Antibiotics should be
administered to a patient with an open fracture as soon as possible to reduce
the risk of infection. A patient with an open
fracture should be taken to the operating room on an urgent basis, with the
stability of the patient, the preparation of the operating room, and the
availability of appropriate assistance taken into account. Questions remain
regarding the optimal solution and method of delivery for irrigation of open
fracture wounds. Early closure of
adequately débrided wounds is safe and can improve outcomes. Adjunctive therapies,
such as the early application of bone grafts and rhBMP-2, may improve healing
of open fractures.
Antibiotics should be
administered to a patient with an open fracture as soon as possible to reduce
the risk of infection.
A patient with an open
fracture should be taken to the operating room on an urgent basis, with the
stability of the patient, the preparation of the operating room, and the
availability of appropriate assistance taken into account.
Questions remain
regarding the optimal solution and method of delivery for irrigation of open
fracture wounds.
Early closure of
adequately débrided wounds is safe and can improve outcomes.
Adjunctive therapies,
such as the early application of bone grafts and rhBMP-2, may improve healing
of open fractures.
One hundred and fifty years ago, mortality was common following open
fracture1,2.
With the advent of modern therapy, however, the expected outcome has improved
dramatically. In the treatment of open fractures, the surgeon's objectives are
to prevent infection, promote fracture-healing, and restore function. All
patients presenting with an open fracture require initial stabilization,
tetanus prophylaxis, systemic antibiotic therapy, prompt surgical
débridement and copious irrigation, fracture stabilization, timely
wound closure, thorough rehabilitation, and adequate follow-up. In addition,
certain patients may benefit from local antibiotic therapy, open wound
management (possibly including vacuum-assisted closure), flap closure,
bone-grafting, or other adjunctive therapies.
In this review, we analyze the evidence concerning a number of important
issues in the management of open fractures, including classification, use of
antibiotics, timing of operative intervention, irrigation, fixation,
soft-tissue coverage, and adjunctive therapies.
A fracture is considered to be open when disruption of the skin and
underlying soft tissues results in a communication between the fracture and
the outside environment. Open fractures are most commonly classified according
to the system developed by Gustilo and
Anderson3 and
subsequently modified by Gustilo et
al.4. According to
this system (Table I), type-I
open fractures are characterized by a wound of <1 cm with minimal
contamination, comminution, and soft-tissue damage. Type II features
lacerations of >1 cm and moderate soft-tissue injury, but wound coverage is
adequate and periosteal stripping is not extensive. Type-III open fractures
are divided into three subtypes. Type IIIA is characterized by high-energy
trauma, extensive soft-tissue damage, and substantial contamination, but wound
coverage remains adequate after débridement has been completed. Type
IIIB is similar to IIIA, except that wound coverage is not adequate and
coverage procedures are required. Type IIIC is an open fracture associated
with an arterial injury requiring repair. Given the prognostic relevance of
soft-tissue and bone injury in the depths of the wound, it is important that
open fractures be classified not in the emergency room but in the operating
room, after surgical exploration and débridement have been
completed.
Recently, the authors of two studies found the Gustilo and Anderson
classification system to be associated with low interobserver
agreement5,6.
Brumback and Jones presented 245 orthopaedic surgeons with twelve videotaped
case presentations that included patient demographic data, the history of the
injury, the results of physical examination, the appearance of the wound
before the operation, preoperative radiographs, and narrated portions of the
operative débridement and then asked them to classify the open
fractures with use of the Gustilo and Anderson system. The level of agreement
(defined as the largest percentage of observers choosing a single
classification) averaged just 60%, which the authors characterized as
"moderate to
poor."5
However, it is unclear whether these low levels of agreement were due, at
least in part, to the fact that the classifications were performed on the
basis of videotaped presentations.
In spite of these limitations, the Gustilo and Anderson classification
remains the preferred system for categorizing open fractures since the
fracture type correlates well with the risk of infection and other
complications. For example, rates of infection have been reported to be 0% to
2% for type I, 2% to 5% for type II, 5% to 10% for type IIIA, 10% to 50% for
type IIIB, and 25% to 50% for type
IIIC3,4,7,8
(Table I). The number of
patients studied in these reports ranged from
eighty-seven4 to
11047.
Recently, Bowen and
Widmaier9 studied
174 patients with open fractures of the long bones and found not only the
Gustilo and Anderson classification but also the number of compromising
comorbidities to be significant predictors of infection in the multivariate
analysis. The patients were divided into three classes on the basis of the
presence or absence of fourteen medical and immunocompromising factors,
including an age of eighty years or more, current nicotine use, diabetes,
malignant disease, pulmonary insufficiency, and systemic immunodeficiency.
