A consensus redefinition of transfusion-related acute lung injury.

BACKGROUND: Transfusion-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 METHODS: An 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. RESULTS: In 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. CONCLUSIONS: Clinicians 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.

Proposed revised nomenclature for transfusion-related acute lung injury.

A decade ago, definitions of "transfusionߚrelated acute lung injury (TRALI)" and "possible TRALI" were standardized for research and clinical diagnosis. Since then, evidence has confirmed that TRALI is often due to transfusion of white blood cell antibodies to at-risk patients, and the term "TRALI, antibody mediated" is appropriate for such cases. Other TRALI cases are non-antibody mediated. Because specific, nonantibody transfusion factors have not yet been confirmed to cause TRALI in humans, the general term "TRALI, non-antibody mediated" is appropriate for such cases. In contrast, evidence is against possible TRALI being due to transfusion with the more likely cause of the acute respiratory distress syndrome (ARDS) being the alternative ARDS risk factor present in these patients. We propose to drop the misleading term "possible TRALI" and to rename this category of cases as "transfused ARDS." These nomenclature updates will more accurately categorize ARDS cases that develop after transfusion.

Differentiating pulmonary transfusion reactions using recipient and transfusion factors.

BACKGROUND: It is increasingly recognized that recipient risk factors play a prominent role in possible transfusion-related acute lung injury (pTRALI) and transfusion-associated circulatory overload (TACO). We hypothesized that both transfusion and recipient factors including natriuretic peptides could be used to distinguish TRALI from TACO and pTRALI. STUDY DESIGN AND METHODS: We performed a post hoc analysis of a case-control study of pulmonary transfusion reactions conducted at the University of California at San Francisco and Mayo Clinic, Rochester. We evaluated clinical data and brain natriuretic peptides (BNP) levels drawn after transfusion in patients with TRALI (n = 21), pTRALI (n = 26), TACO (n = 22), and controls (n = 24). Logistic regression and receiver operating characteristics curve analyses were used to determine the accuracy of clinical and biomarker predictors in differentiating TRALI from TACO and pTRALI. RESULTS: We found that pTRALI and TACO were associated with older age, higher fluid balance, and elevated BNP levels relative to those of controls and TRALI. The following variables were useful in distinguishing cases of pTRALI and TACO from TRALI: age more than 70 years, BNP levels more than 1000 pg/mL, 24-hour fluid balance of more than 3 L, and a lower number of transfused blood components. Using the above variables, our logistic model had a 91% negative predictive value in the differential diagnosis of TRALI. CONCLUSIONS: Models incorporating readily available clinical and biomarker data can be used to differentiate transfusion-related respiratory complications. Additional studies examining recipient risk factors and the likelihood of TRALI may be useful in decision making regarding donor white blood cell antibody testing.

Eradicating hepatitis B virus: The critical role of preventing perinatal transmission.

Prevention of hepatitis B virus (HBV) transmission from infected mothers to their newborns is critical to HBV control and eventual eradication. Mother-to-child perinatal transmission causes the highest chronic carrier rate (>85%) with a high rate of subsequent chronic liver disease and hepatocellular carcinoma. This risk is reduced by 90% with HBV vaccine given along with hepatitis B immune globulin (HBIG) starting at birth. New analyses of our data from US trials of HBIG and HBV vaccine in high-risk infants revealed better efficacy with yeast-recombinant vaccine than plasma-derived vaccine, especially in preventing late onset infections, with evidence that vaccine prevented transmission of maternal HBV infection with the glycine to arginine mutation in surface antigen codon 145 (sG145R). Most late infections with sG145R were in vaccine non-responders, suggesting escape from HBIG rather than from vaccine-induced antibody. Our findings also help explain survey results from Taiwan following universal childhood immunization implemented in the mid-1980s. We conclude that current vaccines will remain effective against surface antigen mutants. Anti-viral drugs in high-risk pregnant women, in combination with newborn HBIG and vaccine, show promise for eliminating residual breakthrough neonatal infections, critical to meeting WHO 2030 goals and for eradicating HBV.

