Volume‐dependent effect of stored red blood cells: A secondary analysis of the Age of Blood Evaluation trial

Mack, Johnathan; Kahn, Susan R.; Tinmouth, Alan; Fergusson, Dean; Hébert, Paul C.; Lacroix, Jacques

doi:10.1111/trf.15933

Cited by 5 publications

(4 citation statements)

References 39 publications

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“…One theory should be that the patients in the single‐center trauma studies were characterized by overall higher OEIs since they received larger volumes of RCCs in general, and hence a larger accumulated storage lesion. In fact, a sub‐analysis of the ABLE trial, a multicenter study of 2510 critically ill adults, revealed a dose‐dependent relationship between stored RBCs and mortality, with an increased risk of mortality observed in patients transfused stored RBCs after a threshold of six RBC units 32 . In large volume transfused cohorts, the donor variability may be subsumed by the cumulative OEI.…”

Section: Discussionmentioning

confidence: 99%

The oxygen saturation of red blood cell concentrates: The basis for a novel index of red cell oxidative stress

et al. 2021

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Background Oxidative stress is a major driving force in the development of storage lesions in red cell concentrates (RCCs). Unlike manufactured pharmaceuticals, differences in component preparation methods and genetic/physiological status of donors result in nonuniform biochemical characteristics of RCCs. Various characteristics of donated blood on oxygen saturation (SO2) distribution were investigated, and a model to estimate potential oxidative stress burden of stored RCC at transfusion is proposed. Study design and methods The oxygen content of freshly prepared RCCs (770) was quantified noninvasively as fractional hemoglobin saturation (SO2) with visible reflectance spectrometry. Using separate RCCs and mimicking typical handling of RCCs during routine storage, evolution of SO2 was followed for construction of an empirical model. Based on this model, the oxygen exposure index (OEI) was formulated to estimate the accumulated oxygen exposure burden of RCC at the time of transfusion. Results The SO2 of RCCs varied widely at donation (mean 43% ± 1.3%; range 20%–93%). Multivariate regression model showed that sex and processing method had small effects on SO2 (R2 = 0.12), indicating that variability was mainly attributed to other individual donor characteristics. Storage simulation model indicated that median SO2 increased gradually over 6 weeks (approx. 1.3 fold), while OEI increased at a faster rate (approx. eight‐fold). Conclusion In addition to storage age, the OEI provides a potential new metric to assess the quality of RCCs at the time of transfusion in terms of their oxidative stress. In future studies, a single noninvasive measurement during storage could link OEI to clinical outcomes in transfusion recipients.

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Section: Discussionmentioning

confidence: 99%

The oxygen saturation of red blood cell concentrates: The basis for a novel index of red cell oxidative stress

et al. 2021

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“…In this trial, there was no effect of storage duration on outcomes even in the highest quartile of volume transfused (>30 mL/kg), which equates to approximately 2 to 3 transfusion events per patient over the study period. A dose effect with larger amounts of older red blood cells transfused over short periods of time adversely affecting outcomes is possible and has been reported in retrospective studies and secondary analyses of 2 randomized clinical trials . Third, as a result of using standard delivery of red blood cells, the median storage age was low at 18 days.…”

Section: Discussionmentioning

confidence: 99%

“…Through one or several of these mechanisms, transfusion of older red blood cells may increase the risk of organ failure or death in critically ill patients. Observational studies and exploratory analyses of randomized clinical trials also suggest that for patients who receive larger volumes of older red blood cells, there is an association with poor outcomes …”

Section: Introductionmentioning

confidence: 99%

Effect of Fresh vs Standard-issue Red Blood Cell Transfusions on Multiple Organ Dysfunction Syndrome in Critically Ill Pediatric Patients

