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Current Concepts Review   |    
Trends in the Management of Open FracturesA Critical Analysis
Kanu Okike, BA1; Timothy Bhattacharyya, MD2
1 Harvard University, 64 Linnaean Street, Cambridge, MA 02138
2 Partners Orthopaedic Trauma Service, Massachusetts General Hospital, 55 Fruit Street, Yawkey 3600, Boston, MA 02114
View Disclosures and Other Information
The authors did not receive grants or outside funding in support of their research for or preparation of this manuscript. They did not receive 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, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.
Investigation performed at Partners Orthopaedic Trauma Service, Massachusetts General Hospital and Brigham and Women's Hospital, Boston, Massachusetts

The Journal of Bone and Joint Surgery, Incorporated
J Bone Joint Surg Am, 2006 Dec 01;88(12):2739-2748. doi: 10.2106/JBJS.F.00146
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Image Not Available Antibiotics should be administered to a patient with an open fracture as soon as possible to reduce the risk of infection.Image Not Available 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.Image Not Available Questions remain regarding the optimal solution and method of delivery for irrigation of open fracture wounds.Image Not Available Early closure of adequately débrided wounds is safe and can improve outcomes.Image Not Available Adjunctive therapies, such as the early application of bone grafts and rhBMP-2, may improve healing of open fractures.
Image Not Available Antibiotics should be administered to a patient with an open fracture as soon as possible to reduce the risk of infection.
Image Not Available 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.
Image Not Available Questions remain regarding the optimal solution and method of delivery for irrigation of open fracture wounds.
Image Not Available Early closure of adequately débrided wounds is safe and can improve outcomes.
Image Not Available 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.
 
Anchor for JumpAnchor for JumpTABLE I  Classification System of Gustilo et al.3,4: Definitions and Associated Infection Rates
Fracture Type Definition Historical Infection Rates3,4,7,8 (%)
I Wound <1 cm; minimal contamination, comminution, and soft-tissue damage 0-2
II Wound >1 cm; moderate soft-tissue damage, minimal periosteal stripping 2-5
IIIA Severe soft-tissue damage and substantial contamination; coverage adequate 5-10
IIIB Severe soft-tissue damage and substantial contamination; coverage inadequate 10-50
IIIC Arterial injury requiring repair 25-50
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).
 
Anchor for JumpAnchor for JumpTABLE II  Recommendations for the Management of Open Fractures
Recommendation Grade of Recommendation*
Antibiotics
    Systemic therapy A
    Local therapy B
Timing of operative débridement
    Urgent B
    Within 6 hr C
Irrigation
    High-pressure pulsatile lavage I
    Additives† I
Fixation
    Femur (intramedullary nailing) B
Tibia
    External fixation B
    Intramedullary nailing B
    Reaming I
Coverage and closure
    Primary closure B
    Vacuum-assisted closure I
Adjunctive therapies
    Early prophylactic bone-grafting C
    Local rhBMP-2 B
Modalities not recommended
    Wound culture B
A = Good evidence (Level-I studies with consistent findings) for or against recommending intervention, B = fair evidence (Level-II or III studies with consistent findings) for or against recommending intervention, C = poor-quality evidence (Level-IV or V studies with consistent findings) for or against recommending intervention, and I = there is insufficient or conflicting evidence not allowing a recommendation for or against intervention. †Antibiotic, antiseptic, or soap additives.
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 orthopaedic surgeons. Antibiotics should be administered as soon as possible. Early operative débridement remains essential, although there is limited evidence in support of a firm "six-hour rule." Copious irrigation is crucial, but questions remain regarding the optimal solution and 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 measures (Table II).
Lister J. On a new method of treating compound fracture, abscess, etc. The Lancet. 1867;1: 326, 357, 387, 507.1326  1867  [CrossRef]
 
Patrick JH, Smelt GJ. Surgical progress—100 years ago. An assessment of Listerism at St Thomas's Hospital, London. Ann R Coll Surg Engl. 1977;59: 456-62.59456  1977  [PubMed]
 
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: 453-8.58453  1976 
 
Gustilo RB, Mendoza RM, Williams DN. Problems in the management of type III (severe) open fractures: a new classification of type III open fractures. J Trauma. 1984;24: 742-6.24742  1984  [PubMed][CrossRef]
 
Brumback RJ, Jones AL. Interobserver agreement 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: 1162-6.761162  1994 
 
Horn BD, Rettig ME. Interobserver reliability in the Gustilo and Anderson classification of open fractures. J Orthop Trauma. 1993;7: 357-60.7357  1993  [PubMed][CrossRef]
 
Patzakis MJ, Wilkins J. Factors influencing infection rate in open fracture wounds. Clin Orthop Relat Res. 1989;243: 36-40.24336  1989 
 
Gustilo RB, Gruninger RP, Davis T. Classification of type III (severe) open fractures relative to treatment and results. Orthopedics. 1987;10: 1781-8.101781  1987  [PubMed]
 
Bowen TR, Widmaier JC. Host classification predicts infection after open fracture. Clin Orthop Relat Res. 2005;433: 205-11.433205  2005  [CrossRef]
 
Patzakis MJ, Harvey JP Jr, Ivler D. The role of antibiotics in the management of open fractures. J Bone Joint Surg Am. 1974;56: 532-41.56532  1974 
 
Gosselin RA, Roberts I, Gillespie WJ. Antibiotics for preventing infection in open limb fractures. Cochrane Database Syst Rev. 2004;1: CD003764.1CD003764  2004 
 
Lee J. Efficacy of cultures in the management of open fractures. Clin Orthop Relat Res. 1997;339: 71-5.33971  1997  [PubMed][CrossRef]
 
Valenziano CP, Chattar-Cora D, O'Neill A, Hubli EH, Cudjoe EA. Efficacy of primary wound cultures in long bone open extremity fractures: are they of any value? Arch Orthop Trauma Surg. 2002;122: 259-61.122259  2002  [CrossRef]
 
Carsenti-Etesse H, Doyon F, Desplaces N, Gagey O, Tancrede C, Pradier C, Dunais B, Dellamonica P. Epidemiology of bacterial infection during management of open leg fractures. Eur J Clin Microbiol Infect Dis. 1999;18: 315-23.18315  1999  [CrossRef]
 
Johnson KD, Johnston DW. Orthopedic experience with methicillin-resistant Staphylococcus aureus during a hospital epidemic. Clin Orthop Relat Res. 1986;212: 281-8.212281  1986  [PubMed]
 
Benson DR, Riggins RS, Lawrence RM, Hoeprich PD, Huston AC, Harrison JA. Treatment of open fractures: a prospective study. J Trauma. 1983; 23: 25-30.2325  1983  [PubMed][CrossRef]
 
Patzakis MJ, Bains RS, Lee J, Shepherd L, Singer G, Ressler R, Harvey F, Holtom P. Prospective, randomized, double-blind study comparing single-agent antibiotic therapy, ciprofloxacin, to combination antibiotic therapy in open fracture wounds. J Orthop Trauma. 2000;14: 529-33.14529  2000  [CrossRef]
 
