Transfusion-associated Circulatory Overload Research Articles

Transfusion‐associated circulatory overload (TACO): Time to shed light on the pathophysiology

Transfusion‐associated circulatory overload (TACO) is the most frequent pulmonary complication of transfusion and one of the leading causes of transfusion‐related fatalities. TACO is characterized by new or worsening hydrostatic pulmonary oedema which occurs within 6 h of blood transfusion and results in respiratory distress. Major risk factors for TACO include cardiac failure, renal dysfunction and the degree of positive fluid balance. Suboptimal fluid management and inappropriate infusion practices have also been reported as risk factors for TACO. Unfortunately, the TACO pathophysiology is poorly understood. It can be hypothesized that the pathophysiology of TACO may be generally reflected by a 2‐hit model. The first hit in TACO may be represented by the poor adaptability for volume overload in the transfusion recipient, which is supported by the identification of cardiovascular and renal risk factors for the onset of TACO. The second hit may subsequently be conveyed by the transfused blood product. Remarkably, volume overload alone does not appear to be the only factor triggering the onset of TACO. It can be hypothesized that other factors in the transfused product may play a significant role. In addition, inflammation in the transfused recipient may also be an important feature in TACO. To obtain more insight into the TACO pathophysiology, it will be important to assess and validate potential biomarkers in TACO. In addition, development of currently unavailable TACO‐animal models will provide a useful tool for dissecting the pathophysiologic mechanisms. Collectively, this will aid in improving diagnostic approaches and shed light on possible therapeutic interventions.

Cardiac stress biomarkers after red blood cell transfusion in patients at risk for transfusion-associated circulatory overload: a prospective observational study.

Transfusion-associated circulatory overload (TACO) is a leading cause of serious reactions. In regard to TACO, little is known regarding biomarkers as a predictor, their most informative timing, or thresholds of significance or differentiation from other reactions. In this study of inpatients at risk for TACO (age ≥ 50 years) receiving 1 red blood cell unit, cardiac biomarkers, brain natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), and high-sensitivity troponin were measured at baseline, 6 to 12 hours (except troponin) posttransfusion, and 18 to 24 hours posttransfusion. Primary outcome was a critical increase in biomarkers (>1.5-fold increase and supranormal) at 18 to 24 hours. Fifty-one patients were analyzed; 29% had cardiovascular disease, 73% had one or more cardiac risk factors, and 50% took cardiac or antihypertensive therapies. Although eight (16%) developed an increase in systolic pressure of at least 30 mmHg and four (8%) reported dyspnea and/or cough, none had TACO. At baseline, BNP level was more than 100 ng/L in 59% and NT-proBNP was more than 300 pg/mL in 83%. A total of 25% had a BNP critical increase, 33% had a NT-proBNP critical increase, and 2% had a troponin critical increase at 18 to 24 hours. Overall, 38% had at least one biomarker critical increase and NT-proBNP/BNP concordance was 84%. An increase in the NT-proBNP (>1.5-fold increase and >300 pg/mL) at 18 to 24 hours was the commonest biomarker change. An increase of the NT-proBNP at 18 to 24 hours may be the preferred surrogate marker for identifying a patient experiencing physiologic difficulty in handling the volume challenge. Larger studies are needed to clarify the risk of TACO for a given pretransfusion biomarker profile and the correlation between TACO and increase in biomarkers after transfusion.

How clinicians can minimize transfusion-related adverse events?

ObjectivesTransfusion-related adverse events (TRAE) can contribute to patient morbidity and mortality. In this brief narrative review, the strategies that clinicians can apply at the bedside to avoid TRAE are discussed. MethodsStrategies to avoid the following five types of TRAE were reviewed: transfusion-associated circulatory overload (TACO), transfusion-related acute lung injury (TRALI), transfusion-associated hypothermia (TAH), transfusion-related allergic reactions (TRAR) and acute haemolytic transfusion reactions (AHTR). ResultsMinimizing exposure to blood components is fundamental to TRAE avoidance. Pre-transfusion assessment can identify patients at risk of TACO, TRAR and TAH, and avoidance steps implemented. Preventive strategies for TACO include lower transfusion rate, ‘one unit at a time’ transfusion policy and possibly diuretic medication. Patients with past history of TRAR should preferably be given plasma-free blood components; anti-histamine medication prior to transfusion could be considered. TAH is common in the massive transfusion setting, particularly trauma patients. Warming of patients are key strategies to avoid TAH. Identification of patients at risk of TRALI is more opaque; however, any measures that limit pulmonary inflammation prior to transfusion may decrease the risk of TRALI. Causes of AHTR are commonly due to human error and failure to apply rigorous cross-checks of patient and issued RBC component blood groups. ConclusionsBeneficial strategies to avoid TRAE include judicious use of blood components, identification of high-risk patients, adherence to recommended clinical processes and awareness of TRAE pathophysiology. More evidence is warranted to better guide clinicians in the prevention of TRAE.

