Rhabdomyolysis among Critically Ill Combat Casualties: Long-Term Outcomes.

BACKGROUND: Although rhabdomyolysis has been associated with acute kidney injury and mortality in the short term, the long-term consequences of an episode of rhabdomyolysis remain unknown. We sought to identify the long-term outcomes of rhabdomyolysis, including mortality, renal function, and incidence of hypertension (HTN), among service members initially admitted to the intensive care unit after sustaining a combat injury in Iraq or Afghanistan between February 1, 2002 and February 1, 2011. METHODS: Information on age, sex, injury severity score, mechanism of injury, serum creatinine, burn injury, presenting mean arterial pressure, and creatine kinase were retrospectively collected and analyzed for 2,208 patients. Standard descriptive tests were used to compare characteristics of patients with and without rhabdomyolysis. Competing risk Cox proportional hazards models were performed to assess the associated risk of rhabdomyolysis with both HTN and poor renal function. RESULTS: While rhabdomyolysis was associated with HTN on univariate analysis (hazard ratio [HR] 1.30, 95% CI 1.03-1.64; p = 0.029), this difference did not persist on multivariable analysis (HR 1.27, 95% CI 0.99-1.62; p = 0.058). The median estimated glomerular filtration rate (eGFR) was 119 (interquartile range [IQR] 103-128) among those with rhabdomyolysis, compared with 108 (IQR 94-121) in the group without rhabdomyolysis (p < 0.001). CONCLUSION: After adjustment, patients with rhabdomyolysis were not at an increased risk of HTN compared to patients without rhabdomyolysis. eGFR was paradoxically higher in patients with rhabdomyolysis. There was no association found between rhabdomyolysis and mortality.

Retrospective Analysis of Long-Term Outcomes After Combat Injury: A Hidden Cost of War.

BACKGROUND: During the conflicts in Iraq and Afghanistan, 52,087 service members have been wounded in combat. The long-term sequelae of these injuries have not been carefully examined. We sought to determine the relation between markers of injury severity and the subsequent development of hypertension, coronary artery disease, diabetes mellitus, and chronic kidney disease. METHODS AND RESULTS: Retrospective cohort study of critically injured US military personnel wounded in Iraq or Afghanistan from February 1, 2002 to February 1, 2011. Patients were then followed until January 18, 2013. Chronic disease outcomes were assessed by International Classification of Diseases, 9th edition codes and causes of death were confirmed by autopsy. From 6011 admissions, records were excluded because of missing data or if they were for an individual's second admission. Patients with a disease diagnosis of interest before the injury date were also excluded, yielding a cohort of 3846 subjects for analysis. After adjustment for other factors, each 5-point increment in the injury severity score was associated with a 6%, 13%, 13%, and 15% increase in incidence rates of hypertension, coronary artery disease, diabetes mellitus, and chronic kidney disease, respectively. Acute kidney injury was associated with a 66% increase in rates of hypertension and nearly 5-fold increase in rates of chronic kidney disease. CONCLUSIONS: In Iraq and Afghanistan veterans, the severity of combat injury was associated with the subsequent development of hypertension, coronary artery disease, diabetes mellitus, and chronic kidney disease.

Reciprocal Risk of Acute Kidney Injury and Acute Respiratory Distress Syndrome in Critically Ill Burn Patients.