Spinella

Tucci

Fergusson

et al. 2019

JAMA

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IMPORTANCE The clinical consequences of red blood cell storage age for critically ill pediatric patients have not been examined in a large, randomized clinical trial.OBJECTIVE To determine if the transfusion of fresh red blood cells (stored Յ7 days) reduced new or progressive multiple organ dysfunction syndrome compared with the use of standard-issue red blood cells in critically ill children. DESIGN, SETTING, AND PARTICIPANTSThe Age of Transfused Blood in Critically-Ill Children trial was an international, multicenter, blinded, randomized clinical trial, performed between February 2014 and November 2018 in 50 tertiary care centers. Pediatric patients between the ages of 3 days and 16 years were eligible if the first red blood cell transfusion was administered within 7 days of intensive care unit admission. A total of 15 568 patients were screened, and 13 308 were excluded.INTERVENTIONS Patients were randomized to receive either fresh or standard-issue red blood cells. A total of 1538 patients were randomized with 768 patients in the fresh red blood cell group and 770 in the standard-issue group. MAIN OUTCOMES AND MEASURESThe primary outcome measure was new or progressive multiple organ dysfunction syndrome, measured for 28 days or to discharge or death.RESULTS Among 1538 patients who were randomized, 1461 patients (95%) were included in the primary analysis (median age, 1.8 years; 47.3% girls), in which there were 728 patients randomized to the fresh red blood cell group and 733 to the standard-issue group. The median storage duration was 5 days (interquartile range [IQR], 4-6 days) in the fresh group vs 18 days (IQR, 12-25 days) in the standard-issue group (P < .001). There were no significant differences in new or progressive multiple organ dysfunction syndrome between fresh (147 of 728 [20.2%]) and standard-issue red blood cell groups (133 of 732 [18.2%]), with an unadjusted absolute risk difference of 2.0% (95% CI, -2.0% to 6.1%; P = .33). The prevalence of sepsis was 25.8% (160 of 619) in the fresh group and 25.3% (154 of 608) in the standard-issue group. The prevalence of acute respiratory distress syndrome was 6.6% (41 of 619) in the fresh group and 4.8% (29 of 608) in the standard-issue group. Intensive care unit mortality was 4.5% (33 of 728) in the fresh group vs 3.5 % (26 of 732) in the standard-issue group (P = .34).CONCLUSIONS AND RELEVANCE Among critically ill pediatric patients, the use of fresh red blood cells did not reduce the incidence of new or progressive multiple organ dysfunction syndrome (including mortality) compared with standard-issue red blood cells.

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“…39 Importantly, Markowicz and Engleman showed that dendritic cells are only viable for up to 1 week after blood is donated, which may explain the association between microchimerism and fresh blood transfusion. 20 41 Therefore, if the effect of length of storage time is indeed Ushaped, it is inappropriate to compare the oldest group to the freshest group as the difference between the former and the latter will be smaller. Thus, this may explain why many cohort studies did not report statistically significant differences in the outcome of patients who received very old blood versus those who received fresh blood.…”

Section: Discussionmentioning

confidence: 99%

Association between the length of storage of transfused leukoreduced red blood cell units and hospital‐acquired infections in critically ill children: A secondary analysis of the TRIPICU study

Flatman

Fergusson

Lacroix

et al. 2021

Transfusion Medicine

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Objective: Evaluate the association between leukoreduced red blood cell (RBC) storage length and hospital-acquired infection (HAI) incidence rate in critically ill children.Background: RBC transfusions are common in critically ill children. Despite their benefits, observational studies suggest an association between them and HAIs. One possible mechanism for increased HAI is transfusion-related immunomodulation due to bioactive substances' release as transfused blood ages. Methods: In this secondary analysis of the 'Transfusion Requirement in PaediatricIntensive Care Units' (TRIPICU) study, we analysed a subset of 257 participants that received only one pre-storage leukoreduced RBC transfusion. RBC storage length was classified as 1) transfusion of 'fresh' RBCs (≤10 days), 2) transfusion of 'stored' RBCs (21-34 days), and 3) transfusion of 'long-stored' RBCs (≥35 days). All were compared to a 'golden' period (11-20 days), representing the time between 'fresh' and 'stored'. We used quasi-Poisson multivariable regression models to estimate the HAI incidence rate ratio (IRR) and corresponding 95% confidence interval (CI).Results: We found that the association between the length of storage time of leukoreduced RBCs and HAIs was not significant in the 'fresh' group (IRR 1.23; 95% CI 0.55, 2.78) and the 'stored' group (IRR 1.61; 95% CI 0.63, 4.13) when compared to the 'golden' period. However, we observed a statistically significant association between the 'longstored' group and an increase in the HAI incidence rate (IRR 3.66; 95% CI 1.22, 10.98). Conclusion:Transfusion of leukoreduced RBC units stored for ≥35 days is associated with increased HAI incidence rate in haemodynamically stable, critically ill children. K E Y W O R D S critically ill children, hospital-acquired infections, leukoreduction, length of storage, red blood cell transfusion, secondary analysis 1 | INTRODUCTION Red blood cell (RBC) transfusions are a standard supportive measure for critically ill children. It is estimated that 49% of children admitted to 30 North American Paediatric Intensive Care Units (PICU) received at least one RBC transfusion during their admission. 1 Transfusing RBCs in critically ill patients is primarily performed to increase low haemoglobin levels and oxygen delivery to better support

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Volume‐dependent effect of stored red blood cells: A secondary analysis of the Age of Blood Evaluation trial

Cited by 5 publications

References 39 publications

The oxygen saturation of red blood cell concentrates: The basis for a novel index of red cell oxidative stress

The oxygen saturation of red blood cell concentrates: The basis for a novel index of red cell oxidative stress

Effect of Fresh vs Standard-issue Red Blood Cell Transfusions on Multiple Organ Dysfunction Syndrome in Critically Ill Pediatric Patients

Association between the length of storage of transfused leukoreduced red blood cell units and hospital‐acquired infections in critically ill children: A secondary analysis of the TRIPICU study

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