Carlos J. Rodriguez

Invasive mold infections following combat-related injuries.

BACKGROUND Major advances in combat casualty care have led to increased survival of patients with complex extremity trauma. Invasive fungal wound infections (IFIs) are an uncommon, but increasingly recognized, complication following trauma that require greater understanding of risk factors and clinical findings to reduce morbidity. METHODS The patient population includes US military personnel injured during combat from June 2009 through December 2010. Case definition required wound necrosis on successive debridements with IFI evidence by histopathology and/or microbiology (Candida spp excluded). Case finding and data collected through the Trauma Infectious Disease Outcomes Study utilized trauma registry, hospital records or operative reports, and pathologist review of histopathology specimens. RESULTS A total of 37 cases were identified: proven (angioinvasion, n=20), probable (nonvascular tissue invasion, n=4), and possible (positive fungal culture without histopathological evidence, n=13). In the last quarter surveyed, rates reached 3.5% of trauma admissions. Common findings include blast injury (100%) during foot patrol (92%) occurring in southern Afghanistan (94%) with lower extremity amputation (80%) and large volume blood transfusion (97.2%). Mold isolates were recovered in 83% of cases (order Mucorales, n=16; Aspergillus spp, n=16; Fusarium spp, n=9), commonly with multiple mold species among infected wounds (28%). Clinical outcomes included 3 related deaths (8.1%), frequent debridements (median, 11 cases), and amputation revisions (58%). CONCLUSIONS IFIs are an emerging trauma-related infection leading to significant morbidity. Early identification, using common characteristics of patient injury profile and tissue-based diagnosis, should be accompanied by aggressive surgical and antifungal therapy (liposomal amphotericin B and a broad-spectrum triazole pending mycology results) among patients with suspicious wounds.

Damage control resuscitation in patients with severe traumatic hemorrhage: A practice management guideline from the Eastern Association for the Surgery of Trauma.

Background The resuscitation of severely injured bleeding patients has evolved into a multi-modal strategy termed damage control resuscitation (DCR). This guideline evaluates several aspects of DCR including the role of massive transfusion (MT) protocols, the optimal target ratio of plasma (PLAS) and platelets (PLT) to red blood cells (RBC) during DCR, and the role of recombinant activated factor VII (rVIIa) and tranexamic acid (TXA). Methods Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, a subcommittee of the Practice Management Guidelines (PMG) Section of EAST conducted a systematic review using MEDLINE and EMBASE. Articles in English from1985 through 2015 were considered in evaluating four PICO questions relevant to DCR. Result A total of 37 studies were identified for analysis, of which 31 met criteria for quantitative meta-analysis. In these studies, mortality decreased with use of an MT/DCR protocol vs. no protocol (OR 0.61, 95% CI 0.43–0.87, p = 0.006) and with a high ratio of PLAS:RBC and PLT:RBC (relatively more PLAS and PLT) vs. a low ratio (OR 0.60, 95% CI 0.46–0.77, p < 0.0001; OR 0.44, 95% CI 0.28–0.71, p = 0.0003). Mortality and blood product use were no different with either rVIIa vs. no rVIIa or with TXA vs. no TXA. Conclusion DCR can significantly improve outcomes in severely injured bleeding patients. After a review of the best available evidence, we recommend the use of a MT/DCR protocol in hospitals that manage such patients and recommend that the protocol target a high ratio of PLAS and PLT to RBC. This is best achieved by transfusing equal amounts of RBC, PLAS, and PLT during the early, empiric phase of resuscitation. We cannot recommend for or against the use of rVIIa based on the available evidence. Finally, we conditionally recommend the in-hospital use of TXA early in the management of severely injured bleeding patients.

Combat trauma-associated invasive fungal wound infections: epidemiology and clinical classification

The emergence of invasive fungal wound infections (IFIs) in combat casualties led to development of a combat trauma-specific IFI case definition and classification. Prospective data were collected from 1133 US military personnel injured in Afghanistan (June 2009-August 2011). The IFI rates ranged from 0·2% to 11·7% among ward and intensive care unit admissions, respectively (6·8% overall). Seventy-seven IFI cases were classified as proven/probable (n = 54) and possible/unclassifiable (n = 23) and compared in a case-case analysis. There was no difference in clinical characteristics between the proven/probable and possible/unclassifiable cases. Possible IFI cases had shorter time to diagnosis (P = 0·02) and initiation of antifungal therapy (P = 0·05) and fewer operative visits (P = 0·002) compared to proven/probable cases, but clinical outcomes were similar between the groups. Although the trauma-related IFI classification scheme did not provide prognostic information, it is an effective tool for clinical and epidemiological surveillance and research.

