Kor, Daryl J.

BACKGROUNDRecipients of hematopoietic stem cell transplantation (HSCT) are among the highest consumers of allogeneic red blood cell (RBC) and platelet (PLT) components. The impact of patient blood management (PBM) efforts on HSCT recipients is poorly understood.STUDY DESIGN AND METHODSThis observational study assessed changes in blood product use and patient‐centered outcomes before and after implementing a multidisciplinary PBM program for patients undergoing HSCT at a large academic medical center. The pre‐PBM cohort was treated from January 1 through September 31, 2013; the post‐PBM cohort was treated from January 1 through September 31, 2015.RESULTSWe identified 708 patients; 284 of 352 (80.7%) in the pre‐PBM group and 225 of 356 (63.2%) in the post‐PBM group received allogeneic RBCs (p < 0.001). Median (interquartile range [IQR]) RBC volumes were higher before PBM than after PBM (3 [2‐4] units vs. 2 [1‐4] units; p = 0.004). A total of 259 of 284 pre‐PBM patients (91.2%) and 57 of 225 (25.3%) post‐PBM patients received RBC transfusions when hemoglobin levels were more than 7 g/dL (p < 0.001). The median (IQR) PLT transfusion quantities was 3 (2‐5) units for pre‐PBM patients and 2 (1‐4) units for post‐PBM patients (p < 0.001). For patients with PLT counts of more than 10 × 109/L, a total of 1219 PLT units (73.4%) were transfused before PBM and 691 units (48.8%) were transfused after PBM (p < 0.001). Estimated transfusion expenditures were reduced by $617,152 (18.3%). We noted no differences in clinical outcomes or transfusion‐related adverse events.CONCLUSIONPatient blood management implementation for HSCT recipients was associated with marked reductions in allogeneic RBC and PLT transfusions and decreased transfusion‐related costs with no detrimental impact on clinical outcomes.

BACKGROUNDThe prevention of excessive allogeneic red blood cell (RBC) transfusion is an important component of patient blood management initiatives. In this investigation, changes in transfusion behaviors following modification of computerized physician order entry (CPOE) procedures for RBC transfusions to a single‐unit default quantity were assessed.STUDY DESIGN AND METHODSThis is an observational cohort study of adults for whom nonemergency allogeneic RBC transfusions were ordered in the 2 years before and 2 years after the date of modification of the CPOE system to a single‐unit default (June 18, 2015). Changes in the frequency of single‐ versus multiunit RBC transfusion orders and other transfusion metrics were compared between preintervention and postintervention cohorts.RESULTSA total of 52,773 unique transfusion orders for 61,989 RBC units were included, of which 60,045 (96.9%) were transfused. Single‐unit orders increased annually, from 10,404 (74.1%) in the first year to 11,645 (88.6%) in the last year, while multiunit orders decreased by more than half (p < 0.0001). The number of RBC units transfused decreased by 13.9% from 32,528 in the preintervention cohort to 27,497 in the post intervention cohort (p < 0.0001) with an estimated reduction in transfusion‐related expenditures of nearly $4 million. The percentage of transfusions associated with a posttransfusion hemoglobin of10 g/dL or greater decreased by 34.5% (p < 0.0001).CONCLUSIONModification of the CPOE process such that nonemergency RBC transfusion orders were defaulted to a single unit was associated with decreased rates of multiunit RBC transfusion orders, lower transfusion volumes, and substantial cost savings.

BACKGROUNDTransfusion‐related acute lung injury (TRALI) is a serious complication of blood transfusion and is among the leading causes of transfusion‐related morbidity and mortality in most developed countries. In the past decade, the pathophysiology of this potentially life‐threatening syndrome has been increasingly elucidated, large cohort studies have identified associated patient conditions and transfusion risk factors, and preventive strategies have been successfully implemented. These new insights provide a rationale for updating the 2004 consensus definition of TRALI.STUDY DESIGN AND METHODSAn international expert panel used the Delphi methodology to develop a redefinition of TRALI by modifying and updating the 2004 definition. Additionally, the panel reviewed issues related to TRALI nomenclature, patient conditions associated with acute respiratory distress syndrome (ARDS) and TRALI, TRALI pathophysiology, and standardization of reporting of TRALI cases.RESULTSIn the redefinition, the term “possible TRALI” has been dropped. The terminology of TRALI Type I (without an ARDS risk factor) and TRALI Type II (with an ARDS risk factor or with mild existing ARDS) is proposed. Cases with an ARDS risk factor that meet ARDS diagnostic criteria and where respiratory deterioration over the 12 hours before transfusion implicates the risk factor as causative should be classified as ARDS. TRALI remains a clinical diagnosis and does not require detection of cognate white blood cell antibodies.CONCLUSIONSClinicians should report all cases of posttransfusion pulmonary edema to the transfusion service so that further investigation can allow for classification of such cases as TRALI (Type I or Type II), ARDS, transfusion‐associated circulatory overload (TACO), or TRALI or TACO cannot distinguish or an alternate diagnosis.