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.

Cytokines and clinical predictors in distinguishing pulmonary transfusion reactions.

BACKGROUND: Pulmonary transfusion reactions are important complications of blood transfusion, yet differentiating these clinical syndromes is diagnostically challenging. We hypothesized that biologic markers of inflammation could be used in conjunction with clinical predictors to distinguish transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), and possible TRALI. STUDY DESIGN AND METHODS: In a nested case-control study performed at the University of California at San Francisco and Mayo Clinic, Rochester, we evaluated clinical data and blood samples drawn before and after transfusion in patients with TRALI (n = 70), possible TRALI (n = 48), TACO (n = 29), and controls (n = 147). Cytokines measured included granulocyte-macrophage-colony-stimulating factor, interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-α. Logistic regression and receiver operating characteristics curve analyses were used to determine the accuracy of clinical predictors and laboratory markers in differentiating TACO, TRALI, and possible TRALI. RESULTS: Before and after transfusion, IL-6 and IL-8 were elevated in patients with TRALI and possible TRALI relative to controls, and IL-10 was elevated in patients with TACO and possible TRALI relative to that of TRALI and controls. For all pulmonary transfusion reactions, the combination of clinical variables and cytokine measurements displayed optimal diagnostic performance, and the model comparing TACO and TRALI correctly classified 92% of cases relative to expert panel diagnoses. CONCLUSIONS: Before transfusion, there is evidence of systemic inflammation in patients who develop TRALI and possible TRALI but not TACO. A predictive model incorporating readily available clinical and cytokine data effectively differentiated transfusion-related respiratory complications such as TRALI and TACO.

Recipient clinical risk factors predominate in possible transfusion-related acute lung injury.

BACKGROUND: Possible transfusion-related acute lung injury (pTRALI) cases by definition have a clear temporal relationship to an alternative recipient risk factor for acute respiratory distress syndrome (ARDS). We questioned whether transfusion factors are important for the development of pTRALI. STUDY DESIGN AND METHODS: In this nested case-control study, we prospectively identified 145 consecutive patients with pTRALI and randomly selected 163 transfused controls over a 4-year period at the University of California at San Francisco and the Mayo Clinic (Rochester, Minnesota). RESULTS: For pTRALI, we found evidence against transfusion being important: receipt of plasma from female donors (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.29-2.3; p = 0.70), total number of units transfused (OR, 0.99; 95% CI, 0.89-1.10; p = 0.86), and number of red blood cell and whole blood units transfused (OR, 0.78; 95% CI, 0.59-1.03; p = 0.079). In contrast, we found that risk for pTRALI was associated with additional recipient factors: chronic alcohol abuse (OR, 12.5; 95% CI, 2.8-55; p < 0.001), current smoker (OR, 4.2; 95% CI, 1.67-10.8; p = 0.0024), shock before transfusion (OR, 4.6; 95% CI, 2.0-10.7; p < 0.001), and positive fluid balance before transfusion (OR, 1.32/L; 95% CI, 1.20-1.44; p < 0.001). CONCLUSION: Recipient risk factors for ARDS rather than transfusion risk factors predominate in pTRALI.

A Clinical Trial to Detect Subclinical Transfusion-induced Lung Injury during Surgery.

