Extreme γ' fibrinogen levels in COVID-19 patients.

COVID-19 disease progression can be accompanied by a "cytokine storm" that leads to secondary sequelae such as acute respiratory distress syndrome. Several inflammatory cytokines have been associated with COVID-19 disease progression, but have high daily intra-individual variability. In contrast, we have shown that the inflammatory biomarker γ' fibrinogen (GPF) has a 6-fold lower coefficient of variability compared to other inflammatory markers such as hs-CRP. The aims of the study were to measure GPF in serial blood samples from COVID-19 patients at a tertiary care medical center in order to investigate its association with clinical measures of disease progression. COVID-19 patients were retrospectively enrolled between 3/16/2020 and 8/1/2020. GPF was measured using a commercial ELISA. We found that COVID-19 patients can develop extraordinarily high levels of GPF. Our results showed that ten out of the eighteen patients with COVID-19 had the highest levels of GPF ever recorded. The previous highest GPF level of 80.3 mg/dL was found in a study of 10,601 participants in the ARIC study. GPF levels were significantly associated with the need for ECMO and mortality. These findings have potential implications regarding prophylactic anticoagulation of COVID-19 patients.

Prehospital Time Following Traumatic Injury Is Independently Associated With the Need for In-Hospital Blood and Early Mortality for Specific Injury Types.

OBJECTIVE: Treating traumatic hemorrhage is time sensitive. Prehospital care and transport modes (eg, helicopter and ground) may influence in-hospital events. We hypothesized that prehospital time (on-scene time [OST] and total prehospital time [TPT]) and transport mode are associated with same-day transfusion and mortality. Furthermore, we sought to identify regions of anatomic injury that modify the relationship between prehospital time and outcomes in strata corresponding to transport types. METHODS: We obtained prehospital, in-hospital, and trauma registry data from an 8-center cohort of adult nonburn trauma patients from 2017 to 2022 directly transported from the scene to the hospital and having an Injury Severity Score (ISS) > 9 for the Task Order 1 project of the Linking Investigators in Trauma and Emergency Services research network. We excluded patients missing prehospital times, patients < 18 years of age, patients from interfacility transfers, and recipients of prehospital blood. Our same-day outcomes were in-hospital transfusions within 4 hours and 24-hour mortality. Each outcome was adjusted using multivariable logistic regression for covariates of prehospital phases (OST and TPT), mode of transport (helicopter and ground), age, sex, ISS, Glasgow Coma Scale motor subscale score < 6, and field hypotension (systolic blood pressure < 90 mm Hg). We evaluated the association of prehospital time on outcomes for scene missions by transport mode across severe injury patterns defined by Abbreviated Injury Scale > 2 body regions. RESULTS: Of 78,198 subjects, 34,504 were eligible for the study with a mean age of 47.6 ± 20.3 years, ISS of 18 ± 11, OST of 15.9 ± 9.5 minutes, and TPT of 48.7 ± 20.3 minutes. Adjusted for injury severity and demographic factors, transport type significantly modified the relationship between prehospital time and outcomes. The association of OST and TPT with the odds of 4-hour transfusion was absent for the ground emergency medical services (GEMS) cohort and present for the helicopter emergency medical services (HEMS) ambulance cohort, whereas these times were associated with decreased 24-hour mortality for both transport types. When stratifying by injury to most anatomic regions, OST and TPT were associated with a decreased need for 4-hour transfusions in the GEMS cohort. However, OST was associated with increased early transfusion only among patients with severe injuries of the thorax, and this association persisted after adjusting additionally for injury type (odds ratio [OR] = 1.03; 95% confidence interval [CI], 1.00-1.05; P = .02). The presence of polytrauma supported an association between prehospital time and decreased 24-hour mortality for the GEMS cohort (OST: OR = 0.97; 95% CI, 0.95-0.99; P < .01; TPT: OR = 0.99; 95% CI, 0.98-0.99; P = .02), whereas no injuries showed significant association of helicopter prehospital time on mortality after adjustment. CONCLUSION: We determined that transport type affects the relationship between prehospital time and hospital outcomes (4-hour transfusion: positive relationship for HEMS and negative for GEMS, 24-hour mortality: negative for both transport types). Furthermore, we identified regions of anatomic injury that modify the relationship between prehospital time and outcomes in strata corresponding to transport types. Of these regions, most notable were severe isolated injuries to the thorax that supported a positive relationship between HEMS OST and 4-hour transfusions and polytrauma that showed a negative relationship between GEMS OST or TPT and 24-hour mortality after adjustment.

