Systematic review of plasma/packed red blood cell ratio on survival in ruptured abdominal aortic aneurysms.

BACKGROUND: The ideal perioperative fluid resuscitation for patients with ruptured abdominal aortic aneurysms (rAAAs) is unknown. It has been shown in trauma studies that a higher ratio of plasma and platelets to packed red blood cells confers a mortality benefit. Controversy remains whether this is true also in the rAAA population. The objective of the present study was to investigate the benefit of a greater ratio of plasma/packed red blood cells in patients with rAAAs. METHODS: A health sciences librarian searched four electronic databases, including PubMed, Embase, Cochrane, and ClinicalTrials.gov, using concepts for the terms "fluid resuscitation," "survival," and "ruptured abdominal aortic aneurysm." Two reviewers independently screened the studies that were identified through the search strategy and read in full any study that was potentially relevant. Studies were included if they had compared the mortality of patients with rAAAs who had received a greater ratio of plasma to other component therapy with that of patients who had received a lower ratio. The risk of bias was assessed using the ROBINS-I (risk of bias in nonrandomized studies of interventions) validated tool, and evidence quality was rated using the GRADE (grades of recommendation assessment, development, and evaluation) profile. No data synthesis or meta-analysis was planned or performed, given the anticipated paucity of research on this topic and the high degree of heterogeneity of available studies. RESULTS: Our search identified seven observational studies for inclusion in the present review. Of these seven studies, three found an associated decrease in mortality with a greater ratio of plasma to packed red blood cells. The remaining four found no significant differences. The overall risk of bias was serious, and the evidence quality was very low. CONCLUSIONS: Overall, the findings from the available studies would suggest that for patients who have undergone open surgery for a rAAA, mortality tends to be decreased when the amount of plasma transfused perioperatively is similar to the amount of packed red blood cells. However, the included studies reported very low-quality evidence based solely on highly heterogeneous observational studies, and further research is warranted.

Trends and outcomes in multicomponent blood transfusion: an 11-year cohort study of a large multisite academic center.

BACKGROUND: Most studies reporting on blood component utilization overlook patients transfused with more than one type of blood product (multicomponent transfusion). These patients are of importance, as they are large consumers of blood products and likely have different characteristics and outcomes than nontransfused patients and patients transfused with only one blood component type. Our study aimed to determine the prevalence of multicomponent transfusion at a large multisite academic center, as well as the patient characteristics and outcomes associated with multicomponent transfusion. METHODS: A retrospective cohort study of transfused adult inpatients at the Ottawa Hospital between 2007 and 2017 was performed. Eligible transfusions were red blood cells (RBCs), platelets, plasma, cryoprecipitate, and/or fibrinogen concentrate. Descriptive analyses were done to determine multicomponent transfusion prevalence. Patient characteristics and outcomes associated with multicomponent transfusion were assessed using multivariable regressions. RESULTS: Of 55,719 adult transfused inpatient admissions, 25% received a multicomponent transfusion. Multicomponent transfusion prevalence was highest in hematology (51%), cardiac surgery (45%), and critical care (40%) patients. Multivariable regression analysis showed that compared to RBC-only transfusion, multicomponent transfusion was associated with increased odds of in-hospital mortality (odds ratio, 3.48; 95% confidence interval [CI], 3.26-3.73), greater odds of institutional discharge as opposed to discharge home (odds ratio, 1.22; 95% CI, 1.15-1.30), and a 1.58 time increase in duration of hospitalization (95% CI, 1.54-1.62). CONCLUSION: Multicomponent transfusion recipients make up a large proportion of transfused patients and have poorer outcomes. It is necessary to continue studying these patients, including outcomes and transfusion appropriateness, to inform best practices.

Resuscitation of Endotheliopathy and Bleeding in Thoracic Aortic Dissections: The VIPER-OCTA Randomized Clinical Pilot Trial.

