Management of Mangled Extremities and Orthopaedic War Injuries

SUPPLEMENT ARTICLE Management of Mangled Extremities and Orthopaedic War Injuries Todd O. McKinley, MD,* Jean-Claude D’Alleyrand, MD, LTC, MC,†‡ Ian Valerio, MD, CDR, MC, USNR,§ Seth Schoebel, PhD,k Kevin Tetsworth, MD,¶ and Eric A. Elster, MD, CPT, MC, USN‡ Summary: In 16 years of conflict, primarily in Iraq and AfghaniDownloaded from http://journals.lww.com/jorthotrauma by BhDMf5ePHKbH4TTImqenVI1NGeaZoDmODGCf0Y0DDjIxRYR++mMStvVUEQWskLjafqfYo8MgecY= on 05/11/2018 stan, wounded warriors have primarily been subjected to blast type of injuries. Evacuation strategies have led to unprecedented survival rates in blast-injured soldiers, resulting in large numbers of wounded warriors with complex limb trauma. Bone and soft tissue defects have resulted in increased use of complex reconstructive algorithms to restore limbs and function. In addition, in failed salvage attempts, advances in amputation options are being developed. In this review, we summarize state-of-the-art limb-salvage methods for both soft tissue and bone. In addition, we discuss advances in diagnostic methods with development of personalized clinical decision support tools designed to optimize outcomes after severe blast injuries. Finally, we present new advances in osteointegrated prostheses for above-knee amputations. Key Words: war injuries, wounded warriors, limb salvage, computational biology (J Orthop Trauma 2018;32:S37–S42) INTRODUCTION Fractures are the most common injuries sustained by wounded warriors (WWs).1,2 The complex constellations of orthopaedic and nonorthopaedic injuries frequently mandate that these WWs undergo staged interventions in which decisions on the sequence, timing, and type of procedure must be guided by the type of injuries and patient’s systemic response.3–9 The complexity of staged treatment is further Accepted for publication December 11, 2017. From the *Department of Orthopaedic Surgery, Anatomy and Cell Biology Indiana University School of Medicine, Indianapolis, IN; Departments of †Orthopaedic Traumatology, and ‡Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD; §Departments of Plastic Surgery, Orthopaedic Surgery and General Surgery, The Ohio State University School of Medicine, Columbus, OH; kDepartment of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD; and ¶Department of Orthopaedics, The Royal Brisbane Hospital; Brisbane, Australia. The authors report no conflict of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.jorthotrauma. com). Reprints: Todd O. McKinley, MD, Department of Orthopaedic Surgery, Anatomy and Cell Biology, IU Health Methodist Hospital MPC-1, 1801 North Senate Boulevard, Suite 535, Indianapolis, IN 46202 (e-mail: [email protected]). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/BOT.0000000000001121 magnified in WWs who are treated at a series of military medical facilities along evacuation lines from the battlefield back to domestic hospitals.10–12 Life-saving interventions are the initial care priorities, and skeletal stabilization is often temporary using damage control orthopaedics. However, early total care of major fractures can improve outcomes under certain conditions.8,9,13,14 Decisions regarding the timing of orthopaedic procedures are currently based on the physiologic condition of the patient, resource availability, and the expected magnitude of the physiologic insult of the intervention.6,9,15–18 However, this treatment decision is usually based on the collective anecdotal experience of the surgical team. Improvements in evacuation and treatment strategies of the soldiers sustaining combat injuries have resulted in unprecedented survival rates.10–12,19 An unintended consequence of improved survival of WWs is an increase in organ dysfunction and wound complications, all of which can lead to severe orthopaedic complications. Surgical interventions are frequently staged in an effort to minimize complications that typically affect multiply injured patients.3,4 Many of these complications relate to not only the magnitude of the initial immune response but also to the immune response to subsequent interventions. The “additional hits” of surgical procedures can amplify an already dysfunctional immune response.20 An aberrant immune response is manifested by an excessive and sustained systemic inflammatory response syndrome that puts patients at risk of multiple organ dysfunction syndrome.21,22 Patients who develop multiple organ dysfunction syndrome are at high risk of orthopaedic complications. Collectively, staged orthopaedic interventions have evolved to try to minimize longer term complications and poor function in badly injured soldiers. To improve outcomes and limit complications, surgical techniques have evolved over the past 15 years of conflict. Military