OBJECTIVE: To evaluate the association between acute respiratory distress syndrome and acute kidney injury with respect to their contributions to mortality in critically ill patients. DESIGN: Retrospective analysis of consecutive adult burn patients requiring mechanical ventilation. SETTING: A 16-bed burn ICU at tertiary military teaching hospital. PATIENTS: Adult patients more than 18 years old requiring mechanical ventilation during their initial admission to our burn ICU from January 1, 2003, to December 31, 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total 830 patients were included, of whom 48.2% had acute kidney injury (n = 400). These patients had a 73% increased risk of developing acute respiratory distress syndrome after controlling for age, gender, total body surface area burned, and inhalation injury (hazard ratio, 1.73; 95% CI, 1.18-2.54; p = 0.005). In a reciprocal multivariate analysis, acute respiratory distress syndrome (n = 299; 36%) demonstrated a strong trend toward developing acute kidney injury (hazard ratio, 1.39; 95% CI, 0.99-1.95; p = 0.05). There was a 24% overall in-hospital mortality (n = 198). After adjusting for the aforementioned confounders, both acute kidney injury (hazard ratio, 3.73; 95% CI, 2.39-5.82; p < 0.001) and acute respiratory distress syndrome (hazard ratio, 2.16; 95% CI, 1.58-2.94; p < 0.001) significantly contributed to mortality. Age, total body surface area burned, and inhalation injury were also significantly associated with increased mortality. CONCLUSIONS: Acute kidney injury increases the risk of acute respiratory distress syndrome in mechanically ventilated burn patients, whereas acute respiratory distress syndrome similarly demonstrates a strong trend toward the development of acute kidney injury. Acute kidney injury and acute respiratory distress syndrome are both independent risks for subsequent death. Future research should look at this interplay for possible early interventions.

Acute Kidney Injury in Critically Injured Combat Veterans: A Retrospective Cohort Study.

BACKGROUND: Acute kidney injury (AKI) has been associated with mortality after traumatic injury. However, there is a paucity of data for military service members with injuries received in combat. We sought to identify risk factors for AKI after combat trauma and evaluate whether AKI is a predictor of mortality. STUDY DESIGN: Retrospective observational study. SETTINGS & PARTICIPANTS: US service members who were critically wounded in Iraq or Afghanistan from February 1, 2002, to February 1, 2011, and survived until evacuation to Landstuhl Regional Medical Center, Germany. PREDICTORS: Demographic variables, vital signs, injury severity score, presence of burn injury, and mechanism of injury as defined at the time of initial injury, as well as the presence of AKI ascertained within the first 7 days using KDIGO (Kidney Disease: Improving Global Outcomes) serum creatinine criteria. OUTCOMES: Logistic regression models were used to identify risk factors for both AKI and death. RESULTS: Of 6,011 records, 3,807 were included for analysis after excluding patients with missing data. AKI occurred in 474 (12.5%) patients and 112 (2.9%) died. More patients with versus without AKI died (n=62 [13.1%] vs n=50 [1.5%]; P<0.001). After adjustment, AKI was a predictor of mortality (OR, 5.14; 95% CI, 3.33-7.93; P<0.001). Predictors of AKI were age, African American race, injury severity score, amputations, burns, and presenting vital signs. LIMITATIONS: AKI diagnoses limited to creatinine-based definitions. CONCLUSIONS: AKI predicted mortality in combat veterans injured in the wars in Iraq and Afghanistan.

Pain and Kidney Function Decline and Mortality: A Cohort Study of US Veterans.

BACKGROUND: Chronic pain is a common condition in the general population. However, large epidemiologic studies examining the role of pain in the deterioration of kidney function, development of chronic kidney disease, and risk for death are lacking. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: A nationally representative cohort of 2,360,056 US veterans with baseline estimated glomerular filtration rates (eGFRs) ≥ 60mL/min/1.73m(2), followed up from October 2004 to September 2006. PREDICTOR: 4 pain categories were compared: none (score, 0), mild (1-4), moderate (5-6), or severe (≥7). OUTCOMES: eGFR decline (determined by eGFR slope) and combined incident eGFR<60mL/min/1.73m(2) or all-cause death. MEASUREMENTS: We examined the pain management pattern and association of reported pain with (1) rapid eGFR decline and (2) a composite outcome of incident eGFR<60mL/min/1.73m(2) or all-cause death using logistic regression and Cox models adjusted for baseline eGFR, demographics, comorbid conditions, cardiovascular risk factors, and depression. RESULTS: ∼60% of veterans reported pain of any severity during the baseline period. The most commonly prescribed analgesics were opioids. In a dose-response relationship, veterans reporting moderate or severe pain had a higher risk for faster eGFR decline compared with those reporting none (ORs of 1.11 [95% CI, 1.09-1.14] and 1.17 [95% CI, 1.13-1.21] for moderate and severe pain, respectively). In combined analyses, veterans reporting moderate or severe pain both had 30% higher risk of the combined outcome (incident eGFR, 60 mL/min/1.73 m(2) or death) compared with those reporting none (HRs of 1.30 [95% CI, 1.28-1.31] and 1.30 [95% CI, 1.28-1.32] for moderate and severe pain, respectively). LIMITATIONS: Lack of granular data regarding type and location of pain. CONCLUSIONS: We observed a high prevalence of pain and analgesic prescription in the US veteran population with normal eGFRs. Pain was associated with a higher incidence of eGFRs<60mL/min/1.73m(2), faster kidney function decline, and higher mortality.

