Approaches and reporting of alcohol and other drug testing for injured patients in hospital-based studies: A systematic review.

ISSUE: Hospital alcohol and/or other drug (AOD) testing is important for identifying AOD-related injuries; however, testing methods vary. This systematic review aimed to examine biological AOD testing methods from hospital-based studies of injured patients and quantify what proportion reported key information on those testing methods. APPROACH: Observational studies published in English from 2010 onwards involving biological AOD testing for injured patients presenting to hospital were included. Studies examining single injury causes were excluded. Extracted data included concentration thresholds for AOD detection (e.g., lower limits of detection, author-defined cut-offs), test type (e.g., immunoassay, breathalyser) and approach (e.g., routine, clinical discretion), timing of testing, sample type and the proportion of injured cases tested for AODs. KEY FINDINGS: Of 83 included studies, 76 measured alcohol and 37 other drugs. Forty-nine studies defined blood alcohol concentration thresholds (ranging from 0 to 0.1 g/100 mL). Seven studies defined concentration thresholds for other drugs. Testing approach was reported in 39/76 alcohol and 18/37 other drug studies. Sample type was commonly reported (alcohol: n = 69/76; other drugs: n = 28/37); alcohol was typically measured using blood (n = 60) and other drugs using urine (n = 20). Studies that reported the proportion of cases tested (alcohol: n = 53/76; other drugs: n = 28/37), reported that between 0% and 89% of cases were not tested for alcohol and 0% and 91% for other drugs. Timing of testing was often unreported (alcohol: n = 61; other drugs: n = 30). IMPLICATIONS AND CONCLUSION: Variation in AOD testing methods alongside incomplete reporting of those methods limits data comparability and interpretation. Standardised reporting of testing methods will assist AOD-related injury surveillance and prevention.

Performance of microvesicles as biomarkers of clinical outcome in sepsis and trauma: A pilot study.

Sepsis remains one of the main causes of death in intensive care unit (ICU) worldwide, despite all technological and scientific advances. Microvesicles (MV) have become promising biomarkers for quick and accurate monitoring of several illnesses. The aim of this pilot study was to characterize and evaluate the performance of MV as biomarker of clinical outcome in septic and trauma patients. For this purpose, 39 subjects, both genders, aging from 18 to 85 years were included in three groups referred as Sepsis, Trauma and Healthy Control. Kinetic analysis of MV was carried out at four consecutive time points: admission (baseline)/T1, 24 h/T2, 72 h/T3 and outcome/T4 of discharge or death. At admission, an overall increase in total MV (Annexin V+) was observed in Sepsis.MV CD14+ (monocytes) was a putative biomarker to identify trauma patients, while MV CD3+ (T-cells) and CD41+ (platelets) were qualified to discriminated Trauma from Sepsis. Sepsis (Death) presented an increase in MV Annexin V+, CD45+, CD16+, CD14+, and CD41+ in comparison to Sepsis (Discharge). Moreover, Trauma (Death) presented an increase of MV CD3+ and CD235+ as compared to Trauma (Discharge). Analysing the ROC curve of specific MV evaluated according to performance, an accuracy of 100% was found to segregate the outcome in sepsis, and 95% in trauma. Our findings suggest that MV might be useful as a potential role in discriminating outcome in patients with sepsis/septic shock and trauma with high accuracy. However, further studies with a larger number of participants will be necessary to validate our findings.

Temporal Transitions in Fibrinolysis after Trauma: Adverse Outcome Is Principally Related to Late Hypofibrinolysis.