BACKGROUND: Thoracic aorta dissection is an acute critical condition associated with shock-induced endotheliopathy, coagulopathy, massive bleeding, and significant morbidity and mortality. Our aim was to compare the effect of coagulation support with solvent/detergent-treated pooled plasma (OctaplasLG) versus standard fresh frozen plasma (FFP) on glycocalyx and endothelial injury, bleeding, and transfusion requirements. METHODS: Investigator-initiated, single-center, blinded, randomized clinical pilot trial of adult patients undergoing emergency surgery for thoracic aorta dissection. Patients were randomized to receive OctaplasLG or standard FFP as coagulation factor replacement related to bleeding. The primary outcome was glycocalyx and endothelial injury. Other outcomes included bleeding, transfusions and prohemostatics at 24 hours, organ failure, length of stay in the intensive care unit and in the hospital, safety, and mortality at 30 and 90 days. RESULTS: Fifty-seven patients were included to obtain 44 evaluable on the primary outcome. The OctaplasLG group displayed significantly reduced damage to the endothelial glycocalyx (syndecan-1) and reduced endothelial tight junction injury (sVE-cadherin) compared to standard FFP. In the OctaplasLG group compared to the standard FFP, days on ventilator (1 day [interquartile range, 0-1] vs 2 days [1-3]; P = .013), bleeding during surgery (2150 [1600-3087] vs 2750 [2130-6875]; P = .046), 24-hour total transfusion and platelet transfusion volume (3975 mL [2640-6828 mL] vs 6220 mL [4210-10,245 mL]; P = .040, and 1400 mL [1050-2625 mL] vs 2450 mL [1400-3500 mL]; P = .027), and goal-directed use of prohemostatics (7/23 [30.4%] vs 13/21 [61.9%]; P = .036) were all significantly lower. Among the 57 patients randomized, 30-day mortality was 20.7% (6/29) in the OctaplasLG group and 25% (7/28) in the standard FFP group (P = .760). No safety concern was raised. CONCLUSIONS: In this randomized, clinical pilot trial of patients undergoing emergency surgery for thoracic aorta dissections, we found that OctaplasLG reduced glycocalyx and endothelial injury, reduced bleeding, transfusions, use of prohemostatics, and time on ventilator after surgery compared to standard FFP. An adequately powered multicenter trial is warranted to confirm the clinical importance of the findings.

Implementation of a Massive Transfusion Protocol: Evaluation of Its Use and Efficacy.

Massive transfusion protocols (MTPs) allow practitioners to follow a prescribed algorithm for the rapid replacement of blood products during a massive hemorrhage. They function as an established protocol to provide consistent treatment. Once implemented, the MTP must be evaluated to ensure best practice. The purpose of this clinical improvement project was to formally evaluate the use and efficacy of an MTP during its first year of implementation. The specific aims were to (1) determine whether MTP activations were missed; (2) compare outcomes between those patients managed by the MTP and those who were not; and (3) provide recommendations to the institution's stakeholders. A retrospective medical record review was conducted with 101 electronic medical records of adult trauma patients treated over 1 year. Patients were identified to have experienced massive bleeding if their medical record contained 1 of 4 indicators: (1) transfusion of uncrossmatched blood; (2) tranexamic acid administration; (3) transfusion of 4 or more units of packed red blood cells (PRBCs) in 1 hr; and/or (4) transfusion of 10 or more units of PRBCs in 24 hr. While 58 patients experienced massive bleeding, only 16 (28%) were managed using the MTP. Although the non-MTP group received fewer transfused blood products due to higher initial and 24-hr hemoglobin levels, more deaths occurred in this group than in the MTP group. The recommendations were to (1) establish well-defined criteria for MTP activation based on the 4 indicators of massive bleeding and (2) regularly evaluate the use and efficacy of the MTP to ensure positive patient outcomes.

Optimal Dose, Timing and Ratio of Blood Products in Massive Transfusion: Results from a Systematic Review.

Optimal dose, timing and ratio to red blood cells (RBC) of blood component therapy (fresh frozen plasma [FFP], platelets, cryoprecipitate or fibrinogen concentrate) to reduce morbidity and mortality in critically bleeding patients requiring massive transfusion is unknown. We performed a systematic review for randomized controlled trials (RCT) in MEDLINE, The Cochrane Library, Embase, CINAHL, PubMed the Transfusion Evidence Library and using multiple clinical trials registries to 21 February 2017. Sixteen RCTs were identified: six completed (five in adult trauma patients, one pediatric burn patients) and ten ongoing trials. Of the completed trials: three were feasibility trials, comparing a FFP, platelets and RBC ratio of 1:1:1 to laboratory-guided transfusion practice [n=69], early cryoprecipitate compared to standard practice [n=41], and early fibrinogen concentrate compared to placebo [n=45]; one trial compared the effect of FFP, platelets and RBC ratio of 1:1:1 with 1:1:2 on 24-hour and 30-day mortality [n=680]; one compared whole blood to blood component therapy on 24-hour blood use [n=107]; one compared a FFP to RBC ratio of 1:1 with 1:4 [n=16]. Data from two trials were pooled in a meta-analysis for 28-day mortality because the transfusion ratios achieved were similar. Results from these two trials suggest higher transfusion ratios were associated with transfusion of more FFP and platelets without evidence of significant difference with respect to mortality or morbidity. On the limited evidence available, there is insufficient basis to recommend a 1:1:1 over a 1:1:2 ratio or standard care for adult patients with critical bleeding requiring massive transfusion.

