The effect of storage time of human red cells on intestinal microcirculatory oxygenation in a rat isovolemic exchange model*

Raat, Nicolaas J.H.; Verhoeven, Arthur J.; Mik, Egbert G.; Gouwerok, C. W. N.; Verhaar, Robin; Goedhart, P.T.; Korte, Dirk de; İnce, Can

doi:10.1097/01.ccm.0000150655.75519.02

Cited by 118 publications

(137 citation statements)

References 30 publications

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“…The outcome of (some of) these studies are probably confounded by a lack of transfusion policy and the use of leukocyte-non-depleted RBC preparations. Our observations on lack of correlation between change in oxygenation, duration of MV or PICU stay and length of RBC storage are compatible with experimental and clinical data indicating no difference in regional or global indexes of tissue oxygenation, or patient outcome in critically ill adults with organ failure [4][5][6].…”

supporting

confidence: 72%

Length of storage of red blood cells does not affect outcome in critically ill children

et al. 2008

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Sir: Length of red blood cell (RBC) storage has been proposed a contributing factor to adverse outcome after RBC transfusion. This may be explained by an impaired ability to transport or deliver oxygen, or the presence of leukocytes in stored RBC preparations producing potential deleterious pro-inflammatory mediators or bioactive lipids [1]. We hypothesized that length of RBC storage might explain our previously observed independent association between RBC transfusion and increased mortality, duration of mechanical ventilation (MV) and length of paediatric intensive care unit (PICU) stay in critically ill children [2].For each time a patient was transfused in our previous study, length of RBC storage was retrieved from our hospital's blood bank [2]. Since we observed a dose-outcome relation between the number of RBC transfusions and mortality, we separately looked at single transfusion and multiple transfusions. The effect of RBC transfusion on oxygenation was assessed by the oxygenation index (OI, mean airway pressure times FiO 2 divided by PaO 2 ) and PaO 2 /FiO 2 ratio. RBC preparations were leukocyte-depleted, but not irradiated. Statistical analysis was performed using the Student t-test; linear regression analysis was applied to study correlations. P \ 0.05 was accepted as statistically significant.Data of 295 patients were studied, of whom 67 (22.7%) were transfused; 39 (58.2%) were transfused only once, the remaining 28 received multiple transfusions at different time intervals (range 2-14) (Table 1). Seventeen (5.8%) patients died. The mean length of RBC storage was 16.7 ± 0.6 days [25-75% interquartile range (IQR) 9-23 days]. Length of RBC storage was comparable between survivors and non-survivors. This remained after comparing single versus multiple transfusions. Differences in OI and PaO 2 /FiO 2 ratio between the first day and fifth day after transfusion, duration of MV and length of PICU stay were not correlated with length of RBC storage.Our findings indicate that our previous reported observed independent association between transfusion of leucocyte-depleted RBC preparations and increased morbidity in critically ill children could not be explained by length of RBC storage. Mortality was also not influenced by length of RBC storage, although our study might not be powered to detect this. To our knowledge, although the issue of RBC transfusion has been extensively studied in critically ill adults, no other paediatric data on length of RBC storage and outcome in critically ill children have been reported. Results from retrospective and prospective Mean length of RBC storage (days ± SEM) 14.7 ± 1.4 13.5 ± 3.0 15.8 ± 1.5 16.0 ± 3.5 DOI difference in oxygenation index, DPaO 2 /FiO 2 difference in PaO 2 /FiO 2 ratio, RBC red blood cell, SEM standard error of the mean Intensive

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confidence: 72%

Length of storage of red blood cells does not affect outcome in critically ill children

et al. 2008

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“…This has been postulated to lead to reduced oxygen delivery (27,28). In addition, ATP depletion (29,30) and reductions in S-nitrosothiol bioactivity (31,32) are believed to potentially impact the vasodilatory response to regional hypoxia and reduce RBC deformability, which may impede RBC transit through the microcirculation (33)(34)(35). In addition, immunologically active biologic response modifiers within the RBC storage medium such as soluble CD40 ligand (6,36) and lysophosphatidylcholines (22,37) have been associated with the development of ALI.…”

Section: Discussionmentioning

confidence: 99%

Fresh Red Blood Cell Transfusion and Short-Term Pulmonary, Immunologic, and Coagulation Status

