Effects of hydroxyurea treatment on cerebral oxygenation in adult patients with sickle cell disease: an open-label pilot study

Abstract

In patients with sickle cell disease (SCD), cerebral oxygen saturation (rSO(2)) has been reported to be below normal and to increase after red blood cell transfusion. This study was designed to determine the effects of long-term and short-term hydroxyurea (HU) treatment on cerebral oxygenation in patients with SCD. This open-label pilot study was conducted at the Department of Anesthesiology and the Center for Sickle Cell Disease, College of Medicine, Howard University, Washington, DC. Adult African American outpatients with SCD and hemoglobin (Hb) genotype HbSS (homozygous sickle Hb) who were receiving long-term (>6 months) HU treatment (15-30 mg/kg . d PO) or who had never received this treatment (control group) were enrolled. Patients in the treated and control groups were matched for age, sex, race, and Hb genotype. Cerebral oximetry (near-infrared spectroscopy) was performed to determine rSO(2) index. In a separate analysis to determine the effects of short-term HU treatment on cerebral oxygenation, hospitalized patients with SCD and vaso-occlusive crisis (VOC)receiving long-term therapy with HU were enrolled. We performed cerebral and pulse (fingernail) oximetry to determine rSO (2)index and arterial oxygen saturation (SpO(2)) after the administration of a single oral dose of HU (500-mg tablet) alone and again after dosing concomitantly with inhaled oxygen. The study enrolled 11 patients in the HU group (6 women, 5 men; mean [SD] age, 37 [8] years) and 20 controls (8 women, 12 men; mean [SD] age, 35 [6] years). Mean (SD) rSO(2) index was significantly increased (but still low) in patients receiving long-term HU treatment compared with controls