High ratios of plasma and platelets to packed red blood cells do not affect mortality in nonmassively transfused patients.

BACKGROUND: Administration of high transfusion ratios in patients not requiring massive transfusion might be harmful. We aimed to determine the effect of high ratios of fresh frozen plasma (FFP) and platelets (PLT) to packed red blood cells (PRBC) in nonmassively transfused patients. METHODS: Records of 1,788 transfused trauma patients who received <10 units of PRBC in 24 hours at 23 United States Level I trauma centers were reviewed. The relationship between ratio category (low and high) and in-hospital mortality was assessed with propensity-adjusted multivariate proportional hazards models. RESULTS: At baseline, patients transfused with a high FFP:PRBC ratio were younger, had a lower Glasgow Coma Scale score, and a higher Injury Severity Score. Those receiving a high PLT:PRBC ratio were older. The risk of in-hospital mortality did not vary significantly with FFP:PRBC ratio category. Intensive care unit (ICU)-free days, hospital-free days, and ventilator-free days did not vary significantly with FFP:PRBC ratio category. ICU-free days and ventilator-free days were significantly decreased among patients in the high (≥1:1) PLT:PRBC category, and hospital-free days did not vary significantly with PLT:PRBC ratio category. The analysis was repeated using 1:2 as the cutoff for high and low ratios. Using this cutoff, there was still no difference in mortality with either FFP:PRBC ratios or platelet:PRBC ratios. However, patients receiving a >1:2 ratio of FFP:PRBCs or a >1:2 ratio PLT:PRBCs had significantly decreased ICU-free days and ventilator-free days. CONCLUSIONS: FFP:PRBC and PLT:PRBC ratios were not associated with in-hospital mortality. Depending on the threshold analyzed, a high ratio of FFP:PRBC and PLT:PRBC transfusion was associated with fewer ICU-free days and fewer ventilator-free days, suggesting that the damage control infusion of FFP and PLT may cause increased morbidity in nonmassively transfused patients and should be rapidly terminated when it becomes clear that a massive transfusion will not be required.

A normal platelet count may not be enough: the impact of admission platelet count on mortality and transfusion in severely injured trauma patients.

BACKGROUND: Platelets play a central role in hemostasis after trauma. However, the platelet count of most trauma patients does not fall below the normal range (100-450 × 10(9)/L), and as a result, admission platelet count has not been adequately investigated as a predictor of outcome. The purpose of this study was to examine the relationship between admission platelet count and outcomes after trauma. METHODS: A retrospective cohort study of 389 massively transfused trauma patients. Regression methods and the Kruskal-Wallis test were used to test the association between admission platelet count and 24-hour mortality and units of packed red blood cells (PRBCs) transfused. RESULTS: For every 50 × 10(9)/L increase in admission platelet count, the odds of death decreased 17% at 6 hours (p = 0.03; 95% confidence interval [CI], 0.70-0.99) and 14% at 24 hours (p = 0.02; 95% CI, 0.75-0.98). The probability of death at 24 hours decreased with increasing platelet count. For every 50 × 10(9)/L increase in platelet count, patients received 0.7 fewer units of blood within the first 6 hours (p = 0.01; 95% CI, -1.3 to -0.14) and one less unit of blood within the first 24 hours (p = 0.002; 95% CI, -1.6 to -0.36). The mean number of units of PRBCs transfused within the first 6 hours and 24 hours decreased with increasing platelet count. CONCLUSIONS: Admission platelet count was inversely correlated with 24-hour mortality and transfusion of PRBCs. A normal platelet count may be insufficient after severe trauma, and as a result, these patients may benefit from a lower platelet transfusion threshold. Future studies of platelet number and function after injury are needed.

The association of blood component use ratios with the survival of massively transfused trauma patients with and without severe brain injury.

