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Management of Open Fractures and Subsequent Complications

Charalampos G. Zalavras, Randall E. Marcus, L. Scott Levin and Michael J. Patzakis
J Bone Joint Surg Am. 2007;89:884-895.

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THE JOURNAL OF BONE & JOINT SURGER Y JBJS.ORG MA N AG E M EN T OF OP EN FR A C TU RES AND
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Management of Open Fractures and

Subsequent Complications
By Charalampos G. Zalavras, MD, Randall E. Marcus, MD, L. Scott Levin, MD, and Michael J. Patzakis, MD
An Instructional Course Lecture, American Academy of Orthopaedic Surgeons

Open fractures are associated with an
increased risk of infection and healing
complications. Management of open
fractures is based on the following prin-
ciples: assessment of the patient, classi-
fication of the injury, antibiotic therapy,
dbridement and wound management,
fracture stabilization, early bone-
grafting, and supplemental procedures
to achieve healing.
Assessment, Classification,
and Antibiotic Therapy
Open fractures are usually the result
of high-energy trauma and should alert
the treating physician to the possibility
of associated injuries. Therefore, de-
tailed evaluation and appropriate re-
suscitation of the patient are necessary.
The neurovascular status of the in-
jured extremity should be carefully
assessed, and the development of
compartment syndrome should not
be overlooked1. The soft-tissue injury
should be evaluated to determine the
size and location of the wound, the de-
gree of muscle damage, and the pres-
ence of contamination.
The Gustilo and Anderson clas-
sification system2, which was subse-
quently modified by Gustilo et al.3, is
used widely to grade open fractures. In
this system, type I indicates a puncture
wound of 1 cm with minimal contam-
ination or muscle crushing. Type II in-
dicates a laceration of >1 cm in length
with moderate soft-tissue damage and
crushing; bone coverage is adequate
and comminution is minimal. A type-
IIIA open fracture involves extensive
soft-tissue damage, often due to a high-
energy injury with a severe crushing
component. Massively contaminated
wounds and severely comminuted or
segmental fractures are included in this
subtype. Soft-tissue coverage of the
bone is adequate. Type IIIB indicates
extensive soft-tissue damage with peri-
osteal stripping and bone exposure,
usually with severe contamination and
bone comminution. Flap coverage is re-
quired to provide soft-tissue coverage.
A type-IIIC fracture is associated with
an arterial injury requiring repair.
The reliability of this classifica-
tion has been questioned. In a study in
which orthopaedic surgeons had been
asked to classify open fractures of the
tibia on the basis of videotaped case
presentations, the average agreement
among the observers was 60% overall,
which was deemed to be moderate to
poor4. Therefore, classification of the
open fracture should be done only in
the operating room, after wound explo-
ration and dbridement. The degree of
contamination and soft-tissue crushing
are important factors in the classifica-
tion of an open fracture, but they may
be mistakenly overlooked in a wound of
small size.
As most open fractures are con-
taminated with microorganisms, anti-
biotics are used not for prophylaxis but
rather to treat wound contamination.
To prevent a clinical infection, immedi-
ate antibiotic administration, wound
dbridement, soft-tissue coverage, and
fracture stabilization are necessary. Tet-
anus prophylaxis may be necessary, de-
pending on the patients immunization
status. The risk of a clinical infection
depends on the severity of the injury
and ranges from 0% to 2% for type-I

Disclosure: The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a
member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial
entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical prac-
tice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

J Bone Joint Surg Am. 2007;89:883-95

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open fractures, 2% to 10% for type-II,
and 10% to 50% for type-III.
The rate of infection of open
fractures is associated with the fracture
characteristics, antibiotic therapy vari-
ables, and host parameters5,6. Infection
rates progressively increased from 1.4%
(seven of 497) for type-I open fractures
to 3.6% (twenty-five of 695) for type-II
open fractures to 22.7% (forty-five of
198) for type-III5. The location of the
fracture is also important, with the
infection rate for open tibial fractures
being twice that for open fractures in
other locations5.
The administration of antibiot-
ics before dbridement decreased the
infection rate (two of eighty-four frac-
tures) compared with that found when
no antibiotics had been given (eleven
of seventy-nine fractures)7. The antibi-
otics should cover both gram-positive
and gram-negative organisms, and
they should be given as soon as pos-
sible, preferably within three hours
after the injury5. The duration of anti-
biotic therapy, the time between the
injury and the surgery, and the type
of wound closure do not seem to be
significant variables5,8.
Even though the infection rates
associated with primary and secondary
closure are the same, gas gangrene may
occur after primary closure of wounds
contaminated with clostridial organ-
isms. The partial closure technique,
in which the traumatic wound is left
open and the surgical extension of the
wound is closed (Figs. 1-A through 1-
G), is recommended for type-I and II
open fractures9.