Infection rates were found to be 4% (two of fifty-seven) for patients in Class
A (no compromising factors), 15% (thirteen of eighty-nine) for patients in
Class B (one or two compromising factors), and 31% (five of sixteen) for
patients in Class C (three or more compromising factors) (p = 0.007).
Antibiotic use has been considered the standard of care since 1974, when
Patzakis et al. reported their seminal randomized, controlled trial of
cephalothin, a first-generation cephalosporin, for the management of open
fractures10. The
benefit of antibiotics was confirmed by a recent Cochrane systematic
review11, which
showed that the administration of antibiotics after an open fracture reduces
the risk of infection by 59% (relative risk, 0.41; 95% confidence interval,
0.27 to 0.63) (Table II).
Although, in the past, cultures were routinely done before and after
débridement of open fractures, authors of recent studies have
questioned their
utility12,13.
Lee studied predébridement cultures and found that only 8% (eighteen)
of 226 organisms grown on culture eventually caused infection and 7% (seven)
of 106 patients with negative cultures eventually became
infected12.
Post-débridement cultures were not much better, as only 25% (eight) of
thirty-two organisms grown on culture eventually caused infection, and 12%
(ten) of eighty-six patients with negative cultures eventually became
infected12.
Currently, we do not recommend the routine use of cultures either before or
after débridement (Table
II).
As suggested by the above
study12, the
organisms that are found to be contaminating an open fracture on presentation
do not represent the microbes that will eventually cause infection. In fact,
there is evidence that most infections at the sites of open fractures are
caused by nosocomial bacteria. In a study carried out by Carsenti-Etesse et
al., 92% (thirty-five) of thirty-eight open-fracture infections were caused by
bacteria acquired while the patient was in the
hospital14.
Currently, most open-fracture infections are caused by gram-negative rods and
gram-positive
staphylococci3,4,12,14.
However, methicillin-resistant Staphylococcus aureus has recently
emerged as a potential cause of infection of open fractures. During an
epidemic at a hospital in Texas during the 1980s, methicillin-resistant
Staphylococcus aureus developed at the site of an open fracture in
twenty-three patients, most of whom had a less than satisfactory
outcome15.
Methicillin-resistant Staphylococcus aureus infections of open
fractures were also documented in the study by Carsenti-Etesse et al. These
developments underscore the importance of early wound coverage.
While there is ample data supporting the administration of antibiotics
after open fracture, evidence indicating an optimal regimen is lacking. In the
randomized, controlled trial by Patzakis et
al.10, patients
receiving the first-generation cephalosporin cephalothin were found to have a
lower infection rate than those receiving penicillin and streptomycin (2.3%
compared with 9.7%). In a later study by the same group of researchers,
therapy with cefamandole and tobramycin was found to be superior to penicillin
and streptomycin (4.5% compared with 10%), but not better than monotherapy
with cephalothin
(5.6%)7. Also of
interest is the prospective double-blind study by Benson et al., who found
clindamycin to be as effective as cefazolin for preventing infection after
open
fracture16.
Ciprofloxacin has also been considered for the management of open
fractures, given its activity against both gram-positive and gram-negative
organisms. Patzakis et al. conducted a prospective, double-blind, randomized,
controlled trial comparing monotherapy with ciprofloxacin to combination
therapy with cefamandole and gentamicin and found the two types of therapy to
be associated with similar infection rates in patients with a type-I or II
fracture but the use of ciprofloxacin to be associated with a higher rate of
infection in those with a type-III fracture (31% [eight of twenty-six]
compared with 7.7% [two of twenty-six]; p =
0.08)17. While a
number of recent animal and in vitro studies have suggested that ciprofloxacin
and other fluoroquinolones may act to inhibit osteoblast activity and
fracture-healing18,19,
further investigation—especially in the clinical setting—is
required before the use of these antibiotics is discouraged for the management
of open fractures.
There is currently controversy with regard to the specific antibiotic
agent(s) to be given after open fracture. While some have recommended treating
all open fractures with a combination of a first-generation cephalosporin and
an
aminoglycoside20,
others have advocated monotherapy with a first-generation cephalosporin for
type-I and II fractures with the addition of an aminoglycoside (usually
gentamicin) for type-III
fractures21. Most
agree that penicillin or ampicillin should be added when there is a high risk
of anaerobic infection (in association with farm injuries, for example).
