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Research Letter |

Red Blood Cell Concentrate Storage and Survival After Cardiac Surgery FREE

Ulrik Sartipy, MD, PhD1; Martin J. Holzmann, MD, PhD2; Henrik Hjalgrim, MD, DrMedSci3; Gustaf Edgren, MD, PhD4
[+] Author Affiliations
1Department of Cardiothoracic Surgery and Anesthesiology, Karolinska University Hospital, Stockholm, Sweden
2Department of Emergency Medicine, Karolinska University Hospital, Stockholm, Sweden
3Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
4Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
JAMA. 2015;314(15):1641-1643. doi:10.1001/jama.2015.8690.
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Published online

Blood undergoes several physiological changes during storage. Observational studies have suggested that transfusion of stored red blood cell (RBC) concentrates may be harmful1; however, the results are inconsistent.2 We performed a nationwide cohort study of RBC storage and adverse outcomes after cardiac surgery.

We identified all patients who underwent coronary artery bypass graft surgery, heart valve surgery, or both between 1997 and 2012 from the SWEDEHEART register, which records information on patients who undergo heart surgery in Sweden.3 Transfusion data were obtained from the SCANDAT2 database, a nationwide register of blood transfusions.4 Linkage with national health data registers provided vital status and adverse outcomes.

Blood services in Sweden are part of the public health care system and follow national guidelines, whereby the oldest available blood unit of the appropriate blood type is allocated first. Storage of RBCs was classified as previously1,2 with discrete patient groups who had exclusively received blood stored less than 14 days, 14-27 days, or 28-42 days, and a mixed storage category for patients receiving blood of mixed age. Follow-up was completed on December 31, 2013.

We used multivariable Cox regression to estimate the 30-day, 2-year, and 10-year risk of death in relation to storage of transfused RBCs. We also considered the number of transfused units stored 28-42 days and risk of death. Associations between RBC storage and the risk of complications within 30 days of surgery were assessed using multivariable logistic regression. Both regression models were adjusted for all the factors listed in the footnote for Table 1.

Table Graphic Jump LocationTable 1.  Short-, Medium-, and Long-Term Survival of Patients Undergoing Cardiac Surgery in Relation to Duration of Storage of Transfused Red Blood Cell Concentrates or Number of Transfused Units Stored 28 Days or Longer

Statistical analyses were performed using SAS version 9.4 (SAS Institute Inc). All statistical tests were 2-sided. P values <.05 were considered statistically significant. The study was approved by the local ethics committee, which also waived informed consent.

Between 1997 and 2012, 47 071 patients were transfused in connection with cardiac surgery in 9 Swedish hospitals. Women constituted 39.2% and the mean (SD) age was 70.0 (9.7) years. Of these patients, 36.6% exclusively received RBCs stored less than 14 days; 26.8%, RBCs stored 14-27 days; 8.9%, RBCs stored 28-42 days; and 27.8%, RBCs of mixed age. Most clinical parameters were similar in the groups, although the less common blood groups (eg, AB and B) were more common with longer storage. Recipients of the freshest blood received more transfusions, 3.1 vs 2.7 (mean difference, 0.45; 95% CI, 0.37-0.52). No differences were observed for a range of comorbidities.

Compared with recipients of RBCs stored for less than 14 days (49.5 deaths/1000 person-years), there was no association between transfusion of RBCs stored 14-27 days (45.4 deaths/1000 person-years; adjusted hazard ratio, 1.02 [95% CI, 0.94-1.11]) or 28-42 days (41.1 deaths/1000 person-years; adjusted hazard ratio, 0.98 [95% CI, 0.86-1.11]) and 2-year mortality (Table 1). No associations were seen for 30-day and 10-year mortality. We also found no associations between the number of transfused units stored 28-42 days and risk of death (Table 1). There was no association with risk of selected serious complications (Table 2).

Table Graphic Jump LocationTable 2.  Duration of Storage of Transfused Red Blood Cell Concentrates and Risk of Adverse Outcomes Within 30 Days of Surgery

In this cohort study of patients who underwent cardiac surgery in Sweden over a 16-year period, we found no association between RBC storage and adverse outcomes. The key strengths of this study include the large, detailed data set and complete follow-up, which was achievable by linking several high-quality nationwide registers.

The main weakness is the possibility that allocation of especially fresh RBC units was somehow related to patient prognosis. We do not believe this was the case because no such practice was in place, there were no major changes in blood storage during the study period, and blood storage was not associated with any important clinical parameters.

Results are consistent with data from 2 randomized trials that found no effect of RBC storage on change in multiple organ dysfunction score or risk of death.5,6 However, these trials relied on short-term surrogate end points5 or short-term mortality,6 may have limited generalizability, and could not exclude small, yet clinically relevant effects. Therefore, these results complement recent randomized trials in providing further reassurance of the safety of current blood storage practices.

