Philip C. Spinella

The lessons learned regarding the resuscitation of traumatic hemorrhagic shock are numerous and come from a better understanding of the epidemiology, pathophysiology, and experience in this population over 10-plus years of combat operations. We have now come to better understand that the greatest benefit in survival can come from improved treatment of hemorrhage in the prehospital phase of care. We have learned that there is an endogenous coagulopathy that occurs with severe traumatic injury secondary to oxygen debt and that classic resuscitation strategies for severe bleeding based on crystalloid or colloid solutions exacerbate coagulopathy and shock for those with life-threatening hemorrhage. We have relearned that a whole blood-based resuscitation strategy, or one that at least recapitulates the functionality of whole blood, may reduce death from hemorrhage and reduce the risks of excessive crystalloid administration which include acute lung injury, abdominal compartment syndrome, cerebral edema, and anasarca. Appreciation of the importance of shock and coagulopathy management underlies the emphasis on early hemostatic resuscitation. Most importantly, we have learned that there is still much more to understand regarding the epidemiology, pathophysiology, and the resuscitation strategies required to improve outcomes for casualties with hemorrhagic shock.

Introduction: Retrospective studies have demonstrated a potential survival benefit from transfusion strategies using an early and more balanced ratio between fresh frozen plasma (FFP) concentration and packed red blood cell (pRBC) transfusions in patients with acute traumatic coagulopathy requiring massive transfusions. These results have mostly been derived from non-head-injured patients. The aim of the present study was to analyze whether a regime using a high FFP:pRBC transfusion ratio (FFP:pRBC ratio >1:2) would be associated with a similar survival benefit in severely injured patients with traumatic brain injury (TBI) (Abbreviated Injury Scale (AIS) score, head ≥3) as demonstrated for patients without TBI requiring massive transfusion (≥10 U of pRBCs). Methods: A retrospective analysis of severely injured patients from the Trauma Registry of the Deutsche Gesellschaft für Unfallchirurgie (TR-DGU) was conducted. Inclusion criteria were primary admission, age ≥16 years, severe injury (Injury Severity Score (ISS) ≥16) and massive transfusion (≥10 U of pRBCs) from emergency room to intensive care unit (ICU). Patients were subdivided into patients with TBI (AIS score, head ≥3) and patients without TBI (AIS score, head 1:2) and low FFP:pRBC ratio (FFP:pRBC ratio ≤1:2). In addition, morbidity and mortality between the two groups were compared. Results: A total of 1,250 data sets of severely injured patients from the TR-DGU between 2002 and 2008 were analyzed. The mean patient age was 42 years, the majority of patients were male (72.3%), the mean ISS was 41.7 points (±15.4 SD) and the principal mechanism of injury was blunt force trauma (90%). Mortality was statistically lower in the high FFP:pRBC ratio groups versus the low FFP:pRBC ratio groups, regardless of the presence or absence of TBI and across all time points studied (P < 0.001). The frequency of sepsis and multiple organ failure did not differ among groups, except for sepsis in patients with TBI who received a high FFP:pRBC ratio transfusion. Other secondary end points such as ventilator-free days, length of stay in the ICU and overall in-hospital length of stay differed significantly between the two study groups, but not when only data for survivors were analyzed. Conclusions: These results add more detailed knowledge to the concept of a high FFP:pRBC ratio during early aggressive resuscitation, including massive transfusion, to decrease mortality in severely injured patients both with and without accompanying TBI. Future research should be conducted with a larger number of patients to prove these results in a prospective study.

BACKGROUND: Previous surveys have reported variation in transfusion practice or policies in specific pediatric populations. Our objective was to determine the current transfusion policies in US and Canadian children's hospitals for both neonatal and pediatric general populations.STUDY DESIGN AND METHODS: US and Canadian blood bank (BB) personnel at children's hospitals that provide blood products between the dates of October 2008 and January 2009 were surveyed.RESULTS: Of the 90 US and Canadian children's hospitals identified, 51 (56.7%) blood bankers or their designees responded. There were 42 of 51 (82.4%) respondents from the United States and 9 of 51 (17.6%) from Canada. There was wide variation in beliefs regarding the effect of red blood cell (RBC) storage age on outcomes with 66.6% of respondents interested in a prospective randomized trial in critically ill children. There was also wide variation in policies restricting the storage age of RBCs according to patient age and clinical condition. In the United States 28 of 33 (84.8%) respondents provide universal leukoreduction of RBCs whereas it is 9 of 9 (100%) in Canada. Variation of policies existed for RBC irradiation and washing. The majority of respondents indicated that RBC transfusions were audited if the pretransfusion hemoglobin level was more than 8 to 10 mg/dL. Fresh whole blood is available at 6 of 40 (15%) responding children's hospitals.CONCLUSIONS: There is a wide variation in BB policies regarding RBC transfusions at children's hospitals in the United States and Canada. Prospective randomized controlled trials are needed to allow for evidence‐based standards of care regarding RBC transfusions.