The potential utility of urinary biomarkers for risk prediction in combat casualties: a prospective observational cohort study.

INTRODUCTION: Traditional risk scoring prediction models for trauma use either anatomically based estimations of injury or presenting vital signs. Markers of organ dysfunction may provide additional prognostic capability to these models. The objective of this study was to evaluate if urinary biomarkers are associated with poor outcomes, including death and the need for renal replacement therapy. METHODS: We conducted a prospective, observational study in United States Military personnel with traumatic injury admitted to the intensive care unit at a combat support hospital in Afghanistan. RESULTS: Eighty nine patients with urine samples drawn at admission to the intensive care unit were studied. Twelve patients subsequently died or needed renal replacement therapy. Median admission levels of urinary cystatin C (CyC), interleukin 18 (IL-18), L-type fatty acid binding protein (LFABP) and neutrophil gelatinase-associated lipocalin (NGAL) were significantly higher in patients that developed the combined outcome of death or need for renal replacement therapy. Median admission levels of kidney injury molecule-1 were not associated with the combined outcome. The area under the receiver operating characteristic curves for the combined outcome were 0.815, 0.682, 0.842 and 0.820 for CyC, IL-18, LFABP and NGAL, respectively. Multivariable regression adjusted for injury severity score, revealed CyC (OR 1.97, 95 % confidence interval 1.26-3.10, p = 0.003), LFABP (OR 1.92, 95 % confidence interval 1.24-2.99, p = 0.004) and NGAL (OR 1.80, 95 % confidence interval 1.21-2.66, p = 0.004) to be significantly associated with the composite outcome. CONCLUSIONS: Urinary biomarker levels at the time of admission are associated with death or need for renal replacement therapy. Larger multicenter studies will be required to determine how urinary biomarkers can best be used in future prediction models.

Hypertension in military veterans is associated with combat exposure and combat injury.

BACKGROUND: Although the long-term effects of combat injury are not well understood, there is emerging concern that exposure to combat environments and subsequent injury may increase the risk of hypertension through changes in inflammatory responses, psychological stress and mental health, and health behaviors. METHODS: Data from the Millennium Cohort Study and the Department of Defense Trauma Registry were used to identify combat-exposed and combat-injured participants. Incident hypertension diagnoses were ascertained from the Millennium Cohort survey. The associations between combat exposure/injury and hypertension risk was estimated using multivariable complementary log-log survival models. RESULTS: The final analysis sample consisted of 38 734 participants. Of these, 50.8% deployed but were not exposed to combat, 48.6% deployed and were exposed to combat, and 0.6% had combat injury. Overall prevalence of hypertension was 7.6%. Compared with participants who deployed but did not experience combat (mild exposure), elevated odds of hypertension were observed among those who experienced combat but not wounded (moderate exposure; AOR, 1.28; 95% CI, 1.19-1.38) and those wounded in combat (high exposure; AOR, 1.46; 95% CI, 1.07-2.00). Sleep duration of less than 4 h (AOR, 1.21; 95% CI, 1.03-1.43), sleep duration of 4-6 h (AOR, 1.16; 95% CI, 1.05-1.29), posttraumatic stress disorder (AOR, 1.54; 95% CI, 1.26-1.87), and overweight (AOR, 1.77; 95% CI, 1.61-1.95) and obese (AOR, 2.77; 95% CI, 2.45-3.12) status were also associated with higher odds of hypertension. CONCLUSION: Results support the hypotheses that combat exposure increases hypertension risk and that combat injury exacerbates this risk.