Blood Products Provided to Patients Receiving Futile Critical Care.

The number of hospitalized patients receiving treatment perceived to be futile is not insignificant. Blood products are valuable resources that are donated to help others in need. We aimed to quantify the amount of blood transfused into patients who were receiving treatment that the critical care physician treating them perceived to be futile. During a 3-month period, critical care physicians in 5 adult intensive care units completed a daily questionnaire to identify patients perceived as receiving futile treatment. Of 1136 critically ill patients, physicians assessed 123 patients (11%) as receiving futile treatment. Fifty-nine (48%) of the 123 patients received blood products after they were assessed to be receiving futile treatment: 242 units of packed red blood cells (PRBCs) (7.6% of all PRBC units transfused into critical care patients during the 3-month study period); 161 (9.9%) units of plasma, 137 (12.1%) units of platelets, and 21 (10.5%) units of cryoprecipitate. Explicit guidelines on the use of blood products should be developed to ensure that the use of this precious resource achieves meaningful goals.

Safety of the use of group A plasma in trauma: the STAT study.

BACKGROUND: Use of universally ABO-compatible group AB plasma for trauma resuscitation can be challenging due to supply limitations. Many centers are now using group A plasma during the initial resuscitation of traumatically injured patients. This study was undertaken to evaluate the impact of this practice on mortality and hospital length of stay (LOS). STUDY DESIGN AND METHODS: Seventeen trauma centers using group A plasma in trauma patients of unknown ABO group participated in this study. Eligible patients were group A, B, and AB trauma patients who received at least 1 unit of group A plasma. Data collected included patient sex, age, mechanism of injury, Trauma Injury Severity Score (TRISS) probability of survival, and number of blood products transfused. The main outcome of this study was in-hospital mortality differences between group B and AB patients compared to group A patients. Data on early mortality (≤24 hr) and hospital LOS were also collected. RESULTS: There were 354 B and AB patients and 809 A patients. The two study groups were comparable in terms of age, sex, TRISS probability of survival, and total number of blood products transfused. The use of group A plasma during the initial resuscitation of traumatically injured patients of unknown ABO group was not associated with increased in-hospital mortality, early mortality, or hospital LOS for group B and AB patients compared to group A patients. CONCLUSION: These results support the practice of issuing thawed group A plasma for the initial resuscitation of trauma patients of unknown ABO group.

Should All Massively Transfused Patients Be Treated Equally? An Analysis of Massive Transfusion Ratios in the Nontrauma Setting.

OBJECTIVES: Although balanced resuscitation has become integrated into massive transfusion practice, there is a paucity of evidence supporting the delivery of high ratios of plasma and platelet to RBCs in the nontrauma setting. This study investigated the administration of blood component ratios in the massively transfused nontrauma demographic. DESIGN: Retrospective analysis of a prospective, observational cohort of massively bleeding patients. SETTING: Surgical and critically ill patients at a tertiary medical center between 2011 and 2015. PATIENTS: Massively transfused nontrauma patients. INTERVENTIONS: Patients receiving plasma, platelet, and RBC transfusions were categorized into high and low ratio groups and analyzed for differences in characteristics and clinical outcomes. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 30-day mortality. Secondary outcomes included 48-hour mortality, hospital length of stay, ICU length of stay, and ventilator-free days. Among 601 massively transfused nontrauma patients, cardiothoracic surgery and gastrointestinal or hepato-pancreatico-biliary bleeds were the most common indications for massive transfusion. Higher fresh frozen plasma ratios (> 1:2) were not associated with increased 30-day mortality. A high platelets-to-packed RBCs ratio (> 1:2) was associated with decreased 48-hour mortality (10.5% vs 19.3%; p = 0.032), but not 30-day mortality. Fresh frozen plasma-to-packed RBCs and platelets-to-packed RBCs ratios were not associated with 30-day mortality hazard ratios after controlling for baseline characteristics and disease severity. CONCLUSIONS: The benefits of higher ratios of fresh frozen plasma-to-packed RBCs and platelets-to-packed RBCs described in trials of trauma patients were not observed in this analysis of a nontrauma, massively transfused population. These data suggest that greater than 1:2 ratio transfusion in the setting of massive hemorrhage may not be appropriate for all patients, and that further research to guide appropriate resuscitation strategies in nontrauma patients is warranted.