BACKGROUND: The relationship between late clinical outcomes after injury and early dynamic changes between fibrinolytic states is not fully understood. The authors hypothesized that temporal transitions in fibrinolysis states using rotational thromboelastometry (ROTEM) would aid stratification of adverse late clinical outcomes and improve understanding of how tranexamic acid modulates the fibrinolytic response and impacts mortality. METHODS: The authors conducted a secondary analysis of previously collected data from trauma patients enrolled into an ongoing prospective cohort study (International Standard Randomised Controlled Trial Number [ISRCTN] 12962642) at a major trauma center in the United Kingdom. ROTEM was performed on admission and at 24 h with patients retrospectively grouped into three fibrinolysis categories: tissue factor-activated ROTEM maximum lysis of less than 5% (low); tissue factor-activated ROTEM maximum lysis of 5 to 15% (normal); or tissue factor-activated ROTEM maximum lysis of more than 15% (high). Primary outcomes were multiorgan dysfunction syndrome and 28-day mortality. RESULTS: Seven-hundred thirty-one patients were included: 299 (41%) were treated with tranexamic acid and 432 (59%) were untreated. Two different cohorts with low-maximum lysis at 24 h were identified: (1) severe brain injury and (2) admission shock and hemorrhage. Multiple organ dysfunction syndrome was greatest in those with low-maximum lysis on admission and at 24 h, and late mortality was four times higher than in patients who remained normal during the first 24 h (7 of 42 [17%] vs. 9 of 223 [4%]; P = 0.029). Patients that transitioned to or remained in low-maximum lysis had increased odds of organ dysfunction (5.43 [95% CI, 1.43 to 20.61] and 4.85 [95% CI, 1.83 to 12.83], respectively). Tranexamic acid abolished ROTEM hyperfibrinolysis (high) on admission, increased the frequency of persistent low-maximum lysis (67 of 195 [34%]) vs. 8 of 79 [10%]; P = 0.002), and was associated with reduced early mortality (28 of 195 [14%] vs. 23 of 79 [29%]; P = 0.015). No increase in late deaths, regardless of fibrinolysis transition patterns, was observed. CONCLUSIONS: Adverse late outcomes are more closely related to 24-h maximum lysis, irrespective of admission levels. Tranexamic acid alters early fibrinolysis transition patterns, but late mortality in patients with low-maximum lysis at 24 h is not increased.

Inflammatory cytokines associated with outcomes in orthopedic trauma patients independent of New Injury Severity score: A pilot prospective cohort study.

Traumatic injury is the leading cause of mortality in patients under 50. It is associated with a complex inflammatory response involving hormonal, immunologic, and metabolic mediators. The marked elevation of cytokines and inflammatory mediators subsequently correlates with the development of posttraumatic complications. The aim was to determine whether elevated cytokine levels provide a predictive value for orthopedic trauma patients. A prospective cohort study of patients with New Injury Severity Score (NISS) > 5 was undertaken. IL-6, IL-8, IL-10, and migration inhibitory factor levels were measured within 24-h of presentation. Demographic covariates and clinical outcomes were obtained from the medical records. Fifty-eight patients (83% male, 40 years) were included. Addition of IL-6 to baseline models significantly improved prediction of pulmonary complication (LR = 6.21, p = 0.01), ICU (change in R2 = 0.31, p < 0.01), and hospital length of stay (change in R2 = 0.16, p < 0.01). The addition of IL-8 significantly improved the prediction of acute kidney injury (LR = 9.15, p < 0.01). The addition of postinjury IL-6 level to baseline New Injury Severity Score model is better able to predict the occurrence of pulmonary complications as well as prolonged ICU and hospital length of stay.

Survival analysis by inflammatory biomarkers in severely injured patients undergoing damage control resuscitation.

BACKGROUND: Although early balanced blood product resuscitation has improved mortality after traumatic injury, many patients still suffer from inflammatory complications. The goal of this study was to identify inflammatory mediators associated with death and multiorgan system failure following severe injury after patients undergo blood product resuscitation. METHODS: A retrospective secondary analysis of inflammatory markers from the Pragmatic Randomized Optimal Platelet and Plasma Ratios study was performed. Twenty-seven serum biomarkers were measured at 8 time points in the first 72 hours of care and were compared between survivors and nonsurvivors. Biomarkers with significant differences were further analyzed by adjudicated cause of 30-day mortality. RESULTS: Biomarkers from 680 patients were analyzed. Seven key inflammatory markers (IL-1ra, IL-6, IL-8, IL-10, eotaxin, IP-10, and MCP-1) were further analyzed. These cytokines were also noted to have the highest hazard ratios of death. Stepwise selection was used for multivariate analysis of survival by time point. MCP-1 at 2 hours, eotaxin and IP-10 at 12 hours, eotaxin at 24 hours, and IP-10 at 72 hours were associated with all-cause mortality. CONCLUSION: Early systemic inflammatory markers are associated with increased risk of mortality after traumatic injury. Future studies should use these biomarkers to prospectively calculate risks of morbidity and causes of mortality for all trauma patients.

