Loring W. Rue

The relationship of blood product ratio to mortality: survival benefit or survival bias?

BACKGROUND Recent studies show an apparent survival advantage associated with the administration of higher cumulative ratios of fresh frozen plasma (FFP) to packed red blood cells (PRBC). It remains unclear how temporal factors and survival bias may influence these results. The objective of this study was to evaluate the temporal relationship between blood product ratios and mortality in massively transfused trauma patients. METHODS Patients requiring massive transfusion (>10 units of PRBC within 24 hours of admission) between 2005 and 2007 were identified (n = 134). In-hospital mortality was compared between patients receiving high (>1:2) versus low (<1:2) FFP:PRBC ratios with a regression model, using the FFP:PRBC ratio as a fixed value at 24 hours (method I) and as a time-varying covariate (method II). RESULTS The FFP:PRBC ratio for all patients was low early and increased over time. Sixty-eight percent of total blood products were given and 54% of deaths occurred during the first 6 hours. Using method I, patients receiving a high FFP:PRBC ratio (mean, 1:1.3) by 24 hours had a 63% lower risk of death (RR, 0.37; 95% CI, 0.22-0.64) compared with those receiving a low ratio (mean, 1:3.7). However, this association was no longer statistically significant (RR, 0.84; 95% CI, 0.47-1.50) when the timing of component product transfusion was taken into account (method II). CONCLUSIONS Similar to previous studies, an association between higher FFP:PRBC ratios at 24 hours and improved survival was observed. However, after adjustment for survival bias in the analysis, the association was no longer statistically significant. Prospective trials are necessary to evaluate whether hemostatic resuscitation is clinically beneficial.

Transfusions in the less severely injured: does age of transfused blood affect outcomes?

BACKGROUND Prior studies have demonstrated that transfusion of older stored blood is associated with an increased risk of multiple organ failure, infection, and death. These reports were primarily comprised of severely injured patients, and it remains unknown whether this phenomenon is observed in relatively less injured patients. The purpose of this study was to evaluate the association between the age of stored blood and the morbidity and mortality in a mild to moderately injured patient cohort. METHODS Blunt trauma patients with Injury Severity Score <25 admitted to a Trauma Intensive Care Unit during 7.5 years who received no blood during the first 48 hours of hospitalization were selected for inclusion. Patients who died within 48 hours of admission were excluded from analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the association between morbidity or mortality and the age and amount of blood transfused (>48 hours postadmission), adjusted for age, sex, injury severity, thoracic injury, mechanical ventilation, and transfusion volume. RESULTS During 7.5 years, 1,624 patients met the study criteria. The mean Injury Severity Score was 14.4. Receipt of blood stored beyond 2 weeks was associated with mortality (OR 1.12 [CI 1.02-1.23]), renal failure (OR 1.18 [CI 1.07-1.29]), and pneumonia (OR 1.10 [CI 1.04-1.17]). No such associations were identified, however, concerning the transfusion of blood with a lesser storage age. CONCLUSION In a mild to moderately injured intensive care unit patient cohort, the receipt of blood stored beyond 2 weeks was independently associated with mortality, renal failure, and pneumonia. The deleterious effect of older blood on patient outcome does not appear to be limited to the severely injured.

Identifying risk for massive transfusion in the relatively normotensive patient: utility of the prehospital shock index.

