Matthew A. Borgman

Ten-year analysis of transfusion in Operation Iraqi Freedom and Operation Enduring Freedom: increased plasma and platelet use correlates with improved survival.

BACKGROUND The Joint Theater Trauma Registry database, begun early in Operation Iraqi Freedom and Operation Enduring Freedom, created a comprehensive repository of information that facilitated research efforts and produced rapid changes in clinical care. New clinical practice guidelines were adopted throughout the last decade. The damage-control resuscitation clinical practice guideline sought to provide high-quality blood products in support of tissue perfusion and hemostasis. The goal was to reduce death from hemorrhagic shock in patients with severe traumatic bleeding. This 10-year review of the Joint Theater Trauma Registry database reports the military’s experience with resuscitation and coagulopathy, evaluates the effect of increased plasma and platelet (PLT)–to–red blood cell ratios, and analyzes other recent changes in practice. METHODS Records of US active duty service members at least 18 years of age who were admitted to a military hospital from March 2003 to February 2012 were entered into a database. Those who received at least one blood product (n = 3,632) were included in the analysis. Data were analyzed with respect to interactions within and between categories (demographics, admission characteristics, hospital course, and outcome). Transfusions were analyzed with respect to time, survival, and effect of increasing transfusion ratios. RESULTS Coagulopathy was prevalent upon presentation (33% with international normalized ratio ≥ 1.5), correlated with increased mortality (fivefold higher), and was associated with the need for massive transfusion. High transfusion ratios of fresh frozen plasma and PLT to red blood cells were correlated with higher survival but not decreased blood requirement. Survival was most correlated with PLT ratio, but high fresh frozen plasma ratio had an additive effect (PLT odds ratio, 0.22). CONCLUSION This 10-year evaluation supports earlier studies reporting the benefits of damage-control resuscitation strategies in military casualties requiring massive transfusion. The current analysis suggests that defects in PLT function may contribute to coagulopathy of trauma. LEVEL OF EVIDENCE Epidemiologic study, level IV.

Constant Challenges and Evolution of US Military Transfusion Medicine and Blood Operations in Combat

BACKGROUND: Blood operations are constrained by many limitations in combat settings. As a result there are many challenges that require innovative solutions.

Timing and location of blood product transfusion and outcomes in massively transfused combat casualties.

BACKGROUND Hemostatic resuscitation using blood components in a 1:1:1 ratio of platelets:fresh frozen plasma:red blood cells (RBCs) is based on analyses of massive transfusion (MT, ≥10 RBC units in 24 hours). These 24-hour analyses are weakened by survival bias and do not describe the timing and location of transfusions. Mortality outcomes associated with early (first 6 hours) resuscitation incorporating platelets, for combat casualties requiring MT, have not been reported. METHODS We analyzed records for 8,618 casualties treated at the United States military hospital in Baghdad, Iraq, between January 2004 and December 2006. Patients (n = 414) requiring MT, not receiving fresh whole blood, and surviving at least 1 hour (reducing survival bias) were divided into 6-hour apheresis platelet (aPLT) transfusion ratio groups: LOW (aPLT:RBC, ⩽0.1, n = 344) and HIGH (aPLT:RBC, >0.1, n = 70). Baseline characteristics of groups were compared. Factors influencing survival on univariate analysis were included in Cox proportional hazards models of 24-hour and 30-day survival. RESULTS Patients received aPLT in the emergency department (4%), operating room (45%), intensive care unit (51%). The HIGH group presented with higher (p < 0.05) admission International Normalized Ratio (1.6 vs. 1.4), base deficit (8 vs. 7), and temperature (36.7 vs. 36.4). Overall mortality was 27%. At 24 hours, the HIGH group showed lower mortality (10.0% vs. 22.1%, p = 0.02). Absolute differences in 30-day mortality were not significant (HIGH, 18.6%; LOW, 28.8%, p = 0.08). On adjusted analysis, the HIGH group was independently associated with increased survival: LOW group mortality hazard ratios were 4.1 at 24 hours and 2.3 at 30 days compared with HIGH group (p = 0.03 for both). Increasing 6-hour FFP:RBC ratio was also independently associated with increased survival. CONCLUSION Early (first 6 hours) hemostatic resuscitation incorporating platelets and plasma is associated with improved 24-hour and 30-day survival in combat casualties requiring MT. LEVEL OF EVIDENCE Therapeutic study, level III.

Ten years of military pediatric care in Afghanistan and Iraq.

