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Table 2 Overview of the studies reporting the age of transfused red blood cells (RBCs) and patient outcomes.

From: Relationship between red cell storage duration and outcomes in adults receiving red cell transfusions: a systematic review

First author

Year

Year(s) of enrollment

Design

Country/continent

Leuko-reduction

Setting

Number of patients transfused

Summary of main results

Studies addressing mortality

Purdy et al. [42]

1997

1992

Retrospective single-center

Canada

NR

ICU septic

31

Non-survivors received a greater proportion of older RBCs

Mynster et al. [53]

2001

1991-1993

Retrospective multicenter

Europe

No

Cancer

740

Mortality not different between patients transfused with RBCs aged more or less than 21 days

Murrell et al. [48]

2005

2001-2003

Retrospective single-center

USA

Mix (95% LR)

Trauma

275

No correlation between 'dose of aged blood' and hospital mortality

van de Watering et al. [38]

2006

1993-1999

Retrospective single-center

Europe

No

Cardiac surgery

2,732

No correlation between storage time variables and 30-day mortality

Koch et al. [32]

2008

1998-2006

Retrospective single-center

USA

Mix

Cardiac surgery

6,002

Higher hospital and one-year mortality rate in older blood group

Yap et al. [41]

2008

2001-2007

Retrospective single-center

Australia

Mix (3.8% LR)

Cardiac surgery

670

No association between storage duration and mortality

Dessertaine et al. [43]

2008

2005-2006

Retrospective single-center

Europe

Yes

ICU

534

No association between the age of transfused red cells and mortality

Weinberg et al. [44]

2008

2000-2007

Retrospective single-center

USA

Yes

Trauma

1,813

Transfusion of large (but not small) volumes of older blood associated with an increased risk of death

Weinberg et al. [46]

2008

2000-2007

Retrospective single-center

USA

Yes

Trauma

430

Slightly increased mortality with transfusion of older blood (> 14 days old)

Spinella et al. [47]

2009

2004-2007

Retrospective single-center

USA

Mix

Trauma

202

Hospital mortality higher for patients transfused with older RBCs; increased storage time independently associated with mortality

Edgren et al. [30]

2010

1995-2002

Retrospective multicenter

Europe

Mix

Mix

364,037

5% increased mortality after two years of follow-up

Weinberg et al. [45]

2010

2000-2009

Retrospective single-center

USA

Yes

Trauma

1,647

Trend toward higher mortality rate with older blood when transfused more than three RBC units

Eikelboom et al. [50]

2010

2002-2006

Retrospective single-center

Canada

Yes

Cardiovascular disease

4,933

Greater risk of hospital mortality in the highest age quartile of RBCs

Robinson et al. [51]

2010

1999-2005

Retrospective single-center

Canada

NR

PCI

909

Storage duration associated with 30-day mortality

van Straten et al. [40]

2011

1998-2007

Retrospective single-center

Europe

Yes

Cardiac surgery

3,597

No effect of RBC storage duration on early or late postoperative mortality

McKenny et al. [39]

2011

2002-2007

Retrospective single-center

Europe

Yes

Cardiac surgery

1,153

No association between RBC storage duration and postoperative mortality

Kekre et al. [54]

2011

2002-2007

Retrospective single-center

Canada

Yes

HSCT

555

Non-relapse 100-day mortality reduced in the subgroup of patients receiving exclusively old blood (> 14 days old)

Pettila et al. [29]

2011

2008

Prospective, multicenter

Australia - New Zealand

Mix

ICU

757

Exposure to the highest age quartile of RBCs associated with a higher hospital mortality rate compared to lowest quartile

Hassan et al. [49]

2011

2003-2005

Retrospective single-center

USA

NR

Trauma

820

Number of older units not associated with increased mortality

Saager et al. [31]

2012

2005-2009

Retrospective single-center

USA

Yes

Non-cardiac surgery

6,994

No relationship between median RBC storage duration and postoperative mortality (up to two years)