Holtom PD, Pavkovic SA, Bravos PD, Patzakis MJ, Shepherd LE, Frenkel B. Inhibitory effects of the quinolone antibiotics trovafloxacin, ciprofloxacin, and levofloxacin on osteoblastic cells in vitro. J Orthop Res. 2000;18: 721-7.18721  2000  [PubMed][CrossRef]
 
Huddleston PM, Steckelberg JM, Hanssen AD, Rouse MS, Bolander ME, Patel R. Ciprofloxacin inhibition of experimental fracture healing. J Bone Joint Surg Am. 2000;82: 161-73.82161  2000  [PubMed]
 
Zalavras CG, Patzakis MJ, Holtom PD, Sherman R. Management of open fractures. Infect Dis Clin North Am. 2005;19: 915-29.19915  2005  [CrossRef]
 
Olson SA, Finkemeier CG, Moehring ND. Open Fractures. In: Bucholz RW, Heckman JD, editors. Rockwood and Greene's fractures in adults. 5th ed. Philadelphia: Lippincott, Williams and Wilkins; 2001. p 285-318.285  2001 
 
Dellinger EP, Caplan ES, Weaver LD, Wertz MJ, Droppert BM, Hoyt N, Brumback R, Burgess A, Poka A, Benirschke SK, Lennard S, Lou MA. Duration of preventive antibiotic administration for open extremity fractures. Arch Surg. 1988;123: 333-9.123333  1988  [PubMed]
 
Eckman JB Jr, Henry SL, Mangino PD, Seligson D. Wound and serum levels of tobramycin with the prophylactic use of tobramycin-impregnated polymethylmethacrylate beads in compound fractures. Clin Orthop Relat Res. 1988; 237: 213-5.237213  1988  [PubMed]
 
Miclau T, Edin ML, Lester GE, Lindsey RW, Dahners LE. Bone toxicity of locally applied aminoglycosides. J Orthop Trauma. 1995;9: 401-6.9401  1995  [CrossRef]
 
Ince A, Schutze N, Karl N, Lohr JF, Eulert J. Gentamicin negatively influenced osteogenic function in vitro. Int Orthop. 2006May20; [Epub ahead of print].  2006 
 
Ostermann PA, Seligson D, Henry SL. Local antibiotic therapy for severe open fractures. A review of 1085 consecutive cases. J Bone Joint Surg Br. 1995;77: 93-7.7793  1995  [PubMed]
 
Keating JF, Blachut PA, O'Brien PJ, Meek RN, Broekhuyse H. Reamed nailing of open tibial fractures: does the antibiotic bead pouch reduce the deep infection rate? J Orthop Trauma. 1996;10: 298-303.10298  1996  [PubMed][CrossRef]
 
Moehring HD, Gravel C, Chapman MW, Olson SA. Comparison of antibiotic beads and intravenous antibiotics in open fractures. Clin Orthop Relat Res. 2000;372: 254-61.372254  2000  [PubMed][CrossRef]
 
Zalavras CG, Patzakis MJ, Holtom P. Local antibiotic therapy in the treatment of open fractures and osteomyelitis. Clin Orthop Relat Res. 2004;427: 86-93.42786  2004  [PubMed][CrossRef]
 
Lindsey RW, Probe R, Miclau T, Alexander JW, Perren SM. The effects of antibiotic-impregnated autogeneic cancellous bone graft on bone healing. Clin Orthop Relat Res. 1993;91: 303-12.91303  1993 
 
Beardmore AA, Brooks DE, Wenke JC, Thomas DB. Effectiveness of local antibiotic delivery with an osteoinductive and osteoconductive bone-graft substitute. J Bone Joint Surg Am. 2005;87: 107-12.87107  2005  [CrossRef]
 
Lazarettos J, Efstathopoulos N, Papagelopoulos PJ, Savvidou OD, Kanellakopoulou K, Giamarellou H, Giamarellos-Bourboulis EJ, Nikolaou V, Kapranou A, Papalois A, Papachristou G. A bioresorbable calcium phosphate delivery system with teicoplanin for treating MRSA osteomyelitis. Clin Orthop Relat Res. 2004;423: 253-8.423253  2004  [PubMed][CrossRef]
 
Thomas DB, Brooks DE, Bice TG, DeJong ES, Lonergan KT, Wenke JC. Tobramycin-impregnated calcium sulfate prevents infection in contaminated wounds. Clin Orthop Relat Res. 2005;441: 366-71.441366  2005  [PubMed][CrossRef]
 
Darouiche RO, Farmer J, Chaput C, Mansouri M, Saleh G, Landon GC. Anti-infective efficacy of antiseptic-coated intramedullary nails. J Bone Joint Surg Am. 1998;80: 1336-40.801336  1998  [PubMed]
 
Friedrich PL. Die aseptische Versorgung frischer Wundern. Arch Klin Chir. 1898;57: 288-310.57288  1898 
 
Robson MC, Duke WF, Krizek TJ. Rapid bacterial screening in the treatment of civilian wounds. J Surg Res. 1973;14: 426-30.14426  1973  [PubMed][CrossRef]
 
Kindsfater K, Jonassen EA. Osteomyelitis in grade II and III open tibia fractures with late debridement. J Orthop Trauma. 1995;9: 121-7.9121  1995  [CrossRef]
 
Kreder HJ, Armstrong P. A review of open tibia fractures in children. J Pediatr Orthop. 1995;15: 482-8.15482  1995  [PubMed][CrossRef]
 
Ashford RU, Mehta JA, Cripps R. Delayed presentation is no barrier to satisfactory outcome in the management of open tibial fractures. Injury. 2004; 35: 411-6.35411  2004  [PubMed][CrossRef]
 
Bednar DA, Parikh J. Effect of time delay from injury to primary management on the incidence of deep infection after open fractures of the lower extremities caused by blunt trauma in adults. J Orthop Trauma. 1993;7: 532-5.7532  1993  [PubMed][CrossRef]
 
Charalambous CP, Siddique I, Zenios M, Roberts S, Samarji R, Paul A, Hirst P. Early versus delayed surgical treatment of open tibial fractures: effect on the rates of infection and need of secondary surgical procedures to promote bone union. Injury. 2005;36: 656-61.36656  2005  [PubMed][CrossRef]
 
Harley BJ, Beaupre LA, Jones CA, Dulai SK, Weber DW. The effect of time to definitive treatment on the rate of nonunion and infection in open fractures. J Orthop Trauma. 2002;16: 484-90.16484  2002  [PubMed][CrossRef]
 
Khatod M, Botte MJ, Hoyt DB, Meyer RS, Smith JM, Akeson WH. Outcomes in open tibia fractures: relationship between delay in treatment and infection. J Trauma. 2003;55: 949-54.55949  2003  [PubMed][CrossRef]
 
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: 8-12.878  2005  [CrossRef]
 
