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Published in: Critical Care 1/2019

Open Access 01-12-2019 | Septicemia | Research

Liberal versus restrictive red blood cell transfusion strategy in sepsis or septic shock: a systematic review and meta-analysis of randomized trials

Authors: Yohei Hirano, Yukari Miyoshi, Yutaka Kondo, Ken Okamoto, Hiroshi Tanaka

Published in: Critical Care | Issue 1/2019

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Abstract

Background

We assessed the effect of liberal versus restrictive red blood cell transfusion strategy on survival outcome in sepsis or septic shock by systematically reviewing the literature and synthesizing evidence from randomized controlled trials (RCTs).

Methods

We searched the MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science databases. We included RCTs that compared mortality between a liberal transfusion strategy with a hemoglobin threshold of 9 or 10 g/dL and a restrictive transfusion strategy with a hemoglobin threshold of 7 g/dL in adults with sepsis or septic shock. Two investigators independently screened citations and conducted data extraction. The primary outcome was 28- or 30-day mortality. Secondary outcomes were 60- and 90-day mortality, use of life support at 28 days of admission, and number of patients transfused during their intensive care unit stay. DerSimonian-Laird random-effects models were used to report pooled odds ratios (ORs).

Results

A total of 1516 patients from three RCTs were included; 749 were randomly assigned to the liberal transfusion group and 767 to the restrictive strategy group. Within 28–30 days, 273 patients (36.4%) died in the liberal transfusion group, while 278 (36.2%) died in the restrictive transfusion group (pooled OR, 0.99; 95% confidence interval [CI], 0.67–1.46). For the primary outcome, heterogeneity was observed among the studies (I2 = 61.0%, χ2 = 5.13, p = 0.08). For secondary outcomes, only two RCTs were included. There were no significant differences in secondary outcomes between the two groups.

Conclusions

We could not show any difference in 28- or 30-day mortality between the liberal and restrictive transfusion strategies in sepsis or septic shock patients by meta-analysis of RCTs. Our results should be interpreted with caution due to the existence of heterogeneity. As sepsis complicates a potentially wide range of underlying diseases, further trials in carefully selected populations are anticipated.