BACKGROUND In the prehospital environment, the failure of medical providers to recognize latent physiologic derangement in patients with compensated shock may risk undertriage. We hypothesized that the shock index (SI; heart rate divided by systolic blood pressure [SBP]), when used in the prehospital setting, could facilitate the identification of such patients. The objective of this study was to assess the association between the prehospital SI and the risk of massive transfusion (MT) in relatively normotensive blunt trauma patients. METHODS Admissions to a Level I trauma center between January 2000 and October 2008 with blunt mechanism of injury and prehospital SBP>90 mm Hg were identified. Patients were categorized by SI, calculated for each patient from prehospital vital signs. Risk ratios (RRs) and 95% confidence intervals (CI) for requiring MT (>10 red blood cell units within 24 hours of admission) were calculated using SI>0.5 to 0.7 (normal range) as the referent for all comparisons. RESULTS A total of 8,111 patients were identified, of whom 276 (3.4%) received MT. Compared with patients with normal SI, there was no significant increased risk for MT for patients with a SI of ≤0.5 (RR, 1.41; 95% CI, 0.90-2.21) or>0.7 to 0.9 (RR, 1.06; 95% CI, 0.77-1.45). However, a significantly increased risk for MT was observed for patients with SI>0.9. Specifically, patients with SI>0.9 to 1.1 were observed to have a 1.5-fold increased risk for MT (RR, 1.61; 95% CI, 1.13-2.31). Further increases in SI were associated with incrementally higher risks for MT, with an more than fivefold increase in patients with SI>1.1 to 1.3 (RR, 5.57; 95% CI, 3.74-8.30) and an eightfold risk in patients with SI>1.3 (RR, 8.13; 95% CI, 4.60-14.36). CONCLUSION Prehospital SI>0.9 identifies patients at risk for MT who would otherwise be considered relatively normotensive under current prehospital triage protocols. The risk for MT rises substantially with elevation of SI above this level. Further evaluation of SI in the context of trauma system triage protocols is warranted to analyze whether it triage precision might be augmented among blunt trauma patients with SBP>90 mm Hg.

Penetrating esophageal injuries: Multicenter study of the American Association for the Surgery of Trauma

OBJECTIVE The purpose of this study was to define the period of time after which delays in management incurred by investigations cause increased morbidity and mortality. The outcome study is intended to correlate time with death from esophageal causes, overall complications, esophageal related complications, and surgical intensive care unit length of stay. METHODS This was a retrospective multicenter study involving 34 trauma centers in the United States, under the auspices of the American Association for the Surgery of Trauma Multi-institutional Trials Committee over a span of 10.5 years. Patients surviving to reach the operating room (OR) were divided into two groups: those that underwent diagnostic studies to identify their injuries (preoperative evaluation group) and those that went immediately to the OR (no preoperative evaluation group). Statistical methods included Fishers exact test, Students T test, and logistic regression analysis. RESULTS The study involved 405 patients: 355 male patients (86.5%) and 50 female patients (13.5%). The mean Revised Trauma Score was 6.3, the mean Injury Severity Score was 28, and the mean time interval to the OR was 6.5 hours. There were associated injuries in 356 patients (88%), and an overall complication rate of 53.5%. Overall mortality was 78 of 405 (19%). Three hundred forty-six patients survived to reach the OR: 171 in the preoperative evaluation group and 175 in the no preoperative evaluation group. No statistically significant differences were noted in the two groups in the following parameters: number of patients, age, Injury Severity Score, admission blood pressure, anatomic location of injury (cervical or thoracic), surgical management (primary repair, resection and anastomosis, resection and diversion, flaps), number of associated injuries, and mortality. Average length of time to the OR was 13 hours in the preoperative evaluation group versus 1 hour in the no preoperative evaluation group (p < 0.001). Overall complications occurred in 134 in the preoperative evaluation group versus 87 in the no preoperative evaluation group (p < 0.001), and 74 (41%) esophageal related complications occurred in the preoperative evaluation group versus 32 (19%) in the no preoperative evaluation group (p = 0.003). Mean surgical intensive care unit length of stay was 11 days in the preoperative evaluation group versus 7 days in the no preoperative evaluation group (p = 0.012). Logistic regression analysis identified as independent risk factors for the development of esophageal related complications included time delays in preoperative evaluation (odds ratio, 3.13), American Association for the Surgery of Trauma Organ Injury Scale grade >2 (odds ratio, 2.62), and resection and diversion (odds ratio, 4.47). CONCLUSION Esophageal injuries carry a high morbidity and mortality. Increased esophageal related morbidity occurs with the diagnostic workup and its inherent delay in operative repair of these injuries. For centers practicing selective management of penetrating neck injuries and transmediastinal gunshot wounds, rapid diagnosis and definitive repair should be made a high priority.

The association between gender and mortality among trauma patients as modified by age.