Application of Incident Command Structure to clinical trial management in the academic setting: principles and lessons learned.

BACKGROUND: Clinical trial success depends on appropriate management, but practical guidance to trial organisation and planning is lacking. The Incident Command System (ICS) is the 'gold standard' management system developed for managing diverse operations in major incident and public health arenas. It enables effective and flexible management through integration of personnel, procedures, resources, and communications within a common hierarchical organisational structure. Conventional ICS organisation consists of five function modules: Command, Planning, Operations, Logistics, and Finance/Administration. Large clinical trials will require a separate Regulatory Administrative arm, and an Information arm, consisting of dedicated data management and information technology staff. We applied ICS principles to organisation and management of the Prehospital Use of Plasma in Traumatic Haemorrhage (PUPTH) trial. This trial was a multidepartmental, multiagency, randomised clinical trial investigating prehospital administration of thawed plasma on mortality and coagulation response in severely injured trauma patients. We describe the ICS system as it would apply to large clinical trials in general, and the benefits, barriers, and lessons learned in utilising ICS principles to reorganise and coordinate the PUPTH trial. RESULTS: Without a formal trial management structure, early stages of the trial were characterised by inertia and organisational confusion. Implementing ICS improved organisation, coordination, and communication between multiple agencies and service groups, and greatly streamlined regulatory compliance administration. However, unfamiliarity of clinicians with ICS culture, conflicting resource allocation priorities, and communication bottlenecks were significant barriers. CONCLUSIONS: ICS is a flexible and powerful organisational tool for managing large complex clinical trials. However, for successful implementation the cultural, psychological, and social environment of trial participants must be accounted for, and personnel need to be educated in the basics of ICS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02303964 . Registered on 28 November 2014.

Effects of Perioperative Fluid Replacement Therapy in Lung Transplant Patients.

OBJECTIVES: Approximately 10 to 25 lung transplant procedures are performed annually in Finland, and 1-year survival has been 95% over the last 10 years. Our aim was to find associations between perioperative fluid replacement therapies and postoperative patient outcomes, with special emphasis on the use of colloids and blood products. MATERIALS AND METHODS: We retrospectively evaluated data from 100 patients who underwent lung transplant with cardiopulmonary bypass support in Finland from 2007 to 2013. Outcomes of interest were length of intensive care unit and hospital stays, time in ventilator, use of extracorporeal membrane oxygenation postoperatively, postoperative renal replacement therapy, postoperative graft failure, and 1-year mortality. RESULTS: Of 100 patients, 12 were on extracorporeal membrane oxygenation preoperatively. The 1-year mortality was 5/100 (5%), and the 3-year mortality was 7/100 (7%). Intraoperative fluid balance was positive (4762 a 3018 mL) but fell significantly postoperatively (below +1000 mL on postoperative day 1). During postoperative days 2 to 7, net fluid balance continued decreasing and stayed negative. Intraoperative use of hydroxyethyl starch and fresh frozen plasma were significantly higher in patients who died during follow-up versus those who survived (P < .05). Intraoperative use of fresh frozen plasma, but not red blood cells or platelets, correlated with graft failure (P = .012). Postoperative use of colloids or blood products did not correlate with mortality or graft failure. Patients who were on extracorporeal membrane oxygenation preoperatively stayed longer on ventilators and had longer intensive care unit and hospital stays (P < .001). Eight patients needed postoperative renal replacement therapy. CONCLUSIONS: Intraoperative use of fresh frozen plasma and hydroxyethyl starch is associated with increased mortality and graft failure. Postoperative use of colloids and red blood cells did not correlate with patient outcome. Use of extracorporeal membrane oxygenation preoperatively resulted in prolonged length of hospital stay.

The survival impact of plasma to red blood cell ratio in massively transfused non-trauma patients.

