Open Fractures

Introduction
Classification
Emergency management
Definitive treatment
Timing of surgery
Antibiotic choice
Special cases
Grade I fractures
Tibial fractures
Calcaneal fractures
Paediatric open fracture

Irrigation
References

Introduction

 

Open fractures remain one of the true orthopaedic emergencies. Current principles of treatment consist of splinting the fracture and administering antibiotics at the time of initial patient assessment, followed by expeditious transfer to the operating room for aggressive debridement, lavage, and stable fixation of the fracture, forty-eight hours of antibiotic prophylaxis after each procedure or debridement, and delayed closure of open wounds when appropriate. The desired outcome includes skeletal union with intact soft tissues and normal function.

 

Classification

 

Current preference in terminology is to use open rather than compound to denote a fracture with an overlying wound.

 

GustilloAnderson \classification (1)

The prevalence of wound infection and nonunion increases with increasing grade of open fracture.
The Gustillo Anderson classification of open fractures looks at several aspects of the injury not just the size of the wound.

  • Prescence or absence of neurovascular injury

  • Degree of contamination (farmyard injuries are grade III injuries)

  • Energy transfer (Degree of comminution and periosteal stripping)

  • Wound dimensions

Grade I
The wound is less than 1cm long. It is usually a moderately clean puncture, through which a spike of bone has pierced the skin. There is little soft-tissue damage and no sign of crushing injury. The fracture is usually simple, transverse, or short oblique, with little comminution.
Grade II
The laceration is more than 1 cm long, and there is no extensive soft-tissue damage, flap, or avulsion. There is slight or moderate crushing injury, moderate comminution of the fracture, and moderate contamination.
Grade III
These are characterized by extensive damage to soft-tissues, including muscles, skin, and neurovascular structures, and a high degree of contamination. The fracture is often caused by high velocity trauma, resulting in a great deal of comminution and instability.

  • III A – Soft tissue coverage of the fractured bone is adequate

  • III B – Extensive injury to, or loss of soft tissue, with periosteal stripping and exposure of bone, massive contamination, and severe comminution of the fracture. After debridement and irrigation a local or free flap is needed for coverage.

  • III C – Any open fracture that is associated with an arterial injury that must be repaired, regardless of the degree of soft tissue injury.
    The definitive grade should be assigned in theatre after thorough debridement.
    The risk of infection in an open fracture depends on the amount of contamination, severity of soft tissue injury, and operative treatment of the fracture.

Gustilo Anderson grade Risk of infection (Sorger)
Grade I 0-12%
Grade II 2-12%
Grade III 9-55%

 

Emergency management of open fractures

 

ATLS resuscitation
Photograph
Wound swab
Remove gross contamination and apply moist sterile dressing (Betadine)
Antibiotics (Give ASAP, make sure they are given not just written on the drug chart)
Splint the limb
Check tetanus prophylaxis (click here)
Arrange for urgent surgical debridement/ washout and stabilization of the fracture
Conventional treatment advocates debridement and washout within 6-8 hours

 

Definitive treatment

 

Early administration of systemic antibiotics and timely surgical debridement, skeletal stabilisation and delayed wound closure are the mainstay principles of treatment in open fractures. In the era of Gustillo Andersons first publication on open fractures they recommended strongly against internal fixation of open fractures with plates or intramedullary nails; instead, they recommended external skeletal fixation of some sort.
Recently clinical studies have shown that with thorough debridement the use of biological fracture fixation techniques, and early soft tissue cover, internal fixation with plates or intramedullary nails are safe and effective.
The restoration of skeletal stability is very important for the treatment of the soft tissues and prevention of infection.
Conventional timing of definitive debridement and washout is 6-8 hours, with advances in treatment of the osseous and soft tissue injury the validity of this dictum has been debated (see below).