Evidence-Based and Clinically Relevant Outcomes for Hemorrhage Control Trauma Trials.

OBJECTIVE: To address the clinical and regulatory challenges of optimal primary endpoints for bleeding patients by developing consensus-based recommendations for primary clinical outcomes for pivotal trials in patients within 6 categories of significant bleeding, (1) traumatic injury, (2) intracranial hemorrhage, (3) cardiac surgery, (4) gastrointestinal hemorrhage, (5) inherited bleeding disorders, and (6) hypoproliferative thrombocytopenia. BACKGROUND: A standardized primary outcome in clinical trials evaluating hemostatic products and strategies for the treatment of clinically significant bleeding will facilitate the conduct, interpretation, and translation into clinical practice of hemostasis research and support alignment among funders, investigators, clinicians, and regulators. METHODS: An international panel of experts was convened by the National Heart Lung and Blood Institute and the United States Department of Defense on September 23 and 24, 2019. For patients suffering hemorrhagic shock, the 26 trauma working-group members met for almost a year, utilizing biweekly phone conferences and then an in-person meeting, evaluating the strengths and weaknesses of previous high quality studies. The selection of the recommended primary outcome was guided by goals of patient-centeredness, expected or demonstrated sensitivity to beneficial treatment effects, biologic plausibility, clinical and logistical feasibility, and broad applicability. CONCLUSIONS: For patients suffering hemorrhagic shock, and especially from truncal hemorrhage, the recommended primary outcome was 3 to 6-hour all-cause mortality, chosen to coincide with the physiology of hemorrhagic death and to avoid bias from competing risks. Particular attention was recommended to injury and treatment time, as well as robust assessments of multiple safety related outcomes.

Civilian walking blood bank emergency preparedness plan.

BACKGROUND: The current global pandemic has created unprecedented challenges in the blood supply network. Given the recent shortages, there must be a civilian plan for massively bleeding patients when there are no blood products on the shelf. Recognizing that the time to death in bleeding patients is less than 2 h, timely resupply from unaffected locations is not possible. One solution is to transfuse emergency untested whole blood (EUWB), similar to the extensive military experience fine-tuned over the last 19 years. While this concept is anathema in current civilian transfusion practice, it seems prudent to have a vetted plan in place. METHODS AND MATERIALS: During the early stages of the 2020 global pandemic, a multidisciplinary and international group of clinicians with broad experience in transfusion medicine communicated routinely. The result is a planning document that provides both background information and a high-level guide on how to emergently deliver EUWB for patients who would otherwise die of hemorrhage. RESULTS AND CONCLUSIONS: Similar plans have been utilized in remote locations, both on the battlefield and in civilian practice. The proposed recommendations are designed to provide high-level guidance for experienced blood bankers, transfusion experts, clinicians, and health authorities. Like with all emergency preparedness, it is always better to have a well-thought-out and trained plan in place, rather than trying to develop a hasty plan in the midst of a disaster. We need to prevent the potential for empty shelves and bleeding patients dying for lack of blood.

Rationale for the clinical use of adipose-derived mesenchymal stem cells for COVID-19 patients.