PURPOSE: High ratios of Plasma to Packed Red Blood Cells (FFP:PRBC) improve survival in massively transfused trauma patients. We hypothesized that non-trauma patients also benefit from this transfusion strategy. METHODS: Non-trauma patients requiring massive transfusion from November 2003 to September 2011 were reviewed. Logistic regression was performed to identify independent predictors of mortality. The population was stratified using two FFP:PRBC ratio cut-offs (1:2 and 1:3) and adjusted mortality derived. RESULTS: Over 8 years, 29 % (260/908) of massively transfused surgical patients were non-trauma patients. Mortality decreased with increasing FFP:PRBC ratios (45 % for ratio ≤1:8, 33 % for ratio >1:8 and ≤1:3, 27 % for ratio >1:3 and ≤1:2 and 25 % for ratio >1:2). Increasing FFP:PRBC ratio independently predicted survival (AOR [95 % CI]: 1.91 [1.35-2.71]; p < 0.001). Patients achieving a ratio >1:3 had improved survival (AOR [95 % CI]: 3.24 [1.24-8.47]; p = 0.016). CONCLUSION: In non-trauma patients undergoing massive transfusion, increasing FFP:PRBC ratio was associated with improved survival. A ratio >1:3 significantly improved survival probability.

No association between donor age and recipient outcomes: transfusion of plasma in patients undergoing coronary artery bypass grafting surgery.

BACKGROUND: Recent animal studies suggest that transfusion of plasma from young donors reverses age-related neurologic and cardiac changes in older recipients. Associations between age of blood product donors and corresponding outcomes in recipients have not been studied in humans. Therefore, our primary objective was to examine this relationship between donor age and recipient outcomes among patients that received plasma during and after coronary artery bypass grafting (CABG) surgery. STUDY DESIGN AND METHODS: This retrospective cohort included patients undergoing CABG surgery who received plasma during or after surgery. All plasma units transfused were evenly divided into tertiles based on the plasma donor age (17-37, 38-50, and 51-86 years), and CABG patients receiving all perioperative plasma within a single donor tertile were studied. Patient demographics and outcomes including mortality, length of stay (LOS), and acute kidney injury (AKI) were measured. RESULTS: Overall, 1306 patients (24% of 5339) received American Red Cross plasma perioperatively, with a median dose of 2 units. In a multivariate model of 1-year mortality, transfusion of a greater number of plasma units (p = 0.0007) and EuroSCORE (p < 0.0001) were significantly associated with patient mortality while donor age was not. There was no difference in mortality between patients receiving plasma from donors in the youngest, middle, or oldest age tertile (10.2 and 8.1% vs. 7.8%, respectively, p = 0.76). Other outcomes, including rates of AKI or LOS, were also independent of plasma donor age. CONCLUSIONS: We did not observe an association between donor age and recipient outcomes among patients who received plasma perioperatively while undergoing CABG surgery.

Perioperative bleeding management in pediatric patients.

PURPOSE OF REVIEW: Managing the bleeding pediatric patient perioperatively can be extremely challenging. The primary goals include avoiding hypotension, maintaining adequate tissue perfusion and oxygenation, and maintaining hemostasis. Traditional bleeding management has consisted of transfusion of autologous blood products, however, there is strong evidence that transfusion-related side-effects are associated with increased morbidity and mortality in children. Especially concerning is the increased reported incidence of noninfectious adverse events such as transfusion-related acute lung injury, transfusion-related circulatory overload and transfusion-related immunomodulation. The current approach in perioperative bleeding management of the pediatric patient should focus on the diagnosis and treatment of anemia and coagulopathy with the transfusion of blood products only when clinically indicated and guided by goal-directed strategies. RECENT FINDINGS: Current guidelines recommend that a comprehensive multimodal patient blood management strategy is critical in optimizing patient care, avoiding unnecessary transfusion of blood and blood product and limiting transfusion-related side-effects. SUMMARY: This article will highlight current guidelines in perioperative bleeding management for our most vulnerable pediatric patients with emphasis on individualized targeted intervention using point-of-care testing and specific coagulation products.

Red blood cell transfusion is associated with further bleeding and fresh-frozen plasma with mortality in nonvariceal upper gastrointestinal bleeding.