Dunn et al. [52]

2012

2000-2010

Retrospective single-center

USA

NR

Liver transplant

509

Transfusion of older blood not associated with increased two-year mortality

Kor et al. [28]

2012

2008-2010

Randomized single-center study

USA

Yes

ICU

100

Similar mortality between fresh and standard issue RBCs but not powered for this outcome

Studies addressing ICU or hospital length of stay

Vamvakas et al. [56]

2000

1995

Retrospective single-center

USA

Mix (mostly not)

Cardiac surgery

268

No association between RBC storage duration and postoperative ICU and hospital LOS

Keller et al. [58]

2002

1998-1999

Retrospective single-center

USA

No

Trauma

86

Number of units of blood older than 14 days associated with an increased hospital LOS

Leal-Noval et al. [55]

2003

1998-2000

Prospective single-center

Europe

No

Cardiac surgery

585

No association between mean duration of RBC storage and ICU LOS

Murrell et al. [48]

2005

2001-2003

Retrospective single-center

USA

Mix (95% LR)

Trauma

275

Association between 'dose of aged blood' and ICU LOS

van de Watering et al. [38]

2006

1993-1999

Retrospective single-center

Europe

No

Cardiac surgery

2,732

No correlation between storage time variables and ICU LOS

Yap et al. [41]

2008

2001-2007

Retrospective single-center

Australia

Mix (3.8% LR)

Cardiac surgery

670

No association between length of storage and ICU LOS

McKenny et al. [39]

2011

2002-2007

Retrospective single-center

Europe

Yes

Cardiac surgery

1,153

No association between length of storage and ICU LOS

Sanders et al. [57]

2011

2005-2007

Retrospective single-center

Europe

Yes

Cardiac surgery

444

Age of blood was a significant but modest predictor of postoperative LOS

Kekre et al. [54]

2011

2002-2007

Retrospective single-center

Canada

Yes

HSCT

555

No correlation between age of transfused RBCs and hospital LOS

Studies addressing age of transfused RBCs and occurrence of infections

Edna et al. [61]

1998

1980-1992

Retrospective single-center

Europe

No

Cancer

240

Age of RBCs not different in subjects developing postoperative infections and those who did not

Vamvakas et al. [59]

1999

1995

Retrospective single-center

USA

Mix

Cardiac surgery

256

Independent relationship between the age of transfused RBCs and the incidence of postoperative pneumonia or wound infection

Mynster et al. [53]

2001

1991-1993

Retrospective multicenter

Europe

No

Cancer

740

Increased risks of postoperative infections with transfusions of RBCs aged 20 days or more

Offner et al. [64]

2002

1992-

Retrospective single-center

USA

No

Trauma

61

Number of units older than 14 and 21 days as an independent risk factor for major infections

Leal-Noval et al. [55]

2003

1998-2000

Prospective single-center

Europe

No

Cardiac surgery

585

Independent relation between the oldest RBC unit and postoperative pneumonia

Taylor et al. [66]

2006

2001-2003

Prospective

USA

Mix

ICU

449

Maximum age of transfused RBCs not associated with increased risks of nosocomial infections

Koch et al. [32]

2008

1998-2006

Retrospective single-center

USA

Mix

Cardiac surgery

6,002

Higher rates of postoperative sepsis or septicemia (but not pneumonia or wound infections) with older RBCs

Weinberg et al. [46]

2008

2000-2007

Retrospective single-center

USA

Yes

Trauma

430

Occurrence of pneumonia related to the volume of old blood (> 14 days old) transfused

Yap et al. [41]

2008

2001-2007

Retrospective single-center

Australia

Mix (3.8% LR)

Cardiac surgery

670

No association between storage of RBCs and postoperative pneumonia

Dessertaine et al. [43]

2008

2005-2006

Retrospective single-center

Europe

Yes

ICU

534

No independent association between the age of RBCs and nosocomial infections

Vandromme et al. [63]