The available evidence suggests that antibiotic treatment should be
initiated as soon as possible following injury. In a study of 1104 open
fractures, Patzakis and Wilkins reported an infection rate of 4.7% (seventeen
of 364) when antibiotics were given within three hours after the injury
compared with a rate of 7.4% (forty-nine of 661) when therapy was begun more
than three hours after the injury (seventy-nine patients did not receive
antibiotics)7. The
optimal duration of antibiotic therapy is less clear. Many authors have
recommended an initial three-day course supplemented by additional three-day
courses at the time of any subsequent
procedures20,
although clinical evidence to support this approach is lacking. Dellinger et
al. advocated a one-day course of antibiotics on the basis of a prospective,
double-blind, randomized, controlled trial that showed a single day of
antibiotics to be as effective as a five-day regimen for preventing
infection22.
At our institution, we recommend the administration of cefazolin (1 g
intravenously) every eight hours until twenty-four hours after the wound is
closed. Intravenous gentamicin (with weight-adjusted dosing) or levofloxacin
(500 mg every twenty-four hours) are added for type-III fractures.
Over the past decade, interest has grown in the use of local antibiotic
therapy to prevent infection after open fracture. Local therapy has been shown
to generate high antibiotic concentrations within the wound while maintaining
low systemic
concentrations23,
which reduces the risk of systemic side effects. Antibiotic agents that are
heat-stable, available in powder form, and active against suspected pathogens
are appropriate choices for local therapy. While aminoglycosides and
vancomycin both meet those criteria, the former is preferred because of
concerns about encouraging resistance to vancomycin.
While very high concentrations of aminoglycosides can certainly impair
osteoblast function, early in vitro studies have suggested that this toxicity
threshold was on the order of several hundred micrograms per milliliter, well
above the concentrations of 10 to 20 µg/mL typically seen in the
wound24. However, a
recent study by Ince et
al.25 suggested
that the toxicity threshold may actually be much lower, on the order of 12.5
µg/mL. This finding should be further investigated in future studies.
Use of aminoglycoside-eluting polymethylmethacrylate beads has been studied
by several investigators. Ostermann et al. conducted a retrospective analysis
of 1085 open fractures and found that patients treated with tobramycin-eluting
beads had a significantly lower rate of infection (3.7% [thirty-one of 845])
than did those not treated with the beads (12.1% [twenty-nine of 240]; p <
0.001)26. However,
wounds treated with local antibiotic therapy were also more likely to be
closed earlier in the study, which introduces the possibility of bias. Keating
et al. conducted a retrospective analysis of eighty-one open tibial fractures
and found tobramycin-eluting beads to be associated with a lower risk of
infection (4% [two of fifty] compared with 16% [four of twenty-five]),
although the result was not significant, at least partly as a result of a
small sample
size27. Recently,
some authors have investigated the use of local antibiotic therapy alone.
Moehring et al. conducted a prospective, randomized, controlled trial
comparing local and systemic antibiotic therapy in the management of type-II,
IIIA, and IIIB open
fractures28. After
receiving standard treatment in the emergency room and operating room
(including an initial dose of systemic antibiotics), patients were randomized
to receive either local therapy with tobramycin-eluting beads or systemic
therapy with a first-generation cephalosporin. Similar rates of infection were
reported in the two groups (8% [two of twenty-four] compared with 5% [two of
thirty-eight], respectively). However, the study was not adequately powered
(it had a small sample size), and a substantial proportion of the study
population (15%) was inadvertently treated with both interventions.
We consider local antibiotic therapy to be a useful adjunct to systemic
antibiotics in the management of open fractures
(Table II). While
gentamicin-impregnated beads are commercially available in Europe,
antibiotic-eluting polymethylmethacrylate cement is not yet available in bead
form in the United States. Instead, antibiotic beads can be made by mixing
polymethylmethacrylate cement with tobramycin powder at a dose of 3.6 g per 40
g of cement29.
Recently, a number of animal studies have suggested the potential utility
of other forms of local antibiotic therapy, including the use of
antibiotic-impregnated bone
graft30,
antibiotic-impregnated bone-graft
substitute31-33,
and antibiotic-coated intramedullary
nails34. However,
these innovations have yet to be studied in a clinical setting, to our
knowledge.
Emergency operative treatment has long been the standard of care for open
fractures. The origin of the so-called "six-hour rule" is unclear,
however. While some believe that it stems from an 1898 experiment by
Friedrich, in which guinea pigs with contaminated soft-tissue wounds had lower
rates of infection when débridement was performed within six
hours35, others
point to a 1973 study by Robson et al., who reported that 105
organisms per gram of tissue was the open-fracture infection threshold, which
was reached in an average of 5.17
hours36.
