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Volume incompliance and transfusion are essential for transfusion-associated circulatory overload: a novel animal model.

ABSTRACT: BACKGROUND:Transfusion-associated circulatory overload (TACO) is the predominant complication of transfusion resulting in death. The pathophysiology is poorly understood, but inability to manage volume is associated with TACO, and observational data suggest it is different from simple cardiac overload due to fluids. We developed a two-hit TACO animal model to assess the role of volume incompliance ("first-hit") and studied whether volume overload ("second-hit") by red blood cell (RBC) transfusion is different compared to fluids (Ringer's lactate [RL]). MATERIALS AND METHODS:Male adult Lewis rats were stratified into a control group (no intervention) or a first hit: either myocardial infarction (MI) or acute kidney injury (AKI). Animals were randomized to a second hit of either RBC transfusion or an equal volume of RL. A clinically relevant difference was defined as an increase in left ventricular end-diastolic pressure (?LVEDP) of +4.0?mm Hg between the RBC and RL groups. RESULTS:In control animals (without first hit) LVEDP was not different between infusion groups (??+?1.6?mm Hg). LVEDP increased significantly more after RBCs compared to RL in animals with MI (?7.4?mm Hg) and AKI (??+?5.4?mm Hg), respectively. Volume-incompliant rats matched clinical TACO criteria in 92% of transfused versus 25% of RL-infused animals, with a greater increase in heart rate and significantly higher blood pressure. CONCLUSION:To our knowledge, this is the first animal model for TACO, showing that a combination of volume incompliance and transfusion is essential for development of circulatory overload. This model allows for further testing of mechanistic factors as well as therapeutic approaches.

SUBMITTER: Klanderman RB

PROVIDER: S-EPMC6916548 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Volume incompliance and transfusion are essential for transfusion-associated circulatory overload: a novel animal model.

Klanderman Robert B RB Bosboom Joachim J JJ Maas Adrie A W AAW Roelofs Joris J T H JJTH de Korte Dirk D van Bruggen Robin R van Buul Jaap D JD Zuurbier Coert J CJ Veelo Denise P DP Hollmann Markus W MW Vroom Margreeth B MB Juffermans Nicole P NP Geerts Bart F BF Vlaar Alexander P J APJ

Transfusion 20191107 12

<h4>Background</h4>Transfusion-associated circulatory overload (TACO) is the predominant complication of transfusion resulting in death. The pathophysiology is poorly understood, but inability to manage volume is associated with TACO, and observational data suggest it is different from simple cardiac overload due to fluids. We developed a two-hit TACO animal model to assess the role of volume incompliance ("first-hit") and studied whether volume overload ("second-hit") by red blood cell (RBC) tr ...[more]

PMID: 31697425

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Project description:OBJECTIVES:Transfusion-associated circulatory overload is characterized by hydrostatic pulmonary edema following blood transfusion. Restrictive transfusion practice may affect the occurrence and severity of transfusion-associated circulatory overload in critically ill patients. We sought to examine contemporary risk factors and outcomes for transfusion-associated circulatory overload. DESIGN:Case-control study. SETTING:Four tertiary care hospitals. PATIENTS:We prospectively enrolled 200 patients with transfusion-associated circulatory overload identified by active surveillance and 405 controls matched by transfusion intensity. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Among 20,845 transfused patients who received 128,263 blood components from May 2015 until July 2016, transfusion-associated circulatory overload incidence was one case per 100 transfused patients. In addition to cardiovascular comorbidities, multivariable analysis identified the following independent predictors of transfusion-associated circulatory overload: acute kidney injury, emergency surgery, pretransfusion diuretic use, and plasma transfusion-the latter especially in females. Compared with matched controls, transfusion-associated circulatory overload cases were more likely to require mechanical ventilation (71% vs 49%; p < 0.001), experienced longer intensive care and hospital lengths of stay following transfusion, and had higher mortality (21% vs 11%; p = 0.02) even after adjustment for other potentially confounding variables. CONCLUSIONS:Despite restrictive transfusion practice, transfusion-associated circulatory overload remains a frequent complication of transfusion and is an independent risk factor for in-hospital morbidity and mortality. In addition to cardiovascular and renal risk factors, plasma transfusion was associated with transfusion-associated circulatory overload after controlling for other covariates. Additional research is needed to examine the benefit of reduced erythrocyte or plasma exposure in patients at high risk for transfusion-associated circulatory overload.