2009

2004-2007

Retrospective single-center

USA

Yes

Trauma

1,183

Increased risks of pneumonia after transfusion of exclusively old RBCs (> 14 days)

Basora et al. [113]

2010

2004-2005

Retrospective single-center

Europe

Yes

Knee arthroplasty

335

No independent association between age of transfused RBCs and postoperative wound infection

McKenny et al. [39]

2011

2002-2007

Retrospective single-center

Europe

Yes

Cardiac surgery

1,153

No association between storage of RBCs and postoperative pneumonia

Andreasen et al. [60]

2011

2003-2008

Retrospective multicenter

Europe

No

Cardiac surgery

1,748

Greater risk of postoperative wound infections and septicemia with RBCs older than 14 days

Hassan et al. [49]

2011

2003-2005

Retrospective single-center

USA

NR

Trauma

820

Number of units older than 14 days as a significant risk factor for severe sepsis or septic shock

Juffermans et al. [67]

2011

2004-2007

Retrospective single-center

Europe

Yes

ICU septic

67

Storage time as a confounder for the association of RBCs with infection

Juffermans et al. [65]

2012

2004-2007

Retrospective single-center

Europe

Yes

Trauma/TBI

196

Modest association between transfusion of RBCs older than 14 days and occurrence of new infections

Dunn et al. [52]

2012

2000-2010

Retrospective single-center

USA

NR

Liver transplant

509

No independent association between the age of RBCs and postoperative infections

Studies addressing organ failure

Zallen et al. [68]

1999

NR

Retrospective single-center

USA

NR

Trauma

63

Mean age of blood (or number of units older than 14 or 21 days) as independent risk factors for MOF

Vamvakas et al. [56]

2000

1995

Retrospective single-center

USA

Mix (mostly not)

Cardiac surgery

268

Length of RBC storage not associated with prolonged endotracheal intubation

Keller et al. [58]

2002

1998-1999

Retrospective single-center

USA

No

Trauma

86

Duration of MV not associated with RBC storage duration

Leal-Noval et al. [55]

2003

1998-2000

Prospective single-center

Europe

No

Cardiac surgery

585

No relationship between RBC storage duration and prolonged MV

Gajic et al. [70]

2004

2001

Retrospective single-center

USA

Mix

ICU

181

No association between mean age or age of the oldest unit transfused and occurrence of ALI

Yap et al. [41]

2008

2001-2007

Retrospective single-center

Australia

Mix (3.8% LR)

Cardiac surgery

670

No association between storage duration and occurrence of postoperative renal failure or prolonged MV

Koch et al. [32]

2008

1998-2006

Retrospective single-center

USA

Mix

Cardiac surgery

6,002

Increased risk of a composite outcome (including MOF and renal failure) with transfusion of older blood; higher rates of MV > 72 hours when patients transfused only old RBC

Weinberg et al. [46]

2008

2000-2007

Retrospective single-center

USA

Yes

Trauma

430

Old blood (> 14 days) associated with acute renal dysfunction after adjustment

McKenny et al. [39]

2011

2002-2007

Retrospective single-center

Europe

Yes

Cardiac surgery

1,153

No association between storage duration and occurrence of postoperative renal failure or prolonged MV

Sanders et al. [57]

2011

2005-2007

Retrospective single-center

Europe

Yes

Cardiac surgery

444

Higher rates of renal failure among patients transfused with old blood

Kor et al. [28]

2012

2008-2010

Randomized single-center study

USA

Yes

ICU

100

Similar measures of pulmonary function after transfusion of either fresh or standard issue RBCs

Weiskopf et al. [69]

2012

NR

Randomized single-center study

USA

Mix

Volunteers

35

Equivalent mild decrements in pulmonary gas exchange variables after transfusion of either fresh (1.7 hour) or older (> 21 days) RBCs

Studies addressing tissue oxygenation and microcirculation

Marik et al. [71]

