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Transfused fresh red cells fail to improve outcomes in critically ill adults
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Critically ill adults who received a transfusion of fresh red cells demonstrated no significant improvement in 90-day mortality compared with those who received standard-issue red cells, according to study results.
“Our findings are not consistent with those of some previous observational studies that suggest prolonged red-cell storage may be deleterious,” Jacques Lacroix, MD, of the department of pediatrics at the Université de Montréal, and colleagues wrote.
Fresh red cells had been thought to improve outcomes through enhanced oxygen delivery, as well as a reduced risk for toxic effects from cellular changes and bioactive materials accumulated during storage, according to study background information.
Lacroix and colleagues evaluated data from 2,430 critically ill patients who underwent blood transfusions at 64 centers in Canada and Europe.
Researchers randomly assigned patients to receive fresh red cells (n = 1,211) — which had been in storage for less than 8 days — or standard-issue red cells (n = 1,219). Standard-issue red cells were the oldest compatible units available in the blood bank.
Fresh red cells were stored for a mean of 6.1 days (± 4.9), compared with 22 days (± 8.4) for standard-issue red cells (P = .0001).
Researchers observed comparable outcomes in both groups.
In the fresh red cell group, 37% (n = 448) of patients died within 90 days of transfusion, compared with 35.3% (n = 430) of patients who received standard-issue red cells. This equated to an HR for death in the fresh red cell group of 1.1 (95% CI, 0.9-1.2).
Factors such as age, number of units transfused, APACHE II score and admission category did not have a significant impact on outcomes. Secondary outcomes — which included major illnesses; transfusion reactions; length of hospital stays; or duration of respiratory, hemodynamic or renal support — also were similar in both groups.
“We did not detect any clinically important improvements in primary or secondary outcomes among critically ill adults who received transfusions of fresh red cells,” Lacroix and colleagues wrote. “These findings have important implications for the critical-care and blood-transfusion communities. We surmise that the use of fresh red cells is not justified at this time. We might also infer that changes to red cells or the storage medium that have been documented in many laboratory studies may have limited clinical consequences.” – by Cameron Kelsall
Disclosure: Lacroix reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.
Perspective
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Jed B. Gorlin, MD, MBA
Franz Messerli published a delightful analysis of the highly statistically significant correlation between a country’s per capita annual rate of chocolate consumption and its rate of Nobel Prize awards (Messerli FH. N Engl J Med. 2012;doi:10.1056/NEJMon1211064). Although clearly tongue in cheek, it is an obvious example that not all correlations are, in fact, causative!However, a previous publication in The New England Journal of Medicine found a strong correlation between red cell storage and increased complications following cardiac surgery (Koch CG, et al. N Engl J Med. 2008;doi:10.1056/NEJMoa070403). “In patients undergoing cardiac surgery, transfusion of red cells that had been stored for more than 2 weeks was associated with a significantly increased risk of postoperative complications, as well as reduced short-term and long-term survival,” the investigators wrote. This widely read publication was followed by other retrospective series, many of which also observed similar correlations.
Alas, the inherent risk of drawing conclusions from such retrospective series is the risk of a confounding variable: Sicker patients are more likely to receive transfusions. Those receiving more transfusions are more likely to receive older units. Sicker patients have worse outcomes. Because this concern was impacting blood collection agencies due to clinician requests for fresher units, the NIH wisely supported parallel sets of investigations. In the event that the observations were real, multiple studies investigated various in vitro parameters of blood storage effects. Many observed real changes in biochemical markers, morphology or transfused red cell survival. Randomized clinical transfusion trials also were supported, but in most cases human subject committees would only allow studies of particularly fresh blood vs. units whose storage age was the “standard of care.”
The ARIPI trial (Fergusson DA, et al. JAMA. 2012;308:1443-1451), the first published of these studies, was limited to premature neonates and failed to show any benefit of the fresher units (< 5 days old vs. 14 days).
The accompanying summaries of the ABLE and RECESS trials document similar failure to observe clinically significant differences in outcomes between groups who received very fresh units vs. standard of care. Although the studies cannot rule out adverse effects from the oldest allowable units (42 days in additive solution), the studies’ designs were dictated by the concern for lack of equipoise following the Koch publication.
It remains to be seen whether clinicians’ concerns about older blood will be sufficiently allayed by these studies or whether additional studies comparing standard-of-care blood (about 3 weeks old) with those units approaching final outdate will ever be carried out.
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