To date, two studies have shown a decreased rate of infection when
débridement is performed within six hours. In a study of forty-seven
open tibial fractures, Kindsfater and Jonassen found that operative treatment
within five hours was associated with a lower risk of infection (7% [one of
fifteen]) compared with 38% [twelve of thirty-two]; p <
0.03)37. However,
severe fractures were more likely to be treated later in this study: type-III
fractures accounted for 33% (five) of the fifteen fractures treated within
five hours but 53% (seventeen) of the thirty-two treated after a delay of five
hours or more. Kreder and Armstrong found that, of fifty-six open tibial
fractures in children, the forty-two that had been treated within six hours
had a lower rate of infection (12% [five infections]) than the eight that had
been treated after a delay of more than six hours (25% [two
infections])38.
However, the study was limited by its small sample size (just one fewer
infection in the delayed-treatment group would have resulted in identical
rates of infection).
A number of studies have called the "six-hour rule" into
question7,39-46.
Bednar and Parikh reviewed the results associated with eighty-two open tibial
and femoral fractures and found no significant differences between those
débrided within six hours and those débrided at seven hours or
later (9% compared with 3.4%; p >
0.05)40. Ashford et
al. reported on open tibial fractures among patients from the Australian
outback, many of whom were unable to reach medical care within six to eight
hours after the injury because of issues related to
distance39. The
authors found no difference in infection rates between those treated within
six hours and those treated after six hours (17% [two of twelve] compared with
11% [four of thirty-six]; p > 0.05). Spencer et al., who prospectively
studied 142 open long-bone fractures in the United Kingdom, also reported no
significant difference in infection rates between those treated within six
hours and those treated after six hours (10.1% [seven of sixty-nine] compared
with 10.9% [five of forty-six]; p >
0.05)45.
Additionally, Pollack and the LEAP investigators studied 315 open fractures of
the lower extremity and found that the time from the injury to the first
débridement did not correlate with the likelihood of
infection46. It is
interesting to note, however, that patients who had been admitted to a
hospital within six hours after the injury had a lower prevalence of infection
than those who had been admitted after six hours (22% compared with 39%; p
< 0.01).
One must use caution, however, when drawing conclusions from these reports.
Since the studies were not randomized, there is the potential for bias; the
fact that severe fractures were more likely to be treated urgently could, for
example, artificially raise the infection rates in the groups treated within
six hours while artificially decreasing the rates in the groups treated after
six hours. Additionally, many of the studies were not adequately powered, with
sample sizes too small to enable detection of a clinically meaningful
difference in infection rates.
A few authors have gone so far as to suggest that operative
débridement might not be necessary for low-grade open
fractures47,48.
Orcutt et al. conducted a retrospective study comparing ninety-nine low-grade
(type-I and II) open fractures managed with local wound care and intravenous
antibiotics (but no operative débridement) with fifty similar fractures
managed with formal operative débridement as well as intravenous
antibiotics47. They
found lower rates of infection (3% compared with 6%) and delayed union (10%
compared with 16%) in the nonoperative group, but these differences were not
significant (p > 0.05). More recently, Yang and Eisler reported favorable
outcomes, including an infection rate of 0%, in a retrospective study of
ninety-one type-I open fractures managed without formal operative
débridement48.
However, the authors acknowledged the difficulty of correctly predicting
fracture severity on the basis of superficial characteristics alone and noted
that many fractures that had been initially labeled type I at their
institution were subsequently reclassified at the time of operative
débridement.
In our opinion, thorough operative débridement should be considered
the standard of care for all open fractures. Even if the benefits of formal
débridement were found to be insignificant for low-grade open
fractures, operative débridement would still be required for proper
classification of the wound. As noted above, open fractures graded on the
basis of superficial characteristics alone are often misclassified. Thus,
failure to adequately explore and débride an open fracture in the
operating room is associated with substantial risk.
In contrast, it is not possible at this point in time to argue for or
against a firm "six-hour rule" in the management of open
fractures. In the prevention of infection after open fracture, the time from
injury to débridement is probably less important than other factors,
such as the adequacy of débridement and the timeliness of soft-tissue
coverage. Patients with an open fracture should be taken to the operating room
on an urgent basis, with the stability of the patient, the preparation of the
operating room, and the availability of appropriate assistance (including
orthopaedic-trained scrub personnel, assistant surgeons, radiography
technicians, and other operatingroom personnel) taken into account
(Table II).