BACKGROUND: The effect of blood component ratios on the survival of patients with traumatic brain injury (TBI) has not been studied. METHODS: A database of patients transfused in the first 24 hours after admission for injury from 22 Level I trauma centers over an 18-month period was queried to find patients who (1) met different definitions of massive transfusion (5 units red blood cell [RBC] in 6 hours vs. 10 units RBC in 24 hours), (2) received high or low ratios of platelets or plasma to RBC units (<1:2 vs. ≥ 1:2), and (3) had severe TBI (head abbreviated injury score ≥ 3) (TBI+). RESULTS: Of 2,312 total patients, 850 patients were transfused with ≥ 5 RBC units in 6 hours and 807 could be classified into TBI+ (n = 281) or TBI- (n = 526). Six hundred forty-three patients were transfused with ≥ 10 RBC units in 24 hours with 622 classified into TBI+ (n = 220) and TBI- (n = 402). For both high-risk populations, a high ratio of platelets:RBCs (not plasma) was independently associated with improved 30-day survival for patients with TBI+ and a high ratio of plasma:RBCs (not platelets) was independently associated with improved 30-day survival in TBI- patients. CONCLUSIONS: High platelet ratio was associated with improved survival in TBI+ patients while a high plasma ratio was associated with improved survival in TBI- patients. Prospective studies of blood product ratios should include TBI in the analysis for determination of optimal use of ratios on outcome in injured patients.

Effect of high product ratio massive transfusion on mortality in blunt and penetrating trauma patients.

BACKGROUND: Recent data suggest that massively transfused patients have lower mortality rates when high ratios (>1:2) of plasma or platelets to red blood cells (RBCs) are used. Blunt and penetrating trauma patients have different injury patterns and may respond differently to resuscitation. This study was performed to determine whether mortality after high product ratio massive transfusion is different in blunt and penetrating trauma patients. METHODS: Patients receiving 10 or more units of RBCs in the first 24 hours after admission to one of 23 Level I trauma centers were analyzed. Baseline physiologic and biochemical data were obtained. Univariate and logistic regression analyses were performed. Adjusted mortality in patients receiving high (≥ 1:2) and low (<1:2) ratios of plasma or platelets to RBCs was calculated for blunt and penetrating trauma patients. RESULTS: The cohort contained 703 patients. Blunt injury patients receiving a high ratio of plasma or platelets to RBCs had lower 24-hour mortality (22% vs. 31% for plasma, p = 0.007; 20% vs. 30% for platelets, p = 0.032), but there was no difference in 30-day mortality (40% vs. 44% for plasma, p = 0.085; 37% vs. 44% for platelets, p = 0.063). Patients with penetrating injuries receiving a high plasma:RBC ratio had lower 24-hour mortality (21% vs. 37%, p = 0.005) and 30-day mortality (29% vs. 45%, p = 0.005). High platelet:RBC ratios did not affect mortality in penetrating patients. CONCLUSION: Use of high plasma:RBC ratios during massive transfusion may benefit penetrating trauma patients to a greater degree than blunt trauma patients. High platelet:RBC ratios did not benefit either group.

A high fresh frozen plasma: packed red blood cell transfusion ratio decreases mortality in all massively transfused trauma patients regardless of admission international normalized ratio.

BACKGROUND: Coagulopathy is present in 25% to 38% of trauma patients on arrival to the hospital, and these patients are four times more likely to die than trauma patients without coagulopathy. Recently, a high ratio of fresh frozen plasma (FFP) to packed red blood cells (PRBCs) has been shown to decrease mortality in massively transfused trauma patients. Therefore, we hypothesized that patients with elevated International Normalized Ratio (INR) on arrival to the hospital may benefit more from transfusion with a high ratio of FFP:PRBC than those with a lower INR. METHODS: Retrospective multicenter cohort study of 437 massively transfused trauma patients was conducted to determine whether the effect of the ratio of FFP:PRBC on death at 24 hours is modified by a patient's admission INR on arrival to the hospital. Contingency tables and logistic regression were used. RESULTS: Trauma patients who arrived to the hospital with an elevated INR had a greater risk of death than those with a lower INR. However, as the ratio of FFP:PRBC transfused increased, mortality decreased similarly between the INR quartiles. CONCLUSIONS: The mortality benefit from a high FFP:PRBC ratio is similar for all massively transfused trauma patients. This is contrary to the current belief that only coagulopathic trauma patients benefit from a high FFP:PRBC ratio. Furthermore, it is unnecessary to determine whether INR is elevated before transfusing a high FFP:PRBC ratio. Future studies are needed to determine the mechanism by which a high FFP:PRBC ratio decreases mortality in all massively transfused trauma patients.