Section Editor: Jody W. Zylke, MD, Deputy Editor.

Corresponding Author: Ulrik Sartipy, MD, PhD, Department of Cardiothoracic Surgery and Anesthesiology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden (ulrik.sartipy@karolinska.se).

Author Contributions: Drs Sartipy and Edgren had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Sartipy, Holzmann, Edgren.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Sartipy, Holzmann, Edgren.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Hjalgrim, Edgren.

Obtained funding: All authors.

Administrative, technical, or material support: Sartipy, Holzmann, Edgren.

Study supervision: Hjalgrim.

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Sartipy reported serving on a scientific advisory board and as a consultant for Bayer.

Funding/Support: Funding was provided by grants from the Swedish Medical Society (SLS-330221 awarded to Dr Sartipy), Karolinska Institutet Foundations and Funds (40842 awarded to Dr Sartipy), and the Mats Kleberg Foundation (2014-00017 awarded to Dr Sartipy). The SCANDAT2 database assembly was financed by Swedish Research Council (2011-30405, 2007-7469), the Swedish Heart-Lung Foundation (20090710), and the Swedish Society for Medical Research (Dr Edgren).

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We are indebted to all the blood banks in Sweden for collecting and contributing data to this study. We also thank the SWEDEHEART steering committee for providing the data.

Trial Registration: clinicaltrials.gov Identifier: NCT02276950

Koch  CG, Li  L, Sessler  DI,  et al.  Duration of red-cell storage and complications after cardiac surgery. N Engl J Med. 2008;358(12):1229-1239.
PubMed   |  Link to Article
Edgren  G, Kamper-Jørgensen  M, Eloranta  S,  et al.  Duration of red blood cell storage and survival of transfused patients (CME). Transfusion. 2010;50(6):1185-1195.
PubMed   |  Link to Article
Jernberg  T, Attebring  MF, Hambraeus  K,  et al.  The Swedish Web-system for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART). Heart. 2010;96(20):1617-1621.
PubMed   |  Link to Article
Edgren  G, Rostgaard  K, Vasan  SK,  et al.  The new Scandinavian Donations and Transfusions database (SCANDAT2): a blood safety resource with added versatility. Transfusion.2015;55(7):1600-1606.
PubMed   |  Link to Article
Steiner  ME, Ness  PM, Assmann  SF,  et al.  Effects of red-cell storage duration on patients undergoing cardiac surgery. N Engl J Med. 2015;372(15):1419-1429.
PubMed   |  Link to Article
Lacroix  J, Hébert  PC, Fergusson  DA,  et al; ABLE Investigators; Canadian Critical Care Trials Group.  Age of transfused blood in critically ill adults. N Engl J Med. 2015;372(15):1410-1418.
PubMed   |  Link to Article

Figures

Tables

Table Graphic Jump LocationTable 1.  Short-, Medium-, and Long-Term Survival of Patients Undergoing Cardiac Surgery in Relation to Duration of Storage of Transfused Red Blood Cell Concentrates or Number of Transfused Units Stored 28 Days or Longer
Table Graphic Jump LocationTable 2.  Duration of Storage of Transfused Red Blood Cell Concentrates and Risk of Adverse Outcomes Within 30 Days of Surgery

References

Koch  CG, Li  L, Sessler  DI,  et al.  Duration of red-cell storage and complications after cardiac surgery. N Engl J Med. 2008;358(12):1229-1239.
PubMed   |  Link to Article
Edgren  G, Kamper-Jørgensen  M, Eloranta  S,  et al.  Duration of red blood cell storage and survival of transfused patients (CME). Transfusion. 2010;50(6):1185-1195.
PubMed   |  Link to Article
Jernberg  T, Attebring  MF, Hambraeus  K,  et al.  The Swedish Web-system for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART). Heart. 2010;96(20):1617-1621.
PubMed   |  Link to Article
Edgren  G, Rostgaard  K, Vasan  SK,  et al.  The new Scandinavian Donations and Transfusions database (SCANDAT2): a blood safety resource with added versatility. Transfusion.2015;55(7):1600-1606.
PubMed   |  Link to Article
Steiner  ME, Ness  PM, Assmann  SF,  et al.  Effects of red-cell storage duration on patients undergoing cardiac surgery. N Engl J Med. 2015;372(15):1419-1429.
PubMed   |  Link to Article
Lacroix  J, Hébert  PC, Fergusson  DA,  et al; ABLE Investigators; Canadian Critical Care Trials Group.  Age of transfused blood in critically ill adults. N Engl J Med. 2015;372(15):1410-1418.
PubMed   |  Link to Article
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