Irrigation is a key component of the effort to prevent infection after open
fracture, as it serves to decrease bacterial load and remove foreign bodies.
Although many guidelines call for so-called "copious" amounts of
irrigation, there are little data on exactly how much volume should be used in
the lavage of open fracture wounds. As irrigation bags typically contain 3 L
of fluid, some have recommended 1 bag (3 L) for type-I open fractures, two
bags (6 L) for type-II, and three bags (9 L) for
type-III49.
With regard to the delivery of irrigation, high-pressure pulsatile lavage
appears to be most effective for the removal of bacteria and other
contaminants. With a standard battery-operated pulsatile irrigation system
(e.g., Surgilav Plus Debridement System, Stryker Instruments, Kalamazoo,
Michigan), high-pressure pulsatile lavage corresponds to a pressure of 70 lb
psi with 1050 pulsations per minute (as opposed to 14 lb psi and 550
pulsations per minute for low-pressure pulsatile lavage). Anglen et
al.50 found that
high-pressure pulsatile lavage increased the removal of slime-producing
bacteria from stainless-steel screws by a factor of 100. In a study of an in
vitro tibial model, Bhandari et
al.51 found that,
although high and low-pressure pulsatile lavage were equally successful in
removing bacteria after a delay of three hours, only high-pressure lavage was
successful after a delay of six hours.
There is increasing evidence from animal and in vitro studies that
high-pressure pulsatile lavage may have deleterious side
effects51-55.
In the in vitro study by Bhandari et al., for example, high-pressure pulsatile
lavage caused significantly more macroscopic bone damage than low-pressure
pulsatile lavage (p <
0.001)51. In
addition, histologic analysis showed high-pressure pulsatile lavage to be
associated with cortical bone defects that were significantly larger and more
numerous than those resulting from low-pressure pulsatile lavage (p <
0.001). In a study of rats, Adili et al. found high-pressure pulsatile lavage
of open noncontaminated femoral diaphyseal fractures to be associated with
reduced mechanical strength at three weeks (but not at six
weeks)52. In
addition, Hassinger et al. found high-pressure lavage to be associated with
increased depths of bacterial penetration in sheep
muscle55. To our
knowledge, however, there have been no clinical studies of high or
low-pressure pulsatile lavage for the irrigation of open fracture wounds.
Thus, there is insufficient evidence to make a recommendation with regard to
the delivery of irrigation (Table
II).
Sterile saline solution, either alone or with an additive, is commonly used
for the irrigation. The available additives can be divided into three general
categories: antiseptics, such as povidone-iodine (Betadine), chlorhexidine
gluconate (Hibitane), and hexachlorophene (pHisoHex); antibiotics, such as
bacitracin; and soaps, which function by removing microbes (instead of killing
them). These solutions have been compared in a number of animal and in vitro
studies50,56,57.
In the study by Anglen et al., soap solutions were found to be most effective
in removing slime-producing bacteria from stainless-steel screws, whereas
antibiotic solutions were not significantly different from normal saline
solution (p >
0.05)50. Bhandari
et al. compared various irrigation solutions in an in vitro model and found
that, while povidone-iodine, chlorhexidine gluconate, and liquid soap were
most effective in removing bacteria from bone, soap had the least injurious
effect on osteoblast and osteoclast
function56.
Recently, Anglen reported the results of a prospective, randomized,
controlled trial comparing nonsterile castile soap with bacitracin solution
for the irrigation of 398 lower-extremity open
fractures58. The
two solutions contained 80 mL of liquid castile soap (Triad Medical, Franklin,
Wisconsin) or 100,000 units of bacitracin (Baciim; Pharma-Tek, Huntington, New
York) in a 3-L bag of saline solution. The irrigation volume varied by
fracture grade (3 L for type I, 6 L for type II, and 9 L for type III) and was
delivered by a power irrigator system (Pulsavac; Zimmer, Dover, Ohio). No
significant differences with respect to infection and bone-healing were found,
but wound-healing problems were more common in the bacitracin group (9.5%
[nineteen of 199] compared with 4% [eight of 199]; p = 0.03). Since the study
was adequately powered, the failure to detect a significant difference in the
rates of infection was probably not related to issues of small sample size.
Therefore, given the available evidence, it is not possible to recommend any
particular additive for the irrigation of open fracture wounds
(Table II).