BACKGROUND Several studies have reported a null association between gender and mortality after traumatic injury, whereas others found an age-specific association between male gender and increased mortality. Relatively small sample sizes may have contributed to the heterogeneity among existing studies; therefore, a large-sample-size study was undertaken. METHODS The National Trauma Data Bank was queried, yielding data for over 150,000 patients involved in blunt or penetrating trauma. Crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the association between gender and mortality, both overall and according to mechanism of injury and age categories. RESULTS Among those who sustained blunt trauma, male patients had a significant increase in the risk of death compared with female patients (OR, 1.49; 95% CI, 1.39-1.59) that was most apparent for those > or = 50 years of age (OR, 1.97; 95% CI, 1.84-2.11). For penetrating trauma patients, essentially no significant association, either overall (OR, 1.03; 95% CI, 0.91-1.17) or by age category, was apparent. CONCLUSION This study found an association between gender and mortality among blunt trauma patients, particularly those aged > or = 50 years. Animal studies demonstrate that the sex hormones influence the inflammatory response to injury. These results may highlight the importance of sex hormones in traumatic injury outcomes.

Preexisting conditions and mortality in older trauma patients.

BACKGROUND Among older trauma patients, those with preexisting chronic medical conditions (CMCs) appear to have an elevated risk of death. Whether this association is dependent on the severity of injury or other occult factors remains unanswered. This study evaluated the association between preexisting CMCs and risk of death among older trauma patients according to injury severity. METHODS This was a retrospective cohort study using data from the National Trauma Data Bank, a registry of trauma patients admitted to 131 trauma centers across the United States. The main outcome measure was in-hospital mortality. RESULTS In patients 50 to 64 years of age who sustain severe (Injury Severity Score [ISS] of 26+) and moderate injuries (ISS of 16-25), the presence of one or more CMCs is not associated with an increased relative risk (RR) of death (RR, 0.80 and 95% confidence interval [CI], 0.71-0.90; RR, 1.09 and 95% CI, 0.95-1.24, respectively). Those with minor injuries (ISS < 16) have increased risk of death (RR, 2.80; 95% CI, 2.33-3.36). For those patients 65 years of age and older who sustain severe, moderate, and minor injuries, the pattern of results is similar (RR, 0.91 and 95% CI, 0.83-1.00; RR, 1.13 and 95% CI, 1.04-1.23; and RR, 1.88 and 95% CI, 1.73-2.05, respectively). CONCLUSION Older trauma patients with CMCs who present with minor injuries should be considered to have an increased risk of death when compared with their nonchronically ill counterparts.

Age-related gender differential in outcome after blunt or penetrating trauma

Although laboratory studies indicate that female rodents better tolerate the deleterious consequences of trauma and have higher survival rates than male rodents, it remains unclear whether a similar gender dimorphic pattern is evident in humans. In view of this, the association between gender and mortality in trauma patients admitted to a University Level I Trauma Center was assessed. All adult patients admitted to the University of Alabama at Birmingham Trauma Center with blunt or penetrating injury between July 1996 and March 2001 were selected for analysis. Patients were categorized by mechanism (blunt or penetrating), and odds ratios (ORs) were used to compare the risk of death among males compared with females. The ORs were stratified according to age and were adjusted for demographic, medical, and injury characteristics. Male blunt trauma patients <50 years old had a 2.5 times (95% CI 1.3–4.9) higher risk of death than females; however, for those ≥50 years old, a smaller, nonstatistically significant difference was apparent (OR 1.4, 95% CI 0.8–2.3). Conversely, for penetrating trauma, males <50 years old exhibited an increased yet nonsignificant risk of death (OR 1.8, 95% CI 0.6–5.4), whereas those ≥50 years old had a survival advantage (OR 0.1, 95% CI 0.02–0.5). Laboratory studies have demonstrated that estrogens are salutary and androgens are detrimental for survival following trauma-hemorrhage. The results of this study suggest that the physiologic pattern of premenopausal adult female sex hormones may provide a survival advantage in blunt trauma patients; however, the converse pattern prevails for the penetrating trauma patients.

Gender differences in mortality following burn injury.