BACKGROUND Besides care for injured US military personnel, doctrine also requires life-, limb-, and eyesight-saving care to all injured casualties, including children. This study’s objective was to evaluate the burden and epidemiology of pediatric medical care during the past decade of military operations in Iraq and Afghanistan. METHODS Retrospective review of two military registries of all patients admitted to combat support hospitals and forward surgical teams from 2001 through 2011 was conducted. Pediatric (PED) patients were defined as younger than 18 years. Adult patients were divided into local civilian/noncoalition military (LOCAL) and coalition (COALITION) soldiers. RESULTS A total of 7,505 PED patients, 25,459 LOCAL adults, and 95,618 COALITION soldiers were analyzed in the primary registry. Children represented 5.8% of all admissions (11% bed days), LOCAL adults represented 20% (36% bed days), and COALITION soldiers represented 74% (53% bed days). PED median (interquartile range) length of stay was 3 days (1–7 days), longer than LOCAL with 2 days (1–6 days), and COALITION with 1 day (1–2 days) (p < 0.001). PED Injury Severity Score (ISS) was 9 (4–16), similar to LOCAL with 9 (4–16) but higher than COALITION with 5 (2–10) (p < 0.001). Mortality in trauma patients was highest in PED (8.5%) compared with LOCAL (7.1%) and COALITION (3%) (p < 0.01). Mechanisms of injury for PED trauma were blast (37%), penetrating (27%), blunt (23%), and burn (13%). Factors independently associated with PED mortality included ISS (odds ratio, 95% confidence interval) (1.08, 1.06–1.09), Glasgow Coma Scale (GCS) score (0.85, 0.82–0.88), base excess (0.87, 0.85–0.90), female sex (1.73, 1.18–2.52), age less than 8 years (1.43, 1.00–2.04), and burns (3.17, 1.89–5.32). CONCLUSION Deployed medical facilities not staffed or equipped to typical civilian standards have a high burden of pediatric casualties requiring care. The cause of increased mortality in pediatric versus adult populations despite similar severity of injury is potentially multifactorial. Military medical planners need to consider pediatric resources and training to improve outcomes for children injured during combat. LEVEL OF EVIDENCE Epidemiologic study, level III.

Clearly defining pediatric massive transfusion: cutting through the fog and friction with combat data.

BACKGROUND Massive transfusion (MT) in pediatric patients remains poorly defined. Using the largest existing registry of transfused pediatric trauma patients, we sought a data-driven MT threshold. METHODS The Department of Defense Trauma Registry was queried from 2001 to 2013 for pediatric trauma patients (<18 years). Burns, drowning, isolated head injury, and missing Injury Severity Score (ISS) were excluded. MT was evaluated as a weight-based volume of all blood products transfused in the first 24 hours. Mortality at 24 hours and in the hospital was calculated for increasing transfusion volumes. Sensitivity and specificity curves for predicting mortality were used to identify an optimal MT threshold. Patients above and below this threshold (MT+ and MT−, respectively) were compared. RESULTS The Department of Defense Trauma Registry yielded 4,990 combat-injured pediatric trauma patients, of whom 1,113 were transfused and constituted the study cohort. Sensitivity and specificity for 24-hour and in-hospital mortality were optimal at 40.1-mL/kg and 38.6-mL/kg total blood products in the first 24 hours, respectively. With the use of a pragmatic threshold of 40 mL/kg, patients were divided into MT+ (n = 443) and MT− (n = 670). MT+ patients were more often in shock (68.1% vs. 47.0%, p < 0.001), hypothermic (13.0% vs. 3.4%, p < 0.001), coagulopathic (45.0% vs. 29.6%, p < 0.001), and thrombocytopenic (10.6% vs. 5.0%, p = 0.002) on presentation. MT+ patients had a higher ISS, more mechanical ventilator days, and longer intensive care unit and hospital stay. MT+ was independently associated with an increased 24-hour mortality (odds ratio, 2.50; 95% confidence interval, 1.28–4.88; p = 0.007) and in-hospital mortality (odds ratio, 2.58; 95% confidence interval, 1.70–3.92; p < 0.001). CONCLUSION Based on this large cohort of transfused combat-injured pediatric patients, a threshold of 40 mL/kg of all blood products given at any time in the first 24 hours reliably identifies critically injured children at high risk for early and in-hospital death. This evidence-based definition will provide a consistent framework for future research and protocol development in pediatric resuscitation. LEVEL OF EVIDENCE Diagnostic study, level II. Prognostic/epidemiologic study, level III.

Thromboelastography to direct the administration of recombinant activated factor VII in a child with traumatic injury requiring massive transfusion.