Assessing the NephroCheck® Test System in Predicting the Risk of Death or Dialysis in Burn Patients.

Acute kidney injury (AKI) is associated with high mortality in burn patients. Urinary biomarkers can aid in the prediction of AKI and its consequences, such as death and the need for renal replacement therapy (RRT). The purpose of this study was to investigate a novel methodology for detecting urinary biomarkers, the NephroCheck® Test System, and assess its ability to predict death or the need for RRT in burn patients. Burn patients admitted to the United States Army Institute of Surgical Research (USAISR) burn intensive care unit were prospectively enrolled between March 2016 and April 2018. A urine sample was obtained from all study participants using the NephroCheck® system. Patient and injury characteristics were gathered, and descriptive statistics were calculated and multivariable logistic regression analyses were performed using these data. Of the 69 patients in this study, 15 patients (21.7%) attained the composite outcome of death or needing RRT within 30 days of urine collection. NephroCheck® scores were higher for patients with the composite outcome, with P = 0.06 for centrifuged scores and P = 0.04 for noncentrifuged scores. Centrifuged and noncentrifuged scores were in high agreement and correlation (R2 = 0.97, P < 0.0001). Noncentrifuged scores were significant in the unadjusted analysis, but they were not significant in the adjusted analysis. Although these scores had a lower sensitivity and negative predictive value compared with other parameters, they had the second highest specificity and positive predictive value. NephroCheck® scores were higher in burn patients with the composite outcome of death or needing RRT, and they demonstrated comparable sensitivity and specificity to creatinine and TBSA.

Predicting and Planning for Musculoskeletal Service-Connected Disabilities in VA Using Disability for Active Duty OEF/OIF Military Service Members.

INTRODUCTION: Musculoskeletal (MSK) conditions are commonly seen among military service members (SM) and Veterans. We explored correlates of award of MSK-related service-connected disability benefits (SCDB) among SM seeking care in Veterans Affairs (VA) hospitals. MATERIALS AND METHODS: Department of Defense data on SM who separated from October 1, 2001 to May 2017 were linked to VA administrative data. Using adjusted logistic regression models, we determined the odds of receiving MSK SCDB. RESULTS: A total of 1,558,449 (79% of separating SM) had at least one encounter in VA during the study period (7.8% disability separations). Overall, 51% of this cohort had at least one MSK SCDB (88% among disability separations, 48% among normal). Those with disability separations (as compared to normal separations) were significantly more likely to receive MSK SCDB (odds ratio 2.37) as were females (compared to males, odds ratio 1.15). CONCLUSIONS: Although active duty SM with disability separations were more likely to receive MSK-related service-connected disability ratings in the VA, those with normal separations also received such awards. Identifying those at highest risk for MSK-related disability could lead to improved surveillance and prevention strategies in the Department of Defense and VA health care systems to prevent further damage and disability.

Exploring Disparities in Awarding VA Service-Connected Disability for Post-Traumatic Stress Disorder for Active Duty Military Service Members from Recent Conflicts in Iraq and Afghanistan.