Pulmonary infectious complications after hematopoietic stem cell transplantation: a practical guide to clinicians.

The current review highlights the most relevant articles on lung infections following hematopoietic stem cell transplantation (HCT) published over the last year. Between 30 and 50% of HCT recipients will develop pulmonary infiltrates. These pulmonary complications may be infectious (caused by virus, bacteria, fungi, or protozoa) or noninfectious (e.g., fluid overload, heart failure, transfusion reactions like transfusion associated lung injury and transfusion-associated circulatory overload, drug reactions, engraftment syndrome, idiopathic pneumonia syndrome, diffuse alveolar hemorrhage, cryptogenic organizing pneumonia, and bronchiolitis obliterans syndrome). New data on the yield of bronchoscopy and bronchoalveolar lavage (BAL), the prevalence and clinical manifestations of respiratory viruses and the usefulness of molecular techniques for diagnosis have been published. In addition, guidelines or meta-analyses on the management of neutropenic fever, serological diagnosis of fungal infections and diagnosis and management of Pneumocystis and aspergillosis have been published. Respiratory viruses are important pathogens after HCT. PCR in the BAL is becoming the diagnostic modality of choice for a variety of infections. The best approach for the empirical management of pulmonary infiltrates following HCT remains to be defined.

Contemporary Risk Factors and Outcomes of Transfusion-Associated Circulatory Overload.

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. Case-control study. Four tertiary care hospitals. We prospectively enrolled 200 patients with transfusion-associated circulatory overload identified by active surveillance and 405 controls matched by transfusion intensity. None. 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. 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.

Adverse transfusion reactions in recipients transfused in out-of-hospital

ObjectivesTransfusion in environments other than inpatient hospitalisation requires a specific management of the patient, particularly concerning adverse transfusion reactions. A three-year study was carried out in order to appreciate the nature of adverse transfusion reactions and their incidence in these patients. Material and methodsAdverse transfusion reaction reports of outpatient clinic, ambulatory hospital, health and dialysis centres and home-transfused patients in the Auvergne Rhône Alpes region were obtained. Diagnosis of adverse transfusion reactions, their incidence, their degree of severity, the imputability of the blood component concerned were evaluated. ResultsFrom 1 January 2014 to 31 December 2016, 3,284 reports were notified. Excluding allo-immunisations, 416 reports were obtained, including 376 (90.4%) in outpatient clinic. The febrile non-haemolytic transfusion reaction was the most frequent adverse transfusion reaction (119 cases, 28.6%) followed by allergy (112 cases, 26.9%). A transfusion-associated circulatory overload was notified in 26 cases (6.3%). Among the 416 reports, 363 were non-severe and in 251, a red blood cell concentrate was involved (60.3%). The imputability of the blood product was certain in 50 cases (12.0%) only. ConclusionWith the exception of inpatient hospitalisation and allo-immunisation, the majority of adverse transfusion reactions was notified in outpatient clinic. The febrile non-haemolytic transfusion reaction was the most frequent.

Transfusion-associated circulatory overload prevention: a retrospective observational study of diuretic use.

Approaches to preventing transfusion-associated circulatory overload (TACO) include the use of diuretics. The purpose of this study was to determine how commonly diuretics are prescribed in patients receiving a red-blood-cell (RBC) transfusion. This was a retrospective study of 200 adult inpatient RBC transfusion orders, 50 consecutive at each of four academic institutions. Only the first transfusion order for each patient was included. Only 1 or 2 unit orders were included. The primary outcome was the percentage of patients receiving furosemide peri-transfusion. Secondary objectives included the dose, route, and timing of furosemide and the association of clinical factors with ordering furosemide. The median age was 62·5 years (IQR 53, 73), and 52% were female. Peri-transfusion furosemide was ordered in 16% (95% CI 11-21%). The most common dose was 20 mg (55%), the route intravenous (90%) and timing post-transfusion (74%). At least one risk factor for TACO was present in 55% of patients: renal dysfunction (33%), older than 70 years (28%), history of congestive heart failure (18%), ejection fraction <60% (16%) and diastolic dysfunction (5%). Low haemoglobin as an indication for transfusion (OR 4·2; 95% CI 1·4-12·8) and diuretics on admission (OR 3·5; 95% CI 1·5-8·0) were associated with ordering furosemide peri-transfusion. Furosemide is not routinely ordered for RBC transfusion, even in patients with risk factors for TACO. Studies assessing the safety, efficacy, optimal dose, and timing of furosemide in preventing TACO are justified.