Project description:BackgroundTransfusion-associated circulatory overload remains underappreciated in the perioperative environment. The authors aimed to characterize risk factors for perioperative transfusion-associated circulatory overload and better understand its impact on patient-important outcomes.MethodsIn this case-control study, 163 adults undergoing noncardiac surgery who developed perioperative transfusion-associated circulatory overload were matched with 726 transfused controls who did not develop respiratory complications. Univariate and multivariable logistic regression analyses were used to evaluate potential risk factors for transfusion-associated circulatory overload. The need for postoperative mechanical ventilation, lengths of intensive care unit and hospital stay, and mortality were compared.ResultsFor this cohort, the mean age was 71 yr and 56% were men. Multivariable analysis revealed the following independent predictors of transfusion-associated circulatory overload: emergency surgery, chronic kidney disease, left ventricular dysfunction, previous β-adrenergic receptor antagonist use, isolated fresh frozen plasma transfusion (vs. isolated erythrocyte transfusion), mixed product transfusion (vs. isolated erythrocyte transfusion), and increasing intraoperative fluid administration. Patients who developed transfusion-associated circulatory overload were more likely to require postoperative mechanical ventilation (73 vs. 33%; P < 0.001) and experienced prolonged intensive care unit (11.1 vs. 6.5 days; P < 0.001) and hospital lengths of stay (19.9 vs. 9.6 days; P < 0.001). Survival was significantly reduced (P < 0.001) in transfusion recipients who developed transfusion-associated circulatory overload (1-yr survival 72 vs. 84%).ConclusionsPerioperative transfusion-associated circulatory overload was associated with a protracted hospital course and increased mortality. Efforts to minimize the incidence of transfusion-associated circulatory overload should focus on the judicious use of intraoperative blood transfusions and nonsanguineous fluid therapies, particularly in patients with chronic kidney disease, left ventricular dysfunction, chronic β-blocker therapy, and those requiring emergency surgery.

Project description:Hemodilutional anemia has been cited as a contributing factor to red blood cell (RBC) transfusions in cardiac surgery patients. Accordingly, efforts have been made to minimize hemodilution by reducing cardiopulmonary bypass (CPB) prime volume. We sought to assess the impact of these efforts on intraoperative RBC transfusions. We evaluated 21,360 patients undergoing coronary artery bypass with or without aortic valve surgery between July 2011 through December 2016 at any of 42 centers participating in the Perfusion Measures and Outcomes registry. The primary exposure was net CPB prime volume (total prime volume minus retrograde autologous prime volume) indexed to body surface area (mL/m2), which was further divided into quartiles (Q1: <262 mL/m2, Q2: 262-377 mL/m2, Q3: 377-516 mL/m2, and Q4: >516 mL/m2). The primary outcome was intraoperative RBC transfusion. We modeled the effect of index net prime volume on transfusion, adjusting for patient (age, gender, race, diabetes, vascular disease, previous myocardial infarction, ejection fraction, creatinine, preoperative hematocrit (HCT), total albumin, status, aspirin, and antiplatelet agents), procedural (procedure types) characteristics, surgical year, and hospital. The median net prime volume was 378 mL/m2 (25th percentile: 262 mL/m2, 75th percentile: 516 mL/m2). Relative to patients in Q1, patients in Q4 were more likely to be older, female, nondiabetic, have higher ejection fraction, have more ultrafiltration volume removed, and undergo more elective and aortic valve procedures (all p < .05). Patients in Q4 relative to Q1 were exposed to lower nadir HCTs on bypass, p < .05. The net prime volume was associated with an increased risk of transfusion (8.9% in Q1 vs. 22.6% in Q4, p < .001). After adjustment, patients in Q4 (relative to Q1) had a 2.9-fold increased odds (ORadj = 2.9, 95% CI [2.4, 3.4]) of intraoperative RBC transfusion. In this large, multicenter experience, patients exposed to larger net prime volumes were associated with greater adjusted odds of receiving intraoperative transfusions. Our findings reinforce the importance of efforts to reduce the net CPB prime volume. Based on these findings and other supporting evidence, the net prime volume should be adopted as a national quality measure.

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Volume incompliance and transfusion are essential for transfusion-associated circulatory overload: a novel animal model.

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Volume incompliance and transfusion are essential for transfusion-associated circulatory overload: a novel animal model.

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