INTRODUCTION: We explore disparities in awarding post-traumatic stress disorder (PTSD) service-connected disability benefits (SCDB) to veterans based on gender, race/ethnicity, and misconduct separation. METHODS: Department of Defense data on service members who separated from October 1, 2001 to May 2017 were linked to Veterans Administration (VA) administrative data. Using adjusted logistic regression models, we determined the odds of receiving a PTSD SCDB conditional on a VA diagnosis of PTSD. RESULTS: A total of 1,558,449 (79% of separating service members) had at least one encounter in VA during the study period (12% female, 4.5% misconduct separations). Females (OR 0.72) and Blacks (OR 0.93) were less likely to receive a PTSD award and were nearly equally likely to receive a PTSD diagnosis (OR 0.97, 1.01). Other racial/ethnic minorities were more likely to receive an award and diagnosis, as were those with misconduct separations (award OR 1.3, diagnosis 2.17). CONCLUSIONS: Despite being diagnosed with PTSD at similar rates to their referent categories, females and Black veterans are less likely to receive PTSD disability awards. Other racial/ethnic minorities and those with misconduct separations were more likely to receive PTSD diagnoses and awards. Further study is merited to explore variation in awarding SCDB.

A bedside clinical tool using creatinine kinetics to predict worsening renal injury and early recovery.

BACKGROUND: Changing creatinine concentrations during acute renal failure are often confusing to clinicians to interpret and can cloud the patient's true current state of renal injury. By modifying the formula for kinetic estimate of glomerular filtration rate (KeGFR), a simple bedside clinical tool can be used to identify subtle changes in renal function. METHODS: The KeGFR was rewritten to instead calculate a predicted peak creatinine after renal injury. By comparing the changes in predicted peak creatinine at two or more subsequent time intervals, the patient's current state of renal injury can be determined: whether improving, worsening or unchanged from prior. RESULTS: Three case examples are provided using the equation for predicted peak creatinine. In each case, the creatinine concentration has continued to rise at three sequentially measured times. The change in predicted peak creatinine is analyzed for each case, demonstrating scenarios involving (i) improving renal injury, (ii) unchanged renal injury continued by unfavorable hemodynamics and (iii) worsening renal injury despite interventions. CONCLUSIONS: The use of this model may provide clinicians with an easy bedside tool to assess a patient's state of acute kidney injury. Reassessment of how the creatinine is changing is already a nonquantitative part of a nephrologist's approach to acute kidney injury. Providing an assessment of the patient's changing renal function would be a useful addition to potentially detect early renal recovery or worsening renal injury and appropriately adjust treatment strategies.

Patterns of Anatomic Injury in Critically Injured Combat Casualties: A Network Analysis.

A mortality review of death caused by injury requires a determination of injury survivability prior to a determination of death preventability. If injuries are nonsurvivable, only non-medical primary prevention strategies have potential to prevent the death. Therefore, objective measures are needed to empirically inform injury survivability from complex anatomic patterns of injury. As a component of injury mortality reviews, network structures show promise to objectively elucidate survivability from complex anatomic patterns of injury resulting from explosive and firearm mechanisms. In this network analysis of 5,703 critically injured combat casualties, patterns of injury among fatalities from explosive mechanisms were associated with both a higher number and severity of anatomic injuries to regions such as the extremities, abdomen, and thorax. Patterns of injuries from a firearm were more isolated to individual body regions with fatal patterns involving more severe injuries to the head and thorax. Each injury generates a specific level of risk as part of an overall anatomic pattern to inform injury survivability not always captured by traditional trauma scoring systems. Network models have potential to further elucidate differences between potentially survivable and nonsurvivable anatomic patterns of injury as part of the mortality review process relevant to improving both the military and civilian trauma care systems.

Presenting hypertension, burn injury, and mortality in combat casualties.