 

Timing of surgery(2,9)

 

Surgical treatment of fractures complicated by soft-tissue wounds has been described over many centuries. Hippocrates (460–377 B.C.) used heat cauterization as a primary means of debridement. Pare in 1579, was the first to advocate “immediate dilatation of wounds, extraction of all lodged foreign bodies.” Karl Reyher, in 1881, demonstrated decreased mortality rates with early debridement during the Franco–Prussian War. This was followed in 1898 by Friedrich's experimental tissue contamination studies in guinea pig soft-tissue wounds, which delimited the time interval for effectiveness of operative debridement to ~6 h.
Many subsequent studies have used modifications of Friedrich's guinea-pig model of soft-tissue contamination. Edlich et al. in 1969, used this model to compare the resistance to infection in open versus closed wounds and to delineate the benefit of delayed primary wound closure. Burke, in 1961, performed tissue-contamination studies to determine the effective period of antibiotic administration. Experimentally created lesions were compared with controls for animals given antibiotics 1 h before to 6 h after injection of the bacterial inoculum. There was no increase in bacterial colony formation in those animals given antibiotics within 3 h from the time of contamination.
Open fractures are generally considered orthopaedic emergencies requiring immediate surgical debridement. Several studies suggest that the timing of surgery is less important than the adequacy of debridement and early use of antibiotics. Patzakis and Wilkins documented infection rates of (6.8%) of 396 for wounds debrided within 12 h, and (7.1%) of 708 for those debrided after 12 h. Bednar and Parikh reviewed 82 adult open fractures and found no statistically significant difference in deep infection rates for those treated within 6 h compared with those treated within 24 h.
Gustillo and Anderson's classic article concluded “Open fractures require emergency treatment, including adequate debridement and copious irrigation.” There are no data in the article to support this claim, as the relation between surgical delay and infection rate was not independently addressed. They reported that the infection rate dropped from 12% to 5% with the advent of four changes in their approach: (a) type III wounds received delayed primary closure, (b) internal fixation was no longer used, (c) open fractures were treated as emergencies, and (d) antibiotics were given before surgery. From their study design, it is impossible to conclude which factors contributed to the decreased infection rate.
Since the advent of the antibiotic era, several studies suggested that the timing of surgical debridement of open fractures may not play such a critical role in preventing infection. Patzakis and Wilkins reviewed 1,104 open fractures with respect to factors influencing infection rates. They reported that the delay from injury to surgery had no effect on the infection rate, with a 7% rate of infection for both fractures debrided <12 h after injury and for those debrided >12 h after injury. They also found that infection occurred in 4.7% of fractures in which antibiotics were started within 3 h of injury compared with 7.4% of fractures in which antibiotics were started >3 h after injury. They concluded, “the single most important factor in reducing the infection rate was the early administration of antibiotics.” Merritt reviewed 70 patients with open fractures and documented that “the time between injury and treatment in the emergency room was not correlated with infection rate, nor was the time between treatment in the emergency room and debridement in the operating room.” Bednar and Parikh examined 82 adult open fractures of the lower extremity caused by blunt trauma with a 5% infection rate, 76% of which were debrided 7–24 h after injury without an increase in infection.
Skaggs et al in a review of 104 open fractures in children (1990-1995), 55 were treated between 6 and 24 h after injury. The infection rate was 2.5% for those treated within 6 h of injury and 1.6% in those with delays >6 h. This difference is not statistically significant (p = 0.77). One confounding variable in this study is that the more severe fractures tended to be treated earlier. In those fractures treated within 6 h, 33% were Gustillo type III injuries, whereas in fractures treated with >6 h delay, only 8% were type III fractures. As this series contained only 18 grade III fractures, the number of grade III fractures is insufficient to draw meaningful conclusions on the effect of surgical delay in this group. This series also included only 9 injuries that had >24 h delay to surgery, making conclusions in this group impossible.
Harley et al reviewed the literature 1966-1999 and found 9 articles dealing with the issue of timing to definitive treatment.
3 articles dealt with patients who did not uniformly receive antibiotics.
The remaining six varied significantly in their structure as well as their results.
Three prospective studies and one retrospective review found no significant difference in infection rates with delayed fracture management.
Two more recent retrospective studies concluded that time was an important factor in the incidence of adverse outcomes. However in one of these (Kinsfater and Jonassen) there was a predominance of Grade III open fractures (77%) in the late treatment group likely biasing the results. In the other Kredar and Armstrong reviewed 56 open tibia fractures in children and found that a delay of >6 h was correlated with a 25% infection rate (two of eight), compared with a 12% infection rate (five of 42) for those fractures treated within 6 h of injury, clearly these numbers are too small to be meaningful. With only eight patients treated >6 h after injury, one less infection would have made the infection rates equal.
Harley et al undertook a retrospective review of 227 skeletally mature patients with 241 open long bone fractures, treated 1996 to 1998. This retrospective review demonstrated no increase in the incidence of infections or nonunions from open fractures managed up to 13 hours from the time of injury. This result is consistent with some of the aforementioned studies.
A number of other observations in this study are worthy of further comment.
No infections occurred in upper extremity injuries despite numerous Grade 3 injuries and prolonged treatment times.
Increasing severity of injury in the lower extremity, particularly the tibia, does result in an increased infection rate.
The time to definitive surgical management did not influence the infection rate in the lower extremity, however, with similar proportions of patients having deep infections in both the early and the late treatment groups.
Nonunions in upper extremity injuries are uncommon events, and they do not appear to be related to delays in time to definitive treatment.
There is a higher complication rate following external fixation. It is likely that this increased complication rate associated with their use is a reflection of the severity of the original injury and not the technique itself.
Although the use of plates and screws in open fractures is thought to be associated with an increased rate of infection, this association was not observed in this study. The majority of plates were used in the upper extremity, however, whereas intramedullary fixation was preferred in the lower extremity. In the setting of a lower extremity fracture with metaphyseal or intraarticular extension and adequate soft tissue coverage, plates remain a viable option and do not appear to predispose to increased complications when used in this manner. The use of antibiotics however should not replace thorough and repeated debridement if necessary of severe open wounds. Emergent open fracture treatment remains the standard of care. However, the observations are important and should not be discounted entirely.
It is important to note that 92% of the study subjects had definitive fracture management within thirteen hours of injury; thus, these conclusions on the effect of time are realistically limited to the initial thirteen hours.
The rate of infection after open fracture is strongly associated with increasing Gustilo grade and lower extremity fractures. Nonunion after open fracture is strongly associated with the presence of infection and increasing Gustilo grade of fracture.