Clinical and experimental studies have demonstrated higher mortality following nonthermal trauma among males compared with females. To date, few clinical retrospective studies have focused on gender differences in outcome following burn injury with respect to age. All patients admitted to the University of Alabama at Birmingham (UAB) Burn Center between January 1994 and December 2000 were selected for inclusion in the study. Gender differences in demographic, clinical, and outcome characteristics were compared. Unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the association between mortality and gender, both overall and stratified by age. Over the 7-year study period, 1229 males and 382 females were admitted to the UAB Burn Center, and mortality rates were 7.2% and 13.4%, respectively (P = 0.0002). Female patients were more likely to be older, of the black race, and in poorer health. In addition, females were more likely to suffer flame and scald burns. The association between mortality and gender was modified by age. Up to age 60, mortality rates among females were over twice that of males (OR 2.3, 95% CI 1.4–3.8); however, no difference was noted among those 60 and older (OR 0.9, 95% CI 0.5–1.6). These associations persisted following adjustment for potentially confounding variables. Causes and timing of death were similar for males and females. Women less than 60 years of age who sustain burn injuries have an increased risk of death compared with males. Differences in the natural history of nonthermal trauma and burn injury may provide insight regarding these divergent findings.

Duration of red cell storage influences mortality after trauma.

BACKGROUND Although previous studies have identified an association between the transfusion of relatively older red blood cells (RBCs) (storage ≥ 14 days) and adverse outcomes, they are difficult to interpret because the majority of patients received a combination of old and fresh RBC units. To overcome this limitation, we compared in-hospital mortality among patients who received exclusively old versus fresh RBC units during the first 24 hours of hospitalization. METHODS Patients admitted to a Level I trauma center between January 2000 and May 2009 who received ≥ 1 unit of exclusively old (≥ 14 days) vs. fresh (< 14 days) RBCs during the first 24 hours of hospitalization were identified. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for the association between mortality and RBC age, adjusted for patient age, Injury Severity Score, gender, receipt of fresh frozen plasma or platelets, RBC volume, brain injury, and injury mechanism (blunt or penetrating). RESULTS One thousand six hundred forty-seven patients met the study inclusion criteria. Among patients who were transfused 1 or 2 RBC units, no difference in mortality with respect to RBC age was identified (adjusted RR, 0.97; 95% CI, 0.72-1.32). Among patients who were transfused 3 or more RBC units, receipt of old versus fresh RBCs was associated with a significantly increased risk of mortality, with an adjusted RR of 1.57 (95% CI, 1.14-2.15). No difference was observed concerning the mean number of old versus fresh units transfused to patients who received 3 or more units (6.05 vs. 5.47, respectively; p = 0.11). CONCLUSION In trauma patients undergoing transfusion of 3 or more RBC units within 24 hour of hospital arrival, receipt of relatively older blood was associated with a significantly increased mortality risk. Reservation of relatively fresh RBC units for the acutely injured may be advisable.

Traumatic brain injury is associated with the development of deep vein thrombosis independent of pharmacological prophylaxis.

INTRODUCTION Deep venous thrombosis (DVT) is common among trauma patients. If left untreated it may result in lethal pulmonary thromboembolism. Previous studies have suggested that intracranial hemorrhage serves as an independent risk factor for the development of DVT. These studies were not able to exclude anticoagulation therapy as a confounding variable in their analysis. Our objective was to determine the association of traumatic brain injury (TBI) to the formation of DVT irrespective of the use of anticoagulation therapy. METHODS All patients admitted to an academic level I Trauma Center between 2000 and 2007 with blunt or penetrating injuries were selected for inclusion in this study. Patients who died or who were discharged within 24 hours of admission were excluded in the analysis. TBI was defined as any intraparenchymal hemorrhage or extra-axial intracranial bleeding identified on radiographic imaging or both. Anticoagulation therapy was defined as the uninterrupted use of either subcutaneous lovenox or heparin. Risk ratios and 95% confidence intervals compared the risk of DVT among patients with and without TBI according to the initiation of anticoagulation therapy (no therapy, <24 hours, 24-48 hours, and >48 hours) adjusted for age, gender, race, injury severity, mechanism of injury, spinal injury, and lower extremity fracture. RESULTS Irrespective of the time of initiation of pharmacologic prophylaxis, TBI is independently associated with the formation of DVT. A threefold to fourfold increased risk of DVT formation is consistent across all prophylaxis groups among patients with TBI. CONCLUSION The incidence of DVT among injured patients with TBI is significantly higher than those patients without head injury independent of anticoagulation therapy. Rigorous surveillance to detect DVT among trauma patients with TBI should be undertaken and where appropriate alternate means for pulmonary thromboembolism prevention used.