Introduction: Transfusion is a common treatment in pediatric intensive care units (PICUs). Studies in adults suggest that prolonged storage of red blood cell units is associated with worse clinical outcome. No prospective study has been conducted in children. Our objectives were to assess the clinical impact of the length of storage of red blood cell units on clinical outcome of critically ill children. Methods: Prospective, observational study conducted in 30 North American centers, in consecutive patients aged P = 0.03). There was also a significant difference in the total PICU length of stay (adjusted median difference +3.7 days, P < 0.001) and no significant change in mortality. Conclusions: In critically ill children, transfusion of red blood cell units stored for ≥ 14 days is independently associated with an increased occurrence of multiple organ dysfunction syndrome and prolonged PICU stay.

Background: Increased understanding of the pathophysiology of the acute coagulopathy of trauma has lead many to question the current transfusion approach to hemorrhagic shock. We hypothesized that warm fresh whole blood (WFWB) transfusion would be associated with improved survival in patients with trauma compared with those transfused only stored component therapy (CT). Methods: We retrospectively studied US Military combat casualty patients transfused ≥1 unit of red blood cells (RBCs). The following two groups of patients were compared: (1) WFWB, who were transfused WFWB, RBCs, and plasma but not apheresis platelets and (2) CT, who were transfused RBC, plasma, and apheresis platelets but not WFWB. The primary outcomes were 24-hour and 30-day survival. Results: Of 354 patients analyzed there were 100 in the WFWB and 254 in the CT group. Patients in both groups had similar severity of injury determined by admission eye, verbal, and motor Glasgow Coma Score, base deficit, international normalized ratio, hemoglobin, systolic blood pressure, and injury severity score. Both 24-hour and 30-day survival were higher in the WFWB cohort compared with CT patients, 96 of 100 (96%) versus 223 of 254 (88%), (p = 0.018) and 95% to 82%, (p = 0.002), respectively. An increased amount (825 mL) of additives and anticoagulants were administered to the CT compared with the WFWB group, (p < 0.001). Upon multivariate logistic regression the use of WFWB and the volume of WFWB transfused was independently associated with improved 30-day survival. Conclusions: In patients with trauma with hemorrhagic shock, resuscitation strategies that include WFWB may improve 30-day survival, and may be a result of less anticoagulants and additives with WFWB use in this population.

The objective of this study was to review the history and current literature regarding the benefits and risks of warm fresh whole blood transfusion to include recent U.S. Army research from Afghanistan and Iraq. We also discuss current indications for its use as well as potential civilian applications for large-scale disasters. The use of warm fresh whole blood currently only persists in emergency life-threatening scenarios when tested stored blood components are not available. Recent combat operations in Afghanistan and Iraq have redirected attention on the benefits and risks of warm fresh whole blood for life-threatening injuries in casualties. Between March 2003 and July 2007, over 6000 units of warm fresh whole blood have been transfused in Afghanistan and Iraq by U.S. medical providers to patients with life-threatening traumatic injuries with hemorrhage. Preliminary results in approximately 500 patients with massive transfusion indicate that the amount of fresh warm whole blood transfused is independently associated with improved 48-hr and 30-day survival and the amount of stored red blood cells is independently associated with decreased 48-hr and 30-day survival for patients with traumatic injuries that require massive transfusion. Risks of warm fresh whole blood transfusion include the transmission of infectious agents and the potential for microchimerism. For patients with life-threatening hemorrhage at risk for massive transfusion, if complete component therapy is not available or not adequately correcting coagulopathy, the risk:benefit ratio of warm fresh whole blood transfusion favors its use. In addition, recent evidence suggests that there is potential for warm fresh whole blood to be more efficacious than stored component therapy that includes stored red blood cells in critically ill patients requiring massive transfusion. Efforts must continue to improve the safety of warm fresh whole blood transfusion for patients when it is required in emergency situations. U.S. civilian disaster agencies are preparing guidelines for its use in massive casualty scenarios and prospective, randomized trials are about to start to determine whether stored warm fresh (<24 hrs) whole blood improves outcomes compared with standard stored component therapy.

