infraorbital hollows, 12 patients had prolonged peri­
orbital edema, which lasted an average of 5.4 months.45
Edema was defined as a clinically significant degree of
swelling that lasted at least 1 month after injection.
The infraorbital hollow is the area bounded by the me­
dial canthus medially, the lateral canthus laterally, and the
inferior border of the orbicularis oculi. This region is partic­
ularly susceptible to adverse events. Malar edema after der­
mal filler injection arises because the malar septum or or­
bitomalar ligament, a band of connective tissue, divides the
suborbicularis oculi fat into a superficial and deep compart­
ment.46 The superficial compartment has compromised lym­
phatic drainage, whereas the lymphatic drainage of the deep
compartment is contiguous with the cheek drainage47,48 (Fig.
16.10). Injection of fillers superficial to the malar septum
may augment the impermeable barrier of the malar septum,
further impeding lymphatic drainage and resulting in fluid
accumulation and malar edema.44 Fillers injected superfi­
cial or deep to the malar septum may also cause edema by
direct pressure on the lymphatics when injection volumes
are too large. In addition, as the viscosity or G′ of the filler
increases, lifting force increases and the lymphatics may be
more compressed. Some patients demonstrate malar edema
before filler treatment, demonstrating existing lymphatic
compromise. Malar edema is likely related to the volume
of injectate, its depth of injection, the physical qualities of
the injectate, and the patient’s degree of preexisting lym­
phatic compromise. No matter the qualities of the injected
filler, if the aesthetic defect is corrected and the patient has
­preexisting lymphatic compromise malar edema will occur.
of units to be beneficial. Others have recommended not us­
ing hyaluronidase in the presence of erythema and inflam­
mation because of the potential for spreading infection.
However, I believe that this risk is more than outweighed
by the benefits of removing the substrate for a potential
biofilm, the effect on the HA component of the potential
biofilm EPS, and eliminating any immune stimulatory ef­
fects of the HA (either as an adjuvant, directly via LMW-HA,
or as an antigen).
It is difficult to distinguish between inflammatory nod­
ules that result from infectious processes versus those that
are immune mediated. Aspirations taken from the lesions
are usually culture negative and require sophisticated stud­
ies of excised tissue to achieve a definitive diagnosis. Based
on the current literature and my experience, initial treat­
ment should be with antibiotics (clarithromycin, minocy­
cline, doxycycline, or combination amoxicillin and clavulanic
acid) and hyaluronidase (if HA filler was used).32,33,37
If there is persisting edema and/or erythema or if they
worsen after the administration of hyaluronidase and oral
antibiotics, then oral steroids are prescribed as a methyl­
prednisolone dose pack. If the inflammation recurs after the
dose pack is completed, in the case of an HA filler, additional
injections of hyaluronidase should be performed, antibiot­
ics should be continued (possibly with the addition of an­
other antibiotic such as a fluoroquinolone), and the patient
should be observed.
If a biofilm is suspected (index of suspicion should be
high) then antibiotics should be continued for 3 to 6 weeks.
If persistent facial edema is present, then a second, longer,
more slowly tapering course of steroids (2 to 3 weeks) can
be administered. The patient’s medical conditions such as
diabetes should be considered when making therapeutic
choices. I have had success in reducing the steroid dose with
concurrent use of montelukast, 10 mg per day. If edema,
nodularity, or induration still persists, consideration should
be given to a nonsteroidal immune modulator to prevent the
development of steroid-related side effects. An immunolo­
gist may be consulted in these cases.
If a discrete nodule (resistant to hyaluronidase) is pres­
ent, it should be treated with intralesional corticosteroid
injection (triamcinolone) (Fig. 16.8). Many patients with
nodules unresponsive to steroids alone will respond to the
addition of 5-FU to the corticosteroids to reduce fibroblast
Fig. 16.9 Malar edema after filler injections to the infraorbital hollows.

SECTION IV AESTHETIC SURGERY
158
to the area prone to lymphatic obstruction. Superficial in­
jection, if properly placed and limited in volume, should not
result in malar edema, but visible material may be appar­
ent. I strongly recommend the use of an HA when treating
the infraorbital hollow so that hyaluronidase may be used
to dissolve the material if adverse events occur. Persistent
malar edema should be distinguished from overcorrection.
