Page 145 - 2018_09-Mondo

Old PRBCs linked to increased mortality across 16 studies
datasets were unavailable (Online Supplementary Table S1). Received datasets included higher proportions of studies conducted in Europe (56.25% versus 25.00%) and ICU patients (31.25% versus 12.50%) compared to excluded studies. Unavailable datasets included higher proportions of studies conducted in the Americas (70.00% versus 25.00%) and trauma patients (32.50% versus 6.25%). Excluded studies also had increased rates of associations between PRBC age versus nosocomial infection (56.26% versus 12.50%) and HLOS (42.86% versus 25.00%).
There were significant variations in demographic, treat- ment and outcome variables released by investigators (Online Supplementary Tables S2-S4). Age (n=15), sex (n=14) and PRBC volume (n=16) transfused were the most consistently reported demographic variables across stud- ies. Mortality (n=16), any infection (n=10) and HLOS (n=12) were the most commonly reported outcome vari- ables.
Mean PRBC age >30 days associated with an increased risk of in-hospital mortality
Thirteen datasets contained the required covariate (age, sex, PRBC volume) and outcome data required for mortal- ity analyses. These datasets covered 14,867 patients and 58,272 transfusions. There was no evidence of a signifi- cant association between mean PRBC age and post-trans- fusion in-hospital mortality (OR: 0.99, 95% CI: 0.98-1.00) (Figure 2). Similarly, there was no association between maximum transfused PRBC age and post-transfusion in- hospital mortality (OR: 1.00, 95% CI: 0.98-1.01, Online Supplementary Figure S5). There was substantial hetero- geneity in both analyses with I2 values of 63.6% and 59.0%, respectively. Sensitivity analyses demonstrated that effects estimates were similar across geographic loca- tion and patient subgroups (Online Supplementary Figure S6). Funnel plots for both analyses suggest that publica- tion bias was not a significant concern. Time-lapse analy- ses demonstrated a trend of increasing OR in favor of fresh PRBCs from 1980-2011 (Online Supplementary Figure S7). Extremes analyses associated mean PRBC stored for at least 30 days with increased in-hospital mortality risk, as compared to mean PRBC stored for less than ten days (OR: 3.25, 95% CI: 1.27-8.29, Table 3). This association persisted in patients who received leukoreduced PRBCs (OR: 2.74, 95% CI: 1.39-5.36, Table 3).
No association between PRBC age and nosocomial infection
Eight datasets were incorporated in the nosocomial infection analyses covering 2716 patients. Mean PRBC age (OR: 0.99, 95% CI: 0.97-1.02, Figure 3) and maximum
PRBC age (OR: 1.00, 95% CI: 0.96-1.04, Online Supplementary Figure S8) transfused were not correlated to nosocomial infection. There was moderate heterogeneity in both analyses with I2 values of 42.5% and 28.6%, respectively. Stratifying analyses by geographical location and patient subgroup did not significantly alter effect esti- mates (Online Supplementary Figure S9). Funnel plots were not constructed as less than ten datasets were analyzed. Nosocomial infection ORs remained consistent across recruitment periods on time lapse analyses (Online Supplementary Figure S10). Extremes analyses did not iden-
Table 2. Demographic features of patients in aggregate dataset.
Demographic Characteristic
Age (years; mean)*
<40 years old (count, %) 40-65 years old (count, %) >65 years old (count, %)
Sex (male; count, %)
Mean volume of PRBC transfused (units)*
>10 units (count, %)
Mean age of PRBC transfused (days)*
<5 days (count, %) 5-14 days (count, %) >20 days (count, %)
Clinical setting
Cardiac surgery (count, %) General surgery (count, %) Acute medicine (count, %) Intensive care unit (count, %) Orthopedic surgery (count, %) Other (count, %)
Geographic location
The Americas (count, %) Europe (count, %) Middle East (count, %) ANZ (count, %)
PRBC dataset (n=17,967)
57.82 ± 0.17 3094 (17.2) 6425 (35.8) 8146 (45.3) 9865 (54.9) 4.34 ± 0.04 1462 (8.1) 16.9 ± 0.12 2771 (15.4) 3399 (18.9) 5010 (27.4) 675 (19.2) 13.92 ± 0.15 3441 (18.8) 7418 (40.5) 2790 (15.2)
4403 (24.0) 412 (2.2) 9967 (54.4) 757 (4.1) 871 (4.8) 1904 (10.4)
1863 (12.5) 7258 (48.8) 1695 (11.4) 4051 (27.3)
<10 days (count, %)
≥ 30 days (count, %)
In-hospital mortality (count, %) Nosocomial infection rate (count, %) Average HLOS
Table 3. Odds ratios from extremes analysis for in-hospital mortality and nosocomial infection risk as a function of mean PRBC age. Patient age, PRBC volume and sex are entered as covariates in the logistic model.
Independent variable
Mean PRBC age
Mortality
Mortality (LR)
Odds ratio 95% CI
2.74* 1.39-5.37
Nosocomial infection
*All means presented ± standard error of the mean.ANZ:Australia and New Zealand: PRBC: packed red blood cells; HLOS; hospital length of stay.
Odds ratio
3.25*
95% CI
1.27-8.29
Odds ratio
1.57
95% CI
0.39-6.27
0.98-1.02 0.86-1.08 1.45-2.74
Patient age
PRBC volume
Sex
*=statistically significant (P<0.05). 95% CI: 95% confidence intervals; LR: leukoreduced patients only; PRBC: packed red blood cell.
1.02* 1.03 1.14
1.01-1.03 0.98-1.07 0.90-1.45
1.03* 1.02-1.03 1.02 0.97-1.07 1.16 0.92-1.47
1.00
0.97 1.99*
haematologica | 2018; 103(9)
1545