RBC Distribution Width: Biomarker for Red Cell Dysfunction and Critical Illness Outcome?

Abstract

Objectives: RBC distribution width is reported to be an independent predictor of outcome in adults with a variety of conditions. We sought to determine if RBC distribution width is associated with morbidity or mortality in critically ill children.

Design: Retrospective observational study.

Setting: Tertiary PICU.

Patients: All admissions to St. Louis Children's Hospital PICU between January 1, 2005, and December 31, 2012.

Interventions: We collected demographics, laboratory values, hospitalization characteristics, and outcomes. We calculated the relative change in RBC distribution width from admission RBC distribution width to the highest RBC distribution width during the first 7 days of hospitalization. Our primary outcome was ICU mortality or use of extracorporeal membrane oxygenation as a composite. Secondary outcomes were ICU- and ventilator-free days.

Measurements and main results: We identified 3,913 eligible subjects with an estimated mortality (by Pediatric Index of Mortality 2) of 2.94% ± 9.25% and an actual ICU mortality of 2.91%. For the study cohort, admission RBC distribution width was 14.12% ± 1.89% and relative change in RBC distribution width was 2.63% ± 6.23%. On univariate analysis, both admission RBC distribution width and relative change in RBC distribution width correlated with mortality or the use of extracorporeal membrane oxygenation (odds ratio, 1.19 [95% CI, 1.12-1.27] and odds ratio, 1.06 [95% CI, 1.04-1.08], respectively; p < 0.001). After adjusting for confounding variables, including severity of illness, both admission RBC distribution width (odds ratio, 1.13; 95% CI, 1.03-1.24) and relative change in RBC distribution width (odds ratio, 1.04; 95% CI, 1.01-1.07) remained independently associated with ICU mortality or the use of extracorporeal membrane oxygenation. Admission RBC distribution width and relative change in RBC distribution width both weakly correlated with fewer ICU- (r = 0.038) and ventilator-free days (r = 0.05) (p < 0.001).

Conclusions: Independent of illness severity in critically ill children, admission RBC distribution width is associated with ICU mortality and morbidity. These data suggest that RBC distribution width may be a biomarker for RBC injury that is of sufficient magnitude to influence critical illness outcome, possibly via oxygen delivery impairment.

Figure 1. Consort diagram for cohort accrual

We screened all PICU admissions from January, 2005 through December, 2012. Using the VPS database, patients with admission diagnoses of anemia, malignancy, seizures or history of organ transplant were excluded. Repeat encounters were excluded as were those lacking admission laboratory data. We also excluded all who had received red blood cell transfusions during the 2-week period prior to PICU admission or 1 week after admission. CBC: complete blood count, VPS: virtual PICU systems.

Figure 2. RBC metrics for the sub-cohorts apportioned by A-RDW quartiles

Box and whisker plot of MCV, MCH and MCHC for the sub-cohorts apportioned by A-RDW quartiles. We observed a significant increase in MCV and decrease in MCHC in the 4^th A-RDW, while no difference was noted in MCH (One way ANOVA, p<0.001). MCH: mean corpuscular hemoglobin, MCHC: mean corpuscular hemoglobin concentration, MCV: mean corpuscular volume, A-RDW: red cell distribution width on ICU admission.

Figure 3

(A) Odds ratio for mortality or use of ECMO by univariate analysis. All patient variables were analyzed for association with mortality or the need for ECMO support. Odds ratios with 95% CI were calculated for all variables including: weight in kg, age in years, first systolic blood pressure on admission to the PICU, highest and lowest heart rates in the first 12 hours on admission to the PICU, PIM 2 score on admission to the PICU, number of ICU free and ventilator free days, CBC data: admission WBC count, admission RDW, highest RDW in first 7 days on admission to the PICU, relative change in RDW in the first 7 days on admission to the PICU, admission Hb, admission HCT, admission MCV, admission MCH, admission MCHC, admission RBC count, admission platelet count and admission MPV. (B) Odds ratio for mortality or use of ECMO by multivariate analysis. Odds ratios for death or the use of ECMO were repeated after controlling for PIM2. Both A-RDW and R-RDW continued to correlate with mortality or use of ECMO support, with OR of 1.127 and 1.037 respectively. ECMO: extracorporeal membrane oxygenation, PIM 2: pediatric index of mortality 2, WBC: white blood cell count, RDW: red cell distribution width, Hb: hemoglobin, HCT: hematocrit, MCV: mean corpuscular volume, MCH: mean corpuscular hemoglobin, MCHC: mean corpuscular hemoglobin concentration, RBC: red blood cell, MPV: mean platelet volume.

Figure 4

(A) Interquartile comparison of actual and estimated mortality and use of ECMO. There were significantly higher rates of all three outcomes in subjects in the 4^th A-RDW quartile as compared to those in the 1^st A-RDW quartile (t test). (B) Interquartile comparison of standardized mortality ratios. Standardized mortality ratios (ratio of actual/PIM2 estimated mortality) indicated that PIM2 overestimated mortality in subjects in the 1^st and 2^nd A-RDW quartiles and underestimated mortality in patients in the 3^rd and 4^th A-RDW quartiles, suggesting a relationship between A-RDW and patient outcome. Chi square and p values comparing observed and estimated mortality are tabulated. (C) Receiver operator characteristics curves for death or use of ECMO. Receiver operator characteristics curves for the incidence of death was calculated for A-RDW, PIM2 score and the combination of PIM2 and A-RDW. AUC was 0.611 for A-RDW, 0.901 for PIM2 and 0.904 for the combined model of A-RDW and PIM2. ECMO: extracorporeal membrane oxygenation, PIM2: Pediatric Index of Mortality 2, A-RDW: red cell distribution width on ICU admission, R-RDW: relative change in RDW.