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Effects of shorter versus longer storage time of transfused red blood cells in adult ICU patients: a systematic review with meta-analysis and Trial Sequential Analysis

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Abstract

Purpose

Patients in the intensive care unit (ICU) are often transfused with red blood cells (RBC). During storage, the RBCs and storage medium undergo changes, which may have clinical consequences. Several trials now have assessed these consequences, and we reviewed the present evidence on the effects of shorter versus longer storage time of transfused RBCs on outcomes in ICU patients.

Methods

We conducted a systematic review with meta-analyses and trial sequential analyses (TSA) of randomised clinical trials including adult ICU patients transfused with fresher versus older or standard issue blood.

Results

We included seven trials with a total of 18,283 randomised ICU patients; two trials of 7504 patients were judged to have low risk of bias. We observed no effects of fresher versus older blood on death (relative risk 1.04, 95% confidence interval (CI) 0.97–1.11; 7349 patients; TSA-adjusted CI 0.93–1.15), adverse events (1.26, 0.76–2.09; 7332 patients; TSA-adjusted CI 0.16–9.87) or post-transfusion infections (1.07, 0.96–1.20; 7332 patients; TSA-adjusted CI 0.90–1.27). The results were unchanged by including trials with high risk of bias. TSA confirmed the results and the required information size was reached for mortality for a relative risk change of 20%.

Conclusions

We may be able to reject a clinically meaningful effect of RBC storage time on mortality in transfused adult ICU patients as our trial sequential analyses reject a 10% relative risk change in death when comparing fresher versus older blood for transfusion.

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Abbreviations

CI:

confidence interval

CL:

confidence limits

ESM:

electronic supplementary material

FNHTR:

febrile non-haemolytic transfusion reactions

FWER:

family-wise error rate

GRADE:

grading of recommendations, assessment, development and evaluation

HRQoL:

health-related quality of life

ICU:

intensive care unit

ICH:

International Conference on Harmonisation

NO:

nitric oxide

PRISMA-P:

preferred reporting items for systematic review and meta-analysis protocols

PROSPERO:

international prospective register of systematic reviews

RBC:

red blood cell

RCT:

randomised clinical trial

RR:

relative risk

RRI:

relative risk increase

RRR:

relative risk reduction

RRT:

renal replacement therapy

SAE:

serious adverse event

TSA:

Trial Sequential Analysis

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Acknowledgements

We would like to thank Sarah Louise Klingenberg, search coordinator for the Cochrane Hepato-Biliary Group, for performing the literature search.

Funding

SLR has received funding from the Research Council at Copenhagen University Hospital Rigshospitalet. The funding parties are not involved in the conduct of this review.

Author information

Authors and Affiliations

  1. Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, Inge Lehmans Vej 5, Opg. 3, 3. sal, 4131, 2100, Copenhagen, Denmark

    Sofie L. Rygård, Andreas B. Jonsson, Martin B. Madsen, Anders Perner & Lars B. Holst

  2. Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen, Denmark

    Jørn Wetterslev

  3. Department of Transfusion Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

    Pär I. Johansson

  4. Centre for Research in Intensive Care (CRIC), Copenhagen, Denmark

    Anders Perner & Jørn Wetterslev

Authors
  1. Sofie L. Rygård
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  2. Andreas B. Jonsson
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  3. Martin B. Madsen
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  4. Anders Perner
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  5. Lars B. Holst
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  6. Pär I. Johansson
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  7. Jørn Wetterslev
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Contributions

SLR, AP and JW contributed to the conception of the study protocol. The manuscript was drafted by SLR and JW and was critically revised by all other authors. All authors reviewed the manuscript and have approved the publication in this current form.

Corresponding author

Correspondence to Sofie L. Rygård.

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Conflicts of interest

JW is a member of the task force at Copenhagen Trial Unit to develop theory and software for doing Trial Sequential Analysis which is presently freeware at www.ctu.dk/tsa. The Department of Intensive Care, Rigshospitalet receives support for research from CSL Behring, Fresenius Kabi and Ferring Pharmaceuticals. No other potential conflict of interest relevant to this manuscript was reported. SLR received funding from the Research Council at Copenhagen University Hospital Rigshospitalet. The funding parties were not involved in the conduct of this review.

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Rygård, S.L., Jonsson, A.B., Madsen, M.B. et al. Effects of shorter versus longer storage time of transfused red blood cells in adult ICU patients: a systematic review with meta-analysis and Trial Sequential Analysis. Intensive Care Med 44, 204–217 (2018). https://doi.org/10.1007/s00134-018-5069-0

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  • DOI: https://doi.org/10.1007/s00134-018-5069-0

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