In late 2019, a novel coronavirus (SARS-CoV-2) emerged in Wuhan, capital city of Hubei province in China. Cases of SARS-CoV-2 infection quickly grew by several thousand per day. Less than 100 days later, the World Health Organization declared that the rapidly spreading viral outbreak had become a global pandemic. Coronavirus disease 2019 (COVID-19) is typically associated with fever and respiratory symptoms. It often progresses to severe respiratory distress and multi-organ failure which carry a high mortality rate. Older patients or those with medical comorbidities are at greater risk for severe disease. Inflammation, pulmonary edema and an over-reactive immune response can lead to hypoxia, respiratory distress and lung damage. Mesenchymal stromal/stem cells (MSCs) possess potent and broad-ranging immunomodulatory activities. Multiple in vivo studies in animal models and ex vivo human lung models have demonstrated the MSC's impressive capacity to inhibit lung damage, reduce inflammation, dampen immune responses and aid with alveolar fluid clearance. Additionally, MSCs produce molecules that are antimicrobial and reduce pain. Upon administration by the intravenous route, the cells travel directly to the lungs where the majority are sequestered, a great benefit for the treatment of pulmonary disease. The in vivo safety of local and intravenous administration of MSCs has been demonstrated in multiple human clinical trials, including studies of acute respiratory distress syndrome (ARDS). Recently, the application of MSCs in the context of ongoing COVID-19 disease and other viral respiratory illnesses has demonstrated reduced patient mortality and, in some cases, improved long-term pulmonary function. Adipose-derived stem cells (ASC), an abundant type of MSC, are proposed as a therapeutic option for the treatment of COVID-19 in order to reduce morbidity and mortality. Additionally, when proven to be safe and effective, ASC treatments may reduce the demand on critical hospital resources. The ongoing COVID-19 outbreak has resulted in significant healthcare and socioeconomic burdens across the globe. There is a desperate need for safe and effective treatments. Cellular based therapies hold great promise for the treatment of COVID-19. This literature summary reviews the scientific rationale and need for clinical studies of adipose-derived stem cells and other types of mesenchymal stem cells in the treatment of patients who suffer with COVID-19.

Early Tranexamic Acid Administration After Traumatic Brain Injury Is Associated With Reduced Syndecan-1 and Angiopoietin-2 in Patients With Traumatic Intracranial Hemorrhage.

OBJECTIVE: To evaluate the effect of early tranexamic acid (TXA) administration on circulating markers of endotheliopathy. SETTING: Twenty trauma centers in the United States and Canada. PARTICIPANTS: Patients with moderate-to-severe traumatic brain injury (TBI) (MS-TBI) and intracranial hemorrhage who were not in shock (systolic blood pressure ≥90 mm Hg). DESIGN: TXA (2 g) or placebo administered prior to hospital arrival, less than 2 hours postinjury. Blood samples and head computed tomographic scan collected upon arrival. Plasma markers measured using Luminex analyte platform. Differences in median marker levels evaluated using t tests performed on log-transformed variables. Comparison groups were TXA versus placebo and less than 45 minutes versus 45 minutes or more from time of injury to treatment administration. MAIN MEASURES: Plasma levels of angiopoietin-1, angiopoietin-2, syndecan-1, thrombomodulin, thrombospondin-2, intercellular adhesion molecule 1, vascular adhesion molecule 1. RESULTS: Demographics and Injury Severity Score were similar between the placebo (n = 129) and TXA (n = 158) groups. Levels of syndecan-1 were lower in the TXA group (median [interquartile range or IQR] = 254.6 pg/mL [200.7-322.0] vs 272.4 pg/mL [219.7-373.1], P = .05. Patients who received TXA less than 45 minutes postinjury had significantly lower levels of angiopoietin-2 (median [IQR] = 144.3 pg/mL [94.0-174.3] vs 154.6 pg/mL [110.4-209.8], P = .05). No differences were observed in remaining markers. CONCLUSIONS: TXA may inhibit early upregulation of syndecan-1 and angiopoietin-2 in patients with MS-TBI, suggesting attenuation of protease-mediated vascular glycocalyx breakdown. The findings of this exploratory analysis should be considered preliminary and require confirmation in future studies.