 

Antibiotic choice (10)

 

Although gram negative and gram positive organisms are pathogens in open fractures, an increase in gram negative infections has been seen during the past 15 years. This increase has been attributed to selection of gram negative pathogens secondary to the extensive use of first generation cephalosporins in prophylaxis, and the possible rise of nosocomial infections.

Grade III injuries also have an increased incidence of gram negative pathogens.

Organisms to cover.

  • Staphylococcus aureus

  • Pseudomonas species

  • Enterococcus

  • Escherichia coli

  • Klebsiella

  • Enterobacter

  • Proteus species

  • Serratia species

Several recommendations for antibiotic prophylaxis exist, consider local policies. In general:

  • Grade I - first-generation cephalosporin

  • Grade II - first-generation cephalosporin +- an aminoglycoside, depending on the level of contamination.

  • Grade III - first-generation cephalosporin with an aminoglycoside.

  • All farm injuries and heavily soil contaminated injuries ensure adequate anaerobic cover, add Metronidazole or Benzyllpenicillin to cover for Clostridium and other anaerobes.

Latest British Orthopaedic Association recommendations (Open fractures of lower limb - Sept 2009).

  • Give antibiotics as soon as possible (within 3 hours).

  • Agent of choice Co-amoxiclav (1.2g 8 hourly), or a cephalosporin (eg cefuroxime1.5g 8 hourly), continued until first debridement (excision).

  • At the time of first debridement, co-amoxiclav (1.2g) or a cephalosporin (such as cefuroxime 1.5 g) and gentamicin (1.5 mg/kg) should be administered and co-amoxiclav/cephalosporin continued until soft tissue closure or for a maximum of 72 hours, whichever is sooner.

  •  Gentamicin 1.5 mg/kg and either vancomycin 1g or teicoplanin 800mg should be administered on induction of anaesthesia at the time of skeletal stabilisation and definitive soft tissue closure. These should not be continued post-operatively. Ideally start the vancomycin infusion at least 90 minutes prior to surgery.

  • True penicillin allergy (anaphylaxis) clindamycin (600mg iv pre-op/qds) in place of co-amoxiclav/cephalosporin. Lesser allergic reaction to penicillin (rash etc) a cephalosporin is considered to be safe and is the agent of choice.

Cochrane review 2004 - Gosselin et al

 

Suggested no value in adding gentamycin to antibiotics and advocate short term gram positive cover eg. cephalosporin.

 

Personally would go with BOA guidance and would add some gram negative cover as it is emerging relatively as a problem as we deal more effectively with the gram positive organisms.