Spencer J, Smith A, Woods D. The effect of time delay on infection in open long-bone fractures: a 5-year prospective audit from a district general hospital. Ann R Coll Surg Engl. 2004;86: 108-12.86108  2004  [PubMed][CrossRef]
 
Pollack AN, Castillo RC, Jones AL, Bosse MJ, MacKenzie EJ, and the LEAP Study Group. Time to definitive treatment significantly influences incidence of infection after open high-energy lower-extremity trauma. Read at the Annual Meeting of the Orthopaedic Trauma Association; 2003Oct9-11; Salt Lake City, UT.  2003 
 
Orcutt S, Kilgus D, Ziner D. The treatment of low-grade open fractures without operative debridement. Read at the Annual Meeting of the Orthopaedic Trauma Association; 1988Oct28; Dallas, TX.  1988 
 
Yang EC, Eisler J. Treatment of isolated type I open fractures: is emergent operative debridement necessary? Clin Orthop Relat Res. 2003;410: 289-94.410289  2003  [PubMed][CrossRef]
 
Anglen JO. Wound irrigation in musculoskeletal injury. J Am Acad Orthop Surg. 2001;9: 219-26.9219  2001  [PubMed]
 
Anglen JO, Apostoles S, Christensen G, Gainor B. The efficacy of various irrigation solutions in removing slime-producing Staphylococcus. J Orthop Trauma. 1994;8: 390-6.8390  1994  [PubMed][CrossRef]
 
Bhandari M, Schemitsch EH, Adili A, Lachowski RJ, Shaughnessy SG. High and low pressure pulsatile lavage of contaminated tibial fractures: an in vitro study of bacterial adherence and bone damage. J Orthop Trauma. 1999;13: 526-33.13526  1999  [PubMed][CrossRef]
 
Adili A, Bhandari M, Schemitsch EH. The biomechanical effect of high-pressure irrigation on diaphyseal fracture healing in vivo. J Orthop Trauma. 2002;16: 413-7.16413  2002  [PubMed][CrossRef]
 
Boyd JI 3rd, Wongworawat MD. High-pressure pulsatile lavage causes soft tissue damage. Clin Orthop Relat Res. 2004;427: 13-7.42713  2004  [CrossRef]
 
Dirschl DR, Duff GP, Dahners LE, Edin M, Rahn BA, Miclau T. High pressure pulsatile lavage irrigation of intraarticular fractures: effects on fracture healing. J Orthop Trauma. 1998;12: 460-3.12460  1998  [PubMed][CrossRef]
 
Hassinger SM, Harding G, Wongworawat MD. High-pressure pulsatile lavage propagates bacteria into soft tissue. Clin Orthop Relat Res. 2005;439: 27-31.43927  2005  [PubMed][CrossRef]
 
Bhandari M, Adili A, Schemitsch EH. The efficacy of low-pressure lavage with different irrigating solutions to remove adherent bacteria from bone. J Bone Joint Surg Am. 2001;83: 412-9.83412  2001  [PubMed]
 
Kaysinger KK, Nicholson NC, Ramp WK, Kellam JF. Toxic effects of wound irrigation solutions on cultured tibiae and osteoblasts. J Orthop Trauma. 1995; 9: 303-11.9303  1995  [PubMed][CrossRef]
 
Anglen JO. Comparison of soap and antibiotic solutions for irrigation of lower-limb open fracture wounds. A prospective, randomized study. J Bone Joint Surg Am. 2005;87: 1415-22.871415  2005  [PubMed][CrossRef]
 
Worlock P, Slack R, Harvey L, Mawhinney R. The prevention of infection in open fractures: an experimental study of the effect of fracture stability. Injury. 1994;25: 31-8.2531  1994  [PubMed][CrossRef]
 
Pallister I, Empson K. The effects of surgical fracture fixation on the systemic inflammatory response to major trauma. J Am Acad Orthop Surg. 2005;13: 93-100.1393  2005  [PubMed]
 
Horn J, Schlegel U, Krettek C, Ito K. Infection resistance of unreamed solid, hollow slotted and cannulated intramedullary nails: an in-vivo experimental comparison. J Orthop Res. 2005;23: 810-5.23810  2005  [CrossRef]
 
Melcher GA, Claudi B, Schlegel U, Perren SM, Printzen G, Munzinger J. Influence of type of medullary nail on the development of local infection. An experimental study of solid and slotted nails in rabbits. J Bone Joint Surg Br. 1994; 76: 955-9.76955  1994  [PubMed]
 
Brumback RJ, Ellison PS Jr, Poka A, Lakatos R, Bathon GH, Burgess AR. Intramedullary nailing of open fractures of the femoral shaft. J Bone Joint Surg Am. 1989;71: 1324-31.711324  1989  [PubMed]
 
Bone LB, Johnson KD, Weigelt J, Scheinberg R. Early versus delayed stabilization of femoral fractures: a prospective randomized study. J Bone Joint Surg Am. 1989;71: 336-40.71336  1989  [PubMed]
 
Grosse A, Christie J, Taglang G, Court-Brown C, McQueen M. Open adult femoral shaft fracture treated by early intramedullary nailing. J Bone Joint Surg Br. 1993;75: 562-5.75562  1993  [PubMed]
 
Lhowe DW, Hansen ST. Immediate nailing of open fractures of the femoral shaft. J Bone Joint Surg Am. 1988;70: 812-20.70812  1988  [PubMed]
 
O'Brien PJ, Meek RN, Powell JN, Blachut PA. Primary intramedullary nailing of open femoral shaft fractures. J Trauma. 1991;31: 113-6.31113  1991  [CrossRef]
 
Wu CC, Shih CH. Treatment of open femoral and tibial shaft fractures preliminary report on external fixation and secondary intramedullary nailing. J Formos Med Assoc. 1991;90: 1179-85.901179  1991  [PubMed]
 
Bach AW, Hansen ST Jr. Plates versus external fixation in severe open tibial shaft fractures. A randomized trial. Clin Orthop Relat Res. 1989;241: 89-94.24189  1989  [PubMed]
 
Edwards CC, Simmons SC, Browner BD, Weigel MC. Severe open tibial fractures. Results treating 202 injuries with external fixation. Clin Orthop Relat Res. 1988;230: 98-115.23098  1988  [PubMed]
 
Henley MB, Chapman JR, Agel J, Harvey EJ, Whorton AM, Swiontkowski MF. Treatment of type II, IIIA, and IIIB open fractures of the tibial shaft: a prospective comparison of unreamed interlocking intramedullary nails and half-pin external fixators. J Orthop Trauma. 1998;12: 1-7.121  1998  [CrossRef]
 
Schandelmaier P, Krettek C, Rudolf J, Tscherne H. Outcome of tibial shaft fractures with severe soft tissue injury treated by unreamed nailing versus external fixation. J Trauma. 1995;39: 707-11.39707  1995  [PubMed][CrossRef]
 