Paresthesia
Inadvertent nerve damage is a rare complication of dermal
filler procedures and can occur as result of direct trauma
in which the nerve is pierced or partially lacerated by the
When caused by a nonreversible filler, malar edema is
long lasting and responds poorly to treatment. Initial mea­
sures include head elevation, cold compresses, manual com­
pression multiple times daily, and a methylprednisolone
dose pack (Fig. 16.11). Intralesional hyaluronidase treatment
should be given to patients injected with HAs.49 The area
should be massaged after hyaluronidase injection to place
the enzyme and substrate in contact. The incidence of malar
edema can be reduced by proper patient and filler selection,
limiting filler volume, and by placing filler material deep to
the malar septum at the immediate preperiosteal level.44 A
filler with low elasticity and viscosity may be placed at the
immediate subcutaneous level (supramuscular), superficial
Fig. 16.10 (a) Anatomic basis for malar edema. (b) The anatomic depth relationships involved in iatrogenic malar mounds. The prezygo­
matic space is demonstrated in the deep suborbicularis plane. The orbitomalar ligament is demonstrated arborizing through the orbicularis
oculi muscle, inserting into the skin forming the tear-trough crease. The zygomaticocutaneous ligaments arborize through the orbicularis,
forming a partition between the infraorbital “malar” fat compartment superiorly and superficial cheek compartment inferiorly. The cuta­
neous insertion of the ligaments forms the characteristic skin crease demonstrated in clinical malar mounds. (Reproduced from Codner M,
McCord D. Eyelid and Periorbital Surgery. 2nd ed. St Louis: CRC Press, 2016.)
a
b

159
Chapter 16 Dermal Fillers and Neurotoxins
an ­intraneural or intraforaminal injection is not possible.
However, even when in contact with bone the nerve can be
pierced or lacerated and material can be compacted into the
foramen through overvigorous massage.
Vascular Compromise
Vascular compromise after filler injection is a major, im­
mediate complication that is always the result of intra­
vascular injection into an artery causing an embolus that
impedes blood flow. All injectors should have a thorough
knowledge of facial vascular anatomy50 (Fig. 16.12). Rec­
ognition of a vascular event and swift and aggressive
treatment is necessary to avoid serious, potentially irre­
versible complications. Filler injected into an artery can
flow both antegrade and retrograde with resulting tissue
compromise or necrosis.
I have been consulted on more than 100 vascular ad­
verse events. Virtually every significant arterial vessel of the
face has been inadvertently injected. The facial artery and
its branches, including mental, inferior labial, superior la­
bial, and lateral nasal arteries, can result in tissue necrosis
when occluded, and these are the most commonly involved
(see Fig. 16.12).50 Preauricular injections into the superficial
temporal artery result in hair loss when the temporal and
parietal branches are occluded (Fig. 16.13) and midfacial
skin compromised when the transverse facial artery is af­
fected. The lateral nasal artery (branch of the external ca­
needle, injection of filler into the nerve, or by excessive
molding and massage of the product into a nerve foramina.
Nerve injury may be transient and reversible or permanent.
Neurapraxia refers to injury to a nerve without axonal dis­
ruption, and improvement should occur in 2 to 3 weeks.
Partial transection of a sensory nerve (axonolytic injury)
may result in anesthesia within that nerve’s zone of inner­
vation. This type of injury may also be reversible; sensation
typically returns within several months. In cases of com­
plete nerve transection, damage may be permanent.
The most common site of dysesthesias, paresthesias, and
anesthesia is in the infraorbital nerve distribution. I have
found that this occurs more often when injections are per­
formed via the intraoral approach (the infraorbital foramen
is canted inferomedially and hooded with bone superiorly).
Care should be taken also when injecting transcutaneously
in close proximity to the infraorbital foramen.
Treatment is in most cases watchful waiting though in­
jection with small doses of triamcinolone at the infraor­
bital foramen, and hydrodisruption of any palpable nodu­
lar ­material with lidocaine or saline has been reported by
some physicians to result in improvement in anesthesia and
dysesthesia. The patient is emotionally supported until the
nerve recovers.
A thorough knowledge of facial anatomy, with special
attention to known danger zones, is required to antici­
pate vital structures as they are approached. If a deep in­
jection is placed with the needle tip in contact with bone,
Persistent swelling within the confines of the orbicularis oculi and malar septum,
becoming evident days to several weeks after treatment.
Presentation
If HA filler
Remove using single or if necessary
multiple injections of hy­al­uron­i­dase
until edema resolves.
Difficult to treat. Persists despite treatment until lymphatic compression is
eliminated.