Does the Degree of Platelet Adenosine Diphosphate and Arachidonic Acid Receptor Inhibition Correlate With the Severity of Injury in Non-Brain-Injured Trauma Patients?

BACKGROUND: Direct correlations between platelet adenosine diphosphate (ADP) and arachidonic acid (AA) receptor inhibition have been described in the traumatic brain injury (TBI) population. Our goal was to evaluate the percent inhibition of ADP receptor inhibition (ADPri) and AA receptor inhibition (AAri) receptors in non-TBI patients and correlate injury severity and outcomes. METHODS: We performed a retrospective review of non-TBI patients admitted to our trauma center, who received thromboelastography with platelet mapping prior to blood transfusion. Exclusion criteria included patients younger than 18 years, current antiplatelet therapy, or history of renal failure. Univariate descriptive statistics and bivariate comparisons were performed on patient demographic and outcomes. Multivariable linear regression models were constructed to quantify any association between ADPri and AAri with injury outcomes. High ADP inhibition was defined >20% and high AA inhibition >7%. RESULTS: 117 patients met inclusion criteria. Mean age was 53 years with 61% male. Mean ADPri was 64% and AAri 42%. On bivariate analysis, no statistically significant differences with respect to injury severity measures or outcomes were identified. On multivariable linear regression, AAri was associated with longer hospital length of stay. DISCUSSION: There was a high degree of platelet dysfunction in this cohort of severely injured patients without TBI. Despite this, the only correlation identified between injury severity and outcomes was AAri correlating with hospital length of stay. Irrespective of injury severity or outcomes, these patients' results were far from reported "normal" values. Further, research is needed to determine the significance and clinical implications of thromboelastography with platelet mapping use in trauma care.

Does Gender Matter: A Multi-Institutional Analysis of Viscoelastic Profiles for 1565 Trauma Patients With Severe Hemorrhage.

BACKGROUND: Viscoelastic tests including thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are being used in patients with severe hemorrhage at trauma centers to guide resuscitation. Several recent studies demonstrated hypercoagulability in female trauma patients that was associated with a survival advantage. The objective of our study was to elucidate the effects of gender differences in TEG/ROTEM values on survival in trauma patients with severe hemorrhage. METHODS: A retrospective review of consecutive adult patients receiving massive transfusion protocol (MTP) at 7 Level I trauma centers was performed from 2013 to 2018. Data were stratified by gender and then further examined by TEG or ROTEM parameters. Results were analyzed using univariate and multi-variate analyses. RESULTS: A total of 1565 patients were included with 70.9% male gender (n = 1110/1565). Female trauma patients were older than male patients (43.5 ± .9 vs 41.1 ± .6 years, P = .01). On TEG, females had longer reaction times (6.1 ± .9 min vs 4.8 ± .2 min, P = .03), increased alpha angle (68.6 ± .8 vs 65.7 ± .4, P < .001), and higher maximum amplitude (59.8 ± .8 vs 56.3 ± .4, P < .001). On ROTEM, females had significantly longer clot time (99.2 ± 13.7 vs 75.1 ± 2.6 sec, P = .09) and clot formation time (153.6 ± 10.6 sec vs 106.9 ± 3.8 sec, P < .001). When comparing by gender, no difference for in-hospital mortality was found for patients in the TEG or ROTEM group (P > .05). Multivariate analysis showed no survival difference for female patients (OR 1.11, 95% CI .83-1.50, P = .48). CONCLUSIONS: Although a difference between male and females was found on TEG/ROTEM for certain clotting parameters, no difference in mortality was observed. Prospective multi-institutional studies are needed.

Thrombelastography and transfusion patterns in severely injured pediatric trauma patients with blunt solid organ injuries.