Tornetta P 3rd, Bergman M, Watnik N, Berkowitz G, Steuer J. Treatment of grade-IIIb open tibial fractures. A prospective randomised comparison of external fixation and non-reamed locked nailing. J Bone Joint Surg Br. 1994;76: 13-9.7613  1994  [PubMed]
 
Forster MC, Bruce AS, Aster AS. Should the tibia be reamed when nailing? Injury. 2005;36: 439-44.36439  2005  [PubMed][CrossRef]
 
Larsen LB, Madsen JE, Hoiness PR, Ovre S. Should insertion of intramedullary nails for tibial fractures be with or without reaming? A prospective, randomized study with 3.8 years' follow-up. J Orthop Trauma. 2004;18: 144-9.18144  2004  [PubMed][CrossRef]
 
Schemitsch EH, Kowalski MJ, Swiontkowski MF, Senft D. Cortical bone blood flow in reamed and unreamed locked intramedullary nailing: a fractured tibia model in sheep. J Orthop Trauma. 1994;8: 373-82.8373  1994  [CrossRef]
 
Keating JF, O'Brien PJ, Blachut PA, Meek RN, Broekhuyse HM. Locking intramedullary nailing with and without reaming for open fractures of the tibial shaft. A prospective, randomized study. J Bone Joint Surg Am. 1997;79: 334-41.79334  1997 
 
Finkemeier CG, Schmidt AH, Kyle RF, Templeman DC, Varecka TF. A prospective, randomized study of intramedullary nails inserted with and without reaming for the treatment of open and closed fractures of the tibial shaft. J Orthop Trauma. 2000;14: 187-93.14187  2000  [PubMed][CrossRef]
 
Ziran BH, Darowish M, Klatt BA, Agudelo JF, Smith WR. Intramedullary nailing in open tibia fractures: a comparison of two techniques. Int Orthop. 2004;28: 235-8.28235  2004  [PubMed]
 
Bhandari M, Guyatt GH, Swiontkowski MF, Schemitsch EH. Treatment of open fractures of the shaft of the tibia: a systematic overview and metaanalysis. J Bone Joint Surg Br. 2001;83: 62-8.8362  2001  [PubMed][CrossRef]
 
Byrd HS, Spicer TE, Cierney G 3rd. Management of open tibial fractures. Plast Reconstr Surg. 1985;76: 719-30.76719  1985  [PubMed][CrossRef]
 
Caudle RJ, Stern PJ. Severe open fractures of the tibia. J Bone Joint Surg Am. 1987;69: 801-7.69801  1987  [PubMed]
 
Cierny G 3rd, Byrd HS, Jones RE. Primary versus delayed soft tissue coverage for severe open tibial fractures. A comparison of results. Clin Orthop Relat Res. 1983;178: 54-63.17854  1983  [PubMed]
 
Fischer MD, Gustilo RB, Varecka TF. The timing of flap coverage, bone-grafting, and intramedullary nailing in patients who have a fracture of the tibial shaft with extensive soft-tissue injury. J Bone Joint Surg Am. 1991; 73: 1316-22.731316  1991  [PubMed]
 
Godina M. Early microsurgical reconstruction of complex trauma of the extremities. Plast Reconstr Surg. 1986;78: 285-92.78285  1986  [CrossRef]
 
Sinclair JS, McNally MA, Small JO, Yeates HA. Primary free-flap cover of open tibial fractures. Injury. 1997;28: 581-7.28581  1997  [PubMed][CrossRef]
 
DeLong WG Jr, Born CT, Wei SY, Petrik ME, Ponzio R, Schwab CW. Aggressive treatment of 119 open fracture wounds. J Trauma. 1999;46: 1049-54.461049  1999  [PubMed][CrossRef]
 
Gopal S, Majumder S, Batchelor AG, Knight SL, De Boer P, Smith RM. Fix and flap: the radical orthopaedic and plastic treatment of severe open fractures of the tibia. J Bone Joint Surg Br. 2000;82: 959-66.82959  2000  [CrossRef]
 
Hertel R, Lambert SM, Muller S, Ballmer FT, Ganz R. On the timing of soft-tissue reconstruction for open fractures of the lower leg. Arch Orthop Trauma Surg. 1999;119: 7-12.1197  1999  [PubMed][CrossRef]
 
Argenta LC, Morykwas MJ. Vacuum-assisted closure: a new method for wound control and treatment: clinical experience. Ann Plast Surg. 1997; 38: 563-77.38563  1997  [PubMed][CrossRef]
 
Morykwas MJ, Argenta LC, Shelton-Brown EI, McGuirt W. Vacuum-assisted closure: a new method for wound control and treatment: animal studies and basic foundation. Ann Plast Surg. 1997;38: 553-62.38553  1997  [PubMed][CrossRef]
 
DeFranzo AJ, Argenta LC, Marks MW, Molnar JA, David LR, Webb LX, Ward WG, Teasdall RG. The use of vacuum-assisted closure therapy for the treatment of lower-extremity wounds with exposed bone. Plast Reconstr Surg. 2001;108: 1184-91.1081184  2001  [PubMed][CrossRef]
 
Herscovici D Jr, Sanders RW, Scaduto JM, Infante A, DiPasquale T. Vacuum-assisted wound closure (VAC therapy) for the management of patients with high-energy soft tissue injuries. J Orthop Trauma. 2003;17: 683-8.17683  2003  [CrossRef]
 
Labler L, Keel M, Trentz O. Vacuum-assisted closure (V.A.C.) for temporary coverage of soft-tissue injury in type III open fracture of the lower extremities. Eur J Trauma. 2004;30: 305-12.30305  2004  [CrossRef]
 
Mooney JF 3rd, Argenta LC, Marks MW, Morykwas MJ, DeFranzo AJ. Treatment of soft tissue defects in pediatric patients using the V.A.C. system. Clin Orthop Relat Res. 2000;376: 26-31.37626  2000  [PubMed][CrossRef]
 
Blick SS, Brumback RJ, Lakatos R, Poka A, Burgess AR. Early prophylactic bone grafting of high-energy tibial fractures. Clin Orthop Relat Res. 1989; 240: 21-41.24021  1989  [PubMed]
 
Trabulsy PP, Kerley SM, Hoffman WY. A prospective study of early soft tissue coverage of grade IIIB tibial fractures. J Trauma. 1994;36: 661-8.36661  1994  [PubMed][CrossRef]
 
Govender S, Csimma C, Genant HK, Valentin-Opran A, Amit Y, Arbel R, Aro H, Atar D, Bishay M, Borner MG, Chiron P, Choong P, Cinats J, Courtenay B, Feibel R, Geulette B, Gravel C, Haas N, Raschke M, Hammacher E, van der Velde D, Hardy P, Holt M, Josten C, Ketterl RL, Lindeque B, Lob G, Mathevon H, McCoy G, Marsh D, Miller R, Munting E, Oevre S, Nordsletten L, Patel A, Pohl A, Rennie W, Reynders P, Rommens PM, Rondia J, Rossouw WC, Daneel PJ, Ruff S, Ruter A, Santavirta S, Schildhauer TA, Gekle C, Schnettler R, Segal D, Seiler H, Snowdowne RB, Stapert J, Taglang G, Verdonk R, Vogels L, Weckbach A, Wentzensen A, Wisniewski T; BMP-2 Evaluation in Surgery for Tibial Trauma (BESST) Study Group. Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Joint Surg Am. 2002;84: 2123-34.842123  2002  [PubMed]
 
