➢ Reported infection rates following severe open fractures of the lower extremity sustained in combat have varied widely, from 23% to 85%. The infection rates have been either similar to or higher than those reported in the civilian trauma literature.
➢ Deployed surgeons have increased the frequency of fasciotomy procedures for limbs with or at risk for clinical compartment syndrome. The long-term sequelae of compartment syndrome and fasciotomies are not clearly defined.
➢ The definition of the term late amputation has varied in the literature, and studies have not consistently included information on the causes of the amputations.
➢ Preclinical and clinical translational studies on the reduction of the rates of infection and other limb morbidities are needed to address the acute care of combat extremity wounds.
Musculoskeletal injuries are the most common war wounds, and injured service members typically have >1 musculoskeletal wound following combat injury1-3. Compared with extremity injuries in the civilian population, injuries sustained in combat are more often due to high-energy explosions, have a greater degree of contamination, and have a different treatment timeline in the operating room environment4. With the frequency of musculoskeletal wounds and the high severity of such prevalent injury patterns, it is no surprise that the care of musculoskeletal wounds consumes the majority of war-related health-care resources5. Long-term disability following combat injury is predominantly due to musculoskeletal sequelae6.
Survival after a combat injury has improved even during the course of the current wars. This improvement is to the credit of translational applications of combat-casualty-care technologies and improved acute and critical care within the deployed military medical system7,8. In fact, the Joint Trauma System (JTS) housed at the United States Army Institute of Surgical Research (USAISR) has supported a trauma registry (Department of Defense Trauma Registry [DoDTR]) for the combat theater where recent military operations have taken place in Iraq, Afghanistan, and other parts of the world. The DoDTR supports prospective quality and process-improvement evaluations. Research studies and process-improvement efforts involving the use of DoDTR data have informed the content of 45 clinical practice guidelines to optimize combat-casualty care9,10. Published studies involving data from the DoDTR have demonstrated the high frequency of musculoskeletal wounds1-6, but only a small number of the current clinical practice guidelines are directed to the care of these musculoskeletal injuries.
The synthesis of current literature on orthopaedic war trauma falls into 2 broad categories: (1) defining the injuries and resultant disabilities1-3,5,6 and (2) attempting to define outcomes and recommending rehabilitation, mental-health services, and multidisciplinary approaches to maximizing outcomes11. While general surgery and critical-care specialties have capitalized on the JTS to develop guidelines for care, opportunities still exist to improve the acute care of musculoskeletal war wounds in orthopaedics12. The purpose of the present review is to examine the current literature on military orthopaedic care of high-energy open fractures in light of the civilian trauma experience. This review will identify where additional preclinical and clinical studies have an opportunity to improve acute combat orthopaedic care. Specifically, the recent military experience with severe lower-extremity fractures commonly caused by explosions and with the various treatments and outcomes for infection, compartment syndrome, and late amputation are presented.
PubMed and Ovid literature searches were conducted for research published between October 2001 and July 2015 with use of the search terms combat fracture, blast injury fracture, compartment syndrome, fasciotomy complications, combat fasciotomy, late amputation, limb salvage, and combat infection. Articles were considered if they discussed lower-extremity war injuries sustained by either United States (U.S.) or United Kingdom (U.K.) forces, specified the location of fracture, and differentiated among mechanisms of injury. Included articles provided data on injuries caused by explosions; severe lower-extremity injuries of the tibia, foot, and/or ankle; and infection, compartment syndrome, and/or treatment with reconstruction or amputation.
