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A Lower Hemoglobin Transfusion Threshold Is Safe for Stable Critically Ill Children

Question

  • In stable, critically ill children, would using a lower hemoglobin threshold for transfusion compared to standard thresholds lead to a similar rate of mortality and morbidity?

Clinical Bottom Lines
1. A lower hemoglobin threshold for transfusion was not inferior to hemoglobin thresholds generally used.
2. The study suggests that using a hemoglobin level of 7 g/dl for a transfusion threshold led to a significant decrease in the number of transfusions compared to 9.5 g/dl, and did not lead to an increase in multiple organ dysfunction, death, nosocomial infections, adverse events, or duration of intensive care unit (ICU) stay.


Summary of Key Evidence
1. A randomized control non-inferiority trial1 was performed on 637 stable, critically ill children who had hemoglobin concentrations below 9.5 g/dl within 7 days after admission to the ICU.
2. Patients were considered stable if they were not hypotensive (mean arterial pressure not less than 2 standard deviations below the mean for age), or the cardiovascular intervention did not increase for at least two hours prior to enrollment.
3. Exclusion criteria included, but were not limited to, acute blood loss, platelet dysfunction, hemolytic anemia, predicted survival less than 24 hours, inability to obtain blood products, or receiving more significant interventions, such as ECMO, hemofiltration, exchange transfusion, or plasmapheresis.
4. Patients were randomized to a restrictive transfusion strategy with a threshold of 7 g/dl versus a liberal transfusion strategy with a threshold of 9.5 g/dl
5. Baseline characteristics were not different between the two groups with respect to age, weight, severity of illness, mechanical ventilation, and number of transfusions prior to randomization.
6. There was no significant difference in the number of patients with new or progressive multiple organ dysfunction syndrome (MODS) (ARR 0.4 [-4.6 to 5.5]), with a 44% reduction in transfusions in the restrictive-strategy group.
7. There was no significant difference between the secondary outcomes of severity of organ dysfunction (p = 0.87), death (p = 0.98), nosocomial infections (p = 0.16), at least one adverse event (p = 0.59), reactions to red-cell transfusion (p = 0.34), and duration of ICU stay (p = 0.39).
8. Unfortunately, the study was not blinded to the randomization groups, and the protocol could be temporarily suspended based on the attending physician’s decision, which led to an significant increase in the number of patients transfused in the restrictive-strategy group during this suspension (39 vs. 20 patients, p = 0.01)

Additional Comments

  • A prospective, observational trial2 found that 33% of children were anemic on admission to the pediatric ICU, and 41% developed anemia. Blood draws accounted for 73% of daily blood loss.
    • A randomized control trial3 on critically ill adult patients showed that a restrictive transfusion threshold of 7.0 g/dl was non-inferior to a liberal transfusion threshold of 10 g/dl and possibly superior for less acutely ill patients.
    • However, the adult trial did not use leukocyte reduced blood, while the pediatric trial did, which may have led to less morbidity related to transfusions in the liberal transfusion strategy group.

Citation

1. Lacroix J et al. Transfusion strategies for patients in pediatric intensive care units. New England Journal of Medicine. 2007; 356: 1609-1619.
2. Bateman ST et al. Anemia, blood loss, and blood transfusions in North American children in the intensive care unit. American Journal of Respiratory and Critical Care Medicine. 2008; 178: 26-33.
3. Hébert PC et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. New England Journal of Medicine. 1999; 340: 409-417.
CAT Author: <Kevin Smith, MD

CAT Appraisers: Kevin Smith, MD

Date appraised: January 28, 2009

Last updated June 15, 2009
Department of Pediatrics and Communicable Diseases
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