Significant practice variability exists in the prevention of venous thromboembolism in injured children: results from a joint survey of the Pediatric Trauma Society and the Trauma Center Association of America.

BACKGROUND/PURPOSE: The purpose of this study was to characterize current practices to prevent venous thromboembolism (VTE) in children and measure adherence to recent joint consensus guidelines from the Pediatric Trauma Society and Eastern Association for the Surgery of Trauma (PTS/EAST). METHODS: An 18-question survey was sent to the membership of PTS and the Trauma Center Association of American. Responses were compared with Chi-square test. RESULTS: One hundred twenty-nine members completed the survey. Most respondents were from academic (84.5%), Level 1 pediatric (62.0%) trauma centers. Criteria for VTE prophylaxis varied between hospitals with freestanding pediatric trauma centers significantly more likely to stratify children by risk factors than adult trauma centers (p = 0.020). While awareness of PTS/EAST guidelines (58.7% overall) was not statistically different between hospital types (44% freestanding adult, 52% freestanding pediatric, 71% combined adult pediatric, p = 0.131), self-reported adherence to these guidelines was uniformly low at 37.2% for all respondents. Lastly, in three clinical scenarios, respondents chose VTE screening and prophylaxis plans in accordance with a prospective application of PTS/EAST guidelines 55.0% correctly. CONCLUSION: Currently no consensus regarding the prevention of VTE in pediatric trauma exists. Prospective application of PTS/EAST guidelines has been limited, likely due to poor quality of evidence and a reliance on post-injury metrics. Results of this survey suggest that further investigation is needed to more clearly define the risk of VTE in children, evaluate, and prospectively validate alternative scoring systems for VTE prevention in injured children. LEVEL OF EVIDENCE: N/A-Survey.

Pediatric trauma venous thromboembolism prediction algorithm outperforms current anticoagulation prophylaxis guidelines: a pilot study.

PURPOSE: Venous thromboembolism (VTE) in injured children is rare, but sequelae can be morbid and life-threatening. Recent trauma society guidelines suggesting that all children over 15 years old should receive thromboprophylaxis may result in overtreatment. We sought to evaluate the efficacy of a previously published VTE prediction algorithm and compare it to current recommendations. METHODS: Two institutional trauma registries were queried for all pediatric (age < 18 years) patients admitted from 2007 to 2018. Clinical data were applied to the algorithm and the area under the receiver operating characteristic (AUROC) curve was calculated to test algorithm efficacy. RESULTS: A retrospective review identified 8271 patients with 30 episodes of VTE (0.36%). The VTE prediction algorithm classified 51 (0.6%) as high risk (> 5% risk), 322 (3.9%) as moderate risk (1-5% risk) and 7898 (95.5%) as low risk (< 1% risk). AUROC was 0.93 (95% CI 0.89-0.97). In our population, prophylaxis of the 'moderate-' and 'high-risk' cohorts would outperform the sensitivity (60% vs. 53%) and specificity (96% vs. 77%) of current guidelines while anticoagulating substantially fewer patients (373 vs. 1935, p < 0.001). CONCLUSION: A VTE prediction algorithm using clinical variables can identify injured children at risk for venous thromboembolic disease with more discrimination than current guidelines. Prospective studies are needed to investigate the validity of this model. LEVEL OF EVIDENCE: III-Clinical decision rule evaluated in a single population.

Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury.

