David Zonies

Prospectively Assessed Clinical Outcomes in Concussive Blast vs Nonblast Traumatic Brain Injury Among Evacuated US Military Personnel

IMPORTANCE Blast injury has been identified as the signature injury in the conflicts in Iraq and Afghanistan. However it remains to be determined whether fundamental differences may exist between blast-related traumatic brain injury (TBI) and TBI due to other mechanisms. OBJECTIVES To determine similarities and differences between clinical outcomes in US military personnel with blast-related vs. non-blast-related concussive TBI and to identify the specific domains of impairment that best correlate with overall disability. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study involving active duty US Military personnel evacuated from Iraq or Afghanistan to Landstuhl Regional Medical Center, in Landstuhl, Germany. Four groups of participants were enrolled from 2010 to 2013: (1) blast plus impact complex TBI (n=53), (2) non-blast related TBI with injury due to other mechanisms (n=29), (3) blast-exposed controls evacuated for other medical reasons (n=27) (4) non-blast-exposed controls evacuated for other medical reasons (n=69). All patients with TBI met Department of Defense criteria for concussive (mild) TBI. The study participants were evaluated 6-12 months after injury at Washington University in St Louis. In total, 255 subjects were enrolled in the study, and 183 participated in follow-up evaluations, 5 of whom were disqualified. MAIN OUTCOMES AND MEASURES In-person clinical examinations included evaluation for overall disability, a standardized neurological exam, headache questionnaires, neuropsychological test battery, combat exposure and alcohol use surveys, and structured interview evaluations for post-traumatic stress disorder (PTSD) and depression. RESULTS Global outcomes, headache severity, neuropsychological performance, and surprisingly even PTSD severity and depression were indistinguishable between the two TBI groups, independent of mechanism of injury. Both TBI groups had higher rates of moderate to severe overall disability than the respective control groups: 41/53 (77%) of blast plus impact TBI and 23/29 (79%) of nonblast TBI vs. 16/27 (59%) of blast-exposed controls and 28/69 (41%) of non-blast-exposed controls. In addition, blast-exposed controls had worse headaches and more severe PTSD than non-blast-exposed controls. Self-reported combat exposure intensity was higher in the blast plus impact TBI group than in nonblast TBI group and was higher in blast-exposed controls than in non-blast-exposed controls. However, combat exposure intensity did not correlate with PTSD severity in the TBI groups, but a modest positive correlation was observed in the controls. Overall outcomes were most strongly correlated with depression, headache severity, and number of abnormalities on neuropsychological testing. However a substantial fraction of the variance in overall outcome was not explained by any of the assessed measures. CONCLUSIONS AND RELEVANCE One potential interpretation of these results is that TBI itself, independent of injury mechanism and combat exposure intensity, is a primary driver of adverse outcomes. Many other important factors may be as yet unmeasured, and adverse outcomes following war-time injuries are difficult to fully explain. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01313130.

A review of the first 10 years of critical care aeromedical transport during operation iraqi freedom and operation enduring freedom: the importance of evacuation timing.

IMPORTANCE Advances in the care of the injured patient are perhaps the only benefit of military conflict. One of the unique aspects of the military medical care system that emerged during Operation Iraqi Freedom and Operation Enduring Freedom has been the opportunity to apply existing civilian trauma system standards to the provision of combat casualty care across an evolving theater of operations. OBJECTIVES To identify differences in mortality for soldiers undergoing early and rapid evacuation from the combat theater and to evaluate the capabilities of the Critical Care Air Transport Team (CCATT) and Joint Theater Trauma Registry databases to provide adequate data to support future initiatives for improvement of performance. DESIGN, SETTING, AND PARTICIPANTS Retrospective review of CCATT records and the Joint Theater Trauma Registry from September 11, 2001, to December 31, 2010, for the in-theater military medicine health system, including centers in Iraq, Afghanistan, and Germany. Of 2899 CCATT transport records, those for 975 individuals had all the required data elements. EXPOSURE Rapid evacuation by the CCATT. MAIN OUTCOMES AND MEASURES Survival as a function of time from injury to arrival at the role IV facility at Landstuhl Regional Medical Center. RESULTS The patient cohort demonstrated a mean Injury Severity Score of 23.7 and an overall 30-day mortality of 2.1%. Mortality en route was less than 0.02%. Statistically significant differences between survivors and decedents with respect to the Injury Severity Score (mean [SD], 23.4 [12.4] vs 37.7 [16.5]; P < .001), cumulative volume of blood transfused among the patients in each group who received a transfusion (P < .001), worst base deficit (mean [SD], -3.4 [5.0] vs -7.8 [6.9]; P = .02), and worst international normalized ratio (median [interquartile range], 1.2 [1.0-1.4] vs 1.4 [1.1-2.2]; P = .03) were observed. We found no statistically significant difference between survivors and decedents with respect to time from injury to arrival at definitive care. CONCLUSIONS AND RELEVANCE Rapid movement of critically injured casualties within hours of wounding appears to be effective, with a minimal mortality incurred during movement and overall 30-day mortality. We found no association between the duration of time from wounding to arrival at Landstuhl Regional Medical Center with respect to mortality.