BACKGROUNDIntraoperative plasma transfusion is common, yet little is known regarding its effects on perioperative coagulation tests or clinical outcomes.STUDY DESIGN AND METHODSThis is a retrospective cohort study of adults receiving intraoperative plasma transfusion at a single center from 2011 to 2015. Relationships between plasma transfusion volume, changes in coagulation test values, and clinical outcomes, including a primary outcome of early postoperative red blood cell (RBC) transfusion, were assessed with multivariable regression analyses. Secondary outcomes included hospital mortality, intensive care unit (ICU)‐ and hospital‐free days, intraoperative RBC transfusions, and estimated blood loss.RESULTSA total of 3393 unique patients were included, with median (IQR) transfusion of 2 (2‐4) units. In multivariable analyses, higher plasma volumes were associated with worse outcomes, with each 1 mL/kg increase associated with increased odds for postoperative (1.02 [1.01‐1.03], p < 0.001) and intraoperative RBCs (1.17 [1.16‐1.19], p < 0.001) and fewer ICU‐ and hospital‐free days (mean difference [95% CI], –0.08 [−0.12 to −0.05], p < 0.001; and −0.09 [−0.13 to −0.06], p < 0.001, respectively). Greater decreases in international normalized ratio (INR) following plasma transfusion were associated with decreased odds of postoperative RBCs (0.35 [0.25‐0.47], p < 0.001), decreased mortality (0.50 [0.31‐0.83], p = 0.007), and increased mean ICU‐ (1.31 [0.41‐2.21], p = 0.004) and hospital‐free days (1.15 [0.19‐2.10], p = 0.018).CONCLUSIONIn patients receiving intraoperative plasma transfusion, higher transfusion volumes were associated with inferior clinical outcomes; however, greater improvements in INR were associated with improved outcomes. Future prospective studies are necessary to better define these relationships and to explore plasma transfusion triggers beyond the limitations of INR.

BACKGROUND: Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are the leading causes of transfusion-related fatalities. While these transfusion-related pulmonary complications (TRPCs) have been well detailed in adults, their burden in pediatric subsets remains poorly defined. We sought to delineate the incidence and epidemiology of pediatric TRPCs after intraoperative blood product transfusion. METHODS: In this retrospective cohort study, we evaluated all consecutive pediatric patients receiving intraoperative blood product transfusions during noncardiac surgeries between January 2010 and December 2014. Exclusion criteria were cyanotic heart disease, preoperative respiratory insufficiency, extracorporeal membrane oxygenation, and American Society of Anesthesiologists physical status VI. Medical records were electronically screened to identify those with evidence of hypoxemia, and in whom a chest x-ray was obtained within 24 hours of surgery. Records were then manually reviewed by 2 physicians to determine whether they met diagnostic criteria for TACO or TRALI. Disagreements were adjudicated by a third senior physician. RESULTS: Of 19,288 unique pediatric surgical patients, 411 were eligible for inclusion. The incidence of TRPCs was 3.6% (95% confidence interval [CI], 2.2–5.9). TACO occurred in 3.4% (95% CI, 2.0–5.6) of patients, TRALI was identified in 1.2% (95% CI, 0.5–2.8), and 1.0% (95% CI, 0.4–2.5) had evidence for both TRALI and TACO. Incidence was not different between males (3.4%) and females (3.8%; P = .815). Although a trend toward an increased incidence of TRPCs was observed in younger patients, this did not reach statistical significance ( P = .109). Incidence was comparable across subsets of transfusion volume ( P = .184) and surgical specialties ( P = .088). Among the 15 patients experiencing TRPCs, red blood cells were administered to 13 subjects, plasma to 3, platelets to 3, cryoprecipitate to 2, and autologous blood to 3. Three patients with TRCPs were transfused mixed blood components. CONCLUSIONS: TRPCs occurred in 3.6% of transfused pediatric surgical patients, with the majority of cases attributable to TACO, congruent with adult literature. The frequency of TRPCs was comparable between genders and across surgical procedures and transfusion volumes. The observed trend toward increased TRPCs in younger children warrants further consideration in future investigations. Red blood cell administration was the associated component for the majority of TRPCs, although platelets demonstrated the highest risk per component transfused. Mitigation of perioperative risk associated with TRPCs in pediatric patients is reliant on further multiinstitutional studies powered to examine patterns and predictors of this highly morbid entity.

