Transfusion-Associated Delirium in Children: No Difference Between Short Storage Versus Standard Issue RBCs

Abstract

OBJECTIVES: Primary objective is to determine if transfusion of short storage RBCs compared with standard issue RBCs reduced risk of delirium/coma in critically ill children. Secondary objective is to assess if RBC transfusion was independently associated with delirium/coma. DESIGN:This study was performed in two stages. First, we compared patients receiving either short storage or standard RBCs in a multi-institutional prospective randomized controlled trial. Then, we compared all transfused patients in the randomized controlled trial with a single-center cohort of nontransfused patients matched for confounders of delirium/coma. SETTING: Twenty academic PICUs who participated in the Age of Transfused Blood in Critically Ill Children trial. PATIENTS:Children 3 days to 16 years old who were transfused RBCs within the first 7 days of admission. INTERVENTIONS:Subjects were randomized to either short storage RBC study arm (defined as RBCs stored for up to seven days) or standard issue RBC study arm. In addition, subjects were screened for delirium prior to transfusion and every 12 hours after transfusion for up to 3 days. MEASUREMENTS AND MAIN RESULTS:Primary outcome measure was development of delirium/coma within 3 days of initial transfusion. Additional outcome measures were dose-response relationship between volume of RBCs transfused and delirium/coma, and comparison of delirium/coma rates between transfused patients and individually matched nontransfused patients. We included 146 subjects in the stage I analysis; 69 were randomized to short storage RBCs and 77 to standard issue. There was no significant difference in delirium/coma development between study arms (79.5% vs 70.1%; p = 0.184). In the stage II analysis, adjusted odds for delirium in the transfused cohort was more than eight-fold higher than in the nontransfused matched cohort, even after controlling for hemoglobin (adjusted odds ratio, 8.9; CI, 2.8-28.4; p < 0.001).CONCLUSIONS: RBC transfusions (and not anemia) are independently associated with increased odds of subsequent delirium/coma. However, storage age of RBCs does not affect delirium risk.KEY WORDS: age of blood; Cornell assessment of pediatric delirium; delirium; pediatric critical care; red blood cell transfusions D elirium occurs frequently in the PICU (1). It is a behavioral syndrome defined as an acute and fluctuating change in awareness and cognition, which occurs as a direct result of the underlying medical condition or as a side effect of treatment (2). Pediatric delirium is strongly associated with substantial morbidity(3-7).

Association between Platelet Transfusion and Delirium in Critically Ill Children

“…In a retrospective study of adult cardiothoracic surgery patients, intra-operative platelet transfusion was independently associated with development of delirium [19]. This is also consistent with the RBC transfusion literature, where several studies showed a strong and independent association between RBC transfusion and the development of pediatric delirium [13,14]. Authors suggested a two-hit mechanism for this relationship: critically ill children had an ongoing inflammatory response due to their underlying illness, and the blood product transfusion then multiplied this pre-existing inflammatory response.…”

“…A systematic review of the studies on adults suggests that platelet transfusion potentiates the body's pro-inflammatory processes [12]. Two recent studies called on a similar inflammation-based mechanism for the development of pediatric delirium and found that RBC transfusions were independently and temporally associated with delirium development [13,14]. Given the lack of current research surrounding platelet transfusion and delirium, it remains unknown whether platelet transfusions play a pathophysiologic role in the development of pediatric delirium.…”

Delirium: The Next Vital Sign in the PICU?*

“…These contradictory findings to our current understanding should be corroborated in subsequent large-scale studies. In addition, there are a number of other previously identified risk factors for delirium that were not included in this meta-analysis: presence of significant organ dysfunction (e.g., congenital heart disease, liver failure, neurological disease), the extent of systemic inflammation, the extent of malnutrition and the use of blood products (16, 17). Hence, there may be a need for serial updates of this systematic review and meta-analysis as future studies are published.…”