Fixation of open fractures has a number of beneficial effects, including
protection of soft tissues from additional injury by fracture fragments,
improvement of wound care and tissue-healing, promotion of mobilization and
rehabilitation, and possibly even reduction of the risk of
infection59. In the
multiply-injured patient, fracture fixation also reduces the risk of acute
respiratory distress syndrome and multiple organ failure, probably by calming
the systemic inflammatory
response60. A
number of methods are available for stabilization of open fractures, including
splinting, cast immobilization, or traction; external fixation; plates and
screws; and intramedullary nailing (with or without reaming). Intramedullary
nails may be solid, hollow slotted, or cannulated, with the solid nails
demonstrating a greater resistance to infection in animal
studies61,62.
In any given situation, the best option for fixation depends on a number of
factors, including the bone involved, the fracture site, the wound location,
and the condition of the patient.
Femur
At this point in time, there is consensus regarding the stabilization of
open fractures of the femoral diaphysis. Most surgeons advocate early
intramedullary nailing with reaming, and there is sufficient evidence to
support this approach (Table
II). In 1989, Brumback et al. conducted a study of eighty-nine
open femoral fractures treated with reamed intramedullary nailing and
documented no infections in association with sixty-two type-I, II, and IIIA
fractures and only three infections (11%) in association with twenty-seven
type-IIIB
fractures63.
Moreover, the rates of infection did not differ between the patients treated
within twenty-four hours after injury (early) and those treated after
forty-eight hours (late). That same year, Bone et al. reported on a
prospective, randomized, controlled trial comparing early stabilization
(within twenty-four hours) and late stabilization (after forty-eight hours) of
178 open and closed femoral
fractures64. While
no differences were observed among patients with an isolated femoral fracture,
multiply-injured patients were found to have a decreased rate of pulmonary
complications (acute respiratory distress syndrome, fat embolism, and
pneumonia), a shorter hospital stay, and less time in the intensive-care unit
when stabilization had been performed within twenty-four hours. Since that
time, a number of other studies have confirmed the favorable outcomes
associated with early intramedullary nailing of open femoral shaft
fractures65-67.
In a small study of fifteen patients treated with external fixation with
secondary intramedullary nailing of an open femoral shaft fracture, Wu and
Shih reported that infection developed in two patients and union occurred in
fourteen68.
Tibia
The optimal treatment of open fractures of the tibial shaft is less clear.
During the late 1980s, a number of studies demonstrated favorable outcomes
with external fixation. Bach and Hansen conducted a prospective, randomized,
controlled trial comparing external fixation with internal fixation with
plates and found that, although both methods yielded favorable outcomes,
external fixation was associated with fewer
complications69. At
approximately the same time, Edwards et al. reported the results of a
prospective study of 202 type-III open tibial fractures treated with external
fixation and concluded that that method was successful for the treatment of
severe open tibial
fractures70.
During the 1990s, a number of studies showed intramedullary nailing to be
preferable to external fixation. Henley et al. prospectively studied 174 open
tibial fractures (types II, IIIA, and IIIB) and found unreamed intramedullary
nailing to be associated with a lower prevalence of malalignment (8% [eight of
104] compared with 31% [twenty-two of seventy] following external fixation; p
< 0.001), fewer subsequent procedures (mean, 1.7 compared with 2.7; p =
0.001), and a lower rate of infection (13% [thirteen of 104] compared with 21%
[fifteen of seventy]; not significant at p =
0.73)71.
Schandelmaier et al. retrospectively reviewed the results of treatment of 114
tibial shaft fractures with severe soft-tissue injury and found unreamed
nailing to be associated with fewer subsequent procedures than were seen after
external fixation (mean, 0.81 compared with 1.84; p < 0.001) and a better
functional outcome (mean Karlstrom outcome score, 31.4 compared with 29.6; p
< 0.02)72.
Finally, Tornetta et al. conducted a prospective, randomized, controlled trial
comparing unreamed intramedullary nailing with external fixation of type-IIIB
open fractures of the tibial
shaft73. Although a
small sample size (twenty-nine fractures) prevented the detection of any
significant differences, the authors concluded that nailing was preferable
because of a perception of easier management and increased patient
satisfaction.
In recent years, the debate has centered on whether intramedullary nailing
should be performed with or without reaming. While reaming is known to have
distinct advantages in the treatment of closed tibial
fractures—including a shorter time to fracture-healing, a lower
prevalence of nonunion, and less screw
breakage74,75—studies
of animals have shown it to be associated with greater reductions in cortical
bone blood flow76.