 

 

Occasionally, antibiotic bead spacers may be used for temporary antibiotic delivery and to maintain soft-tissue tension.

 

Gentamycin dosing (10)

Usual dosing of Gentamycin is 3 to 5 mg per kg of body weight, divided into two or three daily doses have been recommended. Aminoglycosides, unlike beta lactams, have concentration dependent killing and postantibiotic effect. The nephrotoxic effects of the aminoglycosides are related to the trough concentration and not the peak concentration. The duration of treatment also is important in developing nephrotoxicity, with an increased incidence when treatment is longer than 7 to 10 days.
Sorger et al showed that once daily dosing with 6mg/kg daily of gentamicin is safe, effective, and cost efficient in the treatment of open fractures when combined with a cephalosporin and aggressive operative debridement and stabilization.

 

Duration of antibiotics

Continue for 2 to 4 days after each operative manipulation.

 

Special cases

 

Grade I fractures

The infection rate following open grade I fractures is very low.

 

  Gustillo Chapman Yang
Grade I 0% 1.9% 0%

 

Yang et al retrospectively reviewed 91 patients with type I open fractures. They questioned the need for debridement and irrigation of stable type I fractures.
Their protocol is that low-energy Type I open fractures do not require operative debridement. The decision, however, remains the responsibility of the on-call surgeon. Initially, Type I open fractures are classified by the size of the soft tissue wound only. The majority of patients with comminuted open fractures with Type I wounds are taken to the operating room emergently. These fractures are reclassified after operative debridement to a higher-grade injury.

 

Tibial fractures

Universally accepted principles of management of open fractures of the tibia include immediate wound debridement and irrigation, skeletal stabilization, repeated wound debridement, and early soft tissue coverage.
The method of bony stabilization remains controversial.

  • Cast immobilization and plate fixation are unacceptable for the management of these injuries, with high rates of nonunion, malunion, and infection. Bach and Hansen compared ORIF with external fixation in a randomized trial and observed a threefold difference in infection rates (ORIF, 35%; external fixation, 13%).

  • External fixation is an excellent initial method of skeletal stabilization in these injured, often unstable patients. However, several studies have demonstrated that their value in the definitive management of these injuries is questionable, with high rates of pin loosening, sepsis, nonunion, and malunion. Edwards et al. reported a 15% infection rate in 202 consecutive grade III open injuries, with more aggresive debridement they reduced it to 9% in the latter half of their study. The concept of early bone grafting was suggested and has since become part of the baseline protocol used by most trauma centers when using external fixation in open tibial fractures. Malunion is certainly more commonly encountered in patients treated with external fixation with rates of up to 20%

  • Locked reamed and unreamed intramedullary nails. The URTN has the theoretical advantage of preservation of the endosteal blood supply and, because it is a solid device, has a lower chance of harboring infection. However, experience with the solid nail has shown significant rates of hardware failure, particularly locking screws, and increased rates of delayed union or nonunion. Several authors have reported satisfactory results using the reamed technique in open tibia fractures. There is only one prospective, randomized study comparing the intramedullary nail in open tibial fractures inserted with or without reaming. Unfortunately, they excluded grade IIIB and IIIC injuries from their study, and found no increased risk of complications after reaming in the less severe open tibial fractures. Grade IIIB and IIIC injuries remains controversial in this respect.

External fixation versus unreamed intramedullary nail

  • Santoro et al. prospectively compared the use of external fixation and nonreamed locked nailing in open tibial fractures. In 65 patients, they reported a higher union rate, shorter time to union, and fewer malunions in the group treated with the unreamed nail. There were only 12 grade IIIB injuries in this study.

  • Henley et al. reported on a series of 174 type II and III open tibial fractures and found a significantly lower incidence of infection and malunion with URTN compared with external fixation. Although the external fixation group required significantly more secondary procedures, time to union was similar in both groups.

  • Tornetta et al. published the early results of a prospective, randomized study comparing external fixation with the URTN in grade IIIB injuries. All 29 patients healed within 9 months, with a similar time to union in both treatment groups. Of interest, 19 of the more severe injuries were prophylactically bone grafted at 6 weeks.

  • Schandelmaier et al. reviewed 32 patients with grade IIIB injuries treated with either external fixation or the URTN. Time to bony union, infection, and nonunion rates were not significantly different between the two groups, but patients treated with the URTN made an earlier return to full weight bearing and a better functional recovery.