BACKGROUND: Thrombelastography (TEG) has emerged as a useful tool to diagnose coagulopathy and guide blood product usage during trauma resuscitations. This study sought to evaluate the correlation between TEG-directed blood product administration in severely injured pediatric trauma patients with blunt solid organ injuries (BSOIs). METHODS: Patients (≤18 years) with severe BSOIs who presented as highest-level trauma activations at two pediatric trauma centers were included. Thrombelastography results were evaluated to determine indications for blood product administration and rates of TEG-directed resuscitation. Tetrachoric correlations and regression modeling were used to correlate TEG-directed resuscitation with clinical outcomes. RESULTS: Of 64 patients who met the inclusion criteria, 32.8% (21) had elevated R times and 23.4% (15) had shortened α angles. Maximum amplitude was shortened in 29.7% (19), and percent clot lysis 30 minutes after maximum amplitude that is >3% was seen in 17.0% (9). Thrombelastography-directed resuscitation of fresh frozen plasma was followed 54.7% of the time compared with 67.2% and 81.2% for platelets and cryoprecipitate, respectively. Thrombelastography-directed resuscitation with platelets (odds ratio, 0.56; 95% confidence interval, 0.33-0.93; p = 0.03) and/or cryoprecipitate (odds ratio, 0.09; 95% confidence interval, 0.01-0.42, p = 0.003) were associated with decreased hospital length of stay and mortality, respectively. CONCLUSION: Severely injured pediatric trauma patients with BSOIs were often coagulopathic upon presentation to the emergency department. Thrombelastography-directed resuscitation with platelets and/or cryoprecipitate was followed for the majority of patients and was associated with improved outcomes. LEVEL OF EVIDENCE: Therapeutic/Care Management, level III.

The α-globin chain of hemoglobin potentiates tissue plasminogen activator induced hyperfibrinolysis in vitro.

BACKGROUND: Severe injury predisposes patients to trauma-induced coagulopathy, which may be subdivided by the state of fibrinolysis. Systemic hyperfibrinolysis (HF) occurs in approximately 25% of these patients with mortality as high as 70%. Severe injury also causes the release of numerous intracellular proteins, which may affect coagulation, one of which is hemoglobin, and hemoglobin substitutes induce HF in vitro. We hypothesize that the α-globin chain of hemoglobin potentiates HF in vitro by augmenting plasmin activity. METHODS: Proteomic analysis was completed on a pilot study of 30 injured patients before blood component resuscitation, stratified by their state of fibrinolysis, plus 10 healthy controls. Different concentrations of intact hemoglobin A, the α- and ß-globin chains, or normal saline (controls) were added to whole blood, and tissue plasminogen activator (tPA)-challenged thrombelastography was used to assess the degree of fibrinolysis. Interactions with plasminogen (PLG) were evaluated using surface plasmon resonance. Tissue plasminogen activator-induced plasmin activity was evaluated in the presence of the α-globin chain. RESULTS: Only the α- and ß-globin chains increased in HF patients (p < 0.01). The α-globin chain but not hemoglobin A or the ß-globin chain decreased the reaction time and significantly increased lysis time 30 on citrated native thrombelastographies (p < 0.05). The PLG and α-globin chain had interaction kinetics similar to tPA:PLG, and the α-globin chain increased tPA-induced plasmin activity. CONCLUSIONS: The α-globin chain caused HF in vitro by binding to PLG and augmenting plasmin activity and may represent a circulating "moonlighting" mediator released by the tissue damage and hemorrhagic shock inherent to severe injury. LEVEL OF EVIDENCE: Prognostic, level III.

The Impact of Anticoagulant Activity of Tissue Factor Pathway Inhibitor Measured by a Novel Functional Assay for Predicting Deep Venous Thrombosis in Trauma Patients: A Prospective Nested Case-Control Study.