Transportable extracorporeal lung support for rescue of severe respiratory failure in combat casualties

BACKGROUND Advances in oxygenator membrane, vascular cannula, and centrifugal pump technologies led to the miniaturization of extracorporeal lung support (ECLS) and simplified its insertion and use. Support of combat injuries complicated by severe respiratory failure requires critical care resources not sustainable in the deployed environment. In response to this need, a unique international military-civilian partnership was forged to create a transportable ECLS capability to rescue combat casualties experiencing severe respiratory failure. METHODS A multidisciplinary training and consultative relationship developed between the US military at Landstuhl Regional Medical Center (LRMC) and the University Hospital Regensburg (UHR), a German regional “lung failure” center with expertise in ECLS. ECLS circuits used were pumpless arteriovenous extracorporeal lung assist (NovaLung iLA) and pump-driven venovenous extracorporeal membrane oxygenation (PLS Quadrox D Membrane Oxygenator with Rotaflow Centrifugal Pump). US casualties supported by ECLS between June 2005 and August 2011 were identified from the LRMC Trauma Program Registry for review. RESULTS UHR cared for 10 US casualties supported by ECLS. The initial five patients were cannulated with arteriovenous circuits (pumpless arteriovenous extracorporeal lung assist), and the remaining five were cannulated with pump-driven venovenous circuits (extracorporeal membrane oxygenation). Four patients were cannulated in the war zone, and six patients were cannulated at LRMC after evacuation to Germany. All patients were transferred to UHR for continued management (mean, 9.6 ECLS days). In all cases, both hypoxemia and hypercapnia improved, allowing for decreased airway pressures. Nine patients were weaned from ECLS and extubated. One soldier died from progressive multiple-organ failure. CONCLUSION ECLS should be considered in the management of trauma complicated by severe respiratory failure. Modern ECLS technology allows these therapies to be transported for initiation outside of specialized centers even in austere settings. Close collaboration with established centers potentially allows both military and civilian hospitals with infrequent ECLS requirements to use it for initial patient stabilization before transfer for continued care. LEVEL OF EVIDENCE Therapeutic/care management study, level V.

A Clinical Tool for the Prediction of Venous Thromboembolism in Pediatric Trauma Patients

IMPORTANCE Although rare, the incidence of venous thromboembolism (VTE) in pediatric trauma patients is increasing, and the consequences of VTE in children are significant. Studies have demonstrated increasing VTE risk in older pediatric trauma patients and improved VTE rates with institutional interventions. While national evidence-based guidelines for VTE screening and prevention are in place for adults, none exist for pediatric patients, to our knowledge. OBJECTIVES To develop a risk prediction calculator for VTE in children admitted to the hospital after traumatic injury to assist efforts in developing screening and prophylaxis guidelines for this population. DESIGN, SETTING, AND PARTICIPANTS Retrospective review of 536,423 pediatric patients 0 to 17 years old using the National Trauma Data Bank from January 1, 2007, to December 31, 2012. Five mixed-effects logistic regression models of varying complexity were fit on a training data set. Model validity was determined by comparison of the area under the receiver operating characteristic curve (AUROC) for the training and validation data sets from the original model fit. A clinical tool to predict the risk of VTE based on individual patient clinical characteristics was developed from the optimal model. MAIN OUTCOME AND MEASURE Diagnosis of VTE during hospital admission. RESULTS Venous thromboembolism was diagnosed in 1141 of 536,423 children (overall rate, 0.2%). The AUROCs in the training data set were high (range, 0.873-0.946) for each model, with minimal AUROC attenuation in the validation data set. A prediction tool was developed from a model that achieved a balance of high performance (AUROCs, 0.945 and 0.932 in the training and validation data sets, respectively; P = .048) and parsimony. Points are assigned to each variable considered (Glasgow Coma Scale score, age, sex, intensive care unit admission, intubation, transfusion of blood products, central venous catheter placement, presence of pelvic or lower extremity fractures, and major surgery), and the points total is converted to a VTE risk score. The predicted risk of VTE ranged from 0.0% to 14.4%. CONCLUSIONS AND RELEVANCE We developed a simple clinical tool to predict the risk of developing VTE in pediatric trauma patients. It is based on a model created using a large national database and was internally validated. The clinical tool requires external validation but provides an initial step toward the development of the specific VTE protocols for pediatric trauma patients.