Swiontkowski MF, Aro HT, Donell S, Esterhai JL, Goulet J, Jones A, Kregor PJ, Nordsletten L, Paiement G, Patel A. Recombinant human bone morphogenetic protein-2 in open tibial fractures. A subgroup analysis of data combined from two prospective randomized studies. J Bone Joint Surg Am. 2006; 88: 1258-65.q881258  2006  [PubMed][CrossRef]
 

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Anchor for JumpAnchor for JumpTABLE I  Classification System of Gustilo et al.3,4: Definitions and Associated Infection Rates
Fracture Type Definition Historical Infection Rates3,4,7,8 (%)
I Wound <1 cm; minimal contamination, comminution, and soft-tissue damage 0-2
II Wound >1 cm; moderate soft-tissue damage, minimal periosteal stripping 2-5
IIIA Severe soft-tissue damage and substantial contamination; coverage adequate 5-10
IIIB Severe soft-tissue damage and substantial contamination; coverage inadequate 10-50
IIIC Arterial injury requiring repair 25-50
Anchor for JumpAnchor for JumpTABLE II  Recommendations for the Management of Open Fractures
Recommendation Grade of Recommendation*
Antibiotics
    Systemic therapy A
    Local therapy B
Timing of operative débridement
    Urgent B
    Within 6 hr C
Irrigation
    High-pressure pulsatile lavage I
    Additives† I
Fixation
    Femur (intramedullary nailing) B
Tibia
    External fixation B
    Intramedullary nailing B
    Reaming I
Coverage and closure
    Primary closure B
    Vacuum-assisted closure I
Adjunctive therapies
    Early prophylactic bone-grafting C
    Local rhBMP-2 B
Modalities not recommended
    Wound culture B
A = Good evidence (Level-I studies with consistent findings) for or against recommending intervention, B = fair evidence (Level-II or III studies with consistent findings) for or against recommending intervention, C = poor-quality evidence (Level-IV or V studies with consistent findings) for or against recommending intervention, and I = there is insufficient or conflicting evidence not allowing a recommendation for or against intervention. †Antibiotic, antiseptic, or soap additives.

References

Lister J. On a new method of treating compound fracture, abscess, etc. The Lancet. 1867;1: 326, 357, 387, 507.1326  1867  [CrossRef]
 
Patrick JH, Smelt GJ. Surgical progress—100 years ago. An assessment of Listerism at St Thomas's Hospital, London. Ann R Coll Surg Engl. 1977;59: 456-62.59456  1977  [PubMed]
 
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: 453-8.58453  1976 
 
Gustilo RB, Mendoza RM, Williams DN. Problems in the management of type III (severe) open fractures: a new classification of type III open fractures. J Trauma. 1984;24: 742-6.24742  1984  [PubMed][CrossRef]
 
Brumback RJ, Jones AL. Interobserver agreement 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: 1162-6.761162  1994 
 
Horn BD, Rettig ME. Interobserver reliability in the Gustilo and Anderson classification of open fractures. J Orthop Trauma. 1993;7: 357-60.7357  1993  [PubMed][CrossRef]
 
Patzakis MJ, Wilkins J. Factors influencing infection rate in open fracture wounds. Clin Orthop Relat Res. 1989;243: 36-40.24336  1989 
 
Gustilo RB, Gruninger RP, Davis T. Classification of type III (severe) open fractures relative to treatment and results. Orthopedics. 1987;10: 1781-8.101781  1987  [PubMed]
 
Bowen TR, Widmaier JC. Host classification predicts infection after open fracture. Clin Orthop Relat Res. 2005;433: 205-11.433205  2005  [CrossRef]
 
Patzakis MJ, Harvey JP Jr, Ivler D. The role of antibiotics in the management of open fractures. J Bone Joint Surg Am. 1974;56: 532-41.56532  1974 
 
Gosselin RA, Roberts I, Gillespie WJ. Antibiotics for preventing infection in open limb fractures. Cochrane Database Syst Rev. 2004;1: CD003764.1CD003764  2004 
 
Lee J. Efficacy of cultures in the management of open fractures. Clin Orthop Relat Res. 1997;339: 71-5.33971  1997  [PubMed][CrossRef]
 
Valenziano CP, Chattar-Cora D, O'Neill A, Hubli EH, Cudjoe EA. Efficacy of primary wound cultures in long bone open extremity fractures: are they of any value? Arch Orthop Trauma Surg. 2002;122: 259-61.122259  2002  [CrossRef]
 
Carsenti-Etesse H, Doyon F, Desplaces N, Gagey O, Tancrede C, Pradier C, Dunais B, Dellamonica P. Epidemiology of bacterial infection during management of open leg fractures. Eur J Clin Microbiol Infect Dis. 1999;18: 315-23.18315  1999  [CrossRef]
 
Johnson KD, Johnston DW. Orthopedic experience with methicillin-resistant Staphylococcus aureus during a hospital epidemic. Clin Orthop Relat Res. 1986;212: 281-8.212281  1986  [PubMed]
 
Benson DR, Riggins RS, Lawrence RM, Hoeprich PD, Huston AC, Harrison JA. Treatment of open fractures: a prospective study. J Trauma. 1983; 23: 25-30.2325  1983  [PubMed][CrossRef]
 
Patzakis MJ, Bains RS, Lee J, Shepherd L, Singer G, Ressler R, Harvey F, Holtom P. Prospective, randomized, double-blind study comparing single-agent antibiotic therapy, ciprofloxacin, to combination antibiotic therapy in open fracture wounds. J Orthop Trauma. 2000;14: 529-33.14529  2000  [CrossRef]
 
Holtom PD, Pavkovic SA, Bravos PD, Patzakis MJ, Shepherd LE, Frenkel B. Inhibitory effects of the quinolone antibiotics trovafloxacin, ciprofloxacin, and levofloxacin on osteoblastic cells in vitro. J Orthop Res. 2000;18: 721-7.18721  2000  [PubMed][CrossRef]
 
Huddleston PM, Steckelberg JM, Hanssen AD, Rouse MS, Bolander ME, Patel R. Ciprofloxacin inhibition of experimental fracture healing. J Bone Joint Surg Am. 2000;82: 161-73.82161  2000  [PubMed]
 
Zalavras CG, Patzakis MJ, Holtom PD, Sherman R. Management of open fractures. Infect Dis Clin North Am. 2005;19: 915-29.19915  2005  [CrossRef]
 