OBJECTIVE: Deep venous thrombosis (DVT) is a common complication in patients with traumatic injury. Tissue factor pathway inhibitor (TFPI) is a natural anticoagulant protein in the extrinsic coagulation pathway. However, the relationship between DVT after trauma and the anticoagulant activity of TFPI remains unclear. In this prospective study, we investigated the role of TFPI in trauma patients with DVT to evaluate whether the anticoagulant activity of TFPI measured by a new functional assay can be used to help predict the risk of DVT. Patients and methods: This prospective nested case-control study enrolled trauma patients and healthy volunteers. Forty-eight trauma patients diagnosed with DVT and forty-eight matched trauma patients without DVT were included in the study. 120 healthy volunteers were also included as controls. Blood samples and case information were collected at admission. Patients accepted angiography before surgery to diagnose DVT. The parameters examined included TFPI anticoagulant activity, free-TFPI antigen, blood cell counts, and routine clinical coagulation tests. Results: For the parameters of TFPI anticoagulant activity, three were markedly increased in the DVT group compared to the non-DVT group (TFPI initial anticoagulant time ratio, P = .022; TFPI whole anticoagulant time ratio, P = .048; and TFPI anticoagulant rate, P = .034). The free-TFPI antigen concentration also showed a significant increasing trend in trauma patients with DVT compared with trauma patients without DVT (P = .035). Multivariate logistic regression analysis identified four independent factors for the development of DVT (TFPI initial anticoagulant time ratio, free-TFPI antigen, prothrombin time, and red blood cell count). We calculated the TFPI correlation coefficient and found that the area under the receiver operating characteristic curve was .821. Conclusions: A novel functional assay was developed to measure the anticoagulant activity of TFPI. The anticoagulant activity of TFPI can be used as a potential biomarker for diagnosing DVT in trauma patients.

Thromboelastography with platelet mapping: Limited predictive ability in detecting preinjury antiplatelet agent use.

BACKGROUND: Preinjury antiplatelet agent (APA) use in trauma patients can increase traumatic hemorrhage and worsen outcomes. Thromboelastography with platelet mapping (TEGPM) has characterized platelet function via arachidonic acid (AA) and adenosine diphosphate (ADP) inhibition in nontrauma settings, but limited data exist in the acute trauma population. METHODS: A prospective observational study of adult trauma patients with suspected preinjury APA use who received TEGPM testing from 2017 to 2020 was performed. Patients on anticoagulants were excluded. Patients were grouped according to preinjury APA regimen: 81 mg or 325 mg of aspirin daily, 81 mg of aspirin and 75 mg of clopidrogrel daily, 75 mg of clopidrogrel daily, or no antiplatelet. Ability of TEGPM to detect APA use was assessed using predictive statistics and area under receiver operating characteristic curves (AUROCs). RESULTS: A total of 824 patients were included with most patients taking 81 mg of aspirin (n = 558). Patients on no antiplatelet were younger and had higher baseline platelet counts, while patients on 75 mg of clopidrogrel were more likely to be admitted after ground level fall. All other baseline characteristics were balanced. Admission TEG values were similar between groups. Median AA inhibition was higher in patients on aspirin containing regimens (p < 0.0001). Median ADP inhibition was higher in patients on clopidogrel containing regimens and those taking 325 mg of aspirin (p < 0.0001). Arachidonic acid inhibition accurately detected preinjury APA use and aspirin use (AUROC, 0.89 and 0.84, respectively); however, ADP inhibition performed poorly (AUROC, 0.58). Neither AA nor ADP inhibition was able to discern specific APA regimens or rule out APA use entirely. CONCLUSION: High AA inhibition accurately detects preinjury APA use in trauma patients. High ADP inhibition after trauma is common, limiting its utility to accurately identify preinjury APA use. Further study is needed to identify assays that can reliably detect and further characterize preinjury APA use in trauma populations. LEVEL OF EVIDENCE: Diagnostic test, level II.

Serum CD5L predicts acute lung parenchymal injury and acute respiratory distress syndrome in trauma patients.