BACKGROUND: Blood products are commonly transfused for patients with nonvariceal upper gastrointestinal bleeding (NVUGIB). While concerns exist about further bleeding and mortality in subsets of patients receiving red blood cell (RBC) transfusion, the impact of non-RBC blood products has not previously been systematically investigated. The aim of the study was to investigate the associations between blood products transfusion, further bleeding, and mortality after acute NVUGIB. STUDY DESIGN AND METHODS: A retrospective cohort study examined further bleeding and 30-day and 1-year mortality in adult patients who underwent gastroscopy for suspected acute NVUGIB between 2008 and 2010 in three tertiary hospitals in Western Australia. Survival analysis was performed. RESULTS: A total of 2228 adults (63% male) with 2360 hospital admissions for NVUGIB met the inclusion criteria. Median age at presentation was 70 years (range, 19-99 years). Thirty-day mortality was 4.9% and 1-year mortality was 13.9%. Transfusion of 4 or more units of RBCs was associated with greater than 10 times the odds of further bleeding in patients with a hemoglobin level of more than 90 g/L (odds ratio, 11.9; 95% confidence interval [CI], 3.1-45.7; p ≤ 0.001), but was not associated with mortality. Administration of 5 or more units of fresh-frozen plasma (FFP) was associated with increased 30-day (hazard ratio, 2.8; 95% CI, 1.3-5.9; p = 0.008) and 1-year (hazard ratio, 2.6; 95% CI, 1.3-5.0; p = 0.005) mortality after adjusting for coagulopathy, comorbidity, Rockall score, and other covariates. CONCLUSION: In this large, multicenter study of NVUGIB, RBC transfusion was associated with further bleeding but not mortality, while FFP transfusion was associated with increased mortality in a subset of patients.

Prehospital use of plasma in traumatic hemorrhage (The PUPTH Trial): study protocol for a randomised controlled trial.

BACKGROUND: Severe traumatic injury and haemorrhagic shock are frequently associated with disruptions of coagulation function (such as trauma-induced coagulopathy TIC) and activation of inflammatory cascades. These pathologies may be exacerbated by current standard of care resuscitation protocols. Observational studies suggest early administration of plasma to severely-injured haemorrhaging patients may correct TIC, minimise inflammation, and improve survival. The proposed randomised clinical trial will evaluate the clinical effectiveness of pre-hospital plasma administration compared with standard- of-care crystalloid resuscitation in severely-injured patients with major traumatic haemorrhage. METHODS/DESIGN: This is a prospective, randomized, open-label, non-blinded trial to determine the effect of pre-hospital administration of thawed plasma (TP) on mortality, morbidity, transfusion requirements, coagulation, and inflammatory response in severely-injured bleeding trauma patients. Two hundred and ten eligible adult trauma patients will be randomised to receive either two units of plasma, to be administered in-field, vs standard of care normal saline (NS). Main analyses will compare subjects allocated to TP to those allocated to NS, on an intention-to-treat basis. Primary outcome measure is all-cause 30-day mortality. Secondary outcome measures include coagulation and lipidomic/pro-inflammatory marker responses, volume of resuscitation fluids (crystalloid, colloid) and blood products administered, and major hospital outcomes (e.g. incidence of MSOF, length of ICU stay, length of hospital stay). DISCUSSION: This study is part of a US Department of Defense (DoD)-funded multi-institutional investigation, conducted independently of, but in parallel with, the University of Pittsburgh and University of Denver. Demonstration of significant reductions in mortality and coagulopathic/inflammatory-related morbidities as a result of pre-hospital plasma administration would be of considerable clinical importance for the management of haemorrhagic shock in both civilian and military populations. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02303964 on 28 November 2014.

Fresh Frozen Plasma Use in a Neonatal Unit in South Africa.

BACKGROUND: Despite limited evidence, fresh frozen plasma (FFP) transfusions are a relatively common neonatal procedure. OBJECTIVES: Quantify FFP usage in our unit; determine indications for transfusions and compliance with published guidelines. METHODS: Data were retrospectively collected on infants who received FFP from January 2009 to December 2013. RESULTS: Admissions totalled 10 912 infants during the study period. In total, 113 case notes were reviewed and 142 FFP transfusions were administered. Infants receiving FFP had a high mortality rate (54.87%) and an increased odds ratio for mortality 17.9 (95% confidence interval 12.0-26.6). In total, 75% FFP transfusions were compliant with guidelines. The difference between pre- and post-transfusion coagulation profile in 36.3% of infants was not statistically significant. CONCLUSIONS: FFP was often used in accordance with published guidelines in our neonatal unit. However, the appropriate use and effectiveness of FFP in improving neonatal outcomes undermines the rationale for FFP usage in current guidelines.