BACKGROUND: Transfusion-related acute lung injury incidence remains the leading cause of posttransfusion mortality. The etiology may be related to leukocyte antibodies or biologically active compounds in transfused plasma, injuring susceptible recipient's lungs. The authors have hypothesized that transfusion could have less severe effects that are not always appreciated clinically and have shown subtly decreased pulmonary oxygen gas transfer in healthy volunteers after transfusion of fresh and 21-day stored erythrocytes. In this study, the authors tested the same hypothesis in surgical patients. METHODS: Ninety-one patients undergoing elective major spine surgery with anticipated need for erythrocyte transfusion were randomly allocated to receive their first transfusion of erythrocytes as cell salvage (CS), washed stored, or unwashed stored. Clinicians were not blinded to group assignment. Pulmonary gas transfer and mechanics were measured 5 min before and 30 min after erythrocyte transfusion. RESULTS: The primary outcome variable, gas transfer, as assessed by change of PaO2/FIO2, with erythrocyte transfusion was not significant in any group (mean ± SD; CS: 9 ± 59; washed: 10 ± 26; and unwashed: 15 ± 1) and did not differ among groups (P = 0.92). Pulmonary dead space (VD/VT) decreased with CS transfusion (-0.01 ± 0.04; P = 0.034) but did not change with other erythrocytes; the change from before to after erythrocyte transfusion did not differ among groups (-0.01 to +0.01; P = 0.28). CONCLUSIONS: The authors did not find impaired gas exchange as assessed by PaO2/FIO2 with transfused erythrocytes that did or did not contain nonautologous plasma. This clinical trial did not support the hypothesis of erythrocyte transfusion-induced gas exchange deficit that had been found in healthy volunteers.

Prospective study on the clinical course and outcomes in transfusion-related acute lung injury*.

OBJECTIVE: Transfusion-related acute lung injury is the leading cause of transfusion-related mortality. A prospective study using electronic surveillance was conducted at two academic medical centers in the United States with the objective to define the clinical course and outcomes in transfusion-related acute lung injury cases. DESIGN: Prospective case study with controls. SETTING: University of California, San Francisco and Mayo Clinic, Rochester. PATIENTS: We prospectively enrolled 89 patients with transfusion-related acute lung injury, 164 transfused controls, and 145 patients with possible transfusion-related acute lung injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients with transfusion-related acute lung injury had fever, tachycardia, tachypnea, hypotension, and prolonged hypoxemia compared with controls. Of the patients with transfusion-related acute lung injury, 29 of 37 patients (78%) required initiation of mechanical ventilation and 13 of 53 (25%) required initiation of vasopressors. Patients with transfusion-related acute lung injury and possible transfusion-related acute lung injury had an increased duration of mechanical ventilation and increased days in the ICU and hospital compared with controls. There were 15 of 89 patients with transfusion-related acute lung injury (17%) who died, whereas 61 of 145 patients with possible transfusion-related acute lung injury (42%) died and 7 of 164 of controls (4%) died. Patients with transfusion-related acute lung injury had evidence of more systemic inflammation with increases in circulating neutrophils and a decrease in platelets compared with controls. Patients with transfusion-related acute lung injury and possible transfusion-related acute lung injury also had a statistically significant increase in plasma interleukin-8, interleukin-10, and interleukin-1 receptor antagonist posttransfusion compared with controls. CONCLUSIONS: In conclusion, transfusion-related acute lung injury produced a condition resembling the systemic inflammatory response syndrome and was associated with substantial in-hospital morbidity and mortality in patients with transfusion-related acute lung injury compared with transfused controls. Patients with possible transfusion-related acute lung injury had even higher in-hospital morbidity and mortality, suggesting that clinical outcomes in this group are mainly influenced by the underlying acute lung injury risk factor(s).

Transfusion-related acute lung injury: incidence and risk factors.

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. To determine TRALI incidence by prospective, active surveillance and to identify risk factors by a case-control study, 2 academic medical centers enrolled 89 cases and 164 transfused controls. Recipient risk factors identified by multivariate analysis were higher IL-8 levels, liver surgery, chronic alcohol abuse, shock, higher peak airway pressure while being mechanically ventilated, current smoking, and positive fluid balance. Transfusion risk factors were receipt of plasma or whole blood from female donors (odds ratio = 4.5, 95% confidence interval [CI], 1.85-11.2, P = .001), volume of HLA class II antibody with normalized background ratio more than 27.5 (OR = 1.92/100 mL, 95% CI, 1.08-3.4, P = .03), and volume of anti-human neutrophil antigen positive by granulocyte immunofluoresence test (OR = 1.71/100 mL, 95% CI, 1.18-2.5, P = .004). Little or no risk was associated with older red blood cell units, noncognate or weak cognate class II antibody, or class I antibody. Reduced transfusion of plasma from female donors was concurrent with reduced TRALI incidence: 2.57 (95% CI, 1.72-3.86) in 2006 versus 0.81 (95% CI, 0.44-1.49) in 2009 per 10 000 transfused units (P = .002). The identified risk factors provide potential targets for reducing residual TRALI.