Long-term outcomes of combat casualties sustaining penetrating traumatic brain injury

BACKGROUND Previous studies have documented short-term functional outcomes for patients sustaining penetrating brain injuries (PBIs). However, little is known regarding the long-term functional outcome in this patient population. Therefore, we sought to describe the long-term functional outcomes of combat casualties sustaining PBI. METHODS Prospective data were collected from 2,443 patients admitted to a single military institution during an 8-year period from 2003 to 2011. PBI was identified in 137 patients and constitute the study cohort. Patients were stratified by age, Injury Severity Score (ISS) and admission Glasgow Coma Scale (aGCS) score. Glasgow Outcome Scale (GOS) scores were calculated at discharge, 6 months, 1 year and 2 years. Patients with a GOS score of 4 or greater were considered to have attained functional independence (FI). RESULTS The mean (SD) age of the cohort was 25 (7) years, mean (SD) ISS was 28 (9), and mean (SD) aGCS score was 8.8 (4.0). PBI mechanisms included gunshot wounds (31%) and blast injuries (69%). Invasive intracranial monitoring was used in 80% of patients, and 86.9% of the study cohort underwent neurosurgical intervention. Complications included cerebrospinal fluid leak (8.3%), venous thromboembolic events (15.3%), meningitis (24.8%), systemic infection (27.0%), and mortality (5.8%). The cohort was stratified by aGCS score and showed significant improvement in functional status when mean discharge GOS score was compared with mean GOS score at 2 years. For those with aGCS score of 3 to 5 (2.3 [0.9] vs. 2.9 [1.4], p < 0.01), 32% progressed to FI. For those with aGCS score of 6 to 8 (3.1 [0.7] vs. 4.0 [1.2], p < 0.0001), 63% progressed to FI. For those with aGCS score of 9 to 11 (3.3 [0.5] vs. 4.3 [0.8], p < 0.0001), 74% progressed to FI. For those with aGCS score of 12 to 15 (3.9 [0.7] vs. 4.8 [0.4], p < 0.00001), 100% progressed to FI. CONCLUSION Combat casualties with PBI demonstrated significant improvement in functional status up to 2 years from discharge, and a large proportion of patients sustaining severe PBI attained FI. LEVEL OF EVIDENCE Epidemiologic study, level III.

Effect of Early Screening for Invasive Fungal Infections in U.S. Service Members with Explosive Blast Injuries

BACKGROUND An outbreak of invasive fungal infections (IFI) began in 2009 among United States servicemen who sustained blast injuries in Afghanistan. In response, the military trauma community sought a uniform approach to early diagnosis and treatment. Toward this goal, a local clinical practice guideline (CPG) was implemented at Landstuhl Regional Medical Center (LRMC) in early 2011 to screen for IFI in high-risk patients using tissue histopathology and fungal cultures. METHODS We compared IFI cases identified after initiation of the CPG (February through August 2011) to cases from a pre-CPG period (June 2009 through January 2011). RESULTS Sixty-one patients were screened in the CPG period, among whom 30 IFI cases were identified and compared with 44 pre-CPG IFI cases. Demographics between the two study periods were similar, although significantly higher transfusion requirements (p<0.05) and non-significant trends in injury severity scores and early lower extremity amputation rates suggested more severe injuries in CPG-period cases. Pre-CPG IFI cases were more likely to be associated with angioinvasion on histopathology than CPG IFI cases (48% versus 17%; p<0.001). Time to IFI diagnosis (three versus nine days) and to initiation of antifungal therapy (seven versus 14 days) were significantly decreased in the CPG period (p<0.001). Additionally, more IFI patients received antifungal agent at LRMC during the CPG period (30%) versus pre-CPG period (5%; p=0.005). The CPG IFI cases were also prescribed more commonly dual antifungal therapy (73% versus 36%; p=0.002). There was no statistical difference in length of stay or mortality between pre-CPG and CPG IFI cases; although a non-significant reduction in crude mortality from 11.4% to 6.7% was observed. CONCLUSIONS Angioinvasive IFI as a percentage of total IFI cases decreased during the CPG period. Earlier diagnosis and commencement of more timely treatment was achieved. Despite these improvements, no difference in clinical outcomes was observed compared with the pre-CPG period.