Male-predominant plasma transfusion strategy for preventing transfusion-related acute lung injury: a systematic review.

OBJECTIVES: To assess 1) the effectiveness of male-predominant plasma transfusion strategy for preventing transfusion-related acute lung injury and related mortality; and 2) whether this effect varies across different patient subgroups. DESIGN: Systematic Review and meta-analysis: Data were identified by querying MEDLINE and EMBASE (including proceedings of major conferences on blood transfusions), searching the Internet for hemovigilance reports, reviewing reference lists of eligible articles and contacting experts in the field. Eligible were all studies reporting transfusion-related acute lung injury incidence, all-cause mortality (primary outcomes), hospital length of stay, time to extubation, PaO2/FIO2-ratio or blood pressure changes (secondary outcomes) in recipients of plasma transfusions containing relatively more plasma from individuals at low risk of carrying leukocyte-antibodies ("male plasma") than those receiving comparator plasma ("control plasma"). No limits were placed on study design, population or language. The only exclusion criteria were non-human subjects and lack of control group. Prespecified study quality indicators (including risk of bias assessment) and potential effect modifiers were tested using Cochran's Q Test. Final analyses using random-effects models and I2 to assess heterogeneity were performed in the subset of studies judged to provide the best evidence and separately for significantly different subgroups using STATA 12.1 (StataCorp, College Station, TX). SETTING: As per primary studies. PATIENTS/SUBJECTS: As per primary studies. INTERVENTIONS: As per primary studies (generally: exposure to plasma containing relatively more male plasma than comparator plasma). MEASUREMENTS AND MAIN RESULTS: From a total of 850 retrieved records, we identified 45 eligible studies. For transfusion-related acute lung injury incidence, final analysis was restricted to 13 cohort studies and one randomized controlled trial in which transfusion-related acute lung injury cases only involved plasma transfusions. Risk of transfusion-related acute lung injury and mortality in plasma recipients exposed to men when compared with control plasma were 0.27 (95% CI, 0.20-0.38; p < 0.001; I = 0%; n = 14; 286 events) and 0.89 (95% CI, 0.80-1.00; p = 0.04; I = 79%; n = 7; 5, 710 events), respectively. No other significant interactions were found. Secondary outcomes showed similar results but were less reported and the studies were more heterogeneous. Sensitivity analyses did not alter the results. There was no evidence of publication bias. DISCUSSION: More than 800 million people in 17 countries are subject to male-predominant plasma transfusion policy and at least three more countries are planning or considering adoption of this strategy. On the basis of most observational data, judged to be of high quality, male-predominant plasma transfusion strategy reduces plasma-related transfusion-related acute lung injury incidence and possibly mortality. There was no evidence that the effect differs across patient subgroups, but power to detect such differences was low.

Time matters in 1: 1 resuscitations: concurrent administration of blood: plasma and risk of death.

BACKGROUND: The practice of 1:1 transfusion, administering packed red blood cells (PRBCs) with fresh frozen plasma (FFP), has been associated with improved survival. However, the reported ratios are the result of mathematical averages over 24 hours and do not necessarily represent concurrent administration. Using critical administration thresholds (CAT+) of more than 3 U of PRBC per hour to identify hemorrhaging patients, this study evaluates the effect of concurrent administration of PRBC/FFP on patient survival. METHODS: CAT+ patients identified retrospectively were eligible for analysis. The exact time of administration of each unit of PRBC and FFP was calculated. Each PRBC was matched to a corresponding unit of FFP given within 5 minutes before or after. Ideal 1:1 ratios were calculated for each hour during the first day of admission. Hourly ratio groups were created (25%, 50%, 75% of transfusion opportunities) and evaluated as time-varying covariates. Cox proportional hazard ratio (HR) was used to determine risk of mortality, and Student's t test or Wilcoxon signed-rank test was used to compare groups. RESULTS: A total of 169 patients were initially identified (70% with New Injury Severity Score [NISS] > 10), 77 of whom were CAT+. There were no clinical differences between the groups in this study. In terms of mortality, patients who reached the 1:1 ratio 25% of the transfusion opportunities had an HR of 8.806 (95% confidence interval [CI], 1.845-42.034). Patients meeting the 1:1 ratio 50% of the opportunities had an HR of 5.062 (95% CI, 1.115-22.982) while those meeting 75% of the opportunities had an HR of 1.888 (95% CI, 0.198-18.035). CONCLUSION: CAT+ patients represent the trauma subset at highest risk of mortality and may benefit from a focused blood-based resuscitation. Patients who were able to meet the 1:1 ratio more often had a noticeable decrease in risk of death compared with those who achieved less than 1:1 transfusions. Administering FFP concurrently with PRBC is associated with a decrease in mortality in CAT+ patients. LEVEL OF EVIDENCE: Prognostic study, level III; therapeutic study, level IV.