Importance: Traumatic brain injury (TBI) is the leading cause of death and disability due to trauma. Early administration of tranexamic acid may benefit patients with TBI. Objective: To determine whether tranexamic acid treatment initiated in the out-of-hospital setting within 2 hours of injury improves neurologic outcome in patients with moderate or severe TBI. Design, Setting, and Participants: Multicenter, double-blinded, randomized clinical trial at 20 trauma centers and 39 emergency medical services agencies in the US and Canada from May 2015 to November 2017. Eligible participants (N = 1280) included out-of-hospital patients with TBI aged 15 years or older with Glasgow Coma Scale score of 12 or less and systolic blood pressure of 90 mm Hg or higher. Interventions: Three interventions were evaluated, with treatment initiated within 2 hours of TBI: out-of-hospital tranexamic acid (1 g) bolus and in-hospital tranexamic acid (1 g) 8-hour infusion (bolus maintenance group; n = 312), out-of-hospital tranexamic acid (2 g) bolus and in-hospital placebo 8-hour infusion (bolus only group; n = 345), and out-of-hospital placebo bolus and in-hospital placebo 8-hour infusion (placebo group; n = 309). Main Outcomes and Measures: The primary outcome was favorable neurologic function at 6 months (Glasgow Outcome Scale-Extended score >4 [moderate disability or good recovery]) in the combined tranexamic acid group vs the placebo group. Asymmetric significance thresholds were set at 0.1 for benefit and 0.025 for harm. There were 18 secondary end points, of which 5 are reported in this article: 28-day mortality, 6-month Disability Rating Scale score (range, 0 [no disability] to 30 [death]), progression of intracranial hemorrhage, incidence of seizures, and incidence of thromboembolic events. Results: Among 1063 participants, a study drug was not administered to 96 randomized participants and 1 participant was excluded, resulting in 966 participants in the analysis population (mean age, 42 years; 255 [74%] male participants; mean Glasgow Coma Scale score, 8). Of these participants, 819 (84.8%) were available for primary outcome analysis at 6-month follow-up. The primary outcome occurred in 65% of patients in the tranexamic acid groups vs 62% in the placebo group (difference, 3.5%; [90% 1-sided confidence limit for benefit, -0.9%]; P = .16; [97.5% 1-sided confidence limit for harm, 10.2%]; P = .84). There was no statistically significant difference in 28-day mortality between the tranexamic acid groups vs the placebo group (14% vs 17%; difference, -2.9% [95% CI, -7.9% to 2.1%]; P = .26), 6-month Disability Rating Scale score (6.8 vs 7.6; difference, -0.9 [95% CI, -2.5 to 0.7]; P = .29), or progression of intracranial hemorrhage (16% vs 20%; difference, -5.4% [95% CI, -12.8% to 2.1%]; P = .16). Conclusions and Relevance: Among patients with moderate to severe TBI, out-of-hospital tranexamic acid administration within 2 hours of injury compared with placebo did not significantly improve 6-month neurologic outcome as measured by the Glasgow Outcome Scale-Extended. Trial Registration: ClinicalTrials.gov Identifier: NCT01990768.

The Respiratory Rate: A Neglected Triage Tool for Pre-hospital Identification of Trauma Patients.

BACKGROUND: Under-triaged trauma patients have worse clinical outcomes. We evaluated the capability of four pre-hospital variables to identify this population at the lowest level trauma activation (level 3). METHODS: A retrospective review of adult trauma activations from 2004 to 2014 was completed. Pre-hospital vital signs and Glasgow Coma Scale were converted to categorical variables. Patients were under-triaged based on meeting current level 1 or 2 criteria, or requiring a pre-defined critical intervention. Logistic regression was used to determine the association between the pre-hospital variables and under-triaged patients. Odds ratios and 95% confidence intervals were calculated for a comprehensive model, grouping all causes of under-triage as a single unit, and 16 individual models, one for each under-triage criterion. A new level 2 criterion was generated and internally validated. RESULTS: In total, 12,332 activations occurred during the study period. Four hundred and sixty-six (5.9%) patients were under-triaged. Compared to patients with a normal respiratory rate (RR), tachypneic patients were more likely to be under-triaged for any reason, OR 1.7 [1.3-2.1], p < 0.001. In the individual event analysis, tachypneic patients were more likely to have flail chest, OR 22 [2.9-168.3], p = 0.003; require a chest tube, OR 3 [1.8-4.9], p < 0.001; or require emergent intubation, OR 1.6 [1.1-2.8], p = 0.04, compared to patients with a normal RR. The data-driven triage modification was tachypnea with suspected thoracic injury which reduced the under-triage rate by 1.2%. CONCLUSION: Tachypnea with suspected thoracic injury is the strongest level 2 triage modification to reduce level 3 under-triage.