The usefulness of cultures of
wound specimens is controversial,
since they often fail to identify the or-
ganism that subsequently causes the
infection10-12. Cultures of wound speci-
mens obtained prior to wound dbride-
ment are no longer recommended
because of their poor predictive value.
However, the results of cultures of post-
dbridement specimens and sensitivity
testing may help in the selection of the
best agents for subsequent procedures
or in the treatment of an early infection.
Although some authors have re-
commended cephalosporin as a single
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MA N AG E M EN T OF OP EN FR A C TU RES
SUBSEQUENT COMPLICATIONS
agent for patients with a type-I or II
open fracture, the antibiotic therapy
should target both the gram-positive
and the gram-negative pathogens
contaminating the wound13. A com-
monly used regimen consists of a first-
generation cephalosporin (e.g., cefazolin),
which is active against gram-positive
organisms, combined with an ami-
noglycoside (e.g., gentamicin or tobra-
mycin), which is active against gram-
negative organisms. Substitutes for
aminoglycosides include quinolones10,
aztreonam, third-generation cepha-
losporins, or other antibiotics with
gram-negative coverage. Systemic ad-
ministration of aminoglycosides may
not be necessary if aminoglycoside-
impregnated beads are used for local
antibiotic delivery.
Clostridial myonecrosis (gas gan-
grene) is a particular concern when an
injury is contaminated with anaerobic
organisms (e.g., farm injuries) or there
is a vascular injury that may create con-
ditions of ischemia and low oxygen
tension14. Therefore, in such cases,
ampicillin or penicillin should be
added to the antibiotic regimen to
provide coverage against anaerobes.
Antibiotic administration should
be started promptly, as a delay of more
Fig. 1-A
Type-I open fracture of the tibia with a small (<1-cm) traumatic wound. The surgical extension of
the wound, necessary for dbridement, is marked on the skin.
AND
than three hours has been shown to
increase the risk of infection5. The rec-
ommended duration of therapy is three
days5,13,15. An additional three days of
administration of antibioticsselected
on the basis of the results of initial cul-
turesis recommended for subsequent
surgical procedures, such as wound
coverage and bone-grafting.
Local therapy with antibiotic-
impregnated polymethylmethacrylate
cement has been used as an adjunct to
systemic antibiotic therapy in the treat-
ment of open fractures (Figs. 2-A and
2-B) and has been shown to reduce the
infection rate. Ostermann et al.16 re-
ported an infection rate of 3.7% in a
group that received combined treat-
ment with both systemic antibiotics
and antibiotic beads. This rate was
considerably lower than the 12% infec-
tion rate associated with open fractures
treated with systemic antibiotics alone.
The polymethylmethacrylate
powder is mixed with the antibiotic in
powder form, is polymerized, and then
is formed into beads, which are incor-
porated on a 24-gauge wire; usually
3.6 g of tobramycin is mixed with 40 g
of polymethylmethacrylate cement17.
Aminoglycosides are common choices
for the antibiotic because of their broad
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spectrum of activity, heat stability, and ripheral vascular disease, collagen Appropriate dbridement is
low allergenicity. Vancomycin is not rec- vascular disease and chronic venous critical23. A tourniquet should be used
ommended as an initial agent because of insufficiency with underlying venous during the dbridement to distinguish
concerns of overuse leading to develop- stasis, immunocompromise, previous blood-stained tissue from normal tis-
ment of resistant microorganisms. fractures or surgical incisions, and nu- sue, as local hemorrhage obscures de-
The bead-pouch technique tritional deficiencies. bris and dirt that must be removed24.
achieves a high local concentration of
antibiotics; minimizes systemic toxicity;
and seals the wound from the external
environment with a semipermeable
barrier, thereby preventing secondary
contamination by nosocomial patho-
gens and at the same time maintaining
an aerobic wound environment.

Soft-Tissue Management
Open fractures are always associated
with a soft-tissue injury, and they can
be thought of as a soft-tissue injury that
includes a fracture. The management of
both the bone and the soft tissues is the
major determinant of fracture-healing
and functional restoration of the trauma-
tized extremity. An integrated approach,
the so-called orthoplastic approach, takes
into account the importance of early and
definitive treatment of both aspects of
the injury18. Important issues related to
management of the fracture include Fig. 1-B

when to provide coverage, how coverage Following surgical extension of the wound, the open fracture site was dbrided and the fracture
should be provided, who should provide was fixed.
coverage, and where coverage should be
provided.