Electronic health record surveillance algorithms facilitate the detection of transfusion-related pulmonary complications.

BACKGROUND: Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are leading causes of transfusion-related mortality. Notably, poor syndrome recognition and underreporting likely result in an underestimate of their true attributable burden. We aimed to develop accurate electronic health record-based screening algorithms for improved detection of TRALI/transfused acute lung injury (ALI) and TACO. STUDY DESIGN AND METHODS: This was a retrospective observational study. The study cohort, identified from a previous National Institutes of Health-sponsored prospective investigation, included 223 transfused patients with TRALI, transfused ALI, TACO, or complication-free controls. Optimal case detection algorithms were identified using classification and regression tree (CART) analyses. Algorithm performance was evaluated with sensitivities, specificities, likelihood ratios, and overall misclassification rates. RESULTS: For TRALI/transfused ALI detection, CART analysis achieved a sensitivity and specificity of 83.9% (95% confidence interval [CI], 74.4%-90.4%) and 89.7% (95% CI, 80.3%-95.2%), respectively. For TACO, the sensitivity and specificity were 86.5% (95% CI, 73.6%-94.0%) and 92.3% (95% CI, 83.4%-96.8%), respectively. Reduced PaO2 /FiO2 ratios and the acquisition of posttransfusion chest radiographs were the primary determinants of case versus control status for both syndromes. Of true-positive cases identified using the screening algorithms (TRALI/transfused ALI, n = 78; TACO, n = 45), only 11 (14.1%) and five (11.1%) were reported to the blood bank by physicians, respectively. CONCLUSIONS: Electronic screening algorithms have shown good sensitivity and specificity for identifying patients with TRALI/transfused ALI and TACO at our institution. This supports the notion that active electronic surveillance may improve case identification, thereby providing a more accurate understanding of TRALI/transfused ALI and TACO epidemiology.

Lot-to-lot variability in HLA antibody screening using a multiplexed bead-based assay.

BACKGROUND: Identifying antibodies to HLA (anti-HLA) by solid-phase assays is used to screen blood donors to mitigate transfusion-related acute lung injury risk. Various cutoffs for detection assays have been proposed in the literature; however, these do not take into consideration lot-to-lot variability of commercially available assays. STUDY DESIGN AND METHODS: Samples from 93 nontransfused males were tested using five different lots of a multiplex bead-based anti-HLA detection kit. A subset of 17 samples was tested on 5 days using a single lot. An additional 96 samples from donations with varied anti-HLA levels were tested using kits from two different lots. Results were reported as a normalized background (NBG) ratio. RESULTS: For the 93 nontransfused donors, NBG values generated using the reference lot were significantly higher than those obtained with three of the four comparator lots. However, for the 96 samples with low-, moderate-, and higher-level anti-HLA, Class I (CL-I) values were 1.4 times lower and Class II (CL-II) values were 1.2 times lower using the reference versus comparator lot. For CL-I antibodies the between-lot standard deviation (SD) was 1.36 (95% confidence interval [CI], 1.19-1.60), while the between-day SD was 1.27 (95% CI, 1.08-1.52). Similarly, for CL-II antibodies the between-lot SD was 0.81 (95% CI, 0.70-0.95), while the between-day SD was 0.50 (95% CI, 0.43-0.60). CONCLUSIONS: There is interlot variability in the tested HLA detection assay as well as significant bias between lots. It may be reasonable to develop a new cutoff when a new lot is obtained.

Two septic transfusion reactions presenting as transfusion-related acute lung injury from a split plateletpheresis unit.