If not an HA filler
Head elevation
Massage
Nighttime taping and daytime
pressure
Medrol dose pack
Hyaluronidase
Intralesional steroids
Disrupt any nodular material
Treatment
Incidence can be reduced by proper patient, technique, and filler selection. Ask
patients about previous episodes of malar edema. Limit filler volume. Place filler
deep to the malar septum at the immediate preperiosteal level.
Avoidance
Postinjection related edema.
Overcorrection.
Differential diagnosis
Fig. 16.11 Malar edema. HA, Hyaluronic acid.

SECTION IV AESTHETIC SURGERY
160
supraorbital arteries (terminal branches of the ophthalmic
artery) cause glabellar and forehead tissue compromise.
Blindness
Retinal artery occlusion is a rare event that occurs when
dermal filler enters the ocular circulation through retro­
grade filler flow after inadvertent intra-arterial injection
into one of the distal branches of the ophthalmic artery.51
These include the zygomaticotemporal, zygomaticofacial,
and dorsal nasal arteries (see Fig. 16.12). The supratroch­
lear and supraorbital arteries are also terminal branches
of the ophthalmic artery. Injection into the angular artery
can also cause blindness via its anastomosis with the dor­
sal nasal artery. When there is an intravascular injection
into one of these arteries that exceeds intra-arterial pres­
sure, the injectate can move proximal to the origin of the
central retinal artery; when pressure is released, the mate­
rial moves distally into the central retinal artery, blocking
blood supply to the retina.51 Visual impairment and blind­
ness can result.51–54 If the surgeon had exerted even more
pressure on the plunger or for a longer time, the filler could
have flowed retrograde into the internal carotid artery and
then advanced into the cerebral circulation, producing a
stroke.55 Central retinal artery embolism results in blurring
or loss of vision with or without pain. If any acute visual
rotid ­circulation) anastomoses with the dorsal nasal ­artery
(internal carotid circulation), allowing injected material to
affect tissue in both vascular distributions. Material injected
into the infraorbital artery can travel retrograde to more
proximal branches of the third part of the maxillary artery
as well as anterograde. Injections affecting the greater palan­
tine artery cause hemipalatal mucosal changes, and injec­
tions into the anterior and middle superior alveolar arteries
cause ipsilateral compromise of the gingiva surrounding the
upper canine teeth. Injections into the supratrochlear and
Fig. 16.12 Facial vascular anatomy. (Reproduced from Pessa JE, Rohrich RJ. Facial Topography: Clinical Anatomy of the Face. Boca Raton:
CRC Press; 2012.)
Dorsal nasal artery
Angular artery
Lateral nasal artery
Facial artery
Alar branch of superior labial artery
Columellar branch of superior labial artery
Superior labial artery
Fig. 16.13 Temporal hair loss from injection into the superficial tem­
poral artery.

161
Chapter 16 Dermal Fillers and Neurotoxins
carried through the vasculature and may result in local or
distal necrosis with disastrous consequences (Figs. 16.14–
16.18; see also Fig. 16.13). Necrosis has also been reported
to occur secondary to local edema or to occlusion of ad­
jacent vasculature secondary to the hydrophilic properties
of the product.19 I do not believe this is the case; I am con­
vinced all cases of filler-related vascular compromise are
embolic in nature. Necrosis can occur after injection with
any dermal filler, although it appears to be more severe
with particulate fillers. Areas most vulnerable are those in
disturbance occurs during a facial filler injection, prompt
consultation with an ophthalmologist is essential.
Tissue Necrosis
Impending tissue necrosis may occur as a result of inadver­
tent injection of filler into vessels supplying the mucosa or
the skin, resulting in vessel occlusion. As mentioned, the
filler may flow antegrade, retrograde, or both in the vessel.
Once the pressure from injection is stopped, the product is
Fig. 16.14 Vascular compromise. (a) Em­
boli into facial and lateral nasal arteries.
(b) Facial, lateral nasal, and angular artery
emboli. (c) Facial and lateral nasal artery
emboli. (d) Facial, lateral nasal, and colu­
mellar branches of the lateral nasal artery
emboli.
a
b
c
d
Fig. 16.15 Vascular compromise. (a,b) Facial and superior labial artery emboli. (c,d) Inferior labial artery emboli.
a
b
c
d

SECTION IV AESTHETIC SURGERY
162
Fig. 16.16 Vascular compromise. (a,b)
Facial injection into the infraorbital artery
with retrograde involvement of the great­
er palatine artery. (c,d) Injection into the
infraorbital artery with retrograde embo­
lization into the anterior and middle su­
perior alveolar arteries.
a
b
c
d
Fig.