Mechanisms of injury include elec-
trical burns, crushing, avulsion, blasts,
and degloving19. Management of these
injuries requires an understanding of
the personalities of soft-tissue injuries,
which helps to guide decision-making.
For example, soft-tissue degloving,
which is frequently seen in deceleration
injuries, particularly in elderly individu-
als, often results in avulsion of perforat-
ing vessels to the overlying skin20. This is
commonly seen in the pelvis, where it is
called a Morel-Lavalle lesion. The same
pathological entity is found in the ex-
tremities and can progress to necrosis
of the skin envelope with exposure of
hardware and bone21.
It is vital to recognize that, in ad-
dition to the variety of mechanisms that
can cause an acute soft-tissue injury, a Fig. 1-C
variety of underlying morbidities can The wound was managed with the partial closure technique, in which the surgical extension of
be associated with an open fracture. the wound is closed and the traumatic wound is left open. This minimizes the risk of gas gan-
These include diabetes mellitus22, pe- grene without requiring a repeat surgical procedure for wound closure.
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Loop magnification may be needed.
Sharp dbridement is essential, and it
should be done in a centripetal fashion.
Liberal use of fasciotomies facilitates
wound inspection and releases compro-
mised muscle compartments. Radical
excision of necrotic tissue, as proposed
by Godina, should be performed so that
all nonviable tissue including bone is
removed25. The wound should look
healthy and, when there is doubt, all
questionable tissue should be removed.
New techniques for dbridement
such as use of the Versajet device (Smith
and Nephew, Memphis, Tennessee)
have shown the benefit of reducing tis-
sue loss during initial or second-look
procedures. Usually, coverage should
be obtained with one or two formal
dbridements; if more dbridements
are required, then radical dbridement
has not been performed.
After dbridement, one must
decide if the soft-tissue deficiency
associated with the open fracture can
be managed by the orthopaedic trau-
matologist26. If not, it is essential that
a microvascular surgeon be consulted
as soon as possible. If the local surgical
community cannot handle the soft-
tissue problem, then the patient should
be referred to another institution as
soon as possible for definitive wound
coverage.
Vascularity is the single most im-
portant determinant of complications
after an open fracture. Vascularity in-
cludes arterial, venous, and lymphatic
conduits. Knowledge of the angio-
somes helps the surgeons to avoid im-
proper placement of incisions and
surgical approaches that can further
compromise watershed areas, leading
to soft-tissue necrosis following open
reduction and external fixation27. The

Fig. 1-D Fig. 1-E

Preoperative anteroposterior and lateral radiographs of the fractured tibia and fibula.
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Fig. 1-F Fig. 1-G

Postoperative anteroposterior and lateral radiographs following intramedullary nailing of the tibia.

concept of perforators must be under-
stood as well28. These are side branches
from the main arterial vessels that give
rise to skin angiosomes. Tissue necrosis
is the result of compromised perfora-
tors and the watershed areas lying be-
tween angiosomes.
Evaluation of the blood supply in
skin includes hands-on examination as
well as palpation of pulses and apprecia-
tion of temperature differences along
cutaneous surfaces. Skin that has venous
discoloration suggests venous insuffi-
ciency, whereas slow refill indicates an
arterial-side insufficiency. Doppler ex-
aminations, formal arteriography, digi-
tal subtraction arteriography, and at
times venography are important ways
to ascertain the vascular status of an
extremity. Without an anterior tibial
artery29, anterolateral skin territories
may be compromised and incisions in
this region should be avoided.
A soft-tissue-closure plan must be
formulated during the initial wound as-
sessment and the initial fixation of frac-
tures. This is not a consecutive process,
nor does planning occur after skeletal
fixation. There are multiple options
for the treatment of the wound prior
to closure; these include the placement
of antibiotic beads, and recently the
wound VAC (vacuum-assisted closure)
(KCI, San Antonio, Texas) has been
used as a bridging technique before de-
finitive coverage takes place several days
later. Other techniques that can be used
prior to closure include the application
of Epigard (Parke-Davis, Detroit, Mich-
igan)27 or Adaptic gauze (Johnson and
Johnson, Raynham, Massachusetts)
over the wound, porcine allograft, or
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Fig. 2-A
Type-IIIB open fracture of the distal part of the tibia.
antibiotic beads. The goals of wound
coverage are to prevent desiccation of
tissue, optimize antibiotic delivery,
optimize patient comfort, and seal the
wound from the external environment.
At the same time as dbridement or ini-
tial fracture management is performed,
tetanus toxoid prophylaxis, as indicated,
and the appropriate antibiotics should
be administered. Incisions that have
been used to extend the initial wounds
can be closed to decrease the exposure
of deeper tissues9,30.