The Lower Extremity Assessment Project (LEAP) defined the types of injuries classified as “severe lower-extremity trauma” in the civilian trauma literature, including traumatic amputations, Gustilo and Anderson13 grade-III open fractures, dysvascular limbs, major soft-tissue trauma such as crush or degloving injuries, and severe open injuries of the foot and ankle14. For the purpose of this review, open fractures meeting these criteria were included; traumatic amputations, vascular injuries without fracture, and soft-tissue degloving without fracture were excluded. For infection, we included reports describing any deep soft-tissue or bone infection requiring surgical debridement. For compartment syndrome, we included reports describing any soft-tissue injury or abnormality treated with prophylactic or therapeutic fasciotomy. For amputation, we included reports describing any limb amputation performed for any reason following a period of attempted limb reconstruction. Limb salvage was defined as any limb reconstruction following an injury that did not result in amputation.
To our knowledge, the largest study of U.S. forces with combat tibial fractures was a retrospective database study of 192 subjects with 213 grade-III open tibial fractures that had been sustained between 2003 and 200715. In that study, 57 open tibial fractures (27%) were associated with a deep infection and 35 (16%) were associated with osteomyelitis. Although 172 open tibial fractures (81%) were due to an explosion, that mechanism alone was not associated with infection. Infection was associated with amputation, a greater number of surgical procedures, and delayed time for fracture-healing. An analogous registry-based study of U.K. allied forces who sustained open tibial fractures in combat between 2006 and 2010 identified 49 patients (57 open fractures), 35 (71%) of whom were injured by an explosion16. Among those with fractures, 12 (24%) developed an infection. Infection was associated with poor bone-healing outcomes. The location of infection (i.e., soft tissue or bone) was not specified. There was no reported association between the explosion mechanism and the outcome of infection. In a report on 35 open tibial fractures that were treated at a single U.S. military facility, 24 fractures (69%) were classified as Gustilo-Anderson grade-III open fractures and 27 (77%) were due to explosion17. Twenty-seven fractures were associated with infection. Twenty-four of these infections were due to osteomyelitis, and only 3 involved the deep soft tissues alone.
In a British registry study of patients who had been injured between 2003 and 2007, 37 (63%) of 59 mangled lower-extremity injuries were injured by explosions and 50 (85%) had development of an infection18. However, the injury mechanism was not associated with infection. That study included a variety of lower-extremity wounds; however, details about the types of fractures other than tibial fractures were not given. Dickens et al. conducted a registry and medical-record review of 102 combat-associated open calcaneal fractures that had been treated at a single U.S. military treatment facility between 2003 and 201019. Forty-six injuries (45%) were classified as Gustilo-Anderson grade IIIB or IIIC, 91 (89%) were caused by an explosion, and 47 (46%) were associated with an infection. A higher Gustilo-Anderson grade and multiple fractures in the same foot were associated with infection (Table I).
The accepted tenets of thorough wound debridement, irrigation, and early antimicrobial administration are central to the care of open combat wounds, just as they are in civilian trauma practice20,21. These tenets were confirmed in published guidelines regarding the control of combat wound infection22. However, in even the most recent civilian trauma literature, infection rates following open fractures have ranged from 23% to 40%23-27, with the risk of infection increasing with the Gustilo-Anderson grade25-27. Therefore, a persistent issue in open fracture care is the problem of infection. With the presence of severe, contaminated wounds, the battlefield is a potential place to see how new wound-care applications perform under the worst injury and wound conditions.
For example, negative-pressure wound therapy (NPWT) is a type of wound dressing involving a reticulated sponge and vacuum apparatus to provide continuous wound suction. This technique is now endorsed by the JTS as an option for wound dressing21. Early experiences in the combat theater have suggested that NPWT is a practical option and is even preferred by the services that provide air evacuation of combat casualties28-30. The civilian trauma literature contains a number of studies on NPWT in the setting of traumatic wounds31. The current expert consensus regarding both soft-tissue traumatic wounds and open-fracture wounds is that NPWT should be considered until delayed primary closure is possible or as a means of potentially reducing the complexity of final wound coverage if closure is not initially possible31. A recent systematic review and meta-analysis of studies on grade-IIIB tibial fracture wounds treated with NPWT suggested that the acute use of NPWT reduced infection rates and led to fewer flap procedures32. However, several studies have demonstrated no difference in infection rates for open fracture wounds treated with NPWT as opposed to gauze dressing33-35. If the wound treatment of choice was NPWT, the use of NPWT did not justify a delay in closure or coverage of open fracture wounds because prolonged time to wound coverage was associated with more infections34-37. Additional study is needed to determine if the application of NPWT alone or in concert with other wound treatments is a beneficial early wound-treatment option that can support a reduction in the rate of combat wound infection.