Combat-Related Invasive Fungal Wound Infections

Combat-related invasive fungal (mold) wound infections (IFIs) have emerged as an important and morbid complication following explosive blast injuries among military personnel. Similar to trauma-associated IFI cases among civilian populations, as in agricultural accidents and natural disasters, these infections occur in the setting of penetrating wounds contaminated by environmental debris. Specific risk factors for combat-related IFI include dismounted (patrolling on foot) blast injuries occurring mostly in southern Afghanistan, resulting in above knee amputations requiring resuscitation with large-volume blood transfusions. Diagnosis of IFI is based upon early identification of a recurrently necrotic wound following serial debridement and tissue-based histopathology examination with special stains to detect invasive disease. Fungal culture of affected tissue also provides supportive information. Aggressive surgical debridement of affected tissue is the primary therapy. Empiric antifungal therapy should be considered when there is a strong suspicion for IFI. Both liposomal amphotericin B and voriconazole should be considered initially for treatment since many of the cases involve not only Mucorales species but also Aspergillus or Fusarium spp., with narrowing of regimen based upon clinical mycology findings.

Preparing the surgeon for war: present practices of US, UK, and Canadian militaries and future directions for the US military.

T Armed Forces of the United States and their North Atlantic Treaty Organization (NATO) partners continue to be engaged around the world in regions of conflict. Consequently, combat casualty care is a central focus of the military medical community. Accordingly, present deployment requirements demand the sustaining of a significant number of ready and capable trauma surgical providers to optimize outcome for injured combat casualties. Preparing a surgeon for war requires the development and maintenance of skill sets unique to the combat environment. Although modern graduate medical education (GME) surgical training provides civilian trauma case experience with a wide range of experience, it does not adequately prepare graduates of these programs for the injury patterns specific to the battlefield environment. Even among more senior surgical providers, the civilian practice does not adequately prepare the surgeon for combat experiences. Vascular trauma, as a particular example, constitutes a significant portion of the injuries observed in the setting of warfare; yet, the acquisition of the open surgical skills necessary to effectively manage these injuries continues to be considerably challenged both by recent changes in surgical training case volume and the increased use of endovascular techniques. Each branch of the US Armed Services, as well as Canadian and UK NATO partners, has established predeployment training efforts designed to prepare surgeons for dealing effectively with combat-injured. In the United States, these programs began with programs initiated at Ben Taub General Hospital in 1999 and have continued to evolve. Present efforts are highly varied, however, in their constructs and conduct between US branches and NATO partners. There is also evidence to suggest that these programs are not effectively used by deploying surgeons, at least among US military providers. A recent survey of 137 active-duty US military surgeons from all three services revealed that only 44% had attended any form of combat-related trauma predeployment course. The authors have examined the present trauma surgical readiness practices of the US Military Medical Corps, both active and reserve components as well as those of our Canadian and UK NATO partners. Members of each of those medical services have described the present requirements for their surgical community. Capabilities and challenges of each unique community are examined. In final consideration of these efforts, we provide potential options for further optimization of surgical readiness efforts for both present and future conflicts.

Early Complications and Outcomes in Combat Injury-Related Invasive Fungal Wound Infections: A Case-Control Analysis.

Objective: Clinicians have anecdotally noted that combat-related invasive fungal wound infections (IFIs) lead to residual limb shortening, additional days and operative procedures before initial wound closure, and high early complication rates. We evaluated the validity of these observations and identified risk factors that may impact time to initial wound closure. Design: Retrospective review and case–control analysis. Setting: Military hospitals. Patients/Participants: US military personnel injured during combat operations (2009–2011). The IFI cases were identified based on the presence of recurrent, necrotic extremity wounds with mold growth in culture, and/or histopathologic fungal evidence. Non-IFI controls were matched on injury pattern and severity. In a supplemental matching analysis, non-IFI controls were also matched by blood volume transfused within 24 hours of injury. Intervention: None. Main Outcome Measurements: Amputation revision rate and loss of functional levels. Results: Seventy-one IFI cases (112 fungal–infected extremity wounds) were identified and matched to 160 control patients (315 non-IFI extremity wounds). The IFI wounds resulted in significantly more changes in amputation level (P < 0.001). Additionally, significantly (P < 0.001) higher number of operative procedures and longer duration to initial wound closure were associated with IFI. A shorter duration to initial wound closure was significantly associated with wounds lacking IFIs (Hazard ratio: 1.53; 95% confidence interval, 1.17–2.01). The supplemental matching analysis found similar results. Conclusions: Our analysis indicates that IFIs adversely impact wound healing and patient recovery, requiring more frequent proximal amputation revisions and leading to higher early complication rates. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Clinical relevance of mold culture positivity with and without recurrent wound necrosis following combat-related injuries