Profoundly abnormal initial physiologic and biochemical data cannot be used to determine futility in massively transfused trauma patients.

BACKGROUND: Improvements in prehospital care and resuscitation have led to increases in the number of severely injured patients who are salvageable. Massive transfusion has been increasingly used. Patients often present with markedly abnormal physiologic and biochemical data. The purpose of this study was to identify objective data that can be used to identify clinical futility in massively transfused trauma patients to allow for early termination of resuscitative efforts. METHODS: A multicenter database was used. Initial physiologic and biochemical data were obtained, and mortality was determined for patients in the 5th and 10th percentiles for each variable. Raw data from the extreme outliers for each variable were also examined to determine whether a point of excessive mortality could be identified. Injury scoring data were also analyzed. A classification tree model was used to look for variable combinations that predict clinical futility. RESULTS: The cohort included 704 patients. Overall mortality was 40.2%. The highest mortality rates were seen in patients in the 10th percentile for lactate (77%) and pH (72%). Survivors at the extreme ends of the distribution curves for each variable were not uncommon. The classification tree analysis failed to identify any biochemical and physiologic variable combination predictive of >90% mortality. Patients older than 65 years with severe head injuries had 100% mortality. CONCLUSION: Consideration should be given to withholding massive transfusion for patients older than 65 years with severe head injuries. Otherwise we did not identify any objective variables that reliably predict clinical futility in individual cases. Significant survival rates can be expected even in patients with profoundly abnormal physiologic and biochemical data.

A predictive model for mortality in massively transfused trauma patients.

BACKGROUND: Improvements in trauma systems and resuscitation have increased survival in severely injured patients. Massive transfusion has been increasingly used in the civilian setting. Objective predictors of mortality have not been well described. This study examined data available in the early postinjury period to identify variables that are predictive of 24-hour- and 30-day mortality in massively transfused trauma patients. METHODS: Massively transfused trauma patients from 23 Level I centers were studied. Variables available on patient arrival that were predictive of mortality at 24 hours were entered into a logistic regression model. A second model was created adding data available 6 hours after injury. A third model evaluated mortality at 30 days. Receiver operating characteristic curves and the Hosmer-Lemeshow test were used to assess model quality. RESULTS: Seven hundred four massively transfused patients were analyzed. The model best able to predict 24-hour mortality included pH, Glasgow Coma Scale score, and heart rate, with an area under the receiver operating characteristic curve (AUROC) of 0.747. Addition of the 6-hour red blood cell requirement increased the AUROC to 0.769. The model best able to predict 30-day mortality included the above variables plus age and Injury Severity Score with an AUROC of 0.828. CONCLUSION: Glasgow Coma Scale score, pH, heart rate, age, Injury Severity Score, and 6-hour red blood cell transfusion requirement independently predict mortality in massively transfused trauma patients. Models incorporating these data have only a modest ability to predict mortality and should not be used to justify withholding massive transfusion in individual cases.

Gender-based differences in mortality in response to high product ratio massive transfusion.

BACKGROUND: Recent data suggest that patients undergoing massive transfusion have lower mortality rates when ratios of plasma and platelets to red blood cells (RBCs) of ≥ 1:2 are used. This has not been examined independently in women and men. A gender dichotomy in outcome after severe injury is known to exist. This study examined gender-related differences in mortality after high product ratio massive transfusion. METHODS: A retrospective study was conducted using a database containing massively transfused trauma patients from 23 Level I trauma centers. Baseline demographic, physiologic, and biochemical data were obtained. Univariate and logistic regression analyses were performed. Adjusted mortality in patients receiving high (≥ 1:2) or low (<1:2) ratios of plasma or platelets to RBCs was compared in women and men independently. RESULTS: Seven hundred four patients were analyzed. In males, mortality was lower for patients receiving a high plasma:RBC ratio at 24 hours (20.6% vs. 33.0% for low ratio, p = 0.005) and at 30 days (34.9% vs. 42.8%, p = 0.032). Males receiving a high platelet:RBC ratio also had lower 24-hour mortality (17.6% vs. 31.5%, p = 0.004) and 30-day mortality (32.1% vs. 42.2%, p = 0.045). Females receiving high ratios of plasma or platelets to RBCs had no improvement in 24-hour mortality (p = 0.119 and 0.329, respectively) or 30-day mortality (p = 0.199 and 0.911, respectively). Use of high product ratio transfusions did not affect 24-hour RBC requirements in males or females. CONCLUSION: Use of high plasma:RBC or platelet:RBC ratios in massive transfusion may benefit men more than women. This may be due to gender-related differences in coagulability. Further study is needed to determine whether separate protocols for women and men should be established.