Soft tissue cover
Early soft tissue reconstruction is essential and should be performed within 48 hours, usually timed to coincide with the “second look.” Occasionally, it is not possible to achieve this, but every attempt should be made to close the wound within 5 days. Further delay beyond this period leads to increased rates of infection and nonunion. Plastic and reconstructive surgeons must be involved early, at the time of admission or within 24 hours. Inappropriate wound extensions performed by the inexperienced surgeon during the initial debridement may limit further reconstruction options later.

 

Calcaneal fractures (5)

Open calcaneus fractures are devastating injuries with high complication rates. While the use of open reduction and internal fixation for the treatment of long bones with open fractures has been supported by several authors, no such studies exist for the treatment of open calcaneal fractures. Reports of the treatment of calcaneal fractures include a few cases of open fractures, but their numbers are small, and they are not able to separate their results by location of wound, severity of soft tissue disruption, calcaneal fracture type, and definitive treatment.  Heier et al reviewed 42 patients with open calcaneal fractures and suggested that:
Open calcaneal fractures have a high propensity for deep infection despite the use of an aggressive treatment protocol to prevent it. It appears that type-I and type-II open fractures associated with a medial wound can be treated with open reduction and internal fixation. Type-II fractures associated with a wound in another location should be treated with limited or no internal fixation. Type-III open fractures, and especially type-IIIB open fractures, require extensive debridement and prompt soft-tissue coverage as soon as possible. Early internal fixation should be avoided in this subgroup because of the high rates of osteomyelitis and subsequent amputation.
Aldridge et al reviewed open calcaneal fractures and did not find as high a complication rate they agreed that definitive hardware placement at the time of initial irrigation and debridement probably is not warranted: Definitive fracture stabilization can and should wait until soft tissue coverage is achieved.

 

Paediatric cases (9)

Skaggs et al reviewed 104 (1990-1995) open fractures in children and found a 1.0% rate of infection requiring surgical drainage, and a 1.0% rate of soft-tissue infection managed with oral antibiotics alone. The infection rate did not increase with a delay of >6 h between injury and operative debridement. If surgical delay >6 h is necessary for optimal management of a child with an open fracture, it does not appear to increase the rate of infection in children who are started on early intravenous antibiotics. As this series contained only 18 patients with grade III open fractures and 9 patients whose surgery was delayed >24 h, conclusions should not be drawn in these groups.
Song et al (1996) suggested an age related healing response to open tibial fractures with a more benign course in children younger than 11 years.
Wood et al (2001) retrospectively reviewed 87 open tibial fractures in children treated between 1994 and 1999. All patients underwent debridement under anaesthesia within 6 to 20 hours of injury and received antibiotics.
Following debridement, 56 children (42 type-I and 13 type-II fractures) were treated in above-knee plaster casts. All fractures healed in four to eight weeks. Shortening occurred in two patients and two developed 10° of valgus.
External fixation was used in 19 patients (four type-II and 15 type-III fractures). Delayed split skin grafts were done in 12 patients and muscle pedicle flaps in three. To treat compartment syndrome, fasciotomy was performed in two children. Owing to vascular injuries, it was necessary to amputate the legs of two children. No deep infections developed but there were three superficial infections and 12 cases of pin-tract sepsis. Fixators were removed after three to six weeks, and above-knee casts applied until union occurred at 6 to 10 weeks. Nonunion in two patients was treated by bone graft. Valgus deformity occurred in two patients and shortening of 1 cm to 2 cm in three.
Open tibial fractures have a more benign outcome in children than in adults. There were few complications related to vascular injury and nonunion.

 

Irrigation (7)

Despite a lack of clinical studies, the efficacy of high-pressure irrigation in decreasing the bacterial load in soft tissues has been well established in both in vivo and in vitro experimental models. The advent of pulsatile irrigation has further improved bacterial removal from soft tissues. Several authors have noted the complications associated with high-pressure pulsatile irrigation for fracture debridement. Dirschl and colleagues, in an in vivo study on rabbits, found that high-pressure pulsatile lavage resulted in visible damage at the fracture site and resulted in delayed healing. Other investigators examined the effects of high-pressure pulsatile irrigation on contaminated human tibiae in an in vitro model. They reported that high-pressure irrigation of tibiae resulted in significant macroscopic bony damage and carried surface bacteria into the intramedullary canal. In a subsequent study, these investigators have shown that low-pressure irrigation results in significantly less macroscopic and microscopic bone damage and is as efficacious as high-pressure lavage in removing bacteria within 3 hours of contamination. However, after a 3-hour delay in irrigation, low-pressure lavage was ineffective in removing bacteria.