Kor¹,

Kashyap²,

Weiskopf

et al. 2012

Am J Respir Crit Care Med

102

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Rationale: Transfusion-related pulmonary complications are leading causes of morbidity and mortality attributed to transfusion. Observational studies suggest an important role for red blood cell (RBC) storage duration in these adverse outcomes. Objectives: To evaluate the impact of RBC storage duration on shortterm pulmonary function as well as immunologic and coagulation status in mechanically ventilated patients receiving RBC transfusion. Methods: This is a double-blind, randomized, clinical trial comparing fresh (<5 d of storage) versus standard issue single-unit RBC transfusion in adult intubated and mechanically ventilated patients. The primary outcome is the change in pulmonary gas exchange as assessed by the partial pressure of arterial oxygen to fraction of inspired oxygen concentration ratio ( Since the first successful attempt at blood storage almost a century ago, advances in extracorporeal red blood cell (RBC) preservation have incrementally prolonged the viability of stored RBCs. With contemporary preservative solutions, the accepted duration of RBC storage has now been extended to 42 days (1). In the past two decades, there has been increased interest in the time-dependent changes in RBC quantity and quality during this storage period. The various changes that occur within both the RBC and storage media during ex vivo preservation have been collectively termed the RBC "storage lesion." Importantly, alterations that occur during the RBC storage process are believed potentially responsible for many of the adverse effects associated with blood product administration (2). Among these concerns is a potentially increased risk of transfusion-related acute lung injury (TRALI) (3-6) as well as risk-adjusted mortality (7-10). Multiple publications have suggested that these associations become more significant with increased duration of RBC storage (8,(11)(12)(13). In a database analysis, Koch and colleagues found an association of RBC storage duration with mortality in patients undergoing cardiac surgery (8). This association was largely driven by an increased rate of respiratory complications. However, the observational nature of this investigation and concerns over residual confounding preclude definitive statements regarding causality. Moreover, evidence to the contrary exists as well (14-17), and the impact of RBC storage duration on development of transfusion-related complications remains a matter of debate (18,19).While the majority of TRALI cases are believed to be the result of an interaction between donor anti-HLA or anti-leukocyte antibodies and the cognate antigen on recipient leukocytes (20), a second "two-hit" model for TRALI has also been described (21). This model suggests that in a "primed" host, infusion of Author Contributions: D.J.K. contributed to the acquisition of data, and analysis and interpretation of the study results. R.K. contributed to the study design and procedures and the acquisition of the data. R.B.W. contributed to the study conception and design as well as the interpretati...

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“…Both would be expected to reduce flow in the living capillary systems. The problem is that the same cells, stored in solutions of nutrients that maintain ATP concentrations, tend to have normal flow despite the membrane loss, suggesting that the reduced flow is a function of the red blood cells' interaction with its environment [35]. Since rejuvenating solutions rapidly restore red blood cell ATP concentrations and ATP is important for membrane fluidity, by facilitating cytoskeletal rearrangement, and for vascular flow, by the secretion of ATP in response to shear effects resulting in local vasodilation, it seems plausible that ATP is involved.…”

Section: Are Stored Red Blood Cells Effective?mentioning

confidence: 99%

Current issues relating to the transfusion of stored red blood cells

Zimrin¹,

2009

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The development of blood storage systems allowed donation and transfusion to be separated in time and space. This separation has permitted the regionalization of donor services with subsequent economies of scale and improvements in the quality and availability of blood products. However, the availability of storage raises the question of how long blood products can and should be stored and how long they are safe and effective. The efficacy of red blood cells was originally measured as the increment in haematocrit and safety began with typing and the effort to reduce the risk of bacterial contamination. Appreciation of a growing list of storage lesions of red blood cells has developed with our increasing understanding of red blood cell physiology and our experience with red blood cell transfusion. However, other than frank haemolysis, rare episodes of bacterial contamination and overgrowth, the reduction of oxygen-carrying capacity associated with the failure of some transfused cells to circulate, and the toxicity of lysophospholipids released from membrane breakdown, storage-induced lesions have not had obvious correlations with safety or efficacy. The safety of red blood cell storage has also been approached in retrospective epidemiologic studies of transfused patients, but the results are frequently biased by the fact that sicker patients are transfused more often and blood banks do not issue blood products in a random order. Several large prospective studies of the safety of stored red blood cells are planned.

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The effect of storage time of human red cells on intestinal microcirculatory oxygenation in a rat isovolemic exchange model*

Cited by 118 publications

References 30 publications

Length of storage of red blood cells does not affect outcome in critically ill children

Length of storage of red blood cells does not affect outcome in critically ill children

Fresh Red Blood Cell Transfusion and Short-Term Pulmonary, Immunologic, and Coagulation Status

Current issues relating to the transfusion of stored red blood cells

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