Use of older blood also is associated with an increased risk for kidney problems, acute respiratory distress and longer confinement to intensive care units, the researchers found.
The findings may hold important health implications, but they should be viewed with caution, the researchers said.
"We did find a significant association between older blood and adverse outcomes," said Elliott Bennett-Guerrero, M.D., a Duke anesthesiologist who was the study's lead investigator. "However, there have been no large, randomized clinical trials conducted to uncover links between age of transfused blood and patient outcomes, so we cannot say for certain that older blood causes the adverse effects we found in our study.
"Our results show that the number of transfusions given is a robust predictor of long-term mortality, and that the duration of storage also has independent adverse effects as well," he continued. "We believe our findings provide intriguing avenues for future study."
The researchers published their findings on June 22, 2006, in the journal Anesthesia & Analgesia. The study was supported by Duke University Medical Center and the Columbia University College of Physicians & Surgeons.
Patients routinely receive transfusions during and after surgery to replace lost blood. Of the 12 million units of blood administered to patients each year in the United States, more than 2 million units are transfused into heart surgery patients.
National blood banks require that blood can be stored for only 42 days after donation. After that time, unused blood must be discarded.
"Scientists have long known that red blood cells undergo significant changes during their storage, but little had been known about whether or not these changes have any clinical implications for patients," Bennett-Guerrero said.
Previous studies of lower risk cardiac surgical patients found a link between age of transfused blood and adverse outcomes, but no risk of increased mortality, Bennett-Guerrero said.
"We hypothesized that the effects of storage duration would be more pronounced in patients who are more likely to receive multiple blood transfusions, such as those undergoing a repeat open-heart procedure," he said.
Lower-risk heart patients use an average of two units of blood, compared to the current study's high-risk population that received an average of five units of blood. The more units of blood a patient receives increased the probability of receiving an older unit of blood, Bennett-Guerrero said.
For their study, the researchers retrospectively analyzed the medical files of 321 patients who underwent a repeat open-heart procedure for coronary artery bypass or valve replacement between 1995 and 2001 and who received donated blood during surgery or recovery.
The team correlated the clinical findings for each patient with the number and age of the units of blood the patient received, statistically adjusting for a host of patient characteristics such as age, obesity, other diseases, number of units received and hypertension. For comparison purposes, the researchers assigned patients into four groups, based on the age of the oldest unit of blood they received: 1-19 days, 20-26 days, 27-30 days, 31-42 days.
The researchers found that increasing age of the blood corresponded significantly with an increased risk of death. "In terms of mortality, kidney damage and length of stay in the intensive care unit and hospital, we saw the rate of risk increase with each successive quartile," Bennett-Guerrero said.
Specifically, the in-hospital mortality rate for patients who received the "freshest" blood was about 4 percent, compared with a 25 percent rate for patients in the oldest blood group. In terms of kidney damage, the rate increased from about 7 percent in the freshest blood group to almost 45 percent in the oldest group.
Also, patients in the freshest blood group spent an average of 3.5 days in the intensive care unit, compared to about 7 days for those in the oldest blood group. In terms of overall hospital stay, patients in the freshest blood group had a 12-day stay, compared to 17 days for the oldest group.
Of the 295 patients who were ultimately discharged from the hospital, 16 percent died within the follow-up period of up to eight years. The researchers found that after statistically accounting for a number of different factors, both the average age of the blood received, as well as the oldest unit of blood received, were independent predictors of mortality.
The study was not designed to uncover the actual physiological mechanisms that cause the observed health problems, Bennett-Guerrero said. But previous studies have hinted at a number of possibilities, he said. It is known, for example, that transfused blood loses oxygen-carrying ability over time. Transfused blood also may stimulate an immune response in its recipient and red blood cells become stiffer over time, which could affect their ability to fit into or move through capillaries and deliver oxygen, he added.
Other members of the team included Mark Stafford-Smith of Duke and Columbia researchers Sukhjeewan Basran, Robert Frumento, Allison Cohen, Samuel Lee, Yuling Du, Ervant Nishanian and Harold Kaplan.
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