Red Blood Cell Distribution Width as a Pragmatic Marker for Outcome in Pediatric Critical Illness

<div><p>Background</p><p>Red cell distribution width (RDW) is a routine laboratory measure associated with poor outcomes in adult critical illness.</p><p>Objective</p><p>We determined the utility of RDW as an early pragmatic biomarker for outcome in pediatric critical illness.</p><p>Methods</p><p>We used multivariable logistic regression to test the association of RDW on the first day of pediatric intensive care unit (PICU) admission with prolonged PICU length of stay (LOS) >48 hours and mortality. The area under the receiver operating characteristic curve (AUROC) for RDW was compared to the Pediatric Index of Mortality (PIM)-2 score.</p><p>Results</p><p>Over a 13-month period, 596 unique patients had RDW measured on the first day of PICU admission. Sepsis was an effect modifier for LOS >48 hours but not mortality. In sepsis, RDW was not associated with LOS >48 hours. For patients without sepsis, each 1% increase in RDW was associated with 1.17 (95% CI 1.06, 1.30) increased odds of LOS >48 hours. In all patients, RDW was independently associated with PICU mortality (OR 1.25, 95% CI 1.09, 1.43). The AUROC for RDW to predict LOS >48 hours and mortality was 0.61 (95% CI 0.56, 0.66) and 0.65 (95% CI 0.55, 0.75), respectively. Although the AUROC for mortality was comparable to PIM-2 (0.75, 95% CI 0.66, 0.83; p = 0.18), RDW did not increase the discriminative utility when added to PIM-2. Despite the moderate AUROC, RDW <13.4% (upper limit of lower quartile) had 53% risk of LOS >48 hours and 3.3% risk of mortality compared to patients with an RDW >15.7% (lower limit of upper quartile) who had 78% risk of LOS >48 hours and 12.9% risk of mortality (p<0.001 for both outcomes).</p><p>Conclusions</p><p>Elevated RDW was associated with outcome in pediatric critical illness and provided similar prognostic information as the more complex PIM-2 severity of illness score. Distinct RDW thresholds best discriminate low- versus high-risk patients.</p></div

Multivariable association of RDW with PICU mortality.

<p>OR, odds ratio; CI, confidence interval; RDW, red blood cell distribution width; PICU, pediatric intensive care unit; PIM-2, pediatric risk of mortality-2</p><p>¹Analyses adjusted for the other variables listed</p><p>Multivariable association of RDW with PICU mortality.</p

Patient characteristics.

<p>RDW, red blood cell distribution width; MCV, mean corpuscular volume; PIM-2, Pediatric Index of Mortality-2</p><p>¹Data expressed as median (interquartile range) otherwise specified. IQR, interquartile range</p><p>²Statistical comparisons across RDW groups</p><p>³Anemia was defined as by World Health Organization criteria [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0129258#pone.0129258.ref022" target="_blank">22</a>]</p><p>⁴Comorbid conditions do not include the primary admission category.</p><p>⁵Includes all patients with a primary or comorbid hematologic/oncologic condition.</p><p>Patient characteristics.</p

Receiver operating characteristic curves for RDW and outcomes.

<p>Receiver operating characteristic (ROC) curves for RDW measured within 24 hours of PICU admission to predict PICU LOS >48 hours (a) and all-cause PICU mortality (b). AUROC is the area under the ROC curve.</p

Patient Selection.

<p>Flow diagram of patient selection for the study population.</p

Multivariable association of RDW with PICU LOS >48 hours.

<p>OR, odds ratio; CI, confidence interval; RDW, red blood cell distribution width; PICU, pediatric intensive care unit; PIM-2, pediatric risk of mortality-2</p><p>¹Analyses adjusted for the other variables listed</p><p>Multivariable association of RDW with PICU LOS >48 hours.</p

Comparison of receiver operating characteristic curves for RDW and PIM-2.

<p>Receiver operating characteristic (ROC) curves for RDW (solid black line), PIM-2 (dashed maroon line) and the combination of PIM-2 and RDW (dotted green line) to predict all-cause PICU mortality. There was no difference between the AUROC for RDW and PIM-2 (p = 0.18). The addition of RDW to PIM-2 did not increase the AUROC compared to PIM-2 alone (p = 0.49). AUROC is the area under the ROC curve.</p