Transfusion-associated circulatory overload in a pediatric intensive care unit: different incidences with different diagnostic criteria.

The incidence of transfusion-associated circulatory overload (TACO) is not well known in children, especially in pediatric intensive care unit (PICU) patients. All consecutive patients admitted over 1 year to the PICU of CHU Sainte-Justine were included after they received their first red blood cell transfusion. TACO was diagnosed using the criteria of the International Society of Blood Transfusion, with two different ways of defining abnormal values: 1) using normal pediatric values published in the Nelson Textbook of Pediatrics and 2) by using the patient as its own control and comparing pre- and posttransfusion values with either 10 or 20% difference threshold. We monitored for TACO up to 24 hours posttransfusion. A total of 136 patients were included. Using the "normal pediatric values" definition, we diagnosed 63, 88, and 104 patients with TACO at 6, 12, and 24 hours posttransfusion, respectively. Using the "10% threshold" definition we detected 4, 15, and 27 TACO cases in the same periods, respectively; using the "20% threshold" definition, the number of TACO cases was 2, 6, and 17, respectively. Chest radiograph was the most frequent missing item, especially at 6 and 12 hours posttransfusion. Overall, the incidence of TACO varied from 1.5% to 76% depending on the definition. A more operational definition of TACO is needed in PICU patients. Using a threshold could be more optimal but more studies are needed to confirm the best threshold.

Does the administration of loop diuretics at the time of blood transfusion prevent transfusion-associated circulatory overload (TACO)?

EVIDENCE-BASED ANSWER The answer is unknown. In patients identified with TACO, 90% had received loop diuretics before, during, or after receiving blood components. However, mortality was higher in patients receiving diuretics before transfusion than during or after transfusion (SOR: B, longitudinal study with cohort analysis). In preterm infants, furosemide given before packed red blood cell (PRBC) transfusion decreases mean FiO2 compared with baseline (SOR: C, systematic review of RCTs with disease-oriented evidence).

The ABCs of transfusion for hematologists

"Guidelines for the use of red blood cell products, platelet transfusion concentrates and fresh frozen plasma based on scientific evidence" was published by the Japan Society of Transfusion Medicine and Cell Therapy. Each transfused blood product carries a certain risk of an acute or late adverse event. Hematologists must be familiar with transfusion-associated adverse events, such as transfusion-related acute lung injury, transfusion-associated circulatory overload, post-transfusion graft-versus-host disease, transfusion-transmitted viral infection, etc. Thus, these guidelines should be followed for the appropriate use of blood products according to trigger values and indications for transfusion.

Transfusion-associated circulatory overload: A survey among Dutch intensive care fellows

ObjectivesTransfusion-associated circulatory overload (TACO) is a severe pulmonary transfusion reaction and leading cause of transfusion-related morbidity and mortality in Europe. TACO is of particular importance in critically ill patients, since they often receive blood transfusions and have multiple risk factors for TACO. This study investigates transfusion practices in patients at risk of developing TACO, and furthermore knowledge concerning risk factors, diagnoses and treatment strategies among Dutch intensive care unit (ICU) fellows. Material and methodsAn unannounced paper-based survey was conducted among Dutch ICU fellows during an educational conference. The survey consisted of 16 multiple and open choice questions. ResultsOf all 65 Dutch ICU fellows 56.8% completed the survey; of respondents 88.9% identified the correct constellation of symptoms for TACO. In total, 29.7% of the respondents are aware they are obligated to report TACO cases to the blood bank. Major risk factors for TACO that respondents identified were reduced left ventricular function, infusion volume and infusion rate. In a non-emergency setting, 45.9% of fellows start red blood cell transfusion with 2 units or more. Transfusion rates exceeded national guidelines in 15.4% of fictitious cases. TACO is treated with furosemide by 94.5% of the fellows, however goals of the therapy varied greatly. ConclusionDutch ICU fellows are knowledgeable of TACO symptoms, risk factors and treatment, however knowledge on reporting and transfusion practice in the setting of at risk patients for TACO should be improved.

Serious hazards of transfusion - conference report: celebration of 20 years of UK haemovigilance.