Trial registration

This present study was registered in the PROSPERO database (CRD42018108578).
Appendix
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Literature
1.
go back to reference Chan YL, Han ST, Li CH, Wu CC, Chen KF. Transfusion of red blood cells to patients with sepsis. Int J Mol Sci. 2017;18(9).CrossRef Chan YL, Han ST, Li CH, Wu CC, Chen KF. Transfusion of red blood cells to patients with sepsis. Int J Mol Sci. 2017;18(9).CrossRef
2.
go back to reference Docherty AB, Turgeon AF, Walsh TS. Best practice in critical care: anaemia in acute and critical illness. Transfus Med. 2018;28(2):181–9.CrossRef Docherty AB, Turgeon AF, Walsh TS. Best practice in critical care: anaemia in acute and critical illness. Transfus Med. 2018;28(2):181–9.CrossRef
3.
go back to reference Amato A, Pescatori M. Perioperative blood transfusions for the recurrence of colorectal cancer. Cochrane Database Syst Rev. 2006;(1):Cd005033. Amato A, Pescatori M. Perioperative blood transfusions for the recurrence of colorectal cancer. Cochrane Database Syst Rev. 2006;(1):Cd005033.
4.
go back to reference Cata JP, Wang H, Gottumukkala V, Reuben J, Sessler DI. Inflammatory response, immunosuppression, and cancer recurrence after perioperative blood transfusions. Br J Anaesth. 2013;110(5):690–701.CrossRef Cata JP, Wang H, Gottumukkala V, Reuben J, Sessler DI. Inflammatory response, immunosuppression, and cancer recurrence after perioperative blood transfusions. Br J Anaesth. 2013;110(5):690–701.CrossRef
5.
go back to reference Raghavan M, Marik PE. Anemia, allogenic blood transfusion, and immunomodulation in the critically ill. Chest. 2005;127(1):295–307.CrossRef Raghavan M, Marik PE. Anemia, allogenic blood transfusion, and immunomodulation in the critically ill. Chest. 2005;127(1):295–307.CrossRef
6.
go back to reference Dupuis C, Sonneville R, Adrie C, Gros A, Darmon M, Bouadma L, Timsit JF. Impact of transfusion on patients with sepsis admitted in intensive care unit: a systematic review and meta-analysis. Ann Intensive Care. 2017;7(1):5.CrossRef Dupuis C, Sonneville R, Adrie C, Gros A, Darmon M, Bouadma L, Timsit JF. Impact of transfusion on patients with sepsis admitted in intensive care unit: a systematic review and meta-analysis. Ann Intensive Care. 2017;7(1):5.CrossRef
7.
go back to reference Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med. 2017;45(3):486–552.CrossRef Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med. 2017;45(3):486–552.CrossRef
8.
go back to reference Holst LB, Haase N, Wetterslev J, Wernerman J, Guttormsen AB, Karlsson S, Johansson PI, Aneman A, Vang ML, Winding R, et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014;371(15):1381–91.CrossRef Holst LB, Haase N, Wetterslev J, Wernerman J, Guttormsen AB, Karlsson S, Johansson PI, Aneman A, Vang ML, Winding R, et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014;371(15):1381–91.CrossRef
9.
go back to reference Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, Terndrup T, Wang HE, Hou PC, LoVecchio F, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370(18):1683–93.CrossRef Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, Terndrup T, Wang HE, Hou PC, LoVecchio F, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370(18):1683–93.CrossRef
10.
go back to reference Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Jama. 2016;315(8):801–10.CrossRef Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Jama. 2016;315(8):801–10.CrossRef
11.
go back to reference Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.CrossRef Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.CrossRef
12.
go back to reference Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, Norris S, Falck-Ytter Y, Glasziou P, DeBeer H, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64(4):383–94.CrossRef Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, Norris S, Falck-Ytter Y, Glasziou P, DeBeer H, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64(4):383–94.CrossRef
13.
go back to reference Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.CrossRef Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.CrossRef
14.
go back to reference Bergamin FS, Almeida JP, Landoni G, Galas F, Fukushima JT, Fominskiy E, Park CHL, Osawa EA, Diz MPE, Oliveira GQ, et al. Liberal versus restrictive transfusion strategy in critically ill oncologic patients: the transfusion requirements in critically ill oncologic patients randomized controlled trial. Crit Care Med. 2017;45(5):766–73.CrossRef Bergamin FS, Almeida JP, Landoni G, Galas F, Fukushima JT, Fominskiy E, Park CHL, Osawa EA, Diz MPE, Oliveira GQ, et al. Liberal versus restrictive transfusion strategy in critically ill oncologic patients: the transfusion requirements in critically ill oncologic patients randomized controlled trial. Crit Care Med. 2017;45(5):766–73.CrossRef
15.
go back to reference Hebert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, Tweeddale M, Schweitzer I, Yetisir E. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999;340(6):409–17.CrossRef Hebert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, Tweeddale M, Schweitzer I, Yetisir E. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999;340(6):409–17.CrossRef
16.