Olson SA, Finkemeier CG, Moehring ND. Open Fractures. In: Bucholz RW, Heckman JD, editors. Rockwood and Greene's fractures in adults. 5th ed. Philadelphia: Lippincott, Williams and Wilkins; 2001. p 285-318.285  2001 
 
Dellinger EP, Caplan ES, Weaver LD, Wertz MJ, Droppert BM, Hoyt N, Brumback R, Burgess A, Poka A, Benirschke SK, Lennard S, Lou MA. Duration of preventive antibiotic administration for open extremity fractures. Arch Surg. 1988;123: 333-9.123333  1988  [PubMed]
 
Eckman JB Jr, Henry SL, Mangino PD, Seligson D. Wound and serum levels of tobramycin with the prophylactic use of tobramycin-impregnated polymethylmethacrylate beads in compound fractures. Clin Orthop Relat Res. 1988; 237: 213-5.237213  1988  [PubMed]
 
Miclau T, Edin ML, Lester GE, Lindsey RW, Dahners LE. Bone toxicity of locally applied aminoglycosides. J Orthop Trauma. 1995;9: 401-6.9401  1995  [CrossRef]
 
Ince A, Schutze N, Karl N, Lohr JF, Eulert J. Gentamicin negatively influenced osteogenic function in vitro. Int Orthop. 2006May20; [Epub ahead of print].  2006 
 
Ostermann PA, Seligson D, Henry SL. Local antibiotic therapy for severe open fractures. A review of 1085 consecutive cases. J Bone Joint Surg Br. 1995;77: 93-7.7793  1995  [PubMed]
 
Keating JF, Blachut PA, O'Brien PJ, Meek RN, Broekhuyse H. Reamed nailing of open tibial fractures: does the antibiotic bead pouch reduce the deep infection rate? J Orthop Trauma. 1996;10: 298-303.10298  1996  [PubMed][CrossRef]
 
Moehring HD, Gravel C, Chapman MW, Olson SA. Comparison of antibiotic beads and intravenous antibiotics in open fractures. Clin Orthop Relat Res. 2000;372: 254-61.372254  2000  [PubMed][CrossRef]
 
Zalavras CG, Patzakis MJ, Holtom P. Local antibiotic therapy in the treatment of open fractures and osteomyelitis. Clin Orthop Relat Res. 2004;427: 86-93.42786  2004  [PubMed][CrossRef]
 
Lindsey RW, Probe R, Miclau T, Alexander JW, Perren SM. The effects of antibiotic-impregnated autogeneic cancellous bone graft on bone healing. Clin Orthop Relat Res. 1993;91: 303-12.91303  1993 
 
Beardmore AA, Brooks DE, Wenke JC, Thomas DB. Effectiveness of local antibiotic delivery with an osteoinductive and osteoconductive bone-graft substitute. J Bone Joint Surg Am. 2005;87: 107-12.87107  2005  [CrossRef]
 
Lazarettos J, Efstathopoulos N, Papagelopoulos PJ, Savvidou OD, Kanellakopoulou K, Giamarellou H, Giamarellos-Bourboulis EJ, Nikolaou V, Kapranou A, Papalois A, Papachristou G. A bioresorbable calcium phosphate delivery system with teicoplanin for treating MRSA osteomyelitis. Clin Orthop Relat Res. 2004;423: 253-8.423253  2004  [PubMed][CrossRef]
 
Thomas DB, Brooks DE, Bice TG, DeJong ES, Lonergan KT, Wenke JC. Tobramycin-impregnated calcium sulfate prevents infection in contaminated wounds. Clin Orthop Relat Res. 2005;441: 366-71.441366  2005  [PubMed][CrossRef]
 
Darouiche RO, Farmer J, Chaput C, Mansouri M, Saleh G, Landon GC. Anti-infective efficacy of antiseptic-coated intramedullary nails. J Bone Joint Surg Am. 1998;80: 1336-40.801336  1998  [PubMed]
 
Friedrich PL. Die aseptische Versorgung frischer Wundern. Arch Klin Chir. 1898;57: 288-310.57288  1898 
 
Robson MC, Duke WF, Krizek TJ. Rapid bacterial screening in the treatment of civilian wounds. J Surg Res. 1973;14: 426-30.14426  1973  [PubMed][CrossRef]
 
Kindsfater K, Jonassen EA. Osteomyelitis in grade II and III open tibia fractures with late debridement. J Orthop Trauma. 1995;9: 121-7.9121  1995  [CrossRef]
 
Kreder HJ, Armstrong P. A review of open tibia fractures in children. J Pediatr Orthop. 1995;15: 482-8.15482  1995  [PubMed][CrossRef]
 
Ashford RU, Mehta JA, Cripps R. Delayed presentation is no barrier to satisfactory outcome in the management of open tibial fractures. Injury. 2004; 35: 411-6.35411  2004  [PubMed][CrossRef]
 
Bednar DA, Parikh J. Effect of time delay from injury to primary management on the incidence of deep infection after open fractures of the lower extremities caused by blunt trauma in adults. J Orthop Trauma. 1993;7: 532-5.7532  1993  [PubMed][CrossRef]
 
Charalambous CP, Siddique I, Zenios M, Roberts S, Samarji R, Paul A, Hirst P. Early versus delayed surgical treatment of open tibial fractures: effect on the rates of infection and need of secondary surgical procedures to promote bone union. Injury. 2005;36: 656-61.36656  2005  [PubMed][CrossRef]
 
Harley BJ, Beaupre LA, Jones CA, Dulai SK, Weber DW. The effect of time to definitive treatment on the rate of nonunion and infection in open fractures. J Orthop Trauma. 2002;16: 484-90.16484  2002  [PubMed][CrossRef]
 
Khatod M, Botte MJ, Hoyt DB, Meyer RS, Smith JM, Akeson WH. Outcomes in open tibia fractures: relationship between delay in treatment and infection. J Trauma. 2003;55: 949-54.55949  2003  [PubMed][CrossRef]
 
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: 8-12.878  2005  [CrossRef]
 
Spencer J, Smith A, Woods D. The effect of time delay on infection in open long-bone fractures: a 5-year prospective audit from a district general hospital. Ann R Coll Surg Engl. 2004;86: 108-12.86108  2004  [PubMed][CrossRef]
 
Pollack AN, Castillo RC, Jones AL, Bosse MJ, MacKenzie EJ, and the LEAP Study Group. Time to definitive treatment significantly influences incidence of infection after open high-energy lower-extremity trauma. Read at the Annual Meeting of the Orthopaedic Trauma Association; 2003Oct9-11; Salt Lake City, UT.  2003 
 
Orcutt S, Kilgus D, Ziner D. The treatment of low-grade open fractures without operative debridement. Read at the Annual Meeting of the Orthopaedic Trauma Association; 1988Oct28; Dallas, TX.  1988 
 
