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Older stored blood transfused into patients undergoing
repeat heart surgery is associated with a significant increased
risk of death, both during a patient's hospital stay and over
the longer term following discharge, according to a new
analysis by researchers from Duke University Medical Center and
Columbia University.

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.