16.17
Vascular
compromise.
(a) ­Emboli into the supratrochlear artery.
(b) Supratrochlear and dorsal nasal artery
emboli. (c) Submental artery emboli.
(d) Transverse facial artery emboli.
a
b
c
d
Fig. 16.18 Cases of vascular compromise can be severe and result in permanent deformity.

163
Chapter 16 Dermal Fillers and Neurotoxins
grade circulatory compromise. I do not advocate drawing
back on the syringe to look for a flashback before injecting.
In the process of pulling back, injectors have been found to
come off the bone and may be within a vessel immediately
as it leaves its foramina. Aspiration from small-gauge nee­
dles may provide a “false negative.” Cooling an area before
injection may cause vascular constriction, but when the
cold compress is removed the area needs to be re-prepped.
Injecting with a blunt cannula may reduce the risk of an
intravascular injection.
Treatment Recommendations for Vascular
Compromise
The management of vascular compromise after filler injec­
tion is not based on a large body of evidence,57 but rather on
anecdotal experience with multiple cases. In cases of reti­
nal artery occlusion, injection should be ceased immedi­
ately if the subject complains of pain or vision loss. The pa­
tient should be referred to an ophthalmologist immediately
and transported to that consultation; the surgeon must
ensure the ophthalmologist gets a complete history. These
patients should never be sent to seek care in an emergency
room. The treatment of iatrogenic embolic blindness is usu­
ally unsuccessful.58 Retinal circulation needs to be restored
quickly, within 60 to 90 minutes, if the retina is to survive.58
Carruthers et al59 recommend retrobulbar injection of 2 to
4 mL of hyaluronidase (as high a concentration as possible),
because this will decomplex both intravascular hyaluronic
acid and native hyaluronic acid in the surrounding tissues.
It has been suggested that hyaluronidase does not pen­
etrate the choroid and thus may be ineffective. If feasible,
the surgeon should consider direct injection of the oph­
thalmic artery by a neuroradiologist or massive systemic
intravenous injection of hyaluronidase. Other suggested
treatments include ocular massage, intravenous mannitol,
and acetazolamide to rapidly reduce intraocular pressure
in an attempt to move the retinal vascular embolus distally.
Graefe knife evacuation of the anterior chamber fluid under
local anesthesia can also be attempted to acutely reduce in­
traocular pressure.
Skin, mucosa, and subcutaneous tissue compromise is
heralded by disproportionate pain and skin blanching, and
injection should be immediately discontinued. The surgeon
should massage the area vigorously to move the filler more
distally in the vessel.
A “filler crash kit” should be available to treat intra-ar­
terial injection and avert necrosis57 (Fig. 16.19, Box 16.4).
The blocked artery does not have to be found to inject
hyaluronidase; studies in rabbits and fresh human cadaver-
sourced facial artery specimens have shown that hyaluron­
idase can cross the arterial wall to break down the HA.60
Injection of 150 to 2,000 units of hyaluronidase followed
by massage should be performed, but clinicians should be
aware that hyaluronidase will take longer to work with
monophasic fillers than biphasic fillers. If the embolic event
has occurred after injection of an HA filler, injection of hy­
aluronidase should be repeated in conjunction with mas­
sage until circulation is restored regardless of the amount
which blood supply depends strongly on a single arterial
branch (axial pattern blood supply) such as the glabellar
and nasolabial folds (Box 16.3).
Awareness of the signs and symptoms of inadvertent
intravascular injection allows prompt recognition and in­
tervention that may restore circulation. Intense pain imme­
diately on injection (though less common because it may be
masked by lidocaine in the fillers or administered before in­
jection) accompanied by blanching (seconds to minutes) are
the first signs of intra-arterial injection. Skin changes prog­
ress predictably to the appearance of purplish-bluish mot­
tling (livedo reticularis), then dense purple discoloration,
and then hemorrhagic blisters56 (see Fig. 16.16). Eventually
there is resolution or necrosis and scarring (see Fig. 16.17).
Clinicians should be aware of patients who have had
previous rhinoplasties, because they may have diminished
nasal circulation.