Yang EC, Eisler J. Treatment of isolated type I open fractures: is emergent operative debridement necessary? Clin Orthop Relat Res. 2003;410: 289-94.410289  2003  [PubMed][CrossRef]
 
Anglen JO. Wound irrigation in musculoskeletal injury. J Am Acad Orthop Surg. 2001;9: 219-26.9219  2001  [PubMed]
 
Anglen JO, Apostoles S, Christensen G, Gainor B. The efficacy of various irrigation solutions in removing slime-producing Staphylococcus. J Orthop Trauma. 1994;8: 390-6.8390  1994  [PubMed][CrossRef]
 
Bhandari M, Schemitsch EH, Adili A, Lachowski RJ, Shaughnessy SG. High and low pressure pulsatile lavage of contaminated tibial fractures: an in vitro study of bacterial adherence and bone damage. J Orthop Trauma. 1999;13: 526-33.13526  1999  [PubMed][CrossRef]
 
Adili A, Bhandari M, Schemitsch EH. The biomechanical effect of high-pressure irrigation on diaphyseal fracture healing in vivo. J Orthop Trauma. 2002;16: 413-7.16413  2002  [PubMed][CrossRef]
 
Boyd JI 3rd, Wongworawat MD. High-pressure pulsatile lavage causes soft tissue damage. Clin Orthop Relat Res. 2004;427: 13-7.42713  2004  [CrossRef]
 
Dirschl DR, Duff GP, Dahners LE, Edin M, Rahn BA, Miclau T. High pressure pulsatile lavage irrigation of intraarticular fractures: effects on fracture healing. J Orthop Trauma. 1998;12: 460-3.12460  1998  [PubMed][CrossRef]
 
Hassinger SM, Harding G, Wongworawat MD. High-pressure pulsatile lavage propagates bacteria into soft tissue. Clin Orthop Relat Res. 2005;439: 27-31.43927  2005  [PubMed][CrossRef]
 
Bhandari M, Adili A, Schemitsch EH. The efficacy of low-pressure lavage with different irrigating solutions to remove adherent bacteria from bone. J Bone Joint Surg Am. 2001;83: 412-9.83412  2001  [PubMed]
 
Kaysinger KK, Nicholson NC, Ramp WK, Kellam JF. Toxic effects of wound irrigation solutions on cultured tibiae and osteoblasts. J Orthop Trauma. 1995; 9: 303-11.9303  1995  [PubMed][CrossRef]
 
Anglen JO. Comparison of soap and antibiotic solutions for irrigation of lower-limb open fracture wounds. A prospective, randomized study. J Bone Joint Surg Am. 2005;87: 1415-22.871415  2005  [PubMed][CrossRef]
 
Worlock P, Slack R, Harvey L, Mawhinney R. The prevention of infection in open fractures: an experimental study of the effect of fracture stability. Injury. 1994;25: 31-8.2531  1994  [PubMed][CrossRef]
 
Pallister I, Empson K. The effects of surgical fracture fixation on the systemic inflammatory response to major trauma. J Am Acad Orthop Surg. 2005;13: 93-100.1393  2005  [PubMed]
 
Horn J, Schlegel U, Krettek C, Ito K. Infection resistance of unreamed solid, hollow slotted and cannulated intramedullary nails: an in-vivo experimental comparison. J Orthop Res. 2005;23: 810-5.23810  2005  [CrossRef]
 
Melcher GA, Claudi B, Schlegel U, Perren SM, Printzen G, Munzinger J. Influence of type of medullary nail on the development of local infection. An experimental study of solid and slotted nails in rabbits. J Bone Joint Surg Br. 1994; 76: 955-9.76955  1994  [PubMed]
 
Brumback RJ, Ellison PS Jr, Poka A, Lakatos R, Bathon GH, Burgess AR. Intramedullary nailing of open fractures of the femoral shaft. J Bone Joint Surg Am. 1989;71: 1324-31.711324  1989  [PubMed]
 
Bone LB, Johnson KD, Weigelt J, Scheinberg R. Early versus delayed stabilization of femoral fractures: a prospective randomized study. J Bone Joint Surg Am. 1989;71: 336-40.71336  1989  [PubMed]
 
Grosse A, Christie J, Taglang G, Court-Brown C, McQueen M. Open adult femoral shaft fracture treated by early intramedullary nailing. J Bone Joint Surg Br. 1993;75: 562-5.75562  1993  [PubMed]
 
Lhowe DW, Hansen ST. Immediate nailing of open fractures of the femoral shaft. J Bone Joint Surg Am. 1988;70: 812-20.70812  1988  [PubMed]
 
O'Brien PJ, Meek RN, Powell JN, Blachut PA. Primary intramedullary nailing of open femoral shaft fractures. J Trauma. 1991;31: 113-6.31113  1991  [CrossRef]
 
Wu CC, Shih CH. Treatment of open femoral and tibial shaft fractures preliminary report on external fixation and secondary intramedullary nailing. J Formos Med Assoc. 1991;90: 1179-85.901179  1991  [PubMed]
 
Bach AW, Hansen ST Jr. Plates versus external fixation in severe open tibial shaft fractures. A randomized trial. Clin Orthop Relat Res. 1989;241: 89-94.24189  1989  [PubMed]
 
Edwards CC, Simmons SC, Browner BD, Weigel MC. Severe open tibial fractures. Results treating 202 injuries with external fixation. Clin Orthop Relat Res. 1988;230: 98-115.23098  1988  [PubMed]
 
Henley MB, Chapman JR, Agel J, Harvey EJ, Whorton AM, Swiontkowski MF. Treatment of type II, IIIA, and IIIB open fractures of the tibial shaft: a prospective comparison of unreamed interlocking intramedullary nails and half-pin external fixators. J Orthop Trauma. 1998;12: 1-7.121  1998  [CrossRef]
 
Schandelmaier P, Krettek C, Rudolf J, Tscherne H. Outcome of tibial shaft fractures with severe soft tissue injury treated by unreamed nailing versus external fixation. J Trauma. 1995;39: 707-11.39707  1995  [PubMed][CrossRef]
 
Tornetta P 3rd, Bergman M, Watnik N, Berkowitz G, Steuer J. Treatment of grade-IIIb open tibial fractures. A prospective randomised comparison of external fixation and non-reamed locked nailing. J Bone Joint Surg Br. 1994;76: 13-9.7613  1994  [PubMed]
 
Forster MC, Bruce AS, Aster AS. Should the tibia be reamed when nailing? Injury. 2005;36: 439-44.36439  2005  [PubMed][CrossRef]
 
Larsen LB, Madsen JE, Hoiness PR, Ovre S. Should insertion of intramedullary nails for tibial fractures be with or without reaming? A prospective, randomized study with 3.8 years' follow-up. J Orthop Trauma. 2004;18: 144-9.18144  2004  [PubMed][CrossRef]
 
Schemitsch EH, Kowalski MJ, Swiontkowski MF, Senft D. Cortical bone blood flow in reamed and unreamed locked intramedullary nailing: a fractured tibia model in sheep. J Orthop Trauma. 1994;8: 373-82.8373  1994  [CrossRef]
 