Assessment of three point-of-care platelet function assays in adult trauma patients.

BACKGROUND: Antiplatelet (AP) medication use is common among trauma patients and is associated with poor outcomes. Management options for platelet dysfunction in trauma patients are controversial, expensive, and potentially harmful. Although light transmission platelet aggregometry is considered the standard test to assess platelet function, it is cumbersome and not generally available. Currently, there are no widely accepted platelet function point-of-care tests for acute trauma. STUDY DESIGN: Prospective observational study from 2014 to 2015. Baseline Multiplate aggregometry aspirin area under the platelet aggregation curve (ASPI AUC), Thrombelastography Platelet Mapping percent inhibition of arachidonic acid (TEG-PM AA), and VerifyNow Aspirin Test (ARU) were compared for ability to detect any AP medication use (aspirin or clopidogrel), platelet dysfunction, and identify patients at risk for intracranial hemorrhage (ICH) progression by calculating the area under receiver operating characteristic curves (AUC), sensitivity, specificity, and positive and negative predictive values. Adenosine diphosphate assays were similarly evaluated. RESULTS: Sixty-four patients were enrolled, 25 were taking AP medications. AP patients were older (71.6 versus 35.0 y, P < 0.001) and received more platelet transfusions, but other baseline characteristics were similar. Median ASPI AUC (22.0 versus 53.5 P < 0.001) and VerifyNow ARU (503.5 versus 629.0, P < 0.001) were lower, whereas TEG-PM AA (51.8% versus 18.3%, P < 0.001) was higher in AP patients. Multiplate ASPI AUC, TEG-PM AA percent inhibition, and VerifyNow ARU could identify AP medication use (AUC: 0.90, 0.77, and 0.90, respectively). Adenosine diphosphate assays did not correlate with AP medication use in this population. TEG-PM AA percent inhibition and VerifyNow ARU correlated well with Multiplate ASPI AUC to identify platelet dysfunction (AUC: 0.78, 0.89, respectively). ICH occurred in 29 patients; 12 of which had progression of their injury. ASPI AUC (AUC: 0.50) and VerifyNow ARU (AUC: 0.59) did not correlate, and TEG-PM AA percent inhibition (AUC: 0.66) minimally correlated with progression. CONCLUSIONS: Multiplate, TEG-PM, and VerifyNow are useful point-of-care tests which identify AP medication use and platelet dysfunction in trauma patients. Initial TEG-PM AA percent inhibition may be associated with risk for ICH progression. However, additional large, prospective studies are needed.

Novel concepts for damage control resuscitation in trauma.

PURPOSE OF REVIEW: Traumatic injuries are a major cause of mortality worldwide. Damage control resuscitation or balanced transfusion of plasma, platelets, and red blood cells for the management of exsanguinating hemorrhage after trauma has become the standard of care. We review the literature regarding the use of alternatives to achieve the desired 1 : 1:1 ratio as availability of plasma and platelets can be problematic in some environments. RECENT FINDINGS: Liquid and freeze dried plasma (FDP) are logistically easier to use and may be superior to fresh frozen plasma. Cold storage platelets (CSPs) have improved hemostatic properties and resistance to bacterial contamination. Low titer type O whole blood can be transfused safely in civilian patients. SUMMARY: In the face of hemorrhagic shock from traumatic injury, resuscitation should be initiated with 1 : 1 : 1 transfusion of plasma, platelets, and red blood cells with limited to no use of crystalloids. Availability of plasma and platelets is limited in some environments. In these situations, the use of low titer type O whole blood, thawed or liquid plasma, cold stored platelets or reconstituted FDP can be used as substitutes to achieve optimal transfusion ratios. The hemostatic properties of CSPs may be superior to room temperature platelets.