 


References

 

1. GUSTILO, RAMON B. MD; ANDERSON, JOHN T. MD PREVENTION OF INFECTION IN THE TREATMENT OF ONE THOUSAND AND TWENTY-FIVE OPEN FRACTURES OF LONG BONES: RETROSPECTIVE AND PROSPECTIVE; JBJS, Vol. 58-A, No. 4, pp. 453–458, June 1976
 

2. Harley, Brian J.; Beaupre, Lauren A.; Jones, C. Allyson; Dulai, Sukhdeep K.; Weber, Donald W. The Effect of Time to Definitive Treatment on the Rate of Nonunion and Infection in Open Fractures. Journal of Orthopaedic Trauma. 16(7):484-490, August 2002.
 

3.Yang, Edward C. MD; Eisler, Jesse MD Treatment of Isolated Type I Open Fractures: Is Emergent Operative Debridement Necessary? Clinical Orthopaedics & Related Research. 1(410):289-294, May 2003.
 

4. HEIER, KEITH A. MD; INFANTE, ANTHONY F. DO; WALLING, ARTHUR K. MD; SANDERS, ROY W. MD OPEN FRACTURES OF THE CALCANEUS: SOFT-TISSUE INJURY DETERMINES OUTCOME. JBJS - A Vol 85-A(12):2276-2282, December 2003.
 

5.Aldridge, , Julian M. III MD; Easley, Mark MD; Nunley, James A. MD Open Calcaneal Fractures: Results of Operative Treatment. Journal of Orthopaedic Trauma. 18(1):7-11, January 2004.
 

6. Musgrave, Douglas S. MD; Mendelson, Stephen A. MD Pediatric orthopedic trauma: Principles in management. Critical Care Medicine. Critical Care Considerations in Pediatric Trauma. 30(11) Supplement:S431-S443, November 2002.

 

7. Bhandari, Mohit MD, MSc; Guyatt, Gordon H. MD, MSc; Tornetta, Paul III, MD; Swiontkowski, Marc F. MD; Hanson, Beate MD; Sprague, Sheila BSc; Syed, Amena BSc; Schemitsch, Emil H. MD Current Practice in the Intramedullary Nailing of Tibial Shaft Fractures: An International Survey. Journal of Trauma-Injury Infection & Critical Care. 53(4):725-732, October 2002.
 

8. Shannon, Fintan J. AFRCSI; Mullett, Hannan FRCSI; O'Rourke, Kieran FRCSI Unreamed Intramedullary Nail versus External Fixation in Grade III Open Tibial Fractures. Journal of Trauma-Injury Infection & Critical Care. 52(4):650-654, April 2002.
 

9.Skaggs, D. L. M.D.; Kautz, S. M. M.D. *; Kay, R. M. M.D.; Tolo, V. T. M.D. Effect of Delay of Surgical Treatment on Rate of Infection in Open Fractures in Children. Journal of Pediatric Orthopedics. 20(1):19, January/February 2000.
 

10.Sorger, Joel I. MD; Kirk, Patrick G. MD; Ruhnke, Christopher J. MD; Bjornson, Stephen H. MD, PhD; Levy, Martin S. PhD; Cockrin, James PhD; Tang, Peter AB; Once Daily, High Dose Versus Divided, Low Dose Gentamicin for Open Fractures. Clinical Orthopaedics & Related Research. 1(366):197-204, September 1999.
 

11.Song, Kit M. M.D.; Sangeorzan, Bruce M.D.; Benirschke, Steve M.D.; Browne, Richard Ph.D.; Open Fractures of the Tibia in Children. Journal of Pediatric Orthopedics. 16(5):635-639, September/October 1996.
 

12.Wood, G. M. COMPOUND FRACTURES OF THE TIBIA IN CHILDREN. JBJS - B Volume. 83-B Supplement I:5, 2001.

 

13. Gosselin RA, Roberts I, Gillespie WJ. Antibioticsfor preventing infection in open limb fractures.
Cochrane Database Syst Rev. 2004;1:CD003764.
 


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