Avoidance of Vascular Compromise
A thorough knowledge of facial vascular anatomy is essen­
tial. When injecting in the anatomic danger zones, injec­
tions should be directly in contact with bone; if obstruc­
tion of the needle occurs it should be removed, cleared, and
then replaced at the preperiosteal level. At the level of the
periostea there are no vessels, so if in contact with bone
the injector cannot be within a vessel or a foramina. Depot
injections should be performed only when the needle is in
contact with bone or when within the dermis. All other in­
jections should be performed with a moving needle using
an antegrade or retrograde placement technique. A moving
needle will have a very short dwell time even if it is within
a vessel, depositing only minimal material. Injections
should be performed with low plunger pressure and in
small aliquots. When filler is being extruded, the injector’s
eyes should be on the needle tip to watch for blanching,
and not on the syringe barrel. The larger the intravascular
injection and the larger the area served by the artery that
is embolized, the larger the area of necrosis. High-pressure
injections are more likely to cause retrograde and ante­
Box 16.3
•• Injection of large volume bolus injections
•• High–pressure injection (causes larger volume
of intravascular injectate as well as retrograde
flow)
•• Small, sharp needles
•• Stationary rather than moving needle
•• Deep injection (larger vessels are found beneath
the dermis in the subcutaneous fat)
•• Particulate versus gel filler
•• High-risk injection sites (i.e., glabellar,
columella and nasal dorsum, piriform aperture,
infraorbital foramen)
Factors Increasing the
Likelihood of Vessel Occlusion

SECTION IV AESTHETIC SURGERY
164
of hyaluronidase injected. The hyaluronidase should be in­
jected into the area that demonstrates circulatory compro­
mise, which may not be at the initial injection site. The ap­
plication of warm compresses to produce vasodilation and
aspirin for anticoagulation will also help. Nitroglycerin paste
and vigorous massage can improve blood flow to the area.61
Other treatments that may be of value include sildenafil 100
mg for its dilating properties, oral corticosteroids to decrease
edema and inflammation (only if necessary, not routinely),
and hyperbaric oxygen, especially when significant tissue
loss appears imminent.
Prophylactic antibiotic and antiviral therapy should be
initiated. Tobacco use should be discontinued. Good quality
wound care is important, but early débridement should be
avoided, because tissue loss is usually less than would be an­
ticipated by early appearances. While the tissue is ­healing,
Fig. 16.19 Vascular compromise.
Thorough knowledge of facial vascular
anatomy. Inject slowly with needle in contact
with bone or with needle moving at all times,
consider blunt cannula, avoid high–pressure
injections.
Thorough knowledge of facial vascular
­anatomy. Inject slowly, watching the needle
tip, with low pressure on bone or always
­moving needle or blunt cannula. Avoid high–
pressure large–volume bolus injections.
Avoidance
Day 5–7, wound can resemble herpetic
infection.
Differential diagnosis
Retinal occlusion
Immediate pain and/or blurring or loss of
vision during injection
Presentation
Tissue necrosis
Immediate blanching of tissue during injection
followed by livedo reticularis followed by dusky
purple coloration
Higher-risk areas include glabella, forehead,
alar base, lip, nose, and medial superior cheek
Immediately cease injecting; retinal circulation
must be restored quickly.
Retrobulbar injection of 2–4 mL or hy­al­uron­i­
dase (only if capable and no reported success).
Consult ophthalmologist, transfer with history
and ensure that patient is seen (imperative to
restore circulation in short amount of time or
permanent visual impairment or blindness can
occur).
Discontinue injection, massage firmly to
restore circulation.
Initiate treatment with “crash cart” for vascular
occlusion.
Crash cart contents
Hyaluronidase (use whether HA or not; if HA,
repeat injections until circulation is restored
or no improvement)
Warm compresses
Nitroglycerin paste
Aspirin, Viagra, Lovenox
Antibiotics, antivirals
Medrol dose pack (prn control of edema)
Hyperbaric oxygen
Head elevation
Nicotine avoidance
Supportive wound care (open and moist)
Do not rush to early débridement
Sun and cold avoidance while healing
Treatment
Box 16.4
A filler crash kit should include the following:
•• Multiple vials of hyaluronidase for dissolving
hyaluronic acid filler (1600 units)
•• Warm compresses
•• Nitroglycerin paste to induce vasodilation
•• Aspirin
•• Oral vasodilators such as sildenafil or tadalafil,
aspirin, and potentially enoxaparin to prevent
clot propagation
Filler Crash Kit