Early Fever As a Predictor of Paroxysmal Sympathetic Hyperactivity in Traumatic Brain Injury.

OBJECTIVE: Paroxysmal sympathetic hyperactivity (PSH) is characterized by episodic, hyperadrenergic alterations in vital signs after traumatic brain injury (TBI). We sought to apply an objective scale to the vital sign alterations of PSH in order to determine whether 1 element might be predictive of developing PSH. SETTING/PARTICIPANTS/DESIGN: We conducted an observational study of consecutive TBI patients (Glasgow Coma Scale score ≤12) and monitored the cohort for clinical evidence of PSH. PSH was defined as a paroxysm of 3 or more of the following characteristics: (1) tachycardia, (2) tachypnea, (3) hypertension, (4) fever, (5) dystonia (rigidity or decerebrate posturing), and (6) diaphoresis, with no other obvious causation (ie, alcohol withdrawal, sepsis). MAIN MEASURES: The Modified Clinical Feature Severity Scale (mCFSS) was applied to each participant once daily for the first 5 days of hospitalization. RESULTS: Nineteen (11%) of the 167 patients met criteria for PSH. Patients with PSH had a higher 5-day cumulative mCFSS score than those without PSH (median [interquartile range] = 36 [29-42] vs 29 [22-35], P = .01). Of the 4 components of the mCFSS, elevated temperature appeared to be most predictive of the development of PSH, especially during the first 24 hours (odds ratio = 1.95; 95% confidence interval, 1.12-3.40). CONCLUSION: Early fever after TBI may signal impending autonomic dysfunction.

Association of Massive Transfusion for Resuscitation in Gastrointestinal Bleeding with Transfusion-related Acute Lung Injury.

BACKGROUND AND AIMS: This study aimed to understand the use of massive transfusion (MT) for gastrointestinal bleeding (GIB). PATIENTS AND METHODS: We performed a retrospective analysis of patients admitted to our medical Intensive Care Unit (ICU) with GIB for the type of bleeding, quantity of blood products transfused, and risk of transfusion-related acute lung injury (TRALI) and death. MT was defined as transfusion of 10 or more units of red blood cell (RBC) within a 24-h period in a 1-unit RBC: 1-unit fresh frozen plasma: and 1-unit platelet ratio. TRALI was defined as development of acute lung injury (ALI), within 6 h of transfusion, with new bilateral pulmonary infiltrates, absence of circulatory overload, or other explanation for ALI. RESULTS: In a 43-month interval, 169 patients were admitted to the ICU with GIB and received blood products, of whom 13 received MT. Ten patients developed TRALI, of whom 7 (70%) had received MT. MT was associated with an increased risk of TRALI (odds ratio [OR]: 17.9, 95% confidence interval [CI]: 2.9-111.2, P = 0.002) after adjusting for age, sex, body mass index, baseline vitals, and laboratory data. Death was predicted by MT (OR: 5.6, 95% CI: 1.6-19.7, P = 0.007), TRALI (OR: 2.3, 95% CI: 1.1-4.6, P = 0.02), and Acute Physiologic Chronic Health Evaluation II score (OR: 1.17 per unit increase, 95% CI: 1.09-1.26, P < 0.001) after adjusting for age and sex. CONCLUSIONS: MT for GIB is associated with an increased risk of TRALI and death. Prospective studies assessing the use of MT in this population are needed to understand and improve outcomes.

Probiotics for Trauma Patients: Should We Be Taking a Precautionary Approach?