OBJECTIVES: We report two simultaneous cases of Staphylococcus aureus sepsis initially consistent with and diagnosed as transfusion-related acute lung injury. The sepsis in both cases resulted from transfusion of two split products from a single contaminated plateletpheresis unit. In each case, the platelets were given along with numerous other blood products during posterior spine surgery. The discussion includes presentation, clinical course, diagnosis, and similarities between sepsis and transfusion-related acute lung injury. The cases and discussion highlight the importance of considering sepsis as part of the differential for any patient believed to have transfusion-related acute lung injury with clinical features of sepsis. DATA SOURCES: Data were collected from the patients' electronic medical records and the hospital laboratory medicine database. CONCLUSIONS: Our cases highlight the importance of vigilant investigation in patients suspected of transfusion-related acute lung injury, as septic transfusions are easily missed and may mimic or coexist with transfusion-related acute lung injury. Sepsis should be strongly considered whenever clinical features such as hypotension, leucopenia, and fever are noted in patients with suspected transfusion-related acute lung injury. In comparison to patients receiving red blood cells or plasma, platelet transfusion recipients are at a greater risk for sepsis from a contaminated unit. Patients developing sepsis from a contaminated blood product may meet the clinical definition of transfusion-related acute lung injury. In such cases, if the clinical syndrome is attributed solely to transfusion-related acute lung injury and bacterial sepsis is not suspected, the correct diagnosis may be missed or delayed. Consequently, appropriate treatment for sepsis would also be delayed or not provided and likely result in increased morbidity and mortality.

Fresh and stored red blood cell transfusion equivalently induce subclinical pulmonary gas exchange deficit in normal humans.

BACKGROUND: Transfusion can cause severe acute lung injury, although most transfusions do not seem to induce complications. We tested the hypothesis that transfusion can cause mild pulmonary dysfunction that has not been noticed clinically and is not sufficiently severe to fit the definition of transfusion-related acute lung injury. METHODS: We studied 35 healthy, normal volunteers who donated 1 U of blood 4 weeks and another 3 weeks before 2 study days separated by 1 week. On study days, 2 U of blood were withdrawn while maintaining isovolemia, followed by transfusion with either the volunteer's autologous fresh red blood cells (RBCs) removed 2 hours earlier or their autologous stored RBCs (random order). The following week, each volunteer was studied again, transfused with the RBCs of the other storage duration. The primary outcome variable was the change in alveolar to arterial difference in oxygen partial pressure (AaDo(2)) from before to 60 minutes after transfusion with fresh or older RBCs. RESULTS: Fresh RBCs and RBCs stored for 24.5 days equally (P = 0.85) caused an increase of AaDo(2) (fresh: 2.8 mm Hg [95% confidence interval: 0.8-4.8; P = 0.007]; stored: 3.0 mm Hg [1.4-4.7; P = 0.0006]). Concentrations of all measured cytokines, except for interleukin-10 (P = 0.15), were less in stored leukoreduced (LR) than stored non-LR packed RBCs; however, vascular endothelial growth factor was the only measured in vivo cytokine that increased more after transfusion with LR than non-LR stored packed RBCs. Vascular endothelial growth factor was the only cytokine tested with in vivo concentrations that correlated with AaDo(2). CONCLUSION: RBC transfusion causes subtle pulmonary dysfunction, as evidenced by impaired gas exchange for oxygen, supporting our hypothesis that lung impairment after transfusion includes a wide spectrum of physiologic derangements and may not require an existing state of altered physiology. These data do not support the hypothesis that transfusion of RBCs stored for >21 days is more injurious than that of fresh RBCs.

Transfusion-related Acute Lung Injury: 36 Years of Progress (1985-2021).