surgeons have increasingly recognized and leveraged staged interventions, not only out of necessity and resource availability but also by increasingly recognizing indications for staged limb management. Increased survival has been accompanied by increased wound burden in extremity trauma. Accordingly, surgeons have investigated novel approaches to facilitate healing of complex wounds with composite tissue deficits including skin, muscle, and bone. Finally, clinicians have increasingly recognized how systemic injury can have devastating effects on orthopaedic injuries. However, the complexities of the immunologic response that J Orthop Trauma  Volume 32, Number 3 Supplement, March 2018 www.jorthotrauma.com | S37 Copyright Ó 2018 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. McKinley et al J Orthop Trauma  Volume 32, Number 3 Supplement, March 2018 occurs after injury has made it difficult to quantify injuryassociated effects of multisystem trauma by linearreductionist types of models leading clinicians to adopt bioinformatics approaches to better understand the burden of injury. The primary objective of this symposium was to present a composite update on managing severe extremity trauma in WWs who have been treated in Operation Iraqi Freedom and Operation Enduring Freedom. Two of our speakers were military surgeons with extensive experience in treating complex extremity trauma. They discussed orthopaedic and plastic surgical management of complex extremity trauma. Our third speaker presented data from a novel bioinformatics approach to improve outcomes in soldiers sustaining severe blast injuries and complex extremity trauma. Bioinformatics continues to evolve as a powerful tool that incorporates patient-specific information to optimize treatment decisions. This approach has been successfully implemented in WWs sustaining blast injuries to their limbs. Finally, our fourth speaker has been integral in the development of osteointegrated prostheses for patients sustaining above-knee amputations. These methods hold exceptional potential to improve outcomes in WWs and all patients who sustain above-knee amputations. ADVANCES IN ORTHOPAEDIC MANAGEMENT OF WAR EXTREMITY INJURIES DURING RECENT CONFLICTS Combat-related extremity injuries typically have wide, evolving zones of injury punctuated with highenergy open fractures with bone and soft tissue loss. These injuries have resulted in evolution of reconstructive, regenerative, and amputation methods to improve outcomes. Wound expansion after injury is commonplace and results in higher infection rates than in civilian injuries. Postinjury complications are relatively common, as are large composite tissue defects that frequently pose significant challenges with respect to reconstruction. Recently, basic scientific evidence to guide decisions pertaining to wound management has emerged. For example, dehiscence of combat wounds has been associated with vascular injuries and with systemic and wound inflammation, as measured by increased levels of procalcitonin and IL-6 in either serum or wound effluent. However, the appropriate timing of closure of these wounds is generally left to the surgeon’s judgment. Skin management often plays a pivotal role in outcomes after war injuries. When closing the skin envelope, primary closure is preferable to split-thickness skin grafting (STSG) in weight-bearing areas because of superior mechanical properties. Thus, primary closure with native skin should be prioritized while closing lower extremity wounds and amputation stumps. In the lower extremities, it is typically preferable to accept modest skeletal shortening because a slightly shorter limb with a good distal soft tissue envelope is preferable to a longer limb with poor skin coverage. Collagen dermal substitutes are routinely used before grafting, particularly when grafting over high-shear areas or if revision S38 | www.jorthotrauma.com surgeries are remotely anticipated.23,24 These substitutes facilitate a more robust wound closure compared with STSG. Another common denominator leading to skin problems is heterotopic ossification (HO). HO has recently been associated with persistent methicillin resistant staphylococcus aureus infection25 and with systemic and wound inflammation.26,27 Another, less common revision surgery in amputees is targeted muscle reinnervation, a method for improving myoelectric prosthetic control28 and potentially for decreasing neuromarelated pain.29 Often, primary closure and STSG are insufficient to obtain closure. Rotational or free flaps are the standard solutions for this,30 but a paucity of local donor tissue or vasculature may rule these out as options. One possible solution is to temporarily shorten and angulate the fracture to allow primary wound closure. Once the wound has healed, the fracture is gradually reduced with a ringed external fixator and restored through distraction osteogenesis (see Figure, Supplement Digital Content 1, http://links.lww.com/JOT/A284 ). 