ABSTRACT: Cluster of differentiation 5 antigen-like (CD5L), derived from alveolar epithelial cells partly, is a secreted protein. It is shown that CD5L is associated with lung inflammation and systemic inflammatory diseases, but the relationship between CD5L and trauma-related acute lung parenchymal injury (PLI), acute lung injury or acute respiratory distress syndrome (ARDS) is unclear. This study aims to explore the value of serum CD5L levels in predicting trauma-associated PLI/ARDS and its potential clinical significance.This is a prospective observational study, and a total of 127 trauma patients were recruited from the emergency department (ED), and among them, 81 suffered from PLI/ARDS within 24 hours after trauma, and 46 suffered from trauma without PLI/ARDS. Fifty healthy subjects from the medical examination center were also recruited as controls for comparison. The serum CD5L level was measured within 24 hours of admission. The receiver operating characteristic analysis and logistic regression analysis were used to identify the correlation between high CD5L and trauma associated-PLI/ARDS within 24 hours following trauma.The trauma associated-PLI/ARDS subjects showed a significantly higher level of serum CD5L on emergency department admission within 24 hours after trauma compared with its level in non-trauma associated-PLI/ARDS subjects and healthy subjects. The initial CD5L concentration higher than 150.3 ng/mL was identified as indicating a high risk of PLI/ARDS within 24 hours following trauma (95% confidence interval: 0.674-0.878; P < .001). Moreover, CD5L was an independent risk factor for trauma associated-PLI/ARDS within 24 hours following trauma.CD5L could predict PLI/ARDS within 24 hours following trauma.

Effect of Bone Marrow Mesenchymal Stem Cell Sheets on Skin Capillary Parameters in a diabetic wound model: A Novel Preliminary Study

Background: Treatment with BMMSCs has anti-inflammatory, tissue regenerative, angiogenic, and immune-stimulating effects. When using as sheets or accumulate, BMMSCs causes the development of neoangiogenesis in damaged skin tissue. Diabetes, a metabolic disorder, can negatively affect many physiological functions, including the process of skin injury repair. This adverse impact may increase the risk of skin surgery. RSF is commonly used in reconstructive surgery. The terminal part of the RSF is often affected by necrosis because of impaired blood flow, which is exacerbated in diabetes. This study investigated the effect of stem cells, applied as accumulated or cell sheets, along with RSF surgery on skin capillaries in STZ-induced diabetic rats. Methods: Thirty male Wistar rats were divided into three groups (n = 10): diabetes-RSF control, diabetes-RSF local applied stem cells (loc-BMMSCs), diabetes-RSF applied stem cells as accumulated or cell sheets (ac-BMMSCs). Two weeks after the STZ injection, RSF surgery and stem cell therapy (6 × 109) were carried out (day zero). Furthermore, stereological methods were used to investigate the capillary patterns among the groups. Anti-CD31/PCAM1 immunohistochemistry was also used for further confirmation of changes in capillary parameters. Results: The results demonstrated that capillaries were protected by MSC sheets in the flap tissue, and the thickness of the epidermal layer was improved, indicationg the possible beneficial effects of MSC sheets on diabetic wound treatment. Conclusion: Stem cells, as ac-BMMSCs, may decrease the levels of wound healing complications in diabetes and can be considered as a cell therapy option in such conditions.

The rebirth of the cool: a narrative review of the clinical outcomes of cold stored low titer group O whole blood recipients compared to conventional component recipients in trauma.

There has been renewed interest in the use of low titer group O whole blood (LTOWB) for the resuscitation of civilian casualties. LTOWB offers several advantages over conventional components such as providing balanced resuscitation in one bag that contains less additive/preservative solution than an equivalent volume of conventional components, is easier and faster to transfuse than multiple components, avoids blood product ratio confusion, contains cold stored platelets, and reduces donor exposures. The resurgence in its use in the resuscitation of civilian trauma patients has led to the publication of an increasing number of studies on its use, primarily amongst adult recipients but also in pediatric patients. These studies have indicated that hemolysis does not occur amongst adult and pediatric non-group O recipients of a modest quantity of LTOWB. The published studies to date on mortality have shown conflicting results with some demonstrating a reduction following LTOWB transfusion while most others have not shown a reduction; there have not been any studies to date that have found significantly increased overall mortality amongst LTOWB recipients. Similarly, when other clinical outcomes, such as venous thromboembolism, sepsis, hospital or intensive care unit lengths of stay are evaluated, LTOWB recipients have not demonstrated worse outcomes compared to conventional component recipients. While definitive proof of the trends in these morbidity and mortality outcomes awaits confirmation in randomized controlled trials, the evidence to date indicates the safety of transfusing LTOWB to injured civilians.

Dose-dependent association between blood transfusion and nosocomial infections in trauma patients: A secondary analysis of patients from the PAMPer trial.