Objective: To describe the use of thromboelastography (TEG) to direct hemostatic resuscitation in a child with traumatic injury requiring massive transfusion. Design: Case report. Setting: Level 1 pediatric trauma center in an academic tertiary care facility. Patient: A 5-year-old boy with grade IV liver injury and right common hepatic artery laceration. Intervention: TEG-directed resuscitation, including recombinant activated factor VII. Measurements and Main Results: Measurements included vital signs, laboratory results to include TEG values, and blood product administration. TEG-directed resuscitation with recombinant activated factor VII was associated with the prevention of increased intracranial hemorrhage and survival in a coagulopathic patient with a life-threatening traumatic injury. Conclusion: Our clinical and TEG laboratory results postresuscitation support the potential use of TEG as a tool to direct hemostatic resuscitation in patients with severe trauma requiring massive transfusion. TEG is a quick and focused method of qualitatively assessing the entire coagulation cascade, from clot formation to fibrinolysis that permits a targeted transfusion approach to the treatment of coagulopathy. TEG has the potential to rapidly and effectively direct hemostatic resuscitation in patients with the coagulopathy of trauma.

Comparison of the predictive performance of the BIG, TRISS and PS09 score in an adult trauma population derived from multiple international trauma registries

BackgroundThe BIG score (Admission base deficit (B), International normalized ratio (I), andGlasgow Coma Scale (G)) has been shown to predict mortality on admission inpediatric trauma patients. The objective of this study was to assess itsperformance in predicting mortality in an adult trauma population, and to compareit with the existing Trauma and Injury Severity Score (TRISS) and probability ofsurvival (PS09) score.Materials and methodsA retrospective analysis using data collected between 2005 and 2010 from seventrauma centers and registries in Europe and the United States of America wasperformed. We compared the BIG score with TRISS and PS09 scores in a population ofblunt and penetrating trauma patients. We then assessed the discrimination abilityof all scores via receiver operating characteristic (ROC) curves and compared theexpected mortality rate (precision) of all scores with the observed mortalityrate.ResultsIn total, 12,206 datasets were retrieved to validate the BIG score. The mean ISSwas 15 ± 11, and the mean 30-day mortality rate was 4.8%. With an AUROC of0.892 (95% confidence interval (CI): 0.879 to 0.906), the BIG score performed wellin an adult population. TRISS had an area under ROC (AUROC) of 0.922 (0.913 to0.932) and the PS09 score of 0.825 (0.915 to 0.934). On a penetrating-traumapopulation, the BIG score had an AUROC result of 0.920 (0.898 to 0.942) comparedwith the PS09 score (AUROC of 0.921; 0.902 to 0.939) and TRISS (0.929; 0.912 to0.947).ConclusionsThe BIG score is a good predictor of mortality in the adult trauma population. Itperformed well compared with TRISS and the PS09 score, although it hassignificantly less discriminative ability. In a penetrating-trauma population, theBIG score performed better than in a population with blunt trauma. The BIG scorehas the advantage of being available shortly after admission and may be used topredict clinical prognosis or as a research tool to risk stratify trauma patientsinto clinical trials.

Glasgow Coma Scale as a predictor for hemocoagulative disorders after blunt pediatric traumatic brain injury.

Objective: Coagulopathy is a complication of traumatic brain injury and its presence after injury has been identified as a risk factor for prognosis. It was our aim to determine whether neurologic findings reflected by Glasgow Coma Scale at initial resuscitation can predict hemocoagulative disorders resulting from traumatic brain injury that may aggravate clinical sequelae and outcome in children. Design: A retrospective analysis of 200 datasets from children with blunt, isolated traumatic brain injury documented in the Trauma Registry of the Deutsche Gesellschaft für Unfallchirurgie was conducted. Inclusion criteria were primary admission, age <14 yrs, and sustained isolated blunt traumatic brain injury. Setting: Trauma Registry of the Deutsche Gesellschaft für Unfallchirurgie-affiliated trauma centers in Germany. Patients: Two hundred datasets of children (age <14 yrs) with blunt isolated traumatic brain injury were analyzed: children were subdivided into two groups according to Glasgow Coma Scale at the scene (Glasgow Coma Scale ⩽8 vs. Glasgow Coma Scale >8) and reviewed for coagulation abnormalities upon emergency room admission and outcome. Measurement and Main Results: Fifty-one percent (n = 102 of 200) of children had Glasgow Coma Scale >8 and 49% (n = 98 of 200) had Glasgow Coma Scale ⩽8 at the scene. The incidence of coagulopathy at admission was higher in children with Glasgow Coma Scale ⩽8 compared to children with Glasgow Coma Scale >8: 44% (n = 31 of 71) vs. 14% (n = 11 of 79) (p < .001). Multivariate logistic regression revealed that Glasgow Coma Scale ⩽8 at scene was associated with coagulopathy at admission (odds ratio 3.378, p = .009) and stepwise regression identified Glasgow Coma Scale ⩽8 as an independent risk factor for coagulopathy. Mortality in children with Glasgow Coma Scale ⩽8 at scene was substantially higher with the presence of coagulation abnormalities at admission compared to children in which coagulopathy was absent (51.6%, n = 16 of 31 vs. 5% n = 2 of 40). Conclusions: Glasgow Coma Scale ⩽8 at scene in children with isolated traumatic brain injury is associated with increased risk for coagulopathy and mortality. These results may guide laboratory testing, management, and blood bank resources in acute pediatric trauma care.