1993

NR

Prospective single-center study

USA

NR

ICU

23

Inverse correlation between the age of transfused RBCs and the maximal change in gastric mucosal pH (pHi)

Fernandes et al. [72]

2001

1996

Randomized single-center study

South America

NR

ICU septic

15

No correlation between the age of transfused RBCs and the pHi

Walsh et al. [73]

2004

1999-2000

Randomized single-center study

Europe

Yes

ICU

22

No difference in pHi or gastric to arterial PCO2 gap with transfusions of fresh or older RBCs

Sakr et al. [75]

2007

NR

Prospective single-center

Europe

Yes

ICU

35

No correlation between the storage time and the changes in capillary perfusion

Leal-Noval et al. [77]

2008

2004-2006

Prospective single-center

Europe

Yes

Severe TBI

66

Transfusion of RBCs aged more than 19 days failed to increase cerebral tissue oxygenation

Kiraly et al. [79]

2009

NR

Prospective single-center

USA

NR

Trauma

32

Patients transfused with > 21 days old RBCs had a significant decrease in the area under the curve of tissue saturation (StO2)

Creteur et al. [81]

2009

NR

Prospective single-center

Europe

Yes

ICU

44

No association between RBC storage time and oxygenation variables (NIRS)

Yuruk et al. [76]

2012

NR

Randomized single-center study

Europe

Yes

Hematology patients

20

Increase in perfused vessel density similar in both RBC age groups

Berra et al. [82]

2012

2010

Randomized single-center study

USA

Yes

Healthy volunteers

9

Reactive hyperemia index unchanged after transfusion of 40-day stored blood compared with transfusion of three-day stored blood

Roberson et al. [83]

2012

NR

Prospective single-center

USA

Yes

Healthy volunteers

8

No effect of storage duration on tissue oxygen saturation and sublingual microcirculatory flow index

Kopterides et al. [84]

2012

2008-2011

Prospective single-center

Europe

Mix

ICU septic

37

No relationship between age of RBCs and change in lactate/pyruvate ratio (microdialysis)

Other outcomes

Wasser et al. [87]

1989

NR

Randomized single-center study

Europe

No

Cardiac surgery

237

No differences in postoperative bleeding, coagulation tests, or transfusion requirements

Mynster et al. [53]

2001

1991-1993

Retrospective multicenter

Europe

No

Cancer

740

Higher recurrence rate of cancer in patients who received a transfusion of RBCs stored < 21 days

Leal-Noval et al. [55]

2003

1998-2000

Prospective single-center

Europe

No

Cardiac surgery

585

No association between duration of storage of RBCs and postoperative myocardial infarction

Weiskopf et al. [88]

2006

NR

Randomized single-center study

USA

No

Volunteers

9

Reversal of anemia-induced cognitive dysfunction similar after transfusion of fresh or stored RBCs

Spinella et al. [47]

2009

2004-2007

Retrospective single-center

USA

Mix

Trauma

202

Association between maximum age of RBCs (> 21 or 28 days) and deep vein thrombosis (DVT)

Naidech et al. [86]

2011

NR

Retrospective single-center

USA

NR

SAH

119

No association between age of RBCs and vasospasm or cerebral infarction

Katsios et al. [85]

2011

2001-2002

Prospective single-center

Canada

No

ICU

261

No association between the age of transfused RBCs and the occurrence of DVT

Cata et al. [89]

2011

1998-2007

Retrospective single-center

USA

NR

Prostate cancer

316

No association between the age of transfused RBCs and the five-year prostate cancer recurrence

  1. DVT, deep vein thrombosis; HSCT, hematopoietic stem cell transplantation; ICU, intensive care unit; LOS, length of stay; LR, leukoreduced; MV, mechanical ventilation; NIRS, near-infrared spectroscopy; NR, not reported; PCI, percutaneous coronary intervention; SAH, subarachnoid hemorrhage: TBI, traumatic brain injury.