31–34 Distraction osteogenesis can also address segmental bone loss, as can bone grafting with or without the use of a spacer-induced membrane (IM). This latter technique35 is up to 90% effective.36 The IM is not only structural but also has osteoinductive properties during the first 4–8 weeks.37 Recent investigation into optimizing the efficacy of the IM technique suggests that scraping the exudative inner layer of the membrane can significantly increase the amount of bone formation.38 Some of the major clinical challenges after reconstruction include posttraumatic osteoarthritis and neuromuscular deficits; however, early results with a custom exoskeletal orthosis, paired with a high-intensity sports rehabilitation program, have allowed many military patients with highenergy lower extremity trauma to resume athletic activity, with up to 20% returning to deployment status.39,40 There is also evidence that suggests that US military patients do better with amputation, with better functional scores and return to vigorous activity compared with civilians.41,42 These results must be interpreted with caution, however, because there are many potential differences between military and civilian patients, such as preinjury function, peer support, socioeconomic factors, and access to advanced prosthetics and rehabilitation. ADVANCES IN SOFT TISSUE INJURY RECONSTRUCTION DURING RECENT CONFLICTS Recent conflicts have commonly used improvised explosive devices and explosive munitions. These blast and fragmentation weapons have directly contributed to high rates of orthoplastic injuries because trauma to the musculoskeletal system remains the most common result of exposure to such destructive devices.43,44 Given the complex nature of injuries resulting from such devices, refinements in soft tissue reconstruction and restoration have become critical to achieving successful definitive soft tissue coverage while also optimizing the functional outcomes. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. Copyright Ó 2018 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. J Orthop Trauma  Volume 32, Number 3 Supplement, March 2018 ADJUNCTS TO THE RECONSTRUCTIVE LADDER/ELEVATOR Exposure to blast and fragmentation devices often results in orthoplastic injury patterns, exhibiting massive composite-type tissue defects. Careful evaluation of soft tissue perfusion coupled with serial debridement of soft tissue injury is of paramount importance to decontaminate tissues while determining the actual amount of destruction and structures involved in the composite and soft tissue loss(es). Once the exact tissue restoration needs are determined, the soft tissue reconstruction measures can be achieved. Although the reconstructive ladder/elevator contains common surgical methods to be used in soft tissue coverage—eg, skin grafting, flaps, and microsurgical free-tissue transfers— application of various regenerative medicine adjuncts to these measures has increasingly contributed to the improved outcomes in orthoplastic reconstruction. Thus, the establishment of the “hybrid” reconstructive ladder, which incorporates traditional autologous surgical reconstruction techniques with allograft and man-made regenerative medicine adjuncts, has been an important step in addressing severe soft tissue injuries caused by military-related trauma (see Figure, Supplement Digital Content 2, http://links.lww.com/JOT/A285 ).23,45–47 Autologous adipose tissue grafts, mesenchymal stem cell therapies, nerve autografts/allografts/wraps, dermal regenerate templates (DRTs), and extracellular matrix scaffolds have been incorporated into the “hybrid” reconstructive ladder.23,44–49 DRTs AND EXTRACELLULAR MATRICES DRTs and extracellular matrices (ECMs) have been illustrated to aid in creating a neovascularized soft tissue bed by way of providing a biologic scaffold to support cellular invasion and graft incorporation.45,48 These regenerative medicine tools can be used for soft tissue restoration of full and partial23,47 thickness traumatic and/or burn injuries as well as wounds exhibiting hypovascular structures and/or exposed vital structures such as tendons, nerves, blood vessels, cartilage, and/or bone. These regenerative medicine soft tissue coverage adjuncts have proved to aid in the preservation of residual limb length while providing more stable soft tissue durability and contouring, which has improved function and comfort with prosthetic device wear.23,46,48 Furthermore, DRTs and ECMs have proven to be intimately important in sustaining certain spray skin and cellular skin transplant applications for skin regeneration and restoration strategies that have been