Should we avoid transfusion in the pediatric intensive care unit?

I n this issue of Pediatric Critical Care Medicine, Church et al (1) report the results of descriptive retrospective clinical research that they undertook to determine whether, in critically ill children with acute lung injury (ALI), the administration of red blood cell (RBC), plasma, and/or platelets given 72 hours after the diagnosis of ALI had been recognized, was associated with increased mortality. All patients with ALI hospitalized from 1996 to 2000 in two pediatric intensive care units (PICU) were considered for inclusion: 315 met the diagnostic criteria of ALI advocated by the American European Consensus Committee. The mortality rate was 27% (41 of 152) in children who received at least one transfusion, whereas it was 17% (28 of 163) in those who did not (p 0.04). The association between transfusion of plasma and mortality is quite strong in the study of Church et al (1); it remains statistically significant even after adjustment for some imbalance at baseline. The data in the literature are not so strong, probably because the association is not so well studied. An association between transfusion of platelets and mortality is also reported by Church et al (1), but the association was weaker than with plasma and did not stand up in the multivariate analysis. The risk of mortality attributable to platelet transfusion in the PICU is not well characterized presently. The association between transfusion of RBC and mortality is weak in the study of Church et al (1), but it is quite strong in the literature (2, 3). For example, in the randomized clinical trial conducted by Hébert et al (4), there was more hospital mortality among critically ill adults allocated to a liberal transfusion strategy than in those allocated to a restrictive strategy (28.1% vs. 22.2% respectively, p 0.05). How can transfusion worsen in the patient with ALI? The data of Church et al (1) suggest that a transfusion can aggrevate the respiratory system: the number of ventilator-free days dropped from 17 11 in nontransfused to 12 10 in transfused patients (p 0.01). There is more and more evidence that transfusion of RBC, plasma, and platelets can cause transfusion-associated respiratory dysfunction (TARD), also named transfusion-associated dyspnea by the European Hemovigilance Network. Many mechanisms can be involved in cases of TARD. TARD can be caused by transfusionassociated cardiac overload, the most frequent transfusion reaction according to the Canadian blood monitoring system (5), a systemic inflammatory reaction syndrome (there are always some white blood cells in cellular blood components, as well as many inflammatory mediators and other molecules with adverse effects [6]), transfusion-related acute lung inujry ALI (TRALI, the most important cause of transfusion-related deaths in the United States and Canada [7]), active allergic reaction (the receiver develops its own antibodies [8]), passive allergic reaction (the reaction is caused by antibodies from the donor [9]), etc. Plasma is possibly the main culprit for most TARD. Therefore, even blood products like platelets and RBC, which contain significant volume of plasma (6), may cause similar reactions; on the other hand, a lower volume of plasma may explain why those products did not show a statistically significant association with mortality in the study of Church et al (1). The incidence of transfusion reactions in critically ill children has been studied recently (10), but TARD was not specifically addressed in this study. That children with ALI are more prone to contract TARD remains to be determined. What are the indications for transfusions in PICU patients? Some intensivists believe that more RBC transfusions must be given to critically ill patients with respiratory dysfunction (11, 12). Is this a good idea in patients with ALI? There is no doubt that the transfusion of RBC, plasma, and/or platelets can save the life of some patients. However, there is evidence suggesting that a transfusion can increase the risk of death in other patients. Accordingly, the indications for transfusion must be reviewed. Up to 50% of critically ill children receive an RBC transfusion while in the PICU (12). This proportion can be decreased. A randomized clinical trial, the Transfusion Requirements in PICUs study, showed that a restrictive strategy (RBC transfusion only if the hemoglobin level drops below 7 g/dL) is safe in stable critically ill children (13); the rule should be to adopt such restrictive transfusion strategy, and the study by Church et al (1) suggests that this may be true also for children with ALI. In the PICU, platelet concentrates are usually given to prevent or to treat bleeding in patients with low platelet count or with dysfunctional platelets. Plasma is used to treat disseminated intravascular coagulation, to restore the blood concentration of deficient coagulation factors associated with massive transfusion or some diseases, for rapid reversal of warfarin effect, to prevent bleeding when a surgical or an invasive procedure is planned, or as a volume expander. Plasma is also used as replacement fluid in some plasma exchanges performed to treat thrombotic thrombocytopenic purpura (TTP). Furthermore, plasmapheresis and plasma exchange are advocated by some intensivists to treat septic shock and multiple organ dysfunction syndrome (14). The indications for platelets and plasma transfusion in the PICU are not well supported by good clinical research; more researches are required, including randomized clinical trials. Plasma is not recommended as a volume expander, and it should not be used for such a purpose. We congratulate Church et al for their study, the first looking at critically ill children with ALI receiving transfusions. As stated by the authors, although associations between blood product transfusions and outcomes of pediatric patients *See also p. 297.