BACKGROUND: The Prehospital Air Medical Plasma (PAMPer) trial demonstrated a survival benefit to trauma patients who received thawed plasma as part of early resuscitation. The objective of our study was to examine the association between blood transfusion and nosocomial infections among trauma patients who participated in the PAMPer trial. We hypothesized that transfusion of blood products will be associated with the development of nosocomial infections in a dose-dependent fashion. METHODS: We performed a secondary analysis of prospectively collected data of patients in the PAMPer trial with hospital length of stay of at least 3 days. Demographics, injury characteristics, and number of blood products transfused were obtained to evaluate outcomes. Bivariate analysis was performed to identify differences between patients with and without nosocomial infections. Two logistic regression models were created to evaluate the association between nosocomial infections and (1) any transfusion of blood products, and (2) quantity of blood products. Both models were adjusted for age, sex, and Injury Severity Score. RESULTS: A total of 399 patients were included: age, 46 years (interquartile range, 29-59 years); Injury Severity Score, 22 (interquartile range, 12-29); 73% male; 80% blunt mechanism; and 40 (10%) deaths. Ninety-three (27%) developed nosocomial infections, including pneumonia (n = 67), bloodstream infections (n = 14), catheter-associated urinary tract infection (n = 10), skin and soft tissue infection (n = 8), Clostridium difficile colitis (n = 7), empyema (n = 6), and complicated intra-abdominal infections (n = 3). Nearly 80% (n = 307) of patients received packed red blood cells (PRBCs); 12% received cryoprecipitate, 69% received plasma, and 27% received platelets. Patients who received any PRBCs had more than a twofold increase in nosocomial infections (odds ratio, 2.15; 95% confidence interval, 1.01-4.58; p = 0.047). The number of PRBCs given was also associated with the development of nosocomial infection (odds ratio, 1.10; 95% confidence interval, 1.05-1.16; p < 0.001). CONCLUSION: Trauma patients in the PAMPer trial who received a transfusion of at least 1 U of PRBCs incurred a twofold increased risk of nosocomial infection, and the risk of infection was dose dependent. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Anti-D alloimmunization in Rh(D) negative adults with severe traumatic injury.

INTRODUCTION: Widely varying rates of alloimmunization associated with transfusing uncrossmatched RBC products to trauma patients as part of hemostatic resuscitation have been reported. We characterized the rates of RBC alloimmunization in our severely injured Rh(D) negative trauma population who received uncrossmatched Rh(D) positive RBC products. METHODS: In a 10-year retrospective analysis to assess Rh(D) alloimmunization risks, Rh(D) negative adult trauma patients initially requiring uncrossmatched group O Rh(D) positive RBC products with either RBC units or low titer group O whole blood as part of massive transfusion protocol (MTP) activation were identified. Only those Rh(D) negative patients whose initial antibody screenings were negative were included. Duration of serologic follow-up from date of MTP activation to either date of anti-D detection or most recent negative antibody screening was calculated. RESULTS: There were 129 eligible Rh(D) negative trauma patients identified. Median injury severity score was 25. Anti-D was detected in 10 (7.8%) patients after a median of 161.5 days; the median duration of serologic follow-up in those who did not have anti-D detected was 220 days. Patients who had anti-D detected were less severely injured and received fewer Rh(D) positive RBC products versus those who did not. DISCUSSION: In our severely injured adult trauma patients with MTP activation requiring uncrossmatched group O Rh(D) positive RBC products, the rate of anti-D detection was low. Additional studies are necessary to determine generalizability of these findings and fully characterize alloimmunization risks in trauma patients with varying extents of injury.

A new definition for massive transfusion in the modern era of whole blood resuscitation.