INTRODUCTION: The effect of presenting hypertension is poorly studied in combat casualties. We hypothesized that elevated mean arterial pressure (MAP) on presentation to combat hospitals would be associated with poor outcomes. METHODS: Data was obtained from the Department of Defense Trauma Registry and the Armed Forces Medical Examiner System. Variables analyzed included presenting vital signs to Role II-III military theater hospital, demographic variables, injury severity score (ISS), location and mechanism of injury, presence of traumatic brain injury (TBI), acute kidney injury (AKI), and mortality. Patients were stratified by decile of MAP and logistic regression analysis was employed to adjust for confounders. RESULTS: A total of 4072 subjects injured from February 2002 to February 2011 were identified. Compared to patients in the middle deciles of presenting MAP, patients in the highest and lowest MAP deciles were the only groups that demonstrated a higher mortality on univariate analysis (OR 2.06, 95% CI 1.16-2.31 and OR 2.86, 95% CI 1.76-4.67, respectively), and this relationship persisted after adjustment for ISS, HR, temperature, presence of burn injury, TBI, and AKI. Burn injury was associated with mortality in the full multivariate analysis. However, further analysis limited to patients without burn injury did not demonstrate an association between high MAP and mortality (OR 0.84, 95% CI 0.36-1.99; p=0.70). Conversely, when limited to patients with burn injury, high MAP was associated with mortality (OR 3.78, 95% CI 1.74-8.20; p=0.001). CONCLUSION: The relationship between mortality and presenting MAP appears to be U-shaped, demonstrating increased mortality in the lowest and highest deciles. However, mortality in the highest MAP decile appears to be limited to casualties with associated burn injury, even after adjustment for TBI, AKI, and ISS, which takes into account the severity of the burn injury. Physicians should recognize that burn patients presenting with an elevated MAP are at an increased risk for poor outcomes. LEVEL OF EVIDENCE: III.

Using the injury severity score to adjust for comorbid trauma may be double counting burns: implications for burn research.

BACKGROUND: The injury severity score considers burn size and inhalation injury in estimating overall anatomical injury severity. Models that adjust for injury severity score in addition to total burn size and inhalation injury may therefore be double counting the risk from these individual burn characteristics, and obscuring (or overemphasizing) the contribution of risk from each source. The primary aim of this study was to compare differences in the estimated mortality risk of burn trauma using the traditional injury severity score (ISS) calculation and the non-burn injury severity score (NBISS) to examine how separating out the risk attributable to the burn injury versus other trauma changes the interpretation and clinical assessment. METHODS: Among U.S. casualties sustaining burns during combat operations in Iraq and Afghanistan from March 2003 to October 2013, we performed a retrospective cohort study. Unadjusted, adjusted, and weighted Cox proportional hazards models were performed to estimate the risk of age, burn injury severity, and non-burn injury severity on mortality. Weighted hazard ratios and adjusted survival curves were performed using non-parametric inverse probability weighting. RESULTS: Our final sample consisted of 902 service members with a mortality proportion of 5.7% (n=51). Adjusting for non-burn trauma with traditional ISS attenuated the risk of percent total body surface area burned (%TBSA) by 20% when modeled continuously [HR (95% CI): 1.27 (1.10-1.32) vs. 1.07 (0.99-1.15]. However, the adjusted model using NBISS only attenuated the associated mortality risk of burn size by 5% [HR (95% CI): 1.22 (1.12-1.34)] and had a similar model fit (AIC: 484.2 vs. 478.6). For the weighted Cox proportional hazards models, the risk from a large burn (%TBSA≥60) was also attenuated when adjusting for ISS [HR (95% CI): 2.80 (1.18-6.64)] compared to the model adjusting for NBISS [HR (95% CI): 5.63 (2.79-11.35)]. CONCLUSION: Our analysis comparing the use of traditional ISS and NBISS to measure comorbid non-burn trauma resulted in different interpretations for the effect of %TBSA on subsequent mortality. Our results suggest that the association of %TBSA with death can be obscured by the inclusion of traditional ISS. Therefore, we recommend using NBISS when constructing statistical models in this patient population.

Associations of Initial Injury Severity and Posttraumatic Stress Disorder Diagnoses With Long-Term Hypertension Risk After Combat Injury.