applied to combat soft tissue injuries.45,50 Current and future investigational soft tissue restoration strategies have expanded to incorporate 3D cell bioprinting to in vivo and in vitro–based bioscaffolds, DRTs, and ECMs to restore partial and full thickness soft tissue defects, provide skin restoration strategies, and serve as more functional composite soft tissue replacements. NERVE RESTORATION AND REGENERATION Blast- and fragmentation-type injuries have high rates of peripheral nerve injuries. Given the nonavailability of Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. Mangled Extremities and Orthopaedic War Injuries adequate autologous nerve in certain combat casualties, increased application of peripheral nerve reconstructions using nerve allografts and nerve coaptation wraps/tubes has become more common. Goals of nerve repair not only focus on tension-free coaptation, especially critical to segmental nerve repairs, but also on distal nerve transfers to preserve the motor end units and neuromuscular junction function until nerve regeneration can be successful. In cases where nerve repair is not feasible, nerve and tendon transfers are critical to improving extremity function. In residual limb cases, targeted reinnervation, implantable electrodes, and improved bioprosthetics have aided to restore certain functional goals for our WWs. In select residual limb cases, hand and/or limb allotransplantation has provided restoration of limbs, encouraging functional gains and nerve regeneration in certain cases. INTEGRATING COMPUTATIONAL CLINICAL DECISION-MAKING TOOLS TO OPTIMIZE OUTCOMES IN SEVERE EXTREMITY WOUNDS: EXPERIENCE OF THE SURGICAL CRITICAL CARE INITIATIVE Management of war wounds and civilian traumatic injuries is a complex endeavor. The current practice of managing battle-injured warriors is dependent on visually guided traditional treatments and clinical decision making. The Surgical Critical Care Initiative (SC2i) currently estimates that traditional approaches for complex wound management are 85% successful in predicting successful wound closure at 110% of predicted costs. The SC2i proposes to enhance traditional approaches using evidence-based data science, clinical data, and biomarker data to optimize individualized wound treatment and critical care management.51,52 These focused treatments will use deeper understanding of physiological, psychological, and physical factors that govern injury response with the goal of providing precision medicine to critically ill patients. The SC2i seeks a 95% solution at 95% cost of wound management and critical care management of WWs by developing clinical decision support tools (CDSTs) that guide therapy. This will be achieved by focusing on developing patient-specific wound management CDSTs. The SC2i has identified a variety of potential CDSTs focused on critical care issues from the point of injury to return to duty. The SC2i is developing tools aimed at delivering massive transfusion and avoiding severe traumatic brain injury and invasive fungal infection.52–54 The SC2i has also begun developing tools for identifying patients with and at risk of infectious complications and venous thromboembolism. These tools could be used during the debridement and critical care phase of the treatment. Finally, in the recovery phase, the SC2i is focusing on CDSTs for physiological monitoring, wound closure, acute kidney injury, and HO. To achieve the goal of delivering precision medicine to the war fighter, the SC2i has implemented an event and the time-driven research protocol for collection of biological samples and clinical data called the Tissue and Data Acquisition Protocol (TDAP). The TDAP protocol has been www.jorthotrauma.com | S39 Copyright Ó 2018 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. McKinley et al J Orthop Trauma  Volume 32, Number 3 Supplement, March 2018 implemented at 3 clinical sites (Duke, Walter Reed, and Emory-Grady). The TDAP focuses on collection of serum, tissue, and wound effluent, among other biological samples at specific time intervals after injury or surgical intervention. Sample collection is also driven by adverse events that occur during the course of treatment. With these biological samples and related clinical data, SC2i researchers standardize and aggregate the data on Amazon Web Services GovCloud in a central data repository for analysis and tool development. Two specific tools the SC2i is working to develop are a wound closure timing CDST and a tool for identification of patients at risk of developing pneumonia and/or bacteremia.55–57 Previous work demonstrated that a random forest model using the top 10 variables from a military data set had the best performance to predict successful wound closure demonstrating an area under the curve of 0.79 (95% confidence interval, 0.56–0.88). The