go back to reference Carson JL, Stanworth SJ, Roubinian N, Fergusson DA, Triulzi D, Doree C, Hebert PC. Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion. Cochrane Database Syst Rev. 2016;10:Cd002042.PubMed Carson JL, Stanworth SJ, Roubinian N, Fergusson DA, Triulzi D, Doree C, Hebert PC. Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion. Cochrane Database Syst Rev. 2016;10:Cd002042.PubMed
17.
go back to reference Mueller MM, Van Remoortel H, Meybohm P, Aranko K, Aubron C, Burger R, Carson JL, Cichutek K, De Buck E, Devine D, et al. Patient blood management: recommendations from the 2018 Frankfurt Consensus Conference. Jama. 2019;321(10):983–97.CrossRef Mueller MM, Van Remoortel H, Meybohm P, Aranko K, Aubron C, Burger R, Carson JL, Cichutek K, De Buck E, Devine D, et al. Patient blood management: recommendations from the 2018 Frankfurt Consensus Conference. Jama. 2019;321(10):983–97.CrossRef
18.
go back to reference Carson JL, Terrin ML, Noveck H, Sanders DW, Chaitman BR, Rhoads GG, Nemo G, Dragert K, Beaupre L, Hildebrand K, et al. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med. 2011;365(26):2453–62.CrossRef Carson JL, Terrin ML, Noveck H, Sanders DW, Chaitman BR, Rhoads GG, Nemo G, Dragert K, Beaupre L, Hildebrand K, et al. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med. 2011;365(26):2453–62.CrossRef
19.
go back to reference English SW, Fergusson D, Chasse M, Turgeon AF, Lauzier F, Griesdale D, Algird A, Kramer A, Tinmouth A, Lum C, et al. Aneurysmal subarachnoid hemorrhage-red blood cell transfusion and outcome (SAHaRA): a pilot randomised controlled trial protocol. BMJ Open. 2016;6(12):e012623.CrossRef English SW, Fergusson D, Chasse M, Turgeon AF, Lauzier F, Griesdale D, Algird A, Kramer A, Tinmouth A, Lum C, et al. Aneurysmal subarachnoid hemorrhage-red blood cell transfusion and outcome (SAHaRA): a pilot randomised controlled trial protocol. BMJ Open. 2016;6(12):e012623.CrossRef
20.
go back to reference Jairath V, Kahan BC, Gray A, Dore CJ, Mora A, James MW, Stanley AJ, Everett SM, Bailey AA, Dallal H, et al. Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial. Lancet. 2015;386(9989):137–44.CrossRef Jairath V, Kahan BC, Gray A, Dore CJ, Mora A, James MW, Stanley AJ, Everett SM, Bailey AA, Dallal H, et al. Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial. Lancet. 2015;386(9989):137–44.CrossRef
21.
go back to reference Mazer CD, Whitlock RP, Fergusson DA, Hall J, Belley-Cote E, Connolly K, Khanykin B, Gregory AJ, de Medicis E, McGuinness S, et al. Restrictive or liberal red-cell transfusion for cardiac surgery. N Engl J Med. 2017;377(22):2133–44.CrossRef Mazer CD, Whitlock RP, Fergusson DA, Hall J, Belley-Cote E, Connolly K, Khanykin B, Gregory AJ, de Medicis E, McGuinness S, et al. Restrictive or liberal red-cell transfusion for cardiac surgery. N Engl J Med. 2017;377(22):2133–44.CrossRef
22.
go back to reference Palmieri TL, JHt H, Arnoldo B, Peck M, Potenza B, Cochran A, King BT, Dominic W, Cartotto R, Bhavsar D, et al. Transfusion Requirement in Burn Care Evaluation (TRIBE): a multicenter randomized prospective trial of blood transfusion in major burn injury. Ann Surg. 2017;266(4):595–602.CrossRef Palmieri TL, JHt H, Arnoldo B, Peck M, Potenza B, Cochran A, King BT, Dominic W, Cartotto R, Bhavsar D, et al. Transfusion Requirement in Burn Care Evaluation (TRIBE): a multicenter randomized prospective trial of blood transfusion in major burn injury. Ann Surg. 2017;266(4):595–602.CrossRef
23.
go back to reference Docherty AB, O'Donnell R, Brunskill S, Trivella M, Doree C, Holst L, Parker M, Gregersen M, Pinheiro de Almeida J, Walsh TS, et al. Effect of restrictive versus liberal transfusion strategies on outcomes in patients with cardiovascular disease in a non-cardiac surgery setting: systematic review and meta-analysis. BMJ. 2016;352:i1351.CrossRef Docherty AB, O'Donnell R, Brunskill S, Trivella M, Doree C, Holst L, Parker M, Gregersen M, Pinheiro de Almeida J, Walsh TS, et al. Effect of restrictive versus liberal transfusion strategies on outcomes in patients with cardiovascular disease in a non-cardiac surgery setting: systematic review and meta-analysis. BMJ. 2016;352:i1351.CrossRef
24.
go back to reference Dzik WH. Leukoreduction of blood components. Curr Opin Hematol. 2002;9(6):521–6.CrossRef Dzik WH. Leukoreduction of blood components. Curr Opin Hematol. 2002;9(6):521–6.CrossRef
25.
go back to reference Bailar JC 3rd. The promise and problems of meta-analysis. N Engl J Med. 1997;337(8):559–61.CrossRef Bailar JC 3rd. The promise and problems of meta-analysis. N Engl J Med. 1997;337(8):559–61.CrossRef
26.
go back to reference Gopalakrishnan S, Ganeshkumar P. Systematic reviews and meta-analysis: understanding the best evidence in primary healthcare. J Fam Med Prim Care. 2013;2(1):9–14.CrossRef Gopalakrishnan S, Ganeshkumar P. Systematic reviews and meta-analysis: understanding the best evidence in primary healthcare. J Fam Med Prim Care. 2013;2(1):9–14.CrossRef
Metadata
Title
Liberal versus restrictive red blood cell transfusion strategy in sepsis or septic shock: a systematic review and meta-analysis of randomized trials
Authors
Yohei Hirano
Yukari Miyoshi
Yutaka Kondo
Ken Okamoto
Hiroshi Tanaka
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2019
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-019-2543-1

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