Massive transfusion in paediatric and adolescent trauma patients: incidence, patient profile, and outcomes prior to a massive transfusion protocol.

OBJECTIVES: The purpose of this study was to quantify the incidence, patient profile, and outcomes associated with massive transfusion in paediatric trauma patients prior to establishing a massive transfusion protocol. METHODS: We performed a retrospective review of paediatric trauma patients treated at London Heath Sciences Centre between January 1, 2006, and December 31, 2011. Inclusion criteria were Injury Severity Score (ISS) greater than 12 and age less than 18 years. RESULTS: 435 patients met the inclusion criteria. Three hundred and fifty-six (82%) did not receive packed red blood cells in the first 24h, 66 (15%) received a non-massive transfusion (<40mL/kg), and 13 (3%) received a massive transfusion (>40mL/kg). Coagulopathy of any kind was more common in massive transfusion (11/13; 85%) than non-massive (32/66; 49%) (p=0.037). Hyperkalemia (18% versus 23%; p=0.98) and hypocalcemia (41% versus 46%; p=1.00) were similar in both groups. Of the 13 massively transfused patients, 9 had multisystem injuries due to a motor vehicle collision, 3 had non-accidental head injuries requiring surgical evacuation, and 1 had multiple stab wounds. In the absence of a massive transfusion protocol, only 8 of the 13 patients received both fresh frozen plasma and platelets in the first 24h. Massive transfusion occurred in patients from across the age spectrum and was associated with severe injuries (mean ISS=33), a higher incidence of severe head injuries (92%), longer hospital stay (mean=36 days), and increased mortality (38%). CONCLUSIONS: This study is the first to describe the incidence, complications, and outcomes associated with massive transfusion in paediatric trauma patients prior to a massive transfusion protocol. Massive transfusion occurred in 3% of patients and was associated with coagulopathy and poor outcomes. Protocols are needed to ensure that resuscitation occurs in a coordinated fashion and that patients are given appropriate amounts of fresh frozen plasma, platelets, and cryoprecipitate.

Coagulation management with factor concentrates in liver transplantation: a single-center experience.

BACKGROUND: Allogeneic blood products transfusion during liver transplantation (LT) can be associated with increased morbidity and mortality. Data on thromboelastometry (ROTEM)-guided coagulation management with coagulation factor concentrates (CFCs)-fibrinogen concentrate and/or prothrombin complex concentrate (PCC)-are sparse. We aimed to retrospectively evaluate the safety events observed with this approach in our clinic. STUDY DESIGN AND METHODS: LT patients from January 2009 to December 2010 (n = 266) were identified by chart review. A ROTEM-based algorithm with CFC guided the hemostatic therapy. Doppler ultrasound was used to evaluate thrombosis in the hepatic artery, portal vein, and hepatic veins. Stroke, myocardial ischemia, pulmonary embolism, and transfusion variables were recorded. Patients receiving CFC were included in the CFC group (n = 156); those not receiving CFC were included in the non-CFC group (n = 110). Safety events were compared between these two groups. RESULTS: Allogeneic transfusion(s) in the 266 patients was low, with medians of 2 (interquartile range [IQR], 0-5), 0 (IQR 0-0), and 0 (IQR 0-1) units for red blood cells (RBCs), fresh-frozen plasma (FFP), and platelets (PLTs), respectively. Ninety-seven of 266 LTs (36.5%) were performed without RBCs transfusion, 227 (85.3%) without FFP, and 190 (71.4%) without PLTs. There were no significant differences in thrombotic, thromboembolic, and ischemic adverse events occurrence between the CFC group and the non-CFC group (11/156 patients vs. 5/110; p = 0.31). CONCLUSION: In LT, ROTEM-guided treatment with fibrinogen concentrate and/or PCC did not appear to increase the occurrence of thrombosis and ischemic events compared to patients who did not receive these concentrates.