Compartment syndrome most often occurs following high-energy trauma and can occur in the setting of open fractures. As such, combat extremity wounds caused by high-energy mechanisms are associated with a risk of compartment syndrome. The current clinical practice guidelines recommend early and complete fasciotomies for the treatment of clinical compartment syndrome and prophylactic fasciotomies for at-risk limbs in patients who will be evacuated or otherwise away from monitoring and a surgical environment for some period of time38.
A study on complications of compartment syndrome following combat injury in 336 patients with 643 fasciotomies demonstrated that delayed fasciotomies (defined as fasciotomies performed after a portion of the medical evacuation process rather than as the initial treatment event) and fasciotomies necessitating revision were associated with higher rates of muscle excision, amputation, and mortality39. The authors concluded that early fasciotomy at the time of the initial treatment event, even for prophylactic purposes in limbs at risk, carries fewer serious complications than delayed fasciotomy. This finding helped to inform a change in practice via an educational program and revision of clinical practice guidelines. Following the work by Ritenour et al.39, a subsequent performance-improvement effort conducted by the Joint Trauma System (JTS) showed that fasciotomy rates increased 500% and were associated with decreases in the rates of mortality and revision fasciotomy40,41. We are not aware of any other studies in the current military literature examining the frequency of fasciotomy-related complications.
The civilian trauma literature included a small number of studies that sought to define complication rates and limb outcomes after compartment syndrome42-46. Local complications included sensory deficits, pain, decreased motion and strength, and limb-swelling42-44. Delays in wound closure or skin graft placement were associated with local symptoms whereas delayed primary wound closure was not44. Residual problems may not affect patient-reported functional outcomes but may affect quality of life, especially in the setting of a concern regarding cosmesis45,46.
Regarding more serious systemic complications, historical retrospective results have indicated that delayed fasciotomies are associated with high infection rates, death, and amputations due to local infection47,48. Farber et al. reported that early fasciotomies following vascular trauma were associated with lower rates of infection, shorter hospital stays, and lower amputation rates compared with the findings after late fasciotomies49. Such data could be used to support the use of early or prophylactic fasciotomies as recommended by Ritenour et al.39. However, higher rates of local complications and difficulties with skin closure have been identified in patients who underwent prophylactic fasciotomies50.
On the basis of the extant literature, it is unclear whether these long-term sequelae result from the fasciotomy itself or from the disease state of compartment syndrome, and differentiating between complications due to fasciotomy and side effects of compartment syndrome is difficult with use of observational retrospective data. However, wound complications that add to morbidity might be reduced with improvements in closure techniques, local tissue edema control, or novel grafting techniques. In addition, applications to address muscle loss and fibrosis resulting from the disease and/or muscle debridement are needed.
In a retrospective study of the same tibial fracture cohort studied by Burns et al.15, Huh et al. stratified injury characteristics according to the treatment outcomes of limb salvage, early amputation, and late amputation51. They defined late amputation as an amputation occurring >90 days after an injury, which was consistent with the LEAP designation of late amputation52. Eleven patients (5.2%) underwent late amputation, and amputated limbs were more likely to have a deep soft-tissue infection, osteomyelitis, and/or failure of soft-tissue coverage. While these associations could not be directly linked to the cause of amputation, the authors concluded that infection and the failure of soft-tissue coverage contributed to late amputation.
