All patients were closely observed for the occurrence of a respiratory complication in the 24-hour period following transfusion⁷. Expert intensivists, blinded to specific transfusion factors, reviewed the clinical data of all patients who experienced a respiratory complication and gave the diagnosis of TACO. The diagnosis of TACO was defined by a combination of clinical signs (gallop, jugular venous distension, systolic hypertension), radiographic (cardiothoracic ratio >0.53 and vascular pedicle width >65 mm),⁸ electrocardiographic (new ST segment and T wave changes), laboratory (elevated troponin T > 0.1 ng/mL), hemodynamic (PAOP >18 mmHg, CVP > 12), echocardiographic findings: the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity (E/e' ratio) greater than 15 and/or ejection fraction (EF) of less than 45 percent, new presence of severe left-sided valvular heart disease (aortic or mitral stenosis or regurgitation), and the prompt response to appropriate therapy: diuretic or vasodilator use, treatment of ischemia, and/or inotropic agents.^9,10

Predictor variables were grouped as follows:

Our findings confirmed TACO is a common transfusion-related complication in critically ill patients. The incidence of TACO in this report (6%) is consistent with existing literature which notes an incidence ranging from 1 to 8 percent^3,6,20. Our previous study noted a higher rate of TACO (1 in 356) than TRALI (1 in 534 per unit) per unit of blood component transfused³. This is much higher than the incidence rate in a recent hemovigilance report from Ireland (1/10,000 of all components)²¹. In addition to a different study population (critically ill patients vs all transfused patients), the major difference is likely a result of different identification methods (prospective observation vs passive reporting). Recent reports noted TACO to be the fifth most common cause of death resulting from transfusion in the United States with an estimated mortality ranging from 5–15%²². Although the observed mortality is mostly due to underlying illness, rather than TACO per se⁵, this complication does result in significant morbidity and increase the length of hospital stay⁵.

Despite its importance, TACO has received surprisingly little attention when compared with other transfusion-related complications such as infection and TRALI ⁹. A single report associated age with the occurrence of TACO in an orthopedic surgery population. The mean age of patients who developed TACO in this investigation was 84 years. In contrast, the median age of our TACO patients was 73 years, similar to recent reports from Robillard²³ and Andera²¹. This difference is explained by the differing study populations as patients undergoing total hip or knee replacements are more likely to be of advanced age than an unselected ICU population.

Left ventricular dysfunction is believed to be a risk factor for TACO with previous estimates reporting it’s presence in 73% (131) of TACO cases²¹. TACO often occurs in elderly patients⁶ and those with compromised cardiac function²⁴. FFP remains as the first-line therapy for the urgent/emergent reversal of anticoagulant therapy in the US and American Society of Anesthesiologist’s recommended dose of FFP is 10–15 ml per kg²⁵, which is similar to dosing recommendations provided by the British Committee on Standards in Haematology²⁶. This large volume of FFP (frequently 1 – 2 liters) is clearly undesirable in patients at risk of TACO. Our unmatched univariate and multivariate analysis confirmed cardiovascular dysfunction and FFP use for reversal of anticoagulant therapy before transfusion as important predictors of TACO. Lower volume alternatives to FFP need to be evaluated in future TACO prevention trials. Further, our results identified blood component transfusion rate, cumulative fluid balance, cumulative transfusion volume, and volume of plasma transfused as significant predictors of TACO, independent of pre-existing cardiovasucular disease or left ventricular dysfunction. The average transfusion rate in patients who developed TACO was 225 (IQR 135–350) ml/hour compared to 164 (IQR 99–206) ml/hour in matched controls. Although the AABB Technical Manual²⁷ recommends an infusion rate of 150 to 300 mL per hour for red blood cell transfusion and faster rates for plasma and platelets components, our data suggest slower transfusion rates should be observed when possible. In addition to the faster infusion rates, patients who developed TACO also received a significantly larger volume of blood product. Previous reports have described TACO following 1–4 units of administered blood product^3,20. A smaller volume of blood component therapy (1–2 units) was associated with TACO in the study of Popovsky and colleagues as well⁶. Indeed, even a single transfused unit may be sufficient to precipitate the reaction in a susceptible recipient.^1,28

Pre-transfusion diuretic therapy was not found to be protective. This is similar to the findings of Andrea²¹ where 40% of patients received diuretics but still progressed to TACO. However, infrequent use of diuretics before transfusion make it difficult to determine the benefit of this prevention strategy.

There are a number of potential limitations with this investigation that deserve mention. To begin, the study was conducted in the ICU of a single tertiary center and the results are unlikely to be generalizable to non-ICU patients. In addition, the sample size was limited by the TACO cases observed in the initial prospective cohort study. As a result, the present study was not adequately powered to detect more subtle associations. Although the matched study design minimized confounding from underlying cardiovascular disease and left ventricular dysfunction, the observational nature of this investigation also has the potential for multiple additional measured and unmeasured confounding effects.