Extracorporeal organ support following trauma: the dawn of a new era in combat casualty critical care.

Abstract : Death after severe trauma in the civilian and military setting occurs in a trimodal distribution. Historically, the majority of injury-related mortality occurs in the prehospital setting owing to hemorrhage. Of patients who survive to hospital admission, another group of deaths occurs in the acute phase owing to devastating head injury or uncontrolled hemorrhage. Among patients who survive these immediate and acute phases of trauma, the last significant phase of mortality occurs in the days and weeks following injury from sepsis and multiple organ failure (MOF). The immediate care of the severely injured is guided by structured clinical practice guidelines that have been widely adopted for the prehospital and early hospital settings. Early use of tourniquets, hemostatic dressings, and the concepts of damage-control surgery and hemostatic resuscitation have led to more patients surviving the immediate and early phases of severe trauma. As advances in prevention and treatment of death from hemorrhage occur, there may be an expected decrease in mortality during the early aspects of the trimodal pattern of mortality. Specifically, improved survivability of the initial phases of injury can be expected to result in a greater number of physiologically compromised patients prone to MOF surviving later into the hospitalization. As such, directing a significant portion of current and future clinical expertise and scientific study to advanced organ support techniques is prudent.

Outcome Trends after US Military Concussive Traumatic Brain Injury

Care for US military personnel with combat-related concussive traumatic brain injury (TBI) has substantially changed in recent years, yet trends in clinical outcomes remain largely unknown. Our prospective longitudinal studies of US military personnel with concussive TBI from 2008-2013 at Landstuhl Regional Medical Center in Germany and twp sites in Afghanistan provided an opportunity to assess for changes in outcomes over time and analyze correlates of overall disability. We enrolled 321 active-duty US military personnel who sustained concussive TBI in theater and 254 military controls. We prospectively assessed clinical outcomes 6-12 months later in 199 with concussive TBI and 148 controls. Global disability, neurobehavioral impairment, depression severity, and post-traumatic stress disorder (PTSD) severity were worse in concussive TBI groups in comparison with controls in all cohorts. Global disability primarily reflected a combination of work-related and nonwork-related disability. There was a modest but statistically significant trend toward less PTSD in later cohorts. Specifically, there was a decrease of 5.9 points of 136 possible on the Clinician Administered PTSD Scale (-4.3%) per year (95% confidence interval, 2.8-9.0 points, p = 0.0037 linear regression, p = 0.03 including covariates in generalized linear model). No other significant trends in outcomes were found. Global disability was more common in those with TBI, those evacuated from theater, and those with more severe depression and PTSD. Disability was not significantly related to neuropsychological performance, age, education, self-reported sleep deprivation, injury mechanism, or date of enrollment. Thus, across multiple cohorts of US military personnel with combat-related concussion, 6-12 month outcomes have improved only modestly and are often poor. Future focus on early depression and PTSD after concussive TBI appears warranted. Adverse outcomes are incompletely explained, however, and additional studies with prospective collection of data on acute injury severity and polytrauma, as well as reduced attrition before follow-up will be required to fully address the root causes of persistent disability after wartime injury.

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.