Helgeson et al. reported on the causes of late amputation in a study of 22 patients who had been managed at 1 U.S. Army medical treatment facility53. The patients exhibited a wide variety of injury locations in both the upper and lower extremities. Details regarding the injury itself were not provided. While most patients had >1 reason to undergo a late amputation, the most common reason was chronic pain (12 patients; 55%). Infection was reported as a contributing factor in the decision to proceed with late amputation in 7 patients (32%). Casey et al. reported on 16 patients with a variety of combat-related lower-extremity injuries who were managed in a multidisciplinary limb-preservation clinic at a single institution between 2010 and 201354. Eleven of the 16 patients had been injured by an explosion, and 10 had a late amputation. Six of the 16 patients had a deep soft-tissue infection and/or osteomyelitis that contributed to the late amputation, and 8 of the 16 patients had chronic pain. The authors concluded that the high rate of amputations in their study was likely due to the complex patient population referred to the limb-preservation clinic for care and the resultant inclusion of patients with the most difficult clinical situations.
Dickens et al., in a review of 89 patients with 102 combat-related open calcaneal fractures, reported that a late amputation was performed after 15 fractures (15%)19. While amputation in general was associated with concomitant foot fractures, plantar wounds, and infection, no specific injury characteristic or mechanism of injury was associated with late amputation. The causes of late amputation were not reported. In a retrospective database study of 89 lower-limb injuries sustained by 63 U.K. service members, six limbs (6.7%) were amputated because of chronic pain55. While injury characteristics were not reported for the late amputees specifically, amputation in general was associated with hindfoot injury, open fracture, and vascular injury (Table II).
Reports in both the military and civilian literature have demonstrated a wide range of late amputation frequencies. Infection and flap failure have been commonly reported as causes of late amputation56-60. Many studies on complex open injuries have not specified the underlying cause of late amputation, even when the proportion of late amputations has been reported61. In addition, studies have not always specified the exact timing between the injuries and the amputation. Consideration of timing is important because initial treating physicians may employ scoring systems, such as the Mangled Extremity Severity Score (MESS), to guide clinical decision-making regarding early amputation62. While the utility of MESS and other scoring systems for both civilian and military injuries has been debated, the use of these systems highlights how the decision regarding early versus late amputation depends on different decision-making processes63,64.
The LEAP Study Group set the precedent for dubbing amputations performed after 12 weeks post-injury as “late.” This definition differentiated amputations performed after an attempted period of reconstruction and those performed early for the purposes of acute wound or fracture care52. Not all studies have used this same definition of late amputation. Other studies have used terms such as delayed amputation or secondary amputation to designate the amputations performed at various time points following injury or attempted reconstruction65,66. This variation in definitions made these studies difficult to compare. Furthermore, comparisons between studies evaluating amputation frequencies are difficult because the clinical and patient-driven variables that contribute to amputation are not always reported.
A growing number of studies have attempted to determine which patient population (i.e., patients with amputations or patients with reconstructed limbs) had better outcomes. The LEAP Study Group, in a prospective cohort study, compared patient-reported outcomes for those who underwent limb salvage and those who underwent amputation. Both groups reported lower quality of life compared with population standards, but the findings were similar for the 2 groups52,67. The Military Extremity Trauma Amputation/Limb Salvage (METALS) study also demonstrated that patients managed with amputation and those managed with limb salvage had lower self-reported outcomes compared with population norms; however, in that study, the scores for patients managed with amputation were higher than those for patients managed with limb salvage68. The civilian literature has demonstrated mixed results as to whether complication rates are different for patients with amputations and those with salvaged limbs58,69-73. Mental-health outcomes also have varied. The METALS study demonstrated that the rate of posttraumatic stress disorder (PTSD) was lower in patients who had been managed with amputation than in those who had been managed with limb salvage68, whereas a similar study from the U.K. demonstrated no difference between the groups74. Cross et al., in a study of 115 patients who had sustained a combat-related type-III open tibial fracture, reported that return-to-duty rates were not different between patients who had been managed with amputation and those who been managed with limb reconstruction75.