Open fractures should never be
closed primarily because of the risk
of gas gangrene. While microsurgeons
are able to do an immediate free tissue
transfer31, this method remains con-
troversial. In our opinion, there is no
rationale for performing definitive
closur immediately; returning to the
operating room in twenty-four to forty-
eight hours is a time-tested method,
and the data reported by Godina do not
indicate a difference between wounds
closed at the first operative setting and
those closed seventy-two hours later25.
The majority of open wounds
can be covered with split-thickness
skin grafts. Local or regional flaps
may involve more morbidity because
transposed skin flaps or muscles may
be compromised, particularly in high-
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MA N AG E M EN T OF OP EN FR A C TU RES
SUBSEQUENT COMPLICATIONS
energy injuries, and free tissue trans-
fer may be more reliable. Free tissue
transfer is often the most definitive
form of treatment.
Fracture Management
Stabilizing the open fracture protects
the soft tissues from further injury by
Fig. 2-B
Antibiotic beads were placed in the wound, which was then sealed with a semipermeable
membrane until the time of the soft-tissue coverage procedure.
AND
fracture fragments, facilitates the host
response to microbes despite the pres-
ence of implants32, improves wound
care, and allows early motion of adja-
cent joints and early mobilization of
the patient.
The choice of fracture fixation
depends on the bone that is fractured,
the location of the fracture (intra-
articular, metaphyseal, or diaphyseal),
the extent of soft-tissue injury and
contamination, and the physiologic
status of the patient. Fixation can be
definitive or provisional, and tech-
niques include intramedullary nailing,
external fixation, and plate fixation.
More than one technique may be ap-
plicable to a specific injury.
Intramedullary nailing is widely
used for stabilization of diaphyseal frac-
tures of the lower extremity33-35. External
fixation is indicated for fractures associ-
ated with extensive contamination and
soft-tissue damage and when there is a
need for rapid fracture stabilization or
minimal interference with the patients
physiologic response to the injury (so-
called damage control)36, as in the case
of a type-IIIC fracture in a multiply
injured patient whose condition is un-
stable. Plate fixation is indicated for pe-
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riarticular fractures and for diaphyseal
fractures of the upper extremity.
The method of stabilizing an
open tibial diaphyseal fracture is con-
troversial. Both unreamed intramedul-
lary nailing and external fixation have
been used successfully in the manage-
ment of open tibial fractures. In two
prospective, randomized studies com-
paring the two techniques, half-pin
external fixators were associated with
malalignment in 31% of the cases, and
with pin-track infection in 50%34, but
there were no differences in fracture-
site infection and bone-healing rates
between the two methods34,35. The sever-
ity of the soft-tissue injury rather than
the choice of implant appeared to be the
main factor influencing infection and
bone-healing34. A meta-analysis of the
management of open tibial fractures
demonstrated that unreamed intra-
medullary nailing reduced the risks of
a reoperation, malunion, and superfi-
cial infection compared with the risks
associated with external fixators37. In-
tramedullary nailing does not require
the same high level of patient compli-
ance, but an external fixator may be
particularly useful for patients with
vascular injury or extensive soft-tissue
damage and contamination.
The endosteal blood supply is
preserved to a greater degree with un-
reamed nailing than it is with reamed
nailing34,35,38-40. Thus, unreamed nailing
may be preferable to reamed nailing for
open tibial fractures, where periosteal
vascularity may be already compro-
mised by the traumatic insult. Reamed
nailing, on the other hand, allows in-
sertion of larger-diameter implants, im-
proves stability at the fracture site, and
helps reduce the implant failure rate.
Moreover, the cortical circulation that
is disrupted during reaming is gradually
reconstituted, although this may occur
more slowly than it does with un-
reamed nailing39.
Reamed nailing of open tibial
fractures was compared with unreamed
nailing in two prospective, randomized
studies41,42. Neither established a signifi-
cant difference in infection rates (one
of forty and one of twenty-six with un-
reamed nailing compared with two of
890
MA N AG E M EN T OF OP EN FR A C TU RES
SUBSEQUENT COMPLICATIONS
forty-five and one of nineteen with
reamed nailing). There were fewer screw
failures in the reamed-nailing group in
both studies.
Some complications associated
with external fixation are due to the
transition to another form of fixation,
and external fixation can be success-
fully used as definitive treatment43-45. In
a prospective study of 101 type-II and
III fractures treated with external fixa-
tion, Marsh et al. reported that ninety-
six fractures healed45. There were six
fracture-site infections. Early bone-
grafting of fractures with bone defects
treated with external fixation reduces
healing complications46.