BACKGROUND: Patients who develop ARDS from medical or traumatic causes typically present after the inciting event has already occurred. Postoperative ARDS is unique in that the inciting insult potentially responsible for ARDS is known ahead of time, which provides an opportunity to study the early pathophysiology of ARDS. The objective of this study was to better understand the early pathophysiology of postoperative ARDS through a temporal analysis of key biomarkers of interest. METHODS: We performed a case-control study of adults undergoing elective thoracic, aortic vascular, or cardiac surgery, which placed them at increased risk of developing postoperative ARDS. Biomarkers were measured at baseline, 2 h, and 6 h after the key intraoperative event believed to be responsible for ARDS. RESULTS: Of the 467 subjects enrolled, 26 developed ARDS and were matched to non-ARDS controls 1:2 based on age, sex, surgical procedure, and surgical lung injury prediction score. Patients with ARDS were more likely to have lower preoperative albumin ( P = .029), longer surgery ( P = .007), larger amounts of intraoperative fluid ( P = .036), and higher intraoperative peak inspiratory pressures ( P = .006). Baseline plasminogen activator inhibitor-1 levels were higher in the ARDS group ( P = .03). Changes in postoperative biomarker levels from baseline were greater in the ARDS group for interleukin-8 (baseline to 6 h, P = .02) and surfactant protein-D (baseline to 2 h, P = .009). CONCLUSIONS: Our study supported the hypothesis that dysregulated coagulation, inflammation, and epithelial injury are pathophysiologic features of early postoperative ARDS. Interleukin-8, plasminogen activator-1, and surfactant protein-D may help predict development of postoperative ARDS.

Abstract Rationale Acute respiratory distress syndrome (ARDS) is a devastating illness with limited therapeutic options. A better understanding of early biochemical and immunological events in ARDS could inform the development of new preventive and treatment strategies. Objectives To determine select peripheral blood lipid mediator and leukocyte responses in patients at risk for ARDS. Methods Patients at risk for ARDS were randomized as part of a multicenter, double-blind clinical trial of aspirin versus placebo (the LIPS-A [Lung Injury Prevention Study with Aspirin] trial; NCT01504867). Plasma thromboxane B2 (TXB2), aspirin-triggered lipoxin A4 (15-epi-LXA4, ATL), and peripheral blood leukocyte number and activation were determined on enrollment and after treatment with either aspirin or placebo. Measurements and Main Results Thirty-three of 367 subjects (9.0%) developed ARDS after randomization. Baseline ATL levels, total monocyte counts, intermediate monocyte counts, and monocyte–platelet aggregates were associated with the development of ARDS. Peripheral blood neutrophil count and monocyte–platelet aggregates significantly decreased over time. Of note, nine subjects developed ARDS after randomization yet before study drug initiation, including seven subjects assigned to aspirin treatment. Subjects without ARDS at the time of first dose demonstrated a lower incidence of ARDS with aspirin treatment. Compared with placebo, aspirin significantly decreased TXB2 and increased the ATL/TXB2 ratio. Conclusions Biomarkers of intravascular monocyte activation in at-risk patients were associated with development of ARDS. The potential clinical benefit of early aspirin for prevention of ARDS remains uncertain. Together, results of the biochemical and immunological analyses provide a window into the early pathogenesis of human ARDS and represent potential vascular biomarkers of ARDS risk. Clinical trial registered with www.clinicaltrials.gov (NCT01504867).