The associations between injury severity, posttraumatic stress disorder (PTSD), and development of chronic diseases, such as hypertension, among military service members are not understood. We sought to (1) estimate the prevalence and incidence of PTSD within a severely injured military cohort, (2) assess the association between the presence and chronicity of PTSD and hypertension, and (3) determine whether or not initial injury severity score and PTSD are independent risk factors for hypertension. Administrative and clinical databases were used to conduct a retrospective cohort study of 3846 US military casualties injured in the Iraq and Afghanistan conflicts between February 1, 2002, and February 1, 2011. Development of PTSD and hypertension after combat injury were determined using the International Classification of Diseases, Ninth Revision codes. Multivariable competing risk regression models were used to assess associations between injury severity score, PTSD, and hypertension, while controlling for covariates. Overall prevalence of PTSD was 42.4%, and prevalence of hypertension was 14.3%. Unadjusted risk of hypertension increased significantly with chronicity of PTSD (1-15 diagnoses: hazard ratio, 1.77; 95% confidence interval, 1.46-2.14; P<0.001; >15 diagnoses: hazard ratio, 2.29; 95% confidence interval, 1.85-2.84; P<0.001) compared with patients never diagnosed with PTSD. The association between injury severity score (hazard ratio, 1.06 per 5-U increment; 95% confidence interval, 1.03-1.10; P<0.001) and hypertension was significant, with little change in effect in the multivariable model (hazard ratio, 1.05 per 5-U increment; 95% confidence interval, 1.01-1.09; P=0.03). In a cohort of service members injured in combat, we found that chronicity of PTSD diagnoses and injury severity were independent risk factors for hypertension.

Extracorporeal Filtration of Potassium in a Swine Model of Bilateral Hindlimb Ischemia-Reperfusion Injury With Severe Acute Hyperkalemia.

Introduction: Options for the treatment of hyperkalemia in the pre-hospital setting are limited, particularly in the context of natural disaster or during combat operations. Contemporary interventions require extensive resources and technical expertise. Here we examined the potential for a simple, field deployable bridge-dialysis as a countermeasure for acute hyperkalemia induced by prolonged ischemia-reperfusion. Methods: Twenty female swine were randomized into two experimental groups undergoing a 2-hour bilateral hindlimb ischemia-reperfusion injury. Subsequent to injury, hemoperfusion was performed in the presence (Column) and absence (Sham Control) of a high-affinity potassium-binding column (CytoSorbents, Monmouth Junction, NJ, USA). Serial blood gas and chemistries were sampled. Primary endpoint was changed in serum potassium concentrations post-injury and filtration. Results: Serum potassium was significantly elevated following ischemia-reperfusion injury in both groups (149% (12) and 150% (22), p < 0.05 vs respective baseline values). There were no differences observed between groups in respect to physiologic parameters; mean arterial pressure, heart rate, systemic vascular resistance, cardiac output, or central venous oxygenation. Filtration resulted in a significant relative decrease in potassium compared with controls after the first hour as determined by repeated measures two-way ANOVA (p < 0.0001) which continued through end of the study. Significant thrombocytopenia was observed in animals undergoing filtration with a mean reduction in platelets measured at T = 480 minutes (168 × 103µL, p < 0.0001 vs baseline). Conclusions: We demonstrate that serum potassium can be filtered via hemoperfusion utilizing a simple extracorporeal potassium-binding platform, though evolution of this technology will be required to achieve meaningful reduction of potassium in clinically significant hyperkalemia after trauma.

Coagulopathy and Mortality in Combat Casualties: Do the Kidneys Play a Role?