wound closure model is currently in the process of being externally validated by a civilian data set. Although there are some notable differences in the demographics between the military and civilian data sets, namely, age, sex, body mass index, and injury severity, the biomarker distributions found in the serum and wound effluent were largely the same. The pneumonia- and bacteremia-predictive tool is still in the nascent stages of model construction and tuning. The initial models show area under the curves of 0.856 for pneumonia and 0.834 for bacteremia and use a combination of systemic biomarkers and clinical variables. The SC2i is currently in the process of enrolling about 500 patients per year at its 3 clinical sites. This work will support the development of novel CDSTs in the surgical critical care arena. The end goal of the work of the SC2i is to integrate clinical and biomarker data into CDSTs that are linked with the patient electronic health record. This will enable the fulfillment of the SC2i mission of delivering precision medicine—the right care, at the right time, to the right patient, and in the most cost-effective manner. osseointegration.58,59 This surgical procedure involves the direct attachment of the prosthesis to the skeletal residuum.58,59 This is currently achieved using a highly porouscoated titanium intramedullary implant, analogous to the process used for obtaining press-fit ingrowth during total hip replacement. This consistently results in a structural and functional connection between the macroporous surface of these biocompatible metal implants and living bone.58,59 The titanium intramedullary component is first inserted into the remaining bone in a retrograde fashion, and the implant is rapidly incorporated over several months. This intramedullary implant soon becomes continuous with the amputees’ skeletal residuum, and an abutment that penetrates the skin through a small permanent opening is later used for the attachment of the prosthetic limb itself. By intimately connecting the artificial limb directly to the residual bone, the problematic socket–residuum interface is eliminated.58,59 This technology has been used for over 20 years.58,59 This procedure results in major clinical benefits, including improved quality of life, prosthetic use, body image, hip range of motion, sitting comfort, donning and doffing, osseoperception, and walking ability.58,59 It must be emphasized here that this has been achieved while also maintaining very acceptable levels of risk with respect to the associated potential major complications, including implant stability and rates of infection.58,59 Until very recently these procedures were completed in 2 stages,58,59 but techniques have evolved rapidly, and now 1-stage procedures are performed on a routine basis.60 The postoperative and early follow-up data after single-stage procedures are very encouraging, showing no evidence of an increased risk of related complications, particularly implant loosening or infection. Bone remodelling indicators seem even better than observed after the 2-stage procedure. Although the preliminary results of a pilot study are so far very encouraging, there is clearly a need for more evidence of the efficacy of the 1-stage reconstruction protocol.60 OSSEOINTEGRATION: THE TRANSCUTANEOUS ENDOPROSTHETIC RECONSTRUCTION ALTERNATIVE TO DEVASTATING LOWER LIMB INJURIES 1. Belmont PJ Jr, McCriskin BJ, Hsiao MS, et al. The nature and incidence of musculoskeletal combat wounds in Iraq and Afghanistan (2005– 2009). J Orthopaedic Trauma. 2013;27:e107–113. 2. Schoenfeld AJ, Dunn JC, Bader JO, et al. The nature and extent of war injuries sustained by combat specialty personnel killed and wounded in Afghanistan and Iraq, 2003–2011. J Trauma Acute Care Surg. 2013;75: 287–291. 3. D’Alleyrand JC, O’Toole RV. The evolution of damage control orthopedics: current evidence and practical applications of early appropriate care. Orthop Clin North America. 2013;44:499–507. 4. Lichte P, Kobbe P, Dombroski D, et al. Damage control orthopedics: current evidence. Curr Opin Crit Care. 2012;18:647–650. 5. Morshed S, Miclau T III, Bembom O, et al. Delayed internal fixation of femoral shaft fracture reduces mortality among patients with multisystem trauma. J Bone Joint Surg Am. 2009;91:3–13. 6. Pape HC, Giannoudis PV, Krettek C, et al. Timing of fixation of major fractures in blunt polytrauma: role of conventional indicators in clinical decision making. J Orthop Trauma. 2005;19:551–562. 7. Pape HC, Hildebrand F, Pertschy S, et al. Changes in the management of femoral shaft fractures in polytrauma patients: from early total care to damage control orthopedic surgery. J Trauma. 2002;53:452–461; discussion 461–452. 8. Steinhausen E, Lefering R, Tjardes T, et al. 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