BACKGROUND Invasive fungal wound infections (IFIs) are a recognized threat for personnel who sustain combat-related blast trauma in Afghanistan. Blast trauma, particularly when dismounted, has wounds contaminated with organic debris and potential for mold infection. Trauma-associated IFI is characterized by recurrent wound necrosis on serial debridement with histologic evidence of invasive molds and/or fungal culture growth. Wounds with mold growth but lacking corresponding recurrent necrosis present a clinical dilemma of whether to initiate antifungal treatment. Our objective was to assess the clinical significance of fungal culture growth without recurrent wound necrosis. METHODS US military personnel wounded during combat in Afghanistan (June 2009 to August 2011) were assessed for growth of mold from wound cultures and/or histopathologic evidence of IFI. Identified patients were stratified based on clinical wound appearance (with/without recurrent necrosis), and the resultant groups were compared for injury characteristics, clinical management, and outcomes. RESULTS A total of 96 patients were identified: 77 with fungal elements on histopathology and/or fungal growth plus recurrent wound necrosis and 19 with fungal growth on culture but no wound necrosis after initial debridements. Injury patterns and severity were similar between the groups. Patients with recurrent necrosis had more frequent fevers and leukocytosis during the first 2 weeks after injury, and the majority received antifungal therapy compared with only three patients (16%) without recurrently necrotic wounds. Overall, patients without recurrent wound necrosis had significantly less operative procedures (p = 0.02), shorter stay in the intensive care unit (p < 0.01), and lower rates of high-level amputations (5% vs. 20%) and deaths (none vs. 8%) despite no or infrequent antifungal use. CONCLUSION The finding of molds on wound culture among patients with blast trauma in the absence of recurrently necrotic wounds on serial debridement does not require systemic antifungal chemotherapy. LEVEL OF EVIDENCE Therapeutic study, level IV. Prognosti/epidemiologic study, level III.

Hyperacute adrenal insufficiency after hemorrhagic shock exists and is associated with poor outcomes.

BACKGROUND Adrenal insufficiency (AI) has been extensively described in sepsis but not in acute hemorrhage. We sought to determine the incidence of hyperacute AI (HAI) immediately after hemorrhage and its association with mortality. METHODS Patients with acute traumatic hemorrhagic shock presenting to the R Adams Cowley Shock Trauma Center prospectively had serum cortisol levels collected on admission. Inclusion criteria were hypotension and active hemorrhage. Clinicians were blinded to results, and no patient received steroids in the acute phase. The primary outcome measure was death from hemorrhage within 24 hours of admission. RESULTS Fifty-nine patients were enrolled during an 8-month period. Mean admission cortisol level was 18.3 ± 8.9 &mgr;g/dL. Acute mortality rate from hemorrhage was 27%. Overall mortality rate was 37%. Severe HAI (serum cortisol level <10 &mgr;g/dL) was present in 10 patients (17%). Relative HAI (<25 &mgr;g/dL) was present in 51 patients (86%). Those who died of acute hemorrhage had significantly lower mean cortisol levels (11.4 ± 6.2 &mgr;g/dL vs. 20.9 ± 8.4 &mgr;g/dL, p < 0.001) as did patients who ultimately died in the hospital (12.8 ± 7.6 &mgr;g/dL vs. 21.6 ± 8.1&mgr;g/dL, p < 0.001). In multivariate analysis, cortisol levels were associated with mortality from acute hemorrhage, with an odds ratio of 1.17 (95% confidence interval, 1.02–1.35). Adjusted receiver operating characteristic analysis indicated that serum cortisol has a 91% accuracy in differentiating survivors of acute hemorrhage from nonsurvivors. CONCLUSION This study is the first to report that AI occurs immediately after acute injury during hemorrhagic shock and is strongly associated with mortality. HAI may be a marker of depth of shock but is potentially rapidly modifiable as opposed to other markers, such as lactate or base deficit. Further work is needed to determine whether steroid administration can change outcome in selected patients. LEVEL OF EVIDENCE Prognostic/epidemiologic study, level III.