Derivation of Candidates for the Combat Casualty Critical Care (C4) Database

OBJECTIVE To describe the development of the Combat Casualty Critical Care Database, a comprehensive database of critically injured combat casualties to identify potentially modifiable risk factors for morbidity and mortality in this population. METHODS The Department of Defenses Joint Theater Trauma Registry was queried for all combat casualties injured from February 1, 2002 through February 1, 2011. The search was limited to patients who required admission to the intensive care unit and survived to be evacuated to Landstuhl Regional Medical Center. RESULTS The query yielded 6,011 patients. The mean age was 25.7 ± 6.2 years. The majority of patients were male (98.3%), injured in Iraq (80%) and were members of the U. S. Army (72.6%). Most patients (58.0%) had an injury severity score in the lowest severity category (0-15). The mortality rate was 1.8%. The median day of death after injury (interquartile range) was 6 (3-14). CONCLUSIONS We identified a cohort of critically wounded combat casualties that encompasses the majority of such patients injured in the course of the wars in Iraq and Afghanistan. When this database is fully populated, rigorous epidemiologic analysis will seek to identify factors associated with morbidity and mortality to improve future care.

Combat management of splenic injury: trends during a decade of conflict.

BACKGROUND As a performance improvement measure to optimize patient outcome, theater-wide clinical practice guidelines (CPGs) have been developed to standardize the management of many injury patterns seen during combat operations. Battle-related splenic injury presents differently from civilian practice, and a combat-related CPG was developed. The epidemiology and validation of the spleen injury CPG were analyzed. METHODS The Joint Theater Trauma Registry was queried for splenic injury from 2001 to 2010. Theater of operation (Afghanistan and Iraq), injury year, mechanism, patients’ baseline characteristics, and severity were recorded. Patient charts were reviewed for management decisions and outcomes. RESULTS The 10-year experience identified 393 patients who sustained splenic injury (rate of 16.1 per 1000 injuries). Most victims were men (97.5%), blunt, and severely injured (70.7%; mean Injury Severity Score, 32.5, respectively), with a mean age of 25.4 years. The prominent mechanism was explosion (62.2%), followed by vehicle crash (25.9%). The most prevalent injury was grade II (56.2%), followed by III (21.1%), IV (11.7%), and V (9.7%). More than half of patients underwent splenectomy (52.7%), most of which occurred in theater (95.1%). All nonoperative failures were treated within 4 days of injury at the role IV facility in Landstuhl. Patients who underwent splenectomy received more blood products, crystalloid, and demonstrated a longer length of stay than those treated nonoperatively. High-grade injuries treated nonoperatively were successfully managed. The overall cohort mortality was 9%, and no death was directly related to delayed diagnosis or treatment. CONCLUSION Splenic injury has been successfully managed during combat operations through the use of a well-established CPG. The overall mortality remains low, with few delayed nonoperative failures. Refinements in this validated CPG may now address controversies in higher grade injuries. LEVEL OF EVIDENCE Prognostic/epidemiologic study, level III.

Rhabdomyolysis among critically ill combat casualties: Associations with acute kidney injury and mortality.

BACKGROUND Rhabdomyolysis has been associated with poor outcomes in patients with traumatic injury, especially in the setting of acute kidney injury (AKI). However, rhabdomyolysis has not been systematically examined in a large cohort of combat casualties injured in the wars in Iraq and Afghanistan. METHODS We conducted a retrospective study of casualties injured during combat operations in Iraq and Afghanistan who were initially admitted to the intensive care unit from February 1, 2002, to February 1, 2011. Information on age, sex, Abbreviated Injury Scale (AIS) score, Injury Severity Score (ISS), mechanism of injury, shock index, creatine kinase, and serum creatinine were collected. These variables were examined via multivariate logistic and Cox regression analyses to determine factors independently associated with rhabdomyolysis, AKI, and death. RESULTS Of 6,011 admissions identified, a total of 2,109 patients met inclusion criteria and were included for analysis. Rhabdomyolysis, defined as creatine kinase greater than 5,000 U/L, was present in 656 subjects (31.1%). Risk factors for rhabdomyolysis identified on multivariable analysis included injuries to the abdomen and extremities, increased ISS, male sex, explosive mechanism of injury, and shock index greater than 0.9. After adjustment, patients with rhabdomyolysis had a greater than twofold increase in the odds of AKI. In the analysis for mortality, rhabdomyolysis was significantly associated with death until AKI was added, at which point it lost statistical significance. CONCLUSION We found that rhabdomyolysis is associated with the development of AKI in combat casualties. While rhabdomyolysis was strongly associated with mortality on the univariate model and in conjunction with both ISS and age, it was not associated with mortality after the inclusion of AKI. This suggests that the effect of rhabdomyolysis on mortality may be mediated by AKI. LEVEL OF EVIDENCE Prognostic and epidemiologic study, level III.