Restrictive Red Cell Transfusion in Pediatric ICUs Found Safe

MONTREAL, April 18 -- In stable critically ill children, a lower hemoglobin level plus leukocyte-reduced red cells was found as safe for transfusion as a higher level, found researchers here.

The red-cell "transfusion trigger" of 7 g/dL, versus 9.5 g/dL, decreased transfusion requirements without increasing adverse outcomes, Jacques Lacroix, M.D., of the University of Montreal, and colleagues, in the April 19 issue of the New England Journal of Medicine.

The optimal hemoglobin threshold for erythrocyte transfusions in critically ill children is unknown, he wrote.

The researchers in the Transfusion Requirements in the Pediatric Intensive Care Unit (TRIPICU) trial postulated that in stable, critically ill children using red cells that have been filtered to remove leukocytes and then stored in the usual manner would substantially reduce the inflammatory effects of transfusions without worsening organ dysfunction.

Low death rates in pediatric ICUs precluded the use of death as an endpoint, with multiple organ dysfunction serving as a meaningful primary outcome, according to the investigators.

In a noninferiority trial, 637 stable critically ill children (three days old to 14 years) were enrolled with hemoglobin concentrations below 9.5 g/dL within seven days after admission to an ICU. Patients were enrolled from 19 tertiary-care pediatric ICUs in four countries.

Of the patients, 320 in the restrictive-strategy group were randomly assigned to a hemoglobin threshold of 7 g/dL for red-cell transfusion, while and 317 in the liberal-strategy group were randomized to a threshold of 9.5 g/dL.

Hemoglobin concentrations were maintained at a mean (SD) level that was 2.10.2 g/dL lower in the restrictive-strategy group than in the liberal-strategy group. The lowest average levels were 8.70.4 g/dL and 10.80.5 g/dL, respectively (P

Despite the increased number of suspensions, there was still a significant reduction in the number of red-cell units transfused in the restrictive group, they said.

Although outcomes in a trial of critically ill adults differed from these pediatric findings, critically ill adults may be more vulnerable to adverse consequences of red-cell transfusions, Dr. Lacroix said. Also, the trial did not use prestorage leukocyte-reduced red cells, he added. Leukocytes in transfused red cells may generate cytokines and activate an inflammatory response.

This trial had at least one limitation, the researchers pointed out, and that was the inability to determine a meaningful change in death rates. However, they said, a composite of death or progressive organ failure was used as relevant to pediatricians.

"We recommend a restrictive transfusion strategy in pediatric patients whose condition is stable in the ICU," the researchers wrote.

This recommendation, Dr. Lacroix added, "is not applicable to premature infants, older adults, patients with coronary artery disease, or children with severe hypoxemia, hemodynamic instability, active blood loss, or cyanotic heart disease."

In an accompanying editorial Howard L. Corwin, M.D., of Dartmouth-Hitchcock Medical Center in Lebanon, N.H., and Jeffrey L. Carson, M.D., of the University of Medicine and Dentistry of New Jersey called the study by Dr. Lacroix and colleagues a "notable advance" in the study of red-cell transfusion in children, with "implications for understanding the role of such transfusions in all critically ill patients."

Red-cell transfusion has always made sense to physicians when a hemoglobin concentration is low, particularly in sick patients. The validity of this idea, they said, has driven transfusion practice for much of the past century and frequently does today.

However, they said, the weight of evidence does not support unrestricted use of red-cell transfusion in critically ill patients.

Instead, they wrote, a transfusion trigger of 7.0 g/dL for most critically ill adults and children appears appropriate. A higher threshold might be indicated for patients with cardiovascular disease, pending the completion of further clinical trials.

"Red-cell transfusion should no longer be regarded as 'may help, will not hurt' but rather, should be approached as 'first, do no harm,'" Drs. Corwin and Carson concluded.

Of the editorialists, Dr. Corwin reported receiving grant support and consulting and lecture fees from Ortho Biotech and Johnson & Johnson Pharmaceutical Research Development. Dr. Carson reported receiving grant support from Ortho Biotech.