Background: Acute traumatic coagulopathy (ATC) is a common condition after traumatic injury and is known to be associated with an increase in morbidity and mortality in trauma patients. ATC has been implicated as a causative factor in both early hemorrhage and late organ failure in this population, yet the pathophysiology remains largely unknown. Additionally, acute kidney injury (AKI) is a common condition among critically injured trauma patients. AKI has been associated with an elevated International Normalized Ratio (INR) and warfarin use, but its development has not been well studied in the setting of ATC. We hypothesized that the presence of ATC influences the development of AKI and may mediate mortality in combat casualties. Methods: Data were obtained from the Department of Defense Trauma Registry, Medical Data Store and Composite Healthcare System, and the Armed Forces Medical Examiner System. A retrospective review was conducted of US service members injured in Iraq or Afghanistan between February 1, 2002 and February 1, 2011, who required ICU level care and survived evacuation out of theater. Exclusions were made for missing data. Cox proportional hazard regression was performed to determine the effect of ATC (a priori defined as first INR > 1.3) on the development of AKI. Further analysis was conducted to determine the influence of these variables on 30-d mortality, and multiple sensitivity analyses were performed to determine the effect of ATC on both AKI and mortality. Results: A total of 1,288 patients were identified for analysis. ATC was a risk factor for subsequent AKI after adjustment (HR 1.67, 95% CI 1.28-2.18; p < 0.001). However, ATC was not a risk factor for mortality after adjustment in the full model (HR 1.87, 95% CI 0.95-3.65; p = 0.069). On sensitivity analyses exploring alternate definitions of ATC, an INR of 1.2 remained associated with AKI (HR 1.46, 95% CI 1.13-1.88; p = 0.004) and an INR of 1.5 became significant for mortality (HR 1.76, 95% CI 1.32-2.35; p < 0.001). Conclusion: ATC is independently associated with the development of AKI. Although ATC is associated with mortality in the unadjusted model, it is not significant after adjustment for AKI. This implies that the kidneys may play a role in the adverse outcomes observed after ATC. Increased awareness and monitoring for coagulopathy and the subsequent development of AKI in combat casualty patients may lead to earlier diagnosis and treatment of these conditions, possibly decreasing morbidity and mortality.

Comparison of Military and Civilian Methods for Determining Potentially Preventable Deaths: A Systematic Review.

Importance: Military and civilian trauma experts initiated a collaborative effort to develop an integrated learning trauma system to reduce preventable morbidity and mortality. Because the Department of Defense does not currently have recommended guidelines and standard operating procedures to perform military preventable death reviews in a consistent manner, these performance improvement processes must be developed. Objectives: To compare military and civilian preventable death determination methods to understand the existing best practices for evaluating preventable death. Evidence Review: This systematic review followed the PRISMA reporting guidelines. English-language articles were searched from inception to February 15, 2017, using the following databases: MEDLINE (Ovid), Evidence-Based Medicine Reviews (Ovid), PubMed, CINAHL, and Google Scholar. Articles were initially screened for eligibility and excluded based on predetermined criteria. Articles reviewing only prehospital deaths, only inhospital deaths, or both were eligible for inclusion. Information on study characteristics was independently abstracted by 2 investigators. Reported are methodological factors affecting the reliability of preventable death studies and the preventable death rate, defined as the number of potentially preventable deaths divided by the total number of deaths within a specific patient population. Findings: Fifty studies (8 military and 42 civilian) met the inclusion criteria. In total, 1598 of 6500 military deaths reviewed and 3346 of 19 108 civilian deaths reviewed were classified as potentially preventable. Among military studies, the preventable death rate ranged from 3.1% to 51.4%. Among civilian studies, the preventable death rate ranged from 2.5% to 85.3%. The high level of methodological heterogeneity regarding factors, such as preventable death definitions, review process, and determination criteria, hinders a meaningful quantitative comparison of preventable death rates. Conclusions and Relevance: The reliability of military and civilian preventable death studies is hindered by inconsistent definitions, incompatible criteria, and the overall heterogeneity in study methods. The complexity, inconsistency, and unpredictability of combat require unique considerations to perform a methodologically sound combat-related preventable death review. As the Department of Defense begins the process of developing recommended guidelines and standard operating procedures for performing military preventable death reviews, consideration must be given to the factors known to increase the risk of bias and poor reliability.