Crystalloid resuscitation improves survival in trauma patients receiving low ratios of fresh frozen plasma to packed red blood cells.

BACKGROUND: Current trauma resuscitation guidelines recommend giving an initial crystalloid bolus as first line for resuscitation. Recent studies have shown a survival benefit for trauma patients resuscitated with high ratios of fresh frozen plasma (FFP) to packed red blood cells (PRBC). Our aim was to determine whether the volume of crystalloid given during resuscitation correlated with differences in morbidity or mortality based on the ratio of FFP:PRBC given. METHODS: This was a retrospective review of 2,473 transfused trauma patients at 23 Level I trauma centers from July 2005 to October 2007. Patients were separated based on the ratios of FFP:PRBC they received (<1:4, 1:4-1:1, and >1:1) and then analyzed for morbidity and mortality based on whether or not they received at least 1 L crystalloid for each unit of PRBC. Outcomes analyzed were 6-hour, 24-hour, and 30-day survival as well as intensive care unit (ICU)-free days, ventilator-free days, and hospital-free days. RESULTS: Massive transfusion patients who received <1:4 ratios of FFP:PRBC had significantly improved 6-hour, 24-hour, and 30-day mortality and significantly more ventilator-free days if they received at least 1 L of crystalloid for each unit of PRBC. Nonmassive transfusion patients who received <1:4 ratios of FFP:PRBC had significantly improved 6-hour, 24-hour, and 30-day mortality and significantly more ICU-free days, ventilator-free days, and hospital-free days if they received at least 1 L crystalloid for each unit of PRBC. In both massive and nonmassive transfusion groups, the survival benefit and morbidity benefit was progressively less for the 1:4 to 1:1 FFP:PRBC groups and >1:1 FFP:PRBC groups. CONCLUSIONS: If high ratios of FFP:PRBC are unable to be given to trauma patients, resuscitation with at least 1 L of crystalloid per unit of PRBC is associated with improved overall mortality.

Specific abbreviated injury scale values are responsible for the underestimation of mortality in penetrating trauma patients by the injury severity score.

BACKGROUND: The Injury Severity Score (ISS) is widely used as a method for rating severity of injury. The ISS is the sum of the squares of the three worst Abbreviated Injury Scale (AIS) values from three body regions. Patients with penetrating injuries tend to have higher mortality rates for a given ISS than patients with blunt injuries. This is thought to be secondary to the increased prevalence of multiple severe injuries in the same body region in patients with penetrating injuries, which the ISS does not account for. We hypothesized that the mechanism-based difference in mortality could be attributed to certain ISS ranges and specific AIS values by body region. METHODS: Outcome and injury scoring data were obtained from transfused patients admitted to 23 Level I trauma centers. ISS values were grouped into categories, and a logistic regression model was created. Mortality for each ISS category was determined and compared with the ISS 1 to 15 group. An interaction term was added to evaluate the effect of mechanism. Additional logistic regression models were created to examine each AIS category individually. RESULTS: There were 2,292 patients in the cohort. An overall interaction between ISS and mechanism was observed (p = 0.049). Mortality rates between blunt and penetrating patients with an ISS between 25 and 40 were significantly different (23.6 vs. 36.1%; p = 0.022). Within this range, the magnitude of the difference in mortality was far higher for penetrating patients with head injuries (75% vs. 37% for blunt) than truncal injuries (26% vs. 17% for blunt). Penetrating trauma patients with an AIS head of 4 or 5, AIS abdomen of 3, or AIS extremity of 3 all had adjusted mortality rates higher than blunt trauma patients with those values. CONCLUSION: Significant differences in mortality between blunt and penetrating trauma patients exist at certain ISS and AIS category values. The mortality difference is greatest for head injured patients.

