Although anemia may cause an increase in morbidity and mortality rates in critically ill pediatric patients, transfusion of packed red blood cells (pRBCs) carries significant risks, which have also been demonstrated in pediatric cardiac surgery patients. However, studies related to these risks have had problems with confounding and the use of pRBCs that were not leukoreduced. Kneyber et al address these concerns in their study testing whether transfusion of leukocyte-depleted pRBCs within the first 48 hours after cardiac surgery would be independently associated with prolonged duration of mechanical ventilation. Results were published in the March 2013 issue of Pediatric Critical Care Medicine.

The authors used propensity score analysis to limit the confounding by indication or treatment selection bias that occurs when one attempts to distinguish a risk factor or a risk marker. In his accompanying editorial, Lacroix comments that the relationships between anemia, transfusion and severity of illness are so intertwined that only a randomized trial can determine the causal nature of transfusion and increased morbidity. However, the first step in determining whether a variable is the cause of morbidity involves the completion of a descriptive study that can establish significant associations.

Kneyber and colleagues retrospectively analyzed data from 335 children between the ages of 0 months to 18 years who underwent cardiac surgery between 2007 and 2010. Of these subjects, 111 were transfused, 86 of them within the first 48 hours of admission to the pediatric intensive care unit. The authors then compared the outcomes of these 86 patients to those of the 249 who were not transfused within 48 hours. Without adjusting for severity of illness, the patients who received pRBCs within the first 48 hours had a longer duration of ventilation and inotropic support, longer ICU stay, and a higher rate of ventilator-associated pneumonia. However, after adjusting for the severity of illness, the transfusion of pRBCs within the first 48 hours remained independently associated with only the prolonged duration of mechanical ventilation.

This study was not designed to explain the mechanisms behind these findings, though the immunomodulatory effects of transfused blood have been reported in the past and are cited in this work. For example, Cholette et al recently provided evidence of this in their prospective trial demonstrating increased interleukin-6 levels (a pro-inflammatory cytokine) in pediatric patients who underwent cardiopulmonary bypass and received unwashed pRBCs.

This retrospective, single-center observational study demonstrating the association between increased ventilator days and early transfusion in pediatric cardiac patients provides more evidence against arbitrary decisions to transfuse blood products. Prospective studies are necessary to determine which transfusion triggers will provide more benefit than cost.

This Concise Critical Appraisal is authored by SCCM member Daniel E. Sloniewsky, MD. Each installment highlights journal articles most relevant to the critical care practitioner.