BACKGROUND: Multiple thresholds are defined to identify patients at risk of death from hemorrhage, including massive transfusion (MT), critical administration threshold (CAT), and resuscitation intensity (RI). All fail to account for the use of whole blood (WB). We hypothesized that a definition including WB transfusion would better predict early mortality following trauma. METHODS: This is a retrospective review of all trauma patients with activation of the MT protocol from December 2018 to February 2020. Combinations of WB, RBCs, and fresh frozen plasma (FFP) units transfused during the initial hour of resuscitation were compared using receiver operating characteristic and area under the receiver curve (AUC) for 3- and 6-h mortality. WB massive transfusion (WB MT) score was defined as the sum of each unit RBC plus three times each unit of WB transfused within the first hour of resuscitation. RESULTS: There were 235 patients eligible for analysis with 60 resuscitated using ≥1 unit of WB. Overall, 27 and 29 patients died in the first 3 and 6 h, respectively. WB MT ≥7 had the greatest 3-h and 6-h mortality AUC values (0.78 and 0.79, respectively) when compared to MT, CAT, RI4+, and other attempted definitions using units of WB, RBC, and FFP. Compared to WB MT-, WB MT+ patients died at significantly higher rates at 3 h (28.9% vs. 3.1%, p < .001), 24 h (35.5% vs. 5.7%, p < .001), and 28 days (42.1% vs. 11.9%, p < .001). CONCLUSION: WB MT is the first measure of massive resuscitation to incorporate WB and better identifies early mortality than other definitions.

Massive transfusions and severe hypocalcemia: An opportunity for monitoring and supplementation guidelines.

BACKGROUND: Massive transfusion protocols (MTPs) are associated with severe hypocalcemia, contributing to coagulopathy and mortality in severely injured patients. Severity of hypocalcemia following massive transfusion activation and appropriate treatment strategies remain undefined. STUDY DESIGN AND METHODS: This was a retrospective study of all MTP activations in adult trauma patients at a Level 1 trauma center between August 2016 and September 2017. Units of blood products transfused, ionized calcium levels, and amount of calcium supplementation administered were recorded. Primary outcomes were ionized calcium levels and the incidence of severe ionized hypocalcemia (iCa ≤1.0 mmol/L) in relation to the volume of blood products transfused. RESULTS: Seventy-one patients had an MTP activated during the study period. The median amount of packed red blood cells (PRBCs) transfused was 10 units (range 1-52). A total of 42 (59.1%) patients had periods of severe hypocalcemia. Patients receiving 13 or more units of PRBC had a greater prevalence of hypocalcemia with 83.3% having at least one measured ionized calcium ≤1.0 mmoL/L (p = .001). The number of ionized calcium levels checked and the amount of supplemental calcium given in patients who experienced hypocalcemia varied considerably. DISCUSSION: Severe hypocalcemia commonly occurs during MTP activations and correlates with the number of packed red blood cells transfused. Monitoring of ionized calcium and amount of calcium supplementation administered is widely variable. Standardized protocols for recognition and management of severe hypocalcemia during massive transfusions may improve outcomes.

Compensatory reserve detects subclinical shock with more expeditious prediction for need of life-saving interventions compared to systolic blood pressure and blood lactate.

INTRODUCTION: We conducted a prospective observational study on 205 trauma patients at a level I trauma facility to test the hypothesis that a compensatory reserve measurement (CRM) would identify higher risk for progression to shock and/or need a life-saving interventions (LSIs) earlier than systolic blood pressure (SBP) and blood lactate (LAC). METHODS: A composite outcome metric included blood transfusion, procedural LSI, and mortality. Discrete measures assessed as abnormal (ab) were SBP <90 mmHg, CRM <60%, and LAC >2.0. A graded categorization of shock was defined as: no shock (normal [n] SBP [n-SBP], n-CRM, n-LAC); sub-clinical shock (ab-CRM, n-SBP, n-LAC); occult shock (n-SBP, ab-CRM, ab-LAC); or overt shock (ab-SBP, ab-CRM, ab-LAC). RESULTS: Three patients displayed overt shock, 53 displayed sub-clinical shock, and 149 displayed no shock. After incorporating lactate into the analysis, 86 patients demonstrated no shock, 25 were classified as sub-clinical shock, 91 were classified as occult shock, and 3 were characterized as overt shock. Each shock subcategory revealed a graded increase requiring LSI and transfusion. Initial CRM was associated with progression to shock (odds ratio = 0.97; p < .001) at an earlier time than SBP or LAC. CONCLUSIONS: Initial CRM uncovers a clinically relevant subset of patients who are not detected by SBP and LAC. Our results suggest CRM could be used to more expeditiously identify injured patients likely to deteriorate to shock, with requirements for blood transfusion or procedural LSI.