The Annual SHOT Report for incidents in 2016 was published on July 12 and celebrated of 20 years of UK haemovigilance. Components are very safe, related in part to risk-reduction measures triggered by SHOT reporting. Transfusion-related acute lung injury is now very rare (all plasma components are provided from male donors), and infection transmission is also uncommon - a single transmission of hepatitis E in 2016 and no bacterial transmissions. Human factors (errors) account for 87% of all reports. Deaths and major morbidity most often result from transfusion-associated circulatory overload. Wrong transfusions and deaths from ABO-incompatible transfusion can be reduced by correct bedside checks. It is notable that information technology systems may not be safe. Standardisation is required for flags and alerts. SHOT key recommendations include: assess patients for transfusion-associated circulatory overload prior to transfusion. Be like a pilot - use a bedside checklist when setting up the transfusion.

Respiracijske transfuzijske reakcije

Respiratory transfusion-related reactions are not very frequent, partly also because recognition and reporting transfusion reactions is still underemphasized. Tis article describes the most important respiratory transfusion reactions, their pathophysiology, clinical picture and treatment strategies. Respiratory transfusion related reactions can be primary or secondary. The most important primary transfusion-related reactions are TRALI - transfusion-related acute lung injury, TACO – transfusion-associated circulatory overload, and TAD - transfusion-associated dyspnea. TRALI is immuneassociated injury of alveolar basal membrane, which becomes highly permeable and causes noncardiogenic pulmonary edema. Treatment of TRALI is mainly supportive with oxygen, fluids (in case of hypotension) and in cases of severe acute respiratory failure also mechanic ventilation. TACO is caused by volume overload in predisposed individuals, such as patients with heart failure, the elderly, infants, patients with anemia and patients with positive fluid balance. Clinical picture is that of a typical pulmonary cardiogenic edema, and the therapy is classical: oxygen and diuretics, and in severe cases also non-invasive or invasive mechanical ventilation. TAD is usually a mild reaction of unknown cause and cannot be classified as TACO or TRALI, nor can it be ascribed to patient’s preexisting diseases. Although the transfusion-related reactions are not very common, knowledge about them can prevent serious consequences. On the one hand preventive measures should be sought, and on the other early recognition is beneficial, so that proper treatment can take place.

The administration of blood components: a British Society for Haematology Guideline.

The administration of blood components: a British Society for Haematology Guideline.

Transfusion-associated Circulatory Overload after Rapid Whole Blood Transfusion in a Dog

Transfusion-associated Circulatory Overload after Rapid Whole Blood Transfusion in a Dog

The practice of diagnosing and reporting transfusion-associated circulatory overload: a national survey among physicians and haemovigilance officers.

This study aims at identifying factors that disciplines consider when diagnosing and reporting transfusion-associated circulatory overload ('TACO'). TACO is a clinical diagnosis based mainly on subjective factors. Therefore, TACO could be an underreported complication of blood transfusion. A survey was conducted among critical care physicians, anaesthesiologists, haematologists, transfusion medicine physicians and haemovigilance officers using case vignettes and a questionnaire. Factors that may affect diagnosing TACO were investigated using conjoint analysis. A positive B-coefficient indicates a positive preference for diagnosing TACO. Participants rated factors influencing reporting TACO on a 0- to 100-point scale. One hundred and seven surveys were returned (62%). Vignettes showed preferences in favour of diagnosing TACO with the onset of symptoms within 2 h [β 0·4(-0·1-1·0)], positive fluid balance [β 0·9(0·4-1·5)] and history of renal failure [β 0·6(0·1-1·2)]. Compared with transfusion of a single unit of red blood cells (RBC), respondents showed a preference for diagnosing TACO following a single unit of solvent/detergent (S/D) plasma or pooled platelet concentrate (PPC) [β 0·3(-0·2-0·7) resp. 0·5(-0·1-1·2)]. Multiple transfusion (6 RBC + 4 S/D plasma) was a strong preference for diagnosing TACO compared to 1 RBC and 1 S/D plasma [β 0·3(-0·8-1·3)]. Respondents did not fully take into account new hypertension and tachycardia when reporting TACO [median 70 (IQR 50-80) resp. 60 (IQR 50-80)]. No differences were observed between disciplines involved. When diagnosing and reporting TACO, physicians and haemovigilance officers do consider known risk factors for TACO. Reporting could be improved by increasing the awareness of haemodynamic variables in future education programmes.