Keating JF, O'Brien PJ, Blachut PA, Meek RN, Broekhuyse HM. Locking intramedullary nailing with and without reaming for open fractures of the tibial shaft. A prospective, randomized study. J Bone Joint Surg Am. 1997;79: 334-41.79334  1997 
 
Finkemeier CG, Schmidt AH, Kyle RF, Templeman DC, Varecka TF. A prospective, randomized study of intramedullary nails inserted with and without reaming for the treatment of open and closed fractures of the tibial shaft. J Orthop Trauma. 2000;14: 187-93.14187  2000  [PubMed][CrossRef]
 
Ziran BH, Darowish M, Klatt BA, Agudelo JF, Smith WR. Intramedullary nailing in open tibia fractures: a comparison of two techniques. Int Orthop. 2004;28: 235-8.28235  2004  [PubMed]
 
Bhandari M, Guyatt GH, Swiontkowski MF, Schemitsch EH. Treatment of open fractures of the shaft of the tibia: a systematic overview and metaanalysis. J Bone Joint Surg Br. 2001;83: 62-8.8362  2001  [PubMed][CrossRef]
 
Byrd HS, Spicer TE, Cierney G 3rd. Management of open tibial fractures. Plast Reconstr Surg. 1985;76: 719-30.76719  1985  [PubMed][CrossRef]
 
Caudle RJ, Stern PJ. Severe open fractures of the tibia. J Bone Joint Surg Am. 1987;69: 801-7.69801  1987  [PubMed]
 
Cierny G 3rd, Byrd HS, Jones RE. Primary versus delayed soft tissue coverage for severe open tibial fractures. A comparison of results. Clin Orthop Relat Res. 1983;178: 54-63.17854  1983  [PubMed]
 
Fischer MD, Gustilo RB, Varecka TF. The timing of flap coverage, bone-grafting, and intramedullary nailing in patients who have a fracture of the tibial shaft with extensive soft-tissue injury. J Bone Joint Surg Am. 1991; 73: 1316-22.731316  1991  [PubMed]
 
Godina M. Early microsurgical reconstruction of complex trauma of the extremities. Plast Reconstr Surg. 1986;78: 285-92.78285  1986  [CrossRef]
 
Sinclair JS, McNally MA, Small JO, Yeates HA. Primary free-flap cover of open tibial fractures. Injury. 1997;28: 581-7.28581  1997  [PubMed][CrossRef]
 
DeLong WG Jr, Born CT, Wei SY, Petrik ME, Ponzio R, Schwab CW. Aggressive treatment of 119 open fracture wounds. J Trauma. 1999;46: 1049-54.461049  1999  [PubMed][CrossRef]
 
Gopal S, Majumder S, Batchelor AG, Knight SL, De Boer P, Smith RM. Fix and flap: the radical orthopaedic and plastic treatment of severe open fractures of the tibia. J Bone Joint Surg Br. 2000;82: 959-66.82959  2000  [CrossRef]
 
Hertel R, Lambert SM, Muller S, Ballmer FT, Ganz R. On the timing of soft-tissue reconstruction for open fractures of the lower leg. Arch Orthop Trauma Surg. 1999;119: 7-12.1197  1999  [PubMed][CrossRef]
 
Argenta LC, Morykwas MJ. Vacuum-assisted closure: a new method for wound control and treatment: clinical experience. Ann Plast Surg. 1997; 38: 563-77.38563  1997  [PubMed][CrossRef]
 
Morykwas MJ, Argenta LC, Shelton-Brown EI, McGuirt W. Vacuum-assisted closure: a new method for wound control and treatment: animal studies and basic foundation. Ann Plast Surg. 1997;38: 553-62.38553  1997  [PubMed][CrossRef]
 
DeFranzo AJ, Argenta LC, Marks MW, Molnar JA, David LR, Webb LX, Ward WG, Teasdall RG. The use of vacuum-assisted closure therapy for the treatment of lower-extremity wounds with exposed bone. Plast Reconstr Surg. 2001;108: 1184-91.1081184  2001  [PubMed][CrossRef]
 
Herscovici D Jr, Sanders RW, Scaduto JM, Infante A, DiPasquale T. Vacuum-assisted wound closure (VAC therapy) for the management of patients with high-energy soft tissue injuries. J Orthop Trauma. 2003;17: 683-8.17683  2003  [CrossRef]
 
Labler L, Keel M, Trentz O. Vacuum-assisted closure (V.A.C.) for temporary coverage of soft-tissue injury in type III open fracture of the lower extremities. Eur J Trauma. 2004;30: 305-12.30305  2004  [CrossRef]
 
Mooney JF 3rd, Argenta LC, Marks MW, Morykwas MJ, DeFranzo AJ. Treatment of soft tissue defects in pediatric patients using the V.A.C. system. Clin Orthop Relat Res. 2000;376: 26-31.37626  2000  [PubMed][CrossRef]
 
Blick SS, Brumback RJ, Lakatos R, Poka A, Burgess AR. Early prophylactic bone grafting of high-energy tibial fractures. Clin Orthop Relat Res. 1989; 240: 21-41.24021  1989  [PubMed]
 
Trabulsy PP, Kerley SM, Hoffman WY. A prospective study of early soft tissue coverage of grade IIIB tibial fractures. J Trauma. 1994;36: 661-8.36661  1994  [PubMed][CrossRef]
 
Govender S, Csimma C, Genant HK, Valentin-Opran A, Amit Y, Arbel R, Aro H, Atar D, Bishay M, Borner MG, Chiron P, Choong P, Cinats J, Courtenay B, Feibel R, Geulette B, Gravel C, Haas N, Raschke M, Hammacher E, van der Velde D, Hardy P, Holt M, Josten C, Ketterl RL, Lindeque B, Lob G, Mathevon H, McCoy G, Marsh D, Miller R, Munting E, Oevre S, Nordsletten L, Patel A, Pohl A, Rennie W, Reynders P, Rommens PM, Rondia J, Rossouw WC, Daneel PJ, Ruff S, Ruter A, Santavirta S, Schildhauer TA, Gekle C, Schnettler R, Segal D, Seiler H, Snowdowne RB, Stapert J, Taglang G, Verdonk R, Vogels L, Weckbach A, Wentzensen A, Wisniewski T; BMP-2 Evaluation in Surgery for Tibial Trauma (BESST) Study Group. Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Joint Surg Am. 2002;84: 2123-34.842123  2002  [PubMed]
 
Swiontkowski MF, Aro HT, Donell S, Esterhai JL, Goulet J, Jones A, Kregor PJ, Nordsletten L, Paiement G, Patel A. Recombinant human bone morphogenetic protein-2 in open tibial fractures. A subgroup analysis of data combined from two prospective randomized studies. J Bone Joint Surg Am. 2006; 88: 1258-65.q881258  2006  [PubMed][CrossRef]
 
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