Transfusion of packed red blood cells at the end of shelf life is associated with increased risk of mortality - a pooled patient data analysis of 16 observational trials

Abstract

Observational studies address packed red blood cell effects at the end of shelf life and have larger sample sizes compared to randomized control trials. Meta-analyses combining data from observational studies have been complicated by differences in aggregate transfused packed red blood cell age and outcome reporting. This study abrogated these issues by taking a pooled patient data approach. Observational studies reporting packed red blood cell age and clinical outcomes were identified and patient-level data sets were sought from investigators. Odds ratios and 95% confidence intervals for binary outcomes were calculated for each study, with mean packed red blood cell age or maximum packed red blood cell age acting as independent variables. The relationship between mean packed red blood cell age and hospital length of stay for each paper was analyzed using zero-inflated Poisson regression. Random effects models combined paper-level effect estimates. Extremes analyses were completed by comparing patients transfused with mean packed red blood cell aged less than ten days to those transfused with mean packed red blood cell aged at least 30 days. sixteen datasets were available for pooled patient data analysis. Mean packed red blood cell age of at least 30 days was associated with an increased risk of in-hospital mortality compared to mean packed red blood cell of less than ten days (odds ratio: 3.25, 95% confidence interval: 1.27-8.29). Packed red blood cell age was not correlated to increased risks of nosocomial infection or prolonged length of hospital stay.

Figure 1.

Outline of study selection. Fifty-six observational studies investigated the effects of PRBC storage duration on clinical outcomes, such as mortality, infection risk and hospital length of stay. Forty datasets were unavailable for various reasons: (1) no response from corresponding author after initial email, (2) lack of correspondence after initial contact, (3) institutional policy against data use by external investigators, (4) insufficient staff available to access data on site, (5) investigator retracted participation in study, and (6) other (e.g., data file corrupted). PRBC: packed red blood cells; yo: years old: RCT: randomized controlled trials.

Figure 2.

Forest plots and funnel plots for mortality analysis as a function of mean PRBC age. Mortality odds ratios were calculated for each study using logistic regression with mean PRBC age transfused as the independent variable. Age, sex and PRBC volume were covariates. (A) Odds ratios were then combined using random effects models. (B) Funnel plots were generated for each analyses to assess for publication bias. OR: odds ratio; CI: confidence interval.

Figure 3.

Forest plots for nosocomial infection analysis as a function of PRBC mean age. Nosocomial infection odds ratios were calculated for each study using logistic regression with mean PRBC age transfused as the independent variable. Age, sex and PRBC volume were entered into the model as covariates. Odds ratios were then combined using random effects models. OR: odds ratio; CI: confidence interval.