The objective of this study was to describe the epidemiology of pediatric patients admitted with traumatic injuries to U.S. combat support hospitals and to provide insight into both critical care and noncritical care challenges this presents. The authors provide a descriptive report. This study was conducted at seven combat support hospitals in both Iraq and Afghanistan. Subjects were pediatric patients age <18 yrs. There were 1,305 (7.1%) pediatric patients admitted to Army combat support hospitals who required 12% of all hospital bed days. The hospital length of stay was increased in pediatric patients compared with both adult coalition and noncoalition patients. Thirteen percent of all the patients who died at combat support hospitals and 11% of all transfusions and patients on mechanical ventilation were children. In-hospital mortality for pediatric patients was increased 71 of 1,305 (5.4%) compared with both adult coalition (114 of 8,567 [1.3%]) and noncoalition patients (369 of 8,511 [4.3%]) (p < .05). In-hospital mortality was increased for children <6 yrs of age compared with children 6 to 17 yrs of age, 10.7% versus 3.8%, respectively (p < .05). Pediatric patients with traumatic injuries are common at deployed U.S. military medical facilities as a result of combat-related and noncombat-related injuries and have increased in-hospital mortality compared with adults. Mortality was also increased for younger compared with older children. Innovative adaptations in addition to logistic and organizational changes have potentially improved pediatric care since the early stages of both wars from 2001 to 2003. Self-improvement through coalition support of the Iraqi and Afghani medical systems is needed to permit advancement and self-reliance.

The majority of patients with potentially survivable combat-related injuries die from hemorrhage. Our objective was to determine whether the use of recombinant activated factor VII (rFVIIa) decreased mortality in combat casualties with severe trauma who received massive transfusions and if its use was associated with increased severe thrombotic events. We retrospectively reviewed a database of combat casualty patients with severe trauma (Injury Severity Score [ISS] >15) and massive transfusion (red blood cell [RBCs] ≥10 units/24 hours) admitted to one combat support hospital in Baghdad, Iraq, between December 2003 and October 2005. Admission vital signs and laboratory data, blood products, ISS, 24-hour and 30-day mortality, and severe thrombotic events were compared between patients who received rFVIIa (rFVIIa+) and did not receive rFVIIa (rFVIIa−). Of 124 patients in this study, 49 patients received rFVIIa and 75 did not. ISS, laboratory values, and admission vitals did not differ between rFVIIa+ and rFVIIa− groups, except for systolic blood pressure (mm Hg) 105 ± 33 and 92 ± 28, p = 0.02 and temperature (°F) 96.3 ± 2.1 and 95.2 ± 2.4, p = 0.03, respectively. Interactions between all vital signs and laboratory values measured upon admission, to include systolic blood pressure and temperature, were not significant when measured between rFVIIa use and 30-day mortality. Twenty-four-hour mortality was 7 of 49 (14%) in rFVIIa+ and 26 of 75 (35%) in rFVIIa−, (p = 0.01); 30-day mortality was 15 of 49 (31%) and 38 of 75 (51%), (p = 0.03). Death from hemorrhage was 8 of 14 (57%) for rFVIIa+ patients compared with 29 of 37 (78%) for rFVIIa− patients, (p = 0.12). The incidence of severe thrombotic events was similar in both groups. The early use of rFVIIa was associated with decreased 30-day mortality in severely injured combat casualties requiring massive transfusion, but was not associated with increased risk of severe thrombotic events.

The amount and age of stored red blood cells (RBCs) are independent predictors of multiorgan failure and death in transfused critically ill patients. The independent effect of plasma transfusion on survival has not been evaluated. Our objective was to determine the independent effects of plasma and RBC transfusion on survival for patients with combat-related traumatic injuries receiving any blood products. We performed a retrospective review of 708 patients transfused at least one unit of a blood product at one combat support hospital between November 2003 and December 2004. Admission vital signs, laboratory values, amount of blood products transfused in a 24-hour period, and Injury Severity Score (ISS) were analyzed by multivariate logistic regression to determine independent associations with in-hospital mortality. Seven hundred and eight of 3,287 (22%) patients admitted for traumatic injuries were transfused a blood product. Median ISS was 14 (range, 9–25). In-hospital mortality was 12%. Survival was associated with admission Glasgow Coma Scale score, SBP, temperature, hematocrit, base deficit, INR, amount of RBCs transfused, and massive transfusion. Each transfused FFP unit was independently associated with increased survival (OR: 1.17; 95% CI: [1.06–1.29]; p = 0.002); each transfused RBC unit was independently associated with decreased survival (OR: 0.86; [0.8–0.92]; p = 0.001). A subset analysis of patients (n = 567) without massive transfusion (1–9 RBC/FWB units) also revealed an independent association between each FFP unit and improved survival (OR: 1.22; 95% CI: [1.0–1.48]; p = 0.05) and between each RBC unit and decreased survival (OR: 0.77; [0.64–0.92]; p = 0.004). For trauma patients transfused at least one unit of a blood product, FFP and RBC amounts were independently associated with increased survival and decreased survival, respectively. Prospective studies are needed to determine whether the early and increased use of plasma and decreased use of RBCs affect mortality for patients with traumatic injuries requiring transfusion.