This is of particular concern in open tibial fractures, where soft-tissue
disruption has already compromised blood supply, which is crucial for
wound-healing and the prevention of infection.
Studies comparing reamed and unreamed nailing in patients with an open
tibial fracture have proved inconclusive. Keating et al. conducted a
prospective, randomized, controlled trial of eighty-eight open tibial
fractures treated with either reamed or unreamed intramedullary nailing and
found no significant differences with regard to rates of infection or nonunion
or functional outcome, although screw breakage was significantly less common
in the group treated with reaming (p =
0.014)77.
Finkemeier et al. found no significant differences between reamed and unreamed
nailing with regard to union, number of additional procedures, or infection in
a prospective, randomized, controlled trial of forty-five open tibial
fractures (p >
0.05)78. Ziran et
al. retrospectively reviewed the results in fifty-one patients with an open
tibial fracture and found similar rates of nonunion and infection in the two
treatment groups but a decreased rate of secondary procedures in the group
treated with reaming (41% [nine of twenty-two] compared with 69% [twenty of
twenty-nine]; p <
0.05)79. Given that
this failure to detect significant differences between the results of reamed
and unreamed intramedullary nailing could be due to small study size
(inadequate power), it is worthwhile noting that a recent meta-analysis
conducted by Bhandari et al. also failed to demonstrate any significant
differences with regard to infection, nonunion, or
reoperations80. A
definitive study comparing reamed and unreamed nailing is currently under way,
but the results have not yet become available. At the current time, it is not
possible to make a recommendation for or against reaming in the fixation of
open tibial fractures (Table
II).
Historically, the closure of open fracture wounds has been delayed to
prevent infection with Clostridium and other contaminating organisms. While
this strategy remains the generally accepted approach in settings
characterized by substantial contamination (such as the barnyard and the
battlefield), many orthopaedic surgeons practicing in the developed world have
begun to consider earlier closure of open fracture wounds that have been
adequately débrided. In this setting, where nosocomial organisms have
emerged as the main source of open-fracture
infections14,
several studies have documented significantly better outcomes with early
closure (within seven days) than with late closure (p <
0.05)81-84.
Also, a number of studies have demonstrated excellent outcomes with closure
performed within three days after
injury85,86.
Recently, a number of authors have investigated the feasibility of
immediate closure (within twenty-four hours after injury). In a study of 119
open fractures, DeLong et al. did not find immediate closure (within
twenty-four hours) to be associated with a higher rate of infection or
nonunion when compared with delayed closure (at more than twenty-four
hours)87. Gopal et
al. retrospectively reviewed the results associated with eighty-four type-IIIB
and IIIC open tibial fractures treated with immediate internal fixation and
flap closure and reported lower rates of infection and amputation as well as a
shorter time to union when compared with the outcomes of early closure (at
twenty-four to seventy-two hours) and late closure (at more than seventy-two
hours), although significance was not
assessed88.
Finally, Hertel et al. performed a retrospective study of twenty-nine
type-IIIA and IIIB open tibial fractures and found that immediate coverage was
associated with a lower rate of infection (0% [zero of fourteen] compared with
27% [four of fifteen] after later coverage; p = 0.04), a reduced number of
reoperations (mean, 1.6 compared with 3.9; p = 0.0001), and a decreased time
to definitive union (mean, 5.6 months compared with 11.6 months; p =
0.005)89. In our
opinion, early closure of thoroughly débrided wounds is safe and can
improve outcomes (Table
II).
Of note, the trend toward early closure of open fractures conflicts with
recommendations for routine débridement of open
fractures21. While
the goal is thorough débridement at the time of the initial
presentation, it is possible that polytrauma or other concerns may cause the
surgeon to doubt the adequacy of the initial débridement. In addition,
it may be difficult to evaluate muscle viability in the acute setting. In
these instances, repeat débridement is certainly appropriate.
There are a number of methods for achieving closure, including direct
suturing, split-thickness skin-grafting, and use of free or local muscle
flaps. The optimal method depends on a number of factors, including the
location of the defect, its size, associated injuries, and patient
characteristics such as the amount of function retained and the desired level
of function.
Recently, vacuum-assisted closure (V.A.C.; KCI, San Antonio, Texas) has
emerged as a useful method of accelerating wound-healing by reducing chronic
edema, increasing local blood flow, and enhancing granulation tissue
formation90,91.
A small number of reports have documented the use of vacuum-assisted closure
in the management of orthopaedic wounds, with generally favorable
results92-95.