Isolated pediatric burn injury in Iraq and Afghanistan.

Objectives: To characterize the epidemiology of burn injury in pediatric patients and identify factors associated with mortality based on burn severity. Design: Retrospective cohort study. Setting: U.S. military combat support hospitals and forward surgical hospitals in Iraq and Afghanistan. Patients: Iraqi and Afghan children less than 18 years old admitted with isolated burn injury. Interventions: None. Measurements and Main Results: Burn severity was classified as mild, moderate, and severe based on external Abbreviated Injury Scale score. Patient characteristics and outcomes were described according to burn severity. A multivariate logistic regression was performed on univariate associations with mortality. Of 4,743 pediatric patients, 549 (11.6%) had isolated burn injury. Overall mortality was 13%, median external Abbreviated Injury Scale was 3 (interquartile range, 2–4), and 67% were male. Variables included in the logistic regression were external Abbreviated Injury Scale score, abnormal heart rate for age, hypotension, mechanical ventilation, transfusion, Glasgow Coma Scale, international normalized ratio, base deficit, hematocrit, and platelet count. Factors independently associated with mortality were international normalized ratio (odds ratio, 2.6; 95% CI, 1.2–5.8; p = 0.021) and external Abbreviated Injury Scale (odds ratio, 2.5; 95% CI, 1.3–4.7; p = 0.004). Mortality increased with burn severity: mild 1.7%, moderate 7.2%, and severe 47% (p < 0.001). Conclusions: This is the first in-depth study of pediatric burn injuries in combat. Children with severe burns (total body surface area > 39% or > 29% if < 5 yr) had a high mortality and required significant resources in a setting that is not primarily resourced for long-term care of severe pediatric burn injury. Extraordinary measures are therefore used for the long-term care of these burned children within the war zones of Iraq and Afghanistan.

High ratio plasma resuscitation does not improve survival in pediatric trauma patients

BACKGROUND Damage control resuscitation including balanced resuscitation with high ratios of plasma (PLAS) and platelets (PLT) to packed red blood cells (PRBC) improves survival in adult patients. We sought to evaluate the effect of a high ratio PLAS to PRBC resuscitation strategy in massively transfused pediatric patients with combat injuries. METHODS The Department of Defense Trauma Registry was queried from 2001 to 2013 for pediatric trauma patients (<18 years). Burns, drowning, isolated head trauma, and older teens were excluded. Those who received massive transfusion (≥40 mL/kg total blood products in 24 hours) and early deaths who received any blood products were then evaluated. Primary outcomes were mortality at 24 hours and in-hospital. Secondary outcomes included blood product utilization over 24 hours, ventilator-free days, intensive care unit–free days, and hospital length of stay. RESULTS The Department of Defense Trauma Registry yielded 4,980 combat-injured pediatric trauma patients, of whom 364 met inclusion criteria. Analysis of PLAS/PRBC ratios across the entire spectrum of possible ratios in these patients demonstrated no clear inflection point for mortality. Using a division between low (LO) and high (HI) ratios of PLAS/PRBC 1:2, there was no difference in all-cause mortality at 24 hours (LO, 9.2% vs. HI, 8.0%; p = 0.75) and hospital discharge (LO, 21.5% vs. HI, 17.1%; p = 0.39). HI ratio patients received less PRBC but more PLAS and PLT and more total blood products. Those in the HI ratio group also had longer hospital length of stay. Regression analysis demonstrated no associated mortality benefit with a HI ratio (hazards ratio, 2.04; 95% confidence interval, 0.48–8.73; p = 0.34). CONCLUSION In combat-injured children undergoing a massive transfusion, a high ratio of PLAS/PRBC was not associated with improved survival. Further prospective studies should be performed to determine the optimal resuscitation strategy in critically injured pediatric patients. LEVEL OF EVIDENCE Therapeutic study, level III.