Author: Michael Vlessides
A restrictive transfusion strategy does not have a significant impact on either morbidity or mortality relative to a liberal transfusion strategy.
The systematic review and meta-analysis also found that the restrictive strategy decreased exposure to packed red blood cells (PRBCs) by more than 30%, while saving approximately 0.2 unit of PRBCs per transfused patient.
“The main objective of our study was to identify, appraise and summarize any evidence to compare restrictive and liberal blood transfusion strategies in cardiac surgery,” said Hessam Kashani, MD, MSc, a clinical research associate at the University of Manitoba, in Winnipeg.
As Dr. Kashani explained, the population of interest for the systematic review and meta-analysis was any adult patient undergoing cardiac surgery as part of a randomized controlled trial. The intervention of interest was restrictive transfusion strategy of PRBCs at a lower hemoglobin/hematocrit level, which was compared with liberal transfusion strategies at a higher hemoglobin/hematocrit level.
“We also used the longest follow-ups available for all reported outcomes,” he explained.
As Dr. Kashani reported at the 2019 annual meeting of the International Anesthesia Research Society (abstract F20), he and his colleagues searched a variety of databases for relevant studies, including Medline, Embase and Cochrane Central, from inception through Dec. 1, 2017. The researchers also performed a supplementary search of ClinicalTrials.gov and the World Health Organization’s International Clinical Trials Registry Platform for ongoing or unpublished trials.
In total, the investigators screened 6,491 records. Of these, 32 full-text articles were assessed for eligibility. The final study cohort comprised 18 trials, including 10 primary trial reports and eight companion reports.
“It was interesting to see that there was a variety of definitions with respect to restrictive and liberal transfusion protocols between the 10 primary studies included in the analysis,” Dr. Kashani said. “But most of them start transfusions in the restrictive group at hemoglobin levels between 75 and 80, and in the liberal group between 95 and 100.”
The researchers also assessed the risk for bias in each of the 10 included studies, including selection bias, performance bias, detection bias, attrition bias, reporting bias and other bias. In general, the included studies demonstrated an overall low risk for bias.
The meta-analysis found that seven trials reported rates of mortality. “Some of these favored a restrictive transfusion strategy and some favored a liberal strategy,” Dr. Kashani reported. “But overall, there was no difference between the impact on mortality of restrictive versus liberal.”
Indeed, this part of the analysis found 203 deaths among 4,334 patients who underwent a restrictive strategy. By comparison, there were 197 deaths among 4,327 patients who underwent a liberal strategy. The resulting risk ratio for restrictive transfusion strategies was 1.08 (95% CI, 0.76-1.54).
“To make sure our results are statistically significant, we conducted a trial sequential analysis,” Dr. Kashani said. “We needed approximately 30,000 patients to make sure that our results are statistically significant, but we had fewer than 9,000 in the analysis.
“And while we didn’t cross the line favoring one approach over another, the changes made by each study were so small that if even if there were bigger trials to include, the probability of changing the results would be so low that we can say our results are fairly conclusive.”
The study also found that restrictive transfusion strategies reduced patients’ exposure to PRBCs by more than 30%, while saving 0.2 unit of PRBCs per transfused patient.
The analysis also found that the type of transfusion strategy used had no impact on secondary outcomes such as myocardial infarction, renal failure, stroke, ICU LOS, hospital LOS or days on mechanical ventilation.
“We conclude that using a restrictive transfusion strategy in cardiac surgery can reduce exposure to blood transfusions by more than 30% and save 0.2 unit of PRBCs per transfused patient without impacting their mortality and other comorbidities,” Dr. Kashani noted.
Mortality End Point Questioned
Alex S. Evers, MD, the Henry E. Mallinckrodt Professor and Chair of Anesthesiology at Washington University School of Medicine in St. Louis, was interested in the end point for mortality in these studies. He pointed out that mortality after cardiac surgery may occur well after the 30-day window. “The effects of transfusion or the effects of hypoperfusion might be long term rather than short term,” he said.
“Most of the studies reported 30-day mortality,” Dr. Kashani said. “One reported six-month mortality and one reported 90-day mortality.”