Cerebral tissue hemoglobin saturation in children with sickle cell disease

Abstract

Background: Desaturation of hemoglobin (Hb) in cerebral tissue, a physiologic marker of brain vulnerable to ischemic injury, can be detected non-invasively by transcranial oximetry. Absolute cerebral oximetry has not been studied in sickle cell disease (SCD), a group at very high risk of cerebral infarction in whom prevention of brain injury is key.

Procedure: We measured absolute Hb saturation in cerebral tissue (S(CT)O(2)) in children with SCD using near-infrared spectrophotometry and investigated the contributions of peripheral Hb saturation (S(P)O(2)), hematologic measures, cerebral arterial blood flow velocity, and cerebral arterial stenosis to S(CT)O(2). We also assessed the effects of transfusion.

Results: We studied 149 children with SCD (112 HbSS/Sβ(0); 37 HbSC/Sβ(+)). S(CT)O(2) was abnormally low in 75% of HbSS/Sβ(0) and 35% of HbSC/Sβ(+) patients. S(CT)O(2) (mean ± SD) was 53.2 ± 14.2 in HbSS/Sβ(0) and 66.1 ± 9.2% in SC/Sβ(+) patients. S(CT)O(2) correlated with age, sex, Hb concentration, reticulocytes, Hb F, and S(P)O(2), but not transcranial Doppler arterial blood flow velocities as continuous measures. In multivariable models, S(P)O(2), Hb concentration, and age were significant independent determinants of S(CT)O(2). Cerebral vasculopathy was associated with ipsilateral cerebral desaturation. Transfusion increased S(CT)O(2) and minimized the inter-hemispheric differences in S(CT)O(2) due to vasculopathy.

Conclusions: Cerebral desaturation, a physiologic marker of at-risk brain, is common in SCD, more severe in HbSS/Sβ(0) patients, and associated with peripheral desaturation, more severe anemia, and increasing age. Cerebral oximetry has the potential to improve the identification of children with SCD at highest risk of neurologic injury and possibly serve as a physiologic guide for neuroprotective therapy.

Figure 1. Distribution of cerebral tissue hemoglobin saturation (S_CTO₂) by genotype group

Histograms of S_CTO₂ by right (Panel A) and left (Panel B) hemispheres, respectively, for the entire study population. Participants with sickle cell anemia and sickle-β⁰-thalassaemia (HbSS/Sβ⁰) are differentiated from those with sickle-hemoglobin C disease and sickle-β⁺-thalassemia (HbSC/Sβ⁺). Participants with HbSS/Sβ⁰ had lower S_CTO₂ than HbSC/Sβ⁺ participants in both hemispheres (Panel C). Box-plots depict Tukey’s hinges (box: 25-75^th percentiles with median; whiskers: 1.5 times the interquartile range) and outliers. Dotted lines indicate the upper (90%) and lower (65%) limits of S_CTO₂ for healthy children.

Figure 2. Cerebral tissue hemoglobin saturation (S_CTO₂) decreases with age

Distribution of S_CTO₂ by age groups of uniform width in participants with sickle cell anemia and sickle-β⁰-thalassaemia (HbSS/Sβ⁰) in the right (Panel A) and left (Panel B) hemispheres, respectively. Box-plots depict Tukey’s hinges (box: 25-75^th percentiles with median; whiskers: 1.5 times the interquartile range) and outliers. Dotted lines indicate the upper (90%) and lower (65%) limits of S_CTO₂ for healthy children.

Figure 3. Correlation between peripheral hemoglobin saturation (S_PO₂) and cerebral tissue hemoglobin saturation (S_CTO₂)

(Correlations between S_PO₂ and S_CTO₂ in the right (Panel A) and left (Panel B) hemispheres, respectively, for patients with sickle cell anemia and sickle-β⁰-thalassaemia (HbSS/Sβ⁰). Spearman ρ correlation coefficients are shown, and the lines depict the linear relationships between S_PO₂ and S_CTO₂.

Figure 4. Effect of transfusion on cerebral tissue hemoglobin saturation (S_CTO₂)

S_CTO₂ in the right (Panel A) and left (Panel B) hemispheres, respectively, before and after transfusion. S_CTO₂ increased significantly after transfusion on the left. Median values are shown for each group before and after transfusion. Dotted lines indicate the upper (90%) and lower (65%) limits of S_CTO₂ for healthy children.

Figure 5. Effects of vasculopathy and transfusion on cerebral tissue hemoglobin saturation (S_CTO₂)

Cerebral tissue is relatively desaturated on the side of occlusive sickle cerebral vasculopathy, but transfusion minimizes the difference between the sides. The graph shows the changes in S_CTO₂ on the right (red) and left (blue) during the course of transfusion. Magnetic resonance angiography is shown for both patients. Patient 1 has severe stenosis of the left internal carotid artery (arrows), and patient 2 has a completely occluded right internal carotid artery (arrows). The reasons for the differences in the shapes of the curves between patients is not known, but the response to transfusion in patient 2 suggests a threshold effect for perfusion of the anterior and middle cerebral artery watershed territories. That is, perhaps a small increase in total Hb or blood volume to some minimum critical value that occurred early in transfusion was sufficient to improve blood flow to certain blood vessels by overcoming steal or other abnormalities of cerebral autoregulation).