Delayed conversion of external
fixation to intramedullary nailing can
increase the prevalence of infection to
as high as 50%12,47. On the other hand,
Blachut et al. showed that early conver-
sion of the fixator to a nail (at a mean
of seventeen days) in the absence of
pin-track infection was associated with
an infection rate of only 5%48. Conver-
sion to an intramedullary nail can be
done safely if the fixator had been in
place for a short period of time and in
the absence of pin-track infection.
Otherwise, the fixator should be main-
tained until the fracture heals.
Reamed intramedullary nailing
is the preferred fixation technique for
open diaphyseal femoral fractures, but
external fixation for provisional frac-
ture stabilization is an option in unsta-
ble patients49-51. Brumback et al. found
no infections after the treatment of
sixty-two type-I, II, and IIIA open
femoral fractures with reamed in-
tramedullary nailing and only three
infections (11%) after such treatment
of twenty-seven type-IIIB open femo-
ral fractures33.
Plate fixation is the preferred
method of treatment of open forearm
and humeral fractures52-54. Intramedul-
lary nailing is an option for open dia-
physeal fractures of the humerus, but
there are concerns regarding shoulder
pain and stiffness. External fixation can
be useful in the presence of severe soft-
tissue injury and contamination55,56.
One option for managing open
periarticular fractures is provisional
AND
spanning external fixation (with the
addition of limited internal fixation
with screws to restore articular congru-
ency in intra-articular fractures) with
plate fixation performed later57. Alter-
natively, these fractures can be treated
definitively with use of either a ring
fine-wire fixator (with limited internal
fixation if needed)58,59 or plate fixation60.
The development of locking plates and
minimally invasive osteosynthesis tech-
niques have shown promise recently61,62.
Open fractures associated with
a vascular injury require special con-
siderations. The order of fracture fixa-
tion and arterial repair is controversial.
Available options include (1) fracture
fixation first followed by arterial re-
pair63, (2) arterial repair first followed
by fracture fixation64, and (3) use of an
arterial intraluminal shunt65. Decision-
making depends on an individualized
assessment of the characteristics of
each case in consultation with the
vascular surgeon. Important factors
to be considered are the ischemia time
that has already elapsed (muscle will
not tolerate ischemia for more than six
hours) and the complexity of the frac-
ture pattern (definitive fixation may be
time-consuming).
Bone-Grafting and Other
Techniques to Promote Healing
Bone-grafting can help in fracture re-
pair or the reconstruction of skeletal
defects. The basic types of bone grafts
used in fracture treatment are autoge-
nous cancellous bone, autogenous
cortical bone, vascularized cortico-
cancellous bone, and bone-graft sub-
stitutes. Autogenous cancellous bone
is the gold standard for providing os-
teoconduction, osteoinduction, and
osteogenesis. This bone delivers an
osteoconductive matrix made of both
hydroxyapatite and collagen. Further-
more, it delivers an abundance of
growth factors as well as stromal cells
to the fracture site. It has the obvious
advantage of histocompatibility and it
revascularizes quickly, but it lacks struc-
tural integrity66. In 1952, Marshall Urist
showed that structural integrity be-
comes normal at approximately one
year67. The limited quantity of autoge-
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nous cancellous bone available and
donor site morbidity are disadvantages.
In order to improve osteocyte survival
when obtaining autogenous cancellous
bone, the surgeon should keep the do-
nor cells moist and chilled in a blood-
soaked sponge.
Vascularized corticocancellous
grafts provide excellent osteoconduc-
tion, osteoinduction, and stromal cells
to the fracture site. These grafts have
the advantage of providing good struc-
tural integrity, and they can be used in
defects of >6 cm in size. They usually
consist of vascularized fibular or iliac
crest grafts that maintain the viability
of the bone cells while not undergoing
extensive resorption; they also provide
new blood supply to the fracture site68.
Allografts, bone-graft substitutes,
ceramics, demineralized bone matrix,
bone marrow, and composite grafts
are often used in closed fractures, but
they are less useful in open fractures be-
cause of the decreased vascularity and
the contamination often seen in these
complex fractures.
The timing of bone-grafting is
important, particularly for open frac-
tures. Bone-grafting is usually not per-
formed at the initial open reduction
and internal fixation procedure, except
when the surgeon is dealing with intra-
articular defects. In Gustilo Anderson
type-I and II open fractures, bone-
grafting can usually be performed
safely at the time of the delayed pri-
mary closure. In type-III fractures,
bone-grafting should be performed
only after successful closure, usually at
six to nine weeks after the injury12.