The term transfusion-related acute lung injury (TRALI) was coined in 1985 to describe acute respiratory distress syndrome (ARDS) after transfusion, when another ARDS risk factor was absent; TRALI cases were mostly associated with donor leukocyte antibody. In 2001, plasma from multiparous donors was implicated in TRALI in a randomized controlled trial in Sweden. In 2003 and in many years thereafter, the U.S. Food and Drug Administration reported that TRALI was the leading cause of death from transfusion in the United States. In 2003, the United Kingdom was the first among many countries to successfully reduce TRALI using male-predominant plasma. These successes are to be celebrated. Nevertheless, questions remain about the mechanisms of non-antibody TRALI, the role of blood products in the development of ARDS in patients receiving massive transfusion, the causes of unusual TRALI cases, and how to reduce inaccurate diagnoses of TRALI in clinical practice. Regarding the latter, a study in 2013-2015 at 169 U.S. hospitals found that many TRALI diagnoses did not meet clinical definitions. In 2019, a consensus panel established a more precise terminology for clinical diagnosis: TRALI type I and TRALI type II are cases where transfusion is the likely cause, and ARDS are cases where transfusion is not the likely cause. For accurate diagnosis using these clinical definitions, critical care or pulmonary expertise is needed to distinguish between permeability versus hydrostatic pulmonary edema, to determine whether an ARDS risk factor is present, and, if so, to determine whether respiratory function was stable within the 12 hours before transfusion.

High oxygen partial pressure decreases anemia-induced heart rate increase equivalent to transfusion.

BACKGROUND: Anemia is associated with morbidity and mortality and frequently leads to transfusion of erythrocytes. The authors sought to directly compare the effect of high inspired oxygen fraction versus transfusion of erythrocytes on the anemia-induced increased heart rate (HR) in humans undergoing experimental acute isovolemic anemia. METHODS: The authors combined HR data from healthy subjects undergoing experimental isovolemic anemia in seven studies performed by the group. HR changes associated with breathing 100% oxygen by nonrebreathing facemask versus transfusion of erythrocytes at their nadir hemoglobin concentration of 5 g/dl were examined. Data were analyzed using a mixed-effects model. RESULTS: HR had an inverse linear relationship to hemoglobin concentration with a mean increase of 3.9 beats per min per gram of hemoglobin (beats/min/g hemoglobin) decrease (95% CI, 3.7-4.1 beats/min/g hemoglobin), P < 0.0001. Return of autologous erythrocytes significantly decreased HR by 5.3 beats/min/g hemoglobin (95% CI, 3.8-6.8 beats/min/g hemoglobin) increase, P < 0.0001. HR at nadir hemoglobin of 5.6 g/dl (95% CI, 5.5-5.7 g/dl) when breathing air (91.4 beats/min; 95% CI, 87.6-95.2 beats/min) was reduced by breathing 100% oxygen (83.0 beats/min; 95% CI, 79.0-87.0 beats/min), P < 0.0001. The HR at hemoglobin 5.6 g/dl when breathing oxygen was equivalent to the HR at hemoglobin 8.9 g/dl when breathing air. CONCLUSIONS: High arterial oxygen partial pressure reverses the heart rate response to anemia, probably because of its usability rather than its effect on total oxygen content. The benefit of high arterial oxygen partial pressure has significant potential clinical implications for the acute treatment of anemia and results of transfusion trials.

Cost minimization analysis of preoperative erythropoietin vs autologous and allogeneic blood donation in total joint arthroplasty.

Autologous blood donation and erythropoietin (EPO) have been shown to be effective in reducing allogeneic blood transfusion, but the cost-effectiveness of these interventions remains unclear. A cost minimization analysis was performed, comparing the total costs of allogeneic blood transfusion strategy and autologous and allogeneic blood transfusion strategy for 161 primary total hip arthroplasty (THA) and 195 total knee arthroplasty (TKA) patients. An EPO cost minimization model was constructed using a previously published algorithm for blood management after total joint arthroplasty. The least costly strategy was autologous blood donation in combination with allogeneic blood for THA and TKA patients at $856 and $892 per patient, respectively. The most costly strategy was allogeneic only at $1769 and $1352 per THA and TKA patient, respectively. The EPO strategy model predicted costs similar to the autologous and allogeneic. A strategy that combines autologous blood donation with EPO for patients who cannot donate autologous blood may provide the greatest cost savings and minimize allogeneic blood transfusion.