To date, the current military literature has not thoroughly described the clinical and patient-driven reasons that a patient with a reconstructed limb opts for an amputation at any time following an injury. Addressing this gap will provide evidence that will inform the ongoing amputation-versus-limb-salvage debate by helping to define, from the patient’s perspective, what constitutes “successful” and “failed” limb salvage. It is also important to define what constitutes a “successful” amputation. While the present review suggests that infection, soft-tissue coverage problems, and chronic pain often contribute to late amputations, patients who undergo late amputations may have these persistent clinical problems even after the amputation76-79. Additional research is needed to address these gaps in knowledge.
The major limitation of the current literature on combat-associated infection, sequelae of compartment syndrome, and late amputations is that the majority of research is based on retrospective data. The two most comprehensive articles on open tibial fractures both used combat registry data15,16. However, both the U.S. and U.K. militaries have established combat trauma registries that have contributed valuable information to a variety of clinical practice guidelines. For example, the DoDTR has been fully functional since 2004 and collects real-time data submitted by trauma nurses9,10. The U.K. has a similar combat trauma registry. While the registry studies were prone to errors typical of such data repositories, such as missing data and incorrect coding of diagnoses and treatments, the current combat trauma registries used for the preponderance of those studies were the most comprehensive and thorough repositories of combat injury data to date.
In addition, both infection and late amputation are outcomes that can occur at very late time points following injury. The literature is limited by the duration of time between the injuries and the conduct of the studies. For example, Napierala et al.80 followed the same cohort described by Burns et al.15 for a longer period of time and collected additional longitudinal infection data. The reported infection rates (40% in the study by Napierala et al.80, compared with 27% in the study by Burns et al.15) were very different. This difference may represent an error of missing data on infection at the time of the first publication, but it also could indicate that, because of the longer duration of follow-up, the later report identified more patients who went on to develop late infection. The implication is that some adverse outcomes impose cumulative morbidity on any given study cohort as time passes. This is also true with regard to late amputation, which may be associated with infection and can occur on an elective basis at any time following limb reconstruction.
The current literature on combat injuries of the lower extremity suggests that explosions are the most common mechanism of injury encountered by deployed service members. While exposure to explosion is not directly associated with a particular limb-injury outcome following fracture, the explosion mechanism does contribute to more severe injuries in military populations as compared with the lower-limb injuries encountered in the civilian trauma population. For military service members with open fractures of the tibia, foot, and ankle, infection is a common complication associated with more severe soft-tissue injury. Deployed surgeons are performing more fasciotomies for limbs at risk than earlier in the current wars. However, outcomes and complication rates are not well established for compartment syndrome or for the fasciotomy procedure itself. The causes of late amputations are not always clear; however, infection and pain are known to drive the decision of injured service members to pursue a late amputation.
The present review highlights some current clinical questions that are ripe for translational study. First, what is the best way to manage and transport patients who have severe open fracture wounds in order to minimize infection? While NPWT appears to be a promising wound-care technique, additional study is warranted on how to best augment the standard of care for battlefield medicine in order to accommodate for injury severity, contamination, and treatment and evacuation timelines. Second, what is the best way to treat fasciotomy wounds and the late sequelae of compartment syndrome? This question requires a broader understanding of compartment syndrome detection, the indications for fasciotomy, and the side effects of both the disease and the treatment. Last, what is the best way to select limbs for salvage and to optimize the reconstruction of injured tissues? This question must explore not only the patient’s perspective but also the variety of causes that lead to late amputation.
Investigation performed at the United States Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, Texas
Disclosure: The authors indicated that no external funding was received for any aspect of this work. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article.
Disclaimer: The opinions contained herein are the views of the authors and are not to be construed as the views of the Department of the Army or Department of Defense.
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