Electrical stimulation of the bone
can be accomplished with three clinical
modalities: direct-current stimulation
(implanted electrodes); electromagnetic
stimulation by inductive coupling, with
time-varying magnetic fields (non-
invasive); and capacitive coupling
stimulation with external electrodes
(noninvasive). A double-blinded, ran-
domized clinical study of the use of
pulsed electromagnetic fields on de-
layed tibial unions demonstrated a 45%
union rate compared with a 14% union
rate with use of a placebo device69. In
another study, involving capacitively
891
MA N AG E M EN T OF OP EN FR A C TU RES
SUBSEQUENT COMPLICATIONS
coupled electromagnetic fields, Scott
and King reported a 60% success rate
at twenty-one weeks compared with
a 0% success rate with a placebo70.
Brighton et al. compared 167 fractures
treated with direct current with fifty-
six treated with capacitively coupled
electrical current and with forty-eight
treated with conventional bone-
grafting71. There were no significant
differences among the three groups. As
the number of risk factors such as open
fracture, cigarette smoking, and periph-
eral vascular disease increased, the heal-
ing rate decreased in all three groups
in this unblinded study. Electrical stim-
ulation plays a role in promoting bone-
healing, and probably works as well as
conventional bone-grafting, but its ef-
fects are directly affected by the local
and systemic host biology, a situation
similar to that seen with bone-grafting.
Over the last fifty years, ultra-
sound has also been studied in relation
to the stimulation of bone callus72. In a
prospective, randomized trial of closed
and type-I open tibial fractures treated
with low-intensity ultrasound (30 mW/
cm2 for twenty minutes per day), the
time to healing was reduced by 24%73,74.
Other studies have also demonstrated
benefits75,76.
In 1965, Urist reported his dis-
covery of bone morphogenetic protein
(BMP) in bone matrix, which is re-
sponsible for osteoinduction77. Sub-
sequently, sixteen different proteins
(BMP-1 through BMP-16) have been
identified in bone matrix. All of these,
except BMP-1, are in the family of
transforming growth factor- (TGF-).
Furthermore, all play a role during
embryogenesis and tissue repair in
postnatal life78-84. It is believed that
osteoinduction is mediated by BMP-2
through BMP-7 and BMP-9, which
provide primordial signals for the
differentiation of mesenchymal stem
cells into osteoblasts85. BMP-2, BMP-6,
and BMP-9 have all been shown to be
more effective when pluripotent cells
are present.
Clinical research has revealed
that recombinant BMP (rhBMP) can
be utilized successfully as a supplemen-
tal agent to achieve bone-healing. In
AND
the BESTT study, rhBMP-2 was uti-
lized in an open-fracture setting86. One
hundred and forty-seven fractures were
treated with open reduction and inter-
nal fixation without the use of rh-BMP,
while 145 open tibial fractures were
treated with open reduction and inter-
nal fixation with the addition of either
0.75 mg/mL of rhBMP-2 or 1.50 mg/mL
of rhBMP-2. The group treated with
1.50 mg/mL of BMP-2 had a 44% re-
duction in the need for secondary in-
tervention compared with the control
group. A Canadian study of 124 open
tibial fractures randomized either to
receive rhBMP-7 or to a control group
demonstrated that rhBMP-7 therapy
reduced the need for secondary inter-
vention from 27% to 12%87. In another
study, rhBMP-7 bound to type-1 col-
lagen was compared with conventional
autogenous bone-grafting for the treat-
ment of tibial nonunions88. Similar
union rates were found, both clinically
and radiographically.
In summary, the use of rhBMP
therapy as a supplemental procedure
to achieve bone-healing is safe and ef-
fective as a treatment of delayed union
or nonunion of fractures and it is prob-
ably equivalent to autogenous bone-
grafting. There is no conclusive evi-
dence that the use of rhBMP in fresh
fractures will increase the healing rate89.
Problems encountered with the use of
rhBMP are its short biologic half-life
and difficulties in retaining the product
at the fracture site. Often, a large bolus
dose is required, and the release of
growth factors is not uniform. Finally,
the high cost of rhBMP is a factor that
limits its use.
In the future, gene transfer ther-
apy may be used to deliver growth fac-
tors to the fracture site. Osteogenic
proteins can be encoded directly to the
fracture site, allowing a sustained local
concentration and dose of growth fac-
tors. Furthermore, endogenous synthe-
sized proteins are more effective than
recombinant synthesized proteins, and
the in vivo transfer is minimally inva-
sive and less expensive than rhBMP
therapy. Investigators have utilized a
direct percutaneous gene-delivery
technique to enhance the healing of
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segmental bone defects in a rat model90.
The genetically modified osteoprogeni-
tor cells were delivered directly to the
segmental bone defects with a single
intralesional injection of adenovirus
carrying BMP-2. At eight weeks, the os-
seous union rate was 75% in the treated
animals compared with 4% in control
animals. The authors showed that a
single percutaneous injection of Ad-
BMP-2 can induce healing of critical-
size defects in rats at eight weeks and
that the tissue repair is by trabecular
bone with normal mineral content.
