Cerebral Tissue Desaturation in Children with Sickle Cell Disease
Authors: Quinn Charles T. , Hoof Pamela D. , Dowling Michael M. 
Published: October 2019

Abstract
Abstract 512

Background:
Children with sickle cell disease (SCD) frequently suffer silent and overt cerebral infarction. Current screening and prevention techniques are suboptimal. Absolute cerebral oximetry is a rapid, non-invasive technique to measure hemoglobin (Hb) saturation in the brain. Cerebral tissue Hb saturation (SCTO2) is a physiologic measurement of the balance between oxygen supply and demand that could be used to identify regions of the brain at highest risk of infarction. We aimed to describe the distribution of SCTO2 in children with SCD and to identify its relationships with clinical, laboratory, and neuroimaging characteristics as well as response to transfusion.

Methods:
We used transcutaneous near-infrared spectrophotometry (CASMED FORE-SIGHT®) with bi-frontal probes to measure absolute SCTO2 in children with sickle cell anemia (SS), sickle-β0-thalassemia (Sβ0), sickle hemoglobin C disease (SC), and sickle-β+-thalassemia (Sβ+) during steady-state clinic visits or at the time of transfusion for stroke prophylaxis. Spearman correlation and multivariable modeling were used to test the relationships between SCTO2 and age, sex, genotype, Hb concentration, percent Hb F, percent reticulocytes, peripheral Hb saturation (SPO2), and cerebral arterial blood flow velocities by transcranial Doppler ultrasonography (TCD).

Results:
We studied 149 children (112 SS/Sβ0; 37 SC/Sβ+) with a mean age of 6.6±4.7 years (±S.D.). SCTO2 is known to be 65–80% in normoxic individuals with normal hemoglobin type and concentration breathing room air, but we found SCTO2 to be markedly lower in SCD: 53.2±14.2 (mean±SD) in SS/Sβ0 and 66.1±9.2% in SC/Sβ+ patients. SCTO2 was abnormally low (<65%) in 75% of SS/Sβ0 and 35% of SC/Sβ+ patients. SCTO2 correlated significantly with age (Spearman ρ=-0.54, P<0.001), sex (0.38, P<0.001), Hb concentration (0.38, P<0.001), percent reticulocytes (-0.3, P=0.002), percent Hb F (0.37, P<0.001), and SPO2 (0.4, P<0.001), but not TCD velocities as continuous measurements. However, when TCD velocities were categorized according to STOP criteria (abnormal and conditional vs. normal), SCTO2 was lower when the TCD velocity in the ipsilateral distal internal carotid artery was not normal (right-sided SCTO2: 39.2% for abnormal and conditional TCD vs. 57% for normal TCD, P=0.027). In multivariable models, the significant independent determinants of SCTO2 were SPO2 (P=0.004), Hb concentration (P=0.004), and age (P<0.001). Each unit decrease (1% absolute) in SPO2 gave an odds ratio of 1.4 or 1.5 for an abnormally low (<25th percentile) SCTO2 in the left and right hemispheres, respectively (AUC 0.84; P<0.001). Transfusion increased SCTO2 by 15.3% (absolute) on the left (P=0.002) and 23.6% (absolute) on the right (P=0.06). Two participants had severe unilateral cerebral vasculopathy demonstrated by magnetic resonance angiography. Both had a lower pre-transfusion SCTO2 on the side of the stenosis or occlusion (5-20% lower). The SCTO2 rose during the course of transfusion (10-30% absolute rise in SCTO2), and by the end of the transfusion the right- and left-sided SCTO2 measurements equalized.

Conclusions:
Cerebral tissue Hb desaturation is common in children with SCD and more severe in the SS/Sβ0 genotypes. Cerebral desaturation is associated with peripheral Hb desaturation, more severe anemia, increasing age, and occlusive vasculopathy, and it is ameliorated by transfusion. Cerebral desaturation, which can be detected rapidly and non-invasively, is a physiologic biomarker of brain at risk for ischemic injury. Cerebral oximetry should be studied further as a physiologic means to predict stroke and guide transfusion therapy for the prophylaxis of stroke in SCD.

Disclosures:
No relevant conflicts of interest to declare.