Variations between level I trauma centers in 24-hour mortality in severely injured patients requiring a massive transfusion.

BACKGROUND: Significant differences in outcomes have been demonstrated between Level I trauma centers. Usually these differences are ascribed to regional or administrative differences, although the influence of variation in clinical practice is rarely considered. This study was undertaken to determine whether differences in early mortality of patients receiving a massive transfusion (MT, ≥ 10 units pf RBCs within 24 hours of admission) persist after adjustment for patient and transfusion practice differences. We hypothesized differences among centers in 24-hour mortality could predominantly be accounted for by differences in transfusion practices as well as patient characteristics. METHODS: Data were retrospectively collected over a 1-year period from 15 Level I centers on patients receiving an MT. A purposeful variable selection strategy was used to build the final multivariable logistic model to assess differences between centers in 24-hour mortality. Adjusted odds ratios for each center were calculated. RESULTS: : There were 550 patients evaluated, but only 443 patients had complete data for the set of variables included in the final model. Unadjusted mortality varied considerably across centers, ranging from 10% to 75%. Multivariable logistic regression identified injury severity score (ISS), abbreviated injury scale (AIS) of the chest, admission base deficit, admission heart rate, and total units of RBC transfused, as well as ratios of plasma:RBC and platelet:RBC to be associated with 24-hour mortality. After adjusting for severity of injury and transfusion, treatment variables between center differences were no longer significant. CONCLUSIONS: In the defined population of patients receiving an MT, between-center differences in 24-hour mortality may be accounted for by severity of injury as well as transfusion practices.

Sample entropy predicts lifesaving interventions in trauma patients with normal vital signs.

INTRODUCTION: Heart rate complexity, commonly described as a "new vital sign," has shown promise in predicting injury severity, but its use in clinical practice is not yet widely adopted. We previously demonstrated the ability of this noninvasive technology to predict lifesaving interventions (LSIs) in trauma patients. This study was conducted to prospectively evaluate the utility of real-time, automated, noninvasive, instantaneous sample entropy (SampEn) analysis to predict the need for an LSI in a trauma alert population presenting with normal vital signs. METHODS: Prospective enrollment of patients who met criteria for trauma team activation and presented with normal vital signs was conducted at a level I trauma center. High-fidelity electrocardiogram recording was used to calculate SampEn and SD of the normal-to-normal R-R interval (SDNN) continuously in real time for 2 hours with a portable, handheld device. Patients who received an LSI were compared to patients without any intervention (non-LSI). Multivariable analysis was performed to control for differences between the groups. Treating clinicians were blinded to results. RESULTS: Of 129 patients enrolled, 38 (29%) received 136 LSIs within 24 hours of hospital arrival. Initial systolic blood pressure was similar in both groups. Lifesaving intervention patients had a lower Glasgow Coma Scale. The mean SampEn on presentation was 0.7 (0.4-1.2) in the LSI group compared to 1.5 (1.1-2.0) in the non-LSI group (P < .0001). The area under the curve with initial SampEn alone was 0.73 (95% confidence interval [CI], 0.64-0.81) and increased to 0.93 (95% CI, 0.89-0.98) after adding sedation to the model. Sample entropy of less than 0.8 yields sensitivity, specificity, negative predictive value, and positive predictive value of 58%, 86%, 82%, and 65%, respectively, with an overall accuracy of 76% for predicting an LSI. SD of the normal-to-normal R-R interval had no predictive value. CONCLUSIONS: In trauma patients with normal presenting vital signs, decreased SampEn is an independent predictor of the need for LSI. Real-time SampEn analysis may be a useful adjunct to standard vital signs monitoring. Adoption of real-time, instantaneous SampEn monitoring for trauma patients, especially in resource-constrained environments, should be considered.