Epoetin \u03b2 pegol (continuous erythropoietin receptor activator, CERA) is another choice for the treatment of anemia in myelodysplastic syndrome: a case report

BackgroundIn most patients, anemia is present when myelodysplastic syndrome is diagnosed. Although darbepoetin α is the first-choice supportive therapy for low-risk myelodysplastic syndrome, half of all patients develop a loss of response to darbepoetin α within 12 months. However, few reports have described supportive therapy after the loss of response to darbepoetin α.Case presentationWe herein present a case involving a 65-year-old Japanese woman with low-risk myelodysplastic syndrome whose erythropoiesis-stimulating agent treatment was switched from darbepoetin α to epoetin β pegol (continuous erythropoietin receptor activator) to treat transfusion-dependent anemia. The frequent transfusions required to treat the anemia resulted in transfusion-associated circulatory overload. The transfusion-dependent anemia was initially treated with darbepoetin α, which negated the requirement for transfusion. However, after 12 months of darbepoetin α therapy, the hemoglobin concentration sharply declined. We switched her therapy from darbepoetin α to continuous erythropoietin receptor activator to avoid transfusion. After initiation of continuous erythropoietin receptor activator therapy, the hemoglobin concentration gradually increased and transfusion was not required. At the time of writing, no progression of the anemia had occurred.ConclusionsAlthough darbepoetin α is the first-choice supportive therapy for low-risk myelodysplastic syndrome, continuous erythropoietin receptor activator might be considered the second-choice therapy.

Identification of Transfusion-Associated Circulatory Overload: An Eye-Tracking Study

BackgroundThe identification of transfusion-associated circulatory overload (TACO) relies heavily on the nurse's surveillance activities. Eye tracking can provide important information about nurses' surveillance behaviors as they carry out the blood transfusion process. The purpose of this study was to describe the eye movements of nurses who successfully identified TACO. SampleA convenience sample consisted of 20 acute and critical care nurses. MethodAn observational descriptive study using eye tracking was carried out in a simulated clinical setting. ResultsThe TACO identifying nurses had the longest duration of eye fixations on the nursing shift report, infusion pumps, bedside monitor, and documentation flow sheet. The shortest duration of eye fixations was on the patient and blood product label. ConclusionOur findings suggest that the nursing shift report was a key source of data for the TACO identifying nurses, lending support to the need for accurate and complete handoffs between nurses.

Preceding haemorrhagic shock as a detrimental risk factor for respiratory distress after excessive allogeneic blood transfusion.

Whether transfusion-associated circulatory overload arises as a simple result of over-transfusion or requires another trigger remains unclear. Here, we examined whether respiratory distress could be reproduced by massive transfusion alone in an animal model. A total of 20 anaesthetized swine were equipped with monitors. Allogeneic blood was obtained from 10 donor swine. A 4-stage loading protocol with each stage equivalent to 25% of the blood volume (BV) in the recipient swine was then used to infuse crystalloid (CR), hydroxyethyl starch (HES) or allogeneic blood (TR) (n=5 each). The five remaining animals were subjected to a haemorrhagic shock (HS) prior to an allogeneic blood transfusion (TRS). The PaO2 /FiO2 (P/F) ratio did not decrease to the level of respiratory distress in either the CR group or the HES group after loading with a volume corresponding to 100% of the recipient BV. However, the TRS and TR groups exhibited significant reductions in the P/F ratio after fluid overloading (227±29 and 267±133, respectively). Blood transfusion after HS expanded the blood volume, but over-transfusion alone did not. HS was accompanied by an increase in the white blood cell count. The lung and the heart can tolerate volume overloads with HES, CR and even transfused blood. However, a preceding HS may induce an inflammatory response, making the lung vulnerable to subsequent blood overloads. In this study, a preceding haemorrhagic shock mediated respiratory distress following massive transfusion in a swine model. (247 words).

Transfusion-Associated Circulatory Overload: Evidence-Based Strategies to Prevent, Identify, and Manage a Serious Adverse Event.

Transfusion-associated circulatory overload (TACO) is a potentially life-threatening complication of blood transfusion and is associated with increased morbidity, length of stay (hospital and intensive care unit), and hospital costs. Bedside nurses play a key role in the prevention, identification, and reporting of this complication. A common misperception is that the most frequently encountered serious adverse event during transfusion is a hemolytic reaction in a patient who receives ABO-incompatible blood. In fact, the incidence of TACO-related fatalities is higher than fatalities caused by ABO-related hemolytic reactions. Surveillance and evidence-based strategies such as clinical decision support systems have the potential to reduce the incidence of TACO and mitigate its effects. Practical suggestions for conducting bedside transfusion surveillance and future directions for improving transfusion care are presented.