For example, DeFranzo et al. reported on the use of vacuum-assisted closure in
the treatment of seventy-five lower-extremity wounds with exposed bone and
found it to be successful in reducing tissue edema, shrinking wound size, and
stimulating granulation tissue
formation92. In a
retrospective review, Labler et al. compared vacuum-assisted closure with use
of the synthetic membrane Epigard (Biovision, Ilmenau, Germany) in the
management of type-IIIA and IIIB open fractures of the lower
extremity94.
Vacuum-assisted closure was associated with favorable outcomes, and it
resulted in a lower rate of infection when compared with the Epigard (two of
thirteen compared with six of eleven). The vacuum-assisted-closure device is
typically applied at the end of each irrigation and débridement until
the wound is considered clean. After that point, sponges can be changed at the
bedside every two to three days. Vacuum-assisted closure was used for an
average of ten to twenty days in the studies described above. While
vacuum-assisted closure appears to be a promising modality in the management
of musculoskeletal wounds, additional studies are required before a definitive
recommendation can be made (Table
II).
There is evidence that certain adjunctive therapies may be useful in the
management of open fractures. Early prophylactic bone-grafting, which is
typically performed within twelve weeks after injury (but not before two weeks
after wound closure), has been shown to be useful in a small number of
studies. Blick et al. conducted a retrospective review of fifty-three
high-energy tibial fractures (mostly type III) that had been treated
prophylactically with posterolateral bone-grafting within ten weeks after the
injury (eight weeks after soft-tissue
coverage)96.
Patients treated with early prophylactic bone-grafting had a shorter time to
bone union compared with historical controls (mean, 45.7 weeks compared with
57.4 weeks; p = 0.03). Similarly, Trabulsy et al., in a prospective study of
forty-five type-IIIB open tibial fractures, found that patients who had been
treated with bone-grafting within eight to twelve weeks after injury had a
shorter time to osseous union (mean, forty-one weeks compared with fifty-two
weeks; p value not
reported)97.
However, given that external fixation was the primary means of fracture
stabilization in these studies, one must use caution when generalizing the
results to open tibial fractures treated with intramedullary nailing.
Additional studies are required before a definitive recommendation can be made
regarding the use of early prophylactic bone-grafting in the management of
open fractures (Table II).
Recently, evidence has emerged regarding the use of recombinant human bone
morphogenetic protein-2 (rhBMP-2). In a multicenter, prospective, randomized,
controlled trial of 450 open tibial fractures, the use of local rhBMP-2
implants was found to significantly reduce the risk of secondary invasive
interventions (26% compared with 46%; risk ratio = 0.56; 95% confidence
interval = 0.40 to 0.78; p = 0.0005). Patients treated with rhBMP-2 also had a
lower rate of hardware failure (11% compared with 22%; p = 0.0476), faster
fracture-healing (median healing time, twenty compared with fifty-two weeks),
and faster wound-healing (83% compared with 65% healed at six weeks; p =
0.001)98. Treatment
of type-IIIA and IIIB open fractures with rhBMP-2 was associated with a
significantly lower risk of infection (21% compared with 40%; p = 0.0234) as
well as secondary procedures (9% compared with 28%; p = 0.0065) and
bone-grafting (2% compared with 20%; p =
0.0005)99. Among
patients who were treated with reamed intramedullary nailing (all fracture
types included), use of rhBMP-2 was associated with a trend toward lower rates
of invasive secondary procedures (8% [five of sixty-five] compared with 15%
[seven of forty-eight]) and bone-grafting (2% [one of sixty-five] compared
with 6% [three of forty-eight]), but the results were not significant (p =
0.35 and 0.31, respectively). Given that these subgroup analyses were not
adequately powered and were performed post hoc, however, one must use caution
when drawing conclusions. While additional studies are certainly required,
there does appear to be fair evidence in support of the use of rhBMP-2 in the
management of open fractures, especially those of severe grade
(Table II).
Open fractures represent a challenge to even the most experienced
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limited evidence in support of a firm "six-hour rule." Copious
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method of delivery. Early internal fixation is safe and has a number of
benefits, with the optimal method of stabilization depending on the bone
involved and other factors. The available evidence supports the current trend
toward earlier coverage and closure of open fracture wounds. Vacuum-assisted
closure appears to decrease wound size and improve healing, but additional
studies are required in the field of orthopaedics. Adjunctive therapies, such
as the use of early prophylactic bone-grafting and recombinant human bone
morphogenetic protein-2 (rhBMP-2), may improve bone-healing and other outcome
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