The use of probiotics in the hospital setting is largely understudied and highly controversial. Probiotics are living organisms that, when taken internally, can produce an immunomodulating effect and improve the gastrointestinal (GI) mucosal barrier. Although used for centuries by healthy individuals for GI health, their use in the hospital setting is now gaining wide attention for the prevention of infectious complications such as antibiotic-associated diarrhea, Clostridium difficile infections, multiple-organ dysfunction syndrome, and ventilator-associated pneumonia. However, current understanding of the efficacy of probiotics in the acute care setting is confounded by the inconsistencies in the literature with regard to the strain of probiotic being studied, optimal dosage, and timing and duration of dosing, which make the formulation of clinical practice guidelines difficult. Although the safety of probiotics has been confirmed when used for the prevention and treatment of certain diseases, practitioners remain hesitant to administer them to their patients, citing the lack of high-quality studies clearly demonstrating efficacy and safety. Infection is a cause of late death in trauma patients, but only recently has research been conducted on the use of probiotics specifically for the prevention of hospital-acquired infections in trauma patients. In the face of such limited but promising research, is it reasonable to use probiotics for the prevention of infection in hospitalized trauma patients and improve outcomes? Use of the "precautionary principle" may be useful in this instance.

The pragmatic randomized optimal platelet and plasma ratios trial: what does it mean for remote damage control resuscitation?

BACKGROUND: Implications from the pragmatic, randomize, optimal platelet and plasma ratios (PROPPR) trial are critical for remote damage control resuscitation (DCR). Utilizing DCR principals in remote settings can combat early mortality from hemorrhage. Identifying the appropriate transfusion strategy is mandatory prior to adopting prehospital hemostatic resuscitation strategies. STUDY DESIGN AND METHODS: The PROPPR study was examined in relation to the following questions: 1) Why is it important to have blood products in the prehospital setting?; 2) Which products should be investigated for prehospital hemostatic resuscitation?; 3) What is the appropriate ratio of blood product transfusion?; and 4) What are the appropriate indications for hemostatic resuscitation? RESULTS: PROPPR demonstrates that early and balanced blood product transfusion ratios reduced mortality in all patients at 3 hours and death from exsanguination at 24 hours (p = 0.03). The median time to death from exsanguination was 2.3 hours, highlighting the need for point-of-injury DCR capabilities. A 1:1:1 transfusion ratio of plasma:platelets:packed red blood cells increased the percentage of patients achieving anatomic hemostasis (p = 0.006). PROPPR used the assessment of blood consumption score to identify patients likely to require ongoing hemostatic resuscitation. The critical administration threshold predicted patient mortality and identified patients likely to require ongoing hemostatic resuscitation. CONCLUSION: A balanced resuscitation strategy demonstrates an early survival benefit, decreased death from exsanguination at 24 hours and a greater likelihood of achieving hemostasis in critically injured patients receiving a 1:1:1 ratio of plasma:platelets:PRBCs. This finding highlights the need to import DCR principals to remote locations.

Dried plasma: state of the science and recent developments.

The early transfusion of plasma is important to ensure optimal survival of patients with traumatic hemorrhage. In military and remote or austere civilian settings, it may be impossible to move patients to hospital facilities within the first few hours of injury. A dried plasma product with reduced logistical requirements is needed to enable plasma transfusion where medically needed, instead of only where freezers and other equipment are available. First developed in the 1930s, pooled lyophilized plasma was widely used by British and American forces in WWII and the Korean War. Historical dried plasma products solved the logistical problem but were abandoned because of disease transmission. Modern methods to improve blood safety have made it possible to produce safe and effective dried plasma. Dried plasma products are available in France, Germany, South Africa, and a limited number of other countries. However, no product is available in the US. Promising products are in development that employ different methods of drying, pathogen reduction, pooling, packaging, and other approaches. Although challenges exist, the in vitro and in vivo data suggest that these products have great potential to be safe and effective. The history, state of the science, and recent developments in dried plasma are reviewed.