Although the use of gene trans-
fer therapy is an exciting possibility for
the future enhancement of fracture-
healing, there remain considerable safety
concerns regarding the injection of ade-
novirus with osteoinduction genes and
the fear of transgenic expression91.
Management and Reconstruction
of Infected Fractures
Management of chronic osteomyelitis
with a limb-salvage protocol consists of
dbridement, systemic and local antibi-
otic treatment, skeletal stabilization,
soft-tissue coverage, and bone-grafting
and/or reconstructive procedures for
treatment of ununited fractures and ex-
isting bone defects. These principles can
be incorporated in a staged protocol,
often implemented by a multidisci-
plinary team consisting of an ortho-
paedic surgeon, an infectious disease
specialist, and a microvascular surgeon.
When there is an infection, sev-
eral factors must be evaluated carefully
to develop a detailed management plan.
Imaging studies should be reviewed to
assess the status of bone-healing, the lo-
cation and extent of cortical and med-
ullary bone involvement, and the status
and integrity of existing implants. The
quality and integrity of the soft-tissue
envelope, and the need for flap cover-
age, should be evaluated. The neurovas-
cular status of the extremity should be
determined. Cultures and sensitivity
tests allow the selection of appropriate
antibiotics for local delivery with anti-
biotic beads and for systemic therapy.
Subsequent cultures of intraoperative
specimens should be performed, and
the results may indicate that a different
892
MA N AG E M EN T OF OP EN FR A C TU RES
SUBSEQUENT COMPLICATIONS
antibiotic is required. The medical sta-
tus of the patient should be assessed to
ensure that it allows the safe execution
of a complex reconstructive plan. Inter-
ventions, such as nutritional support
and cessation of smoking, will help to
optimize the patients condition before
surgery.
Radical dbridement of all nonvi-
able tissue, including skin, soft tissue,
and bone, is necessary. Dbridement
proceeds until bleeding, viable tissue is
seen at the resection margins, to ensure
that all foci of infection are removed92,93.
Viable bone is characterized by punctu-
ate bleeding, known as the paprika
sign. Dbridement should not be lim-
ited by concerns about the osseous or
soft-tissue defects. Specimens of puru-
lent fluid, soft tissue, and bone from the
affected area should be sent for aerobic
and anaerobic cultures; it is especially
important to perform cultures for my-
cobacteria and fungi when the patient is
immunocompromised or has a chronic
infection92,94. The wound should be irri-
gated with a copious amount of saline
solution, and antibiotics may be added
to the terminal liter of the irrigation
fluid.
The dead space that results from
dbridement is filled with physician-
made polymethylmethacrylate antibi-
otic-impregnated beads. The pathogen
must be susceptible to the eluted antibi-
otic. If wound closure is not possible,
the wound containing antibiotic beads
is sealed with a semipermeable mem-
brane so that the eluted antibiotic(s) re-
main in the involved area to achieve a
high local concentration17.
When a nonunion is associated
with infection, subsequent procedures
for wound management and bone-
grafting are planned and the beads can
be removed at that time. In the future,
biodegradable delivery systems will
eliminate the need for this surgical
removal95.
The type of systemic antibiotic
therapy is chosen on the basis of the re-
sults of the preoperative cultures, but it
can be modified on the basis of the re-
sults of the intraoperative culture and
sensitivity tests. Administration of anti-
biotics is a key part of the management,
AND
but it will fail without adequate dbri-
dement. Intravenous antibiotics are
generally given for four to six weeks96.
While antibiotic-resistant organisms
are a problem, vancomycin is useful for
oxacillin-resistant Staphylococcus au-
reus infections, and the recently intro-
duced antibiotics linezolid and
quinupristin/dalfopristin have been
used for oxacillin-resistant Staphylococ-
cus aureus and vancomycin-resistant
enterococcus infections97.
The decision to retain or remove
implants from the site of an infected
fracture must be individualized and
depends on the time since the fracture
fixation, bone-healing status, stability
provided by the hardware, and fracture
location92. If the fracture has healed, the
internal fixation device should be re-
moved. When the fracture has not
healed, the internal fixation device
should be left in place as long as it is
stabilizing the fracture. Loose hardware
that is not providing stability should be
removed. If the fracture has not healed
and the hardware is removed, the frac-
ture should be stabilized with another
device; our preference is to use an exter-
nal fixator for diaphyseal nonunions of
the tibia and an intramedullary rod for
diaphyseal nonunions of the femur.
In cases with an adequate soft-tis-
sue envelope, delayed or primary clo-
sure can be performed depending on
the extent of the infection. If soft tissues
are compromised, coverage should be
achieved with local or free muscle flaps.
Soft-tissue coverage is usually per-
formed at three to seven days after the
initial dbridement98-100. The staged cov-
erage allows the treatment of organ-
isms with specific antibiotics based on
the results of cultures of deep-tissue
specimens taken during the first dbri-
dement and permits a repeat dbride-
ment prior to flap transfer.
Autogenous iliac crest bone graft
can be used to manage bone defects up
to 6 cm in size. Bone-grafting tech-
niques for the tibia include anterior,
posterolateral, and free vascularized
grafting of the defect site98,101-103. Bone-
grafting is performed when the soft-
tissue envelope has healed, flap viability
has been determined, and infection has
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been controlled, usually six to eight
weeks after the muscle transfer or when
the soft tissues are healed92. For anterior
tibial defects and most nonunions, the
muscle flap is elevated and the graft is
placed at the nonunion or defect site.
Posterolateral bone-grafting is an alter-
native if infection control has been es-
tablished (on the basis of no anterior
sequestra and no need for anterior
dbridement), there is no anterior
defect, and there is no need for a soft-
tissue transfer.
Bone defects longer than 6 cm
require specialized reconstructive pro-
cedures, such as vascularized bone-
grafting or distraction osteogenesis.
The free vascularized fibular graft is
a versatile flap that, in addition to
bone, can include muscle, skin, and
fascia104. It is particularly useful for
combined bone and soft-tissue defects
and in patients opposed to having an
external fixator. Distraction osteogen-
esis is a useful method for reconstruc-
tion of infected bone defects and for
correction of malalignment and large
limb-length discrepancies105.
1. Blick SS, Brumback RJ, Poka A, Burgess AR,
Ebraheim NA. Compartment syndrome in open
tibial fractures. J Bone Joint Surg Am. 1986;68:
1348-53.
2. Gustilo RB, Anderson JT. Prevention of infection
in the treatment of one thousand and twenty-five
open fractures of long bones: retrospective and
prospective analyses. J Bone Joint Surg Am. 1976;
58:453-8.
3. Gustilo RB, Mendoza RM, Williams DN. Problems
in the management of type III (severe) open frac-
tures: a new classification of type III open frac-
tures. J Trauma. 1984;24:742-6.
4. Brumback RJ, Jones AL. Interobserver agree-
ment in the classification of open fractures of the
tibia. The results of a survey of two hundred and
forty-five orthopaedic surgeons. J Bone Joint Surg
Am. 1994;76:1162-6.
5. Patzakis MJ, Wilkins J. Factors influencing infec-
tion rate in open fracture wounds. Clin Orthop Relat
Res. 1989;243:36-40.
6. Bowen TR, Widmaier JC. Host classification pre-
dicts infection after open fracture. Clin Orthop Relat
Res. 2005;433:205-11.
7. Patzakis MJ, Harvey JP Jr, Ivler D. The role of anti-
biotics in the management of open fractures. J Bone
Joint Surg Am. 1974;56:532-41.
8. Skaggs DL, Friend L, Alman B, Chambers HG,
Schmitz M, Leake B, Kay RM, Flynn JM. The effect
of surgical delay on acute infection following 554
open fractures in children. J Bone Joint Surg Am.
2005;87:8-12.
893
MA N AG E M EN T OF OP EN FR A C TU RES
SUBSEQUENT COMPLICATIONS
Limb salvage based on the de-
scribed principles can be achieved with
eradication of infection and osseous
union in 67% to 100% of cases99,106-109.
Siegel et al. reported that, at a mean of
5.1 years postoperatively, limb salvage
had been accomplished in all of forty-
six patients with chronic tibial osteo-
myelitis and all but two had clinical
and radiographic evidence of union109.
Thirty-nine patients were able to walk
independently, whereas the others
used assistive devices. Thirty-eight of
forty-two patients who had been
working were able to return to work
within six months after union, and
twenty-three of thirty-seven patients
who had been participating in recre-
ational and sports activities were able
to resume those activities. Smoking,
advanced age, and intra-articular in-
volvement were found to adversely af-
fect the outcome.
Management of chronic post-
traumatic osteomyelitis and infected
nonunion of the tibia is challenging;
however, infection control, osseous
union, and a satisfactory functional
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Charalampos G. Zalavras, MD
Michael J. Patzakis, MD
Department of Orthopaedic Surgery, Univer-
sity of Southern California Keck School of
Medicine, 2025 Zonal Avenue, GNH 3900, Los
Angeles, CA 90089-9312
Randall E. Marcus, MD
Department of Orthopaedic Surgery, Case
Western Reserve University/University Hospi-
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L. Scott Levin, MD
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