WHAT THIS REPORT ADDS:

• In patients with intermediate hemoglobin levels, discretionary transfusion should be carefully considered, as the risks are marked, the benefits are unclear, and alternatives are available.

ORLANDO, FLA—The likelihood that a critically ill patient will receive an allogenic blood transfusion varies greatly among hospitals—and among physicians. “That kind of variability means that a lot of transfusions are just capricious,” argued Robert L. Thurer, MD, at the recent annual meeting of the American College of Chest Physicians in Orlando.[1] In fact, he added, it suggests that “we do not know what we are doing.”

There is some justification for the variability in practice, acknowledged Dr. Thurer, an Associate Professor of Surgery at Harvard Medical School in Boston. Medical and surgical ICU patients today are older and sicker than were the patients in most of the published trials of transfusion use. Thus, it is difficult to determine the extent to which the results of those trials can be extrapolated to current practice. Nevertheless, there is sufficient evidence to permit some conclusions to be drawn.

Most physicians, said Dr. Thurer, would agree that transfusions are unnecessary for patients with a hemoglobin level above 9 g/dL and necessary for those with levels below 7 or 8 g/dL. For the patients in the middle, transfusions are discretionary.

Do the benefits of discretionary transfusions outweigh their known risks? Allogenic blood transfusions are expensive, tend to promote inflammation, and may transmit infections. These risks would be reasonable if transfusions markedly improved patient outcomes (as they do in those with extremely low hemoglobin levels). But there is little or no evidence that discretionary transfusions benefit patients. In one study, for example, postoperative blood delivery to patients with a hemoglobin level of 8 or 9 g/dL had no effect on a variety of outcomes, including the rates of cardiac, neurologic, pulmonary, renal, and infectious complications.

In fact, some evidence suggests that discretionary transfusions may be harmful. Another study, which randomized critically ill patients with a hemoglobin level of 7 to 9 g/dL to either a liberal or a restrictive transfusion strategy, found that 30-day mortality was higher in the patients given larger amounts of donor blood.

A third study of patients who underwent coronary artery bypass grafting found that five-year mortality was more than twice as high in those who received perioperative blood transfusions than in those who did not (15% vs 7%, respectively). Even after the authors adjusted for demographic variables and comorbidities, transfusion was still associated with a 70% rise in five-year mortality.

These findings may seem counterintuitive, given the many investigations that have shown that higher hemoglobin levels are associated with better outcomes. “But getting there by transfusion may not be the thing to do,” Dr. Thurer concluded.

IS THE BLOOD SUPPLY SAFE?

Public health officials are claiming that the blood supply is safer than ever, and that probably is true, said Richard K. Spence, MD. Nevertheless, blood transfusions can have a number of deleterious consequences, cautioned Dr. Spence, Chief of Surgery at St. Agnes HealthCare in Baltimore. Perhaps the best way to think about transfusions, he added, is as “liquid organ transplants.”

The current estimated incidence of transfusion-related HIV infection, for example, is one or two in one million. However, other infections, including malaria, hepatitis B or C, and West Nile virus may be transmitted through transfusion; there have also been reports of bacteria, parasites, and prions being transmitted through blood.

Infection may be the least of the risks associated with allogenic transfusions, though. Many well-performed studies have linked such transfusions to higher rates of disease recurrence and decreased survival in cancer patients, pointed out Dr. Spence. Blood recipients may also develop transfusion-related acute lung injury (TRALI), a rare condition involving dyspnea, hypotension, pulmonary edema, and fever. The development of TRALI has been linked with white blood cell antibodies in donor plasma and with biologically active lipids that accumulate in stored red blood cells and platelets.

Immunomodulation is another possible effect of blood transfusions. The transfusions may trigger the systemic inflammatory response syndrome or even multiorgan failure if they increase the circulation of inflammatory cytokines. For example, interleukin-8 accumulates in stored blood as the leukocytes break down; it is also released by the body in response to free hemoglobin in transfused blood.

Some researchers believe that transfusion can lead to microchimerism, a condition in which the blood recipient harbors small amounts of the donor’s genetic material. Microchimerism has been implicated in the development of autoimmune disease and may possibly increase the risk of non-Hodgkin’s lymphoma and chronic lymphocytic leukemia.

Plasma filtration, leukoreduction, and other techniques are available to minimize transfusion-related risks by purifying donor blood. However, it is unrealistic to expect blood transfusion to be completely risk-free because there will always be human error, Dr. Spence asserted.

ALTERNATIVES TO TRANSFUSION

One way to avert the risks and costs of blood transfusion is simply to avoid the procedure whenever possible. Avoidance is usually fairly safe and well tolerated even for patients with a low hemoglobin level, stated Aryeh Shander, MD, Chief of Anesthesiology and Critical Care at Englewood Hospital and Medical Center in New Jersey.

Acutely low hemoglobin value has no central nervous system effects and is associated with acceptable cardiac outcomes as long as the patient is euvolemic, closely monitored, and not tachycardic. Furthermore, said Dr. Shander, it is possible to maintain tissue oxygen tension even after a 60% drop in hemoglobin, as long as the patient is perfused with a high viscosity fluid or colloid. He added that healthy individuals have been shown not to develop oxygen supply dependency when their hemoglobin falls from 13 g/dL to 4.5 or 5 g/dL.

Acute normovolemic hemodilution, cell salvage, and strict indications for blood replacement are a few of the methods used to reduce the need for blood transfusion. “Clearly, recombinant erythropoietin should be on everyone’s mind as the first drug of choice to treat anemia in patients who do not need to be transfused,” said Dr. Shander. Although recombinant erythropoietin is usually given preoperatively, it can be used during surgery in trauma and obstetrics cases, he noted.

“The time is coming when we may see the approval of an artificial oxygen carrier,” Dr. Shander predicted. These oxygen carriers “have a potency that is three times greater than that of your own hemoglobin.” Also, artificial oxygen carriers have a shelf life of up to two years and do not need refrigeration. They can be used regardless of blood type and carry no infection risk.

Adverse reactions may nonetheless occur. For example, rats treated with perfluorocarbon oxygen carriers have been shown to have a greatly increased work of breathing; organ toxicity has been reported after transfusion with a bovine hemoglobin-based oxygen carrier (HBOC). Methemoglobin production, GI symptoms, hypertension, myocardial infarction, and cerebrovascular accident are other possible side effects of HBOC.

—Timothy Begany

Reference
1. Thurer RL, Spence R, Shander A. The cardiopulmonary and critically ill patient and blood transfusion: current status. Presented at: annual meeting of the American College of Chest Physicians; October 29, 2003; Orlando, Fla.

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