Cerebral Tissue Desaturation in Children with Sickle Cell Disease

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 (S CT O 2 ) 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 S CT O 2 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 S CT O 2 in children with sickle cell anemia (SS), sickle-β 0 -thalassemia (Sβ 0 ), 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 S CT O 2 and age, sex, genotype, Hb concentration, percent Hb F, percent reticulocytes, peripheral Hb saturation (S P O 2 ), and cerebral arterial blood flow velocities by transcranial Doppler ultrasonography (TCD). Results: We studied 149 children (112 SS/Sβ 0 ; 37 SC/Sβ + ) with a mean age of 6.6±4.7 years (±S.D.). S CT O 2 is known to be 65–80% in normoxic individuals with normal hemoglobin type and concentration breathing room air, but we found S CT O 2 to be markedly lower in SCD: 53.2±14.2 (mean±SD) in SS/Sβ 0 and 66.1±9.2% in SC/Sβ + patients. S CT O 2 was abnormally low ( 0 and 35% of SC/Sβ + patients. S CT O 2 correlated significantly with age (Spearman ρ=-0.54, P P O 2 (0.4, P CT O 2 was lower when the TCD velocity in the ipsilateral distal internal carotid artery was not normal (right-sided S CT O 2 : 39.2% for abnormal and conditional TCD vs. 57% for normal TCD, P=0.027). In multivariable models, the significant independent determinants of S CT O 2 were S P O 2 (P=0.004), Hb concentration (P=0.004), and age (P P O 2 gave an odds ratio of 1.4 or 1.5 for an abnormally low ( th percentile) S CT O 2 in the left and right hemispheres, respectively (AUC 0.84; P CT O 2 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 S CT O 2 on the side of the stenosis or occlusion (5-20% lower). The S CT O 2 rose during the course of transfusion (10-30% absolute rise in S CT O 2 ), and by the end of the transfusion the right- and left-sided S CT O 2 measurements equalized. Conclusions: Cerebral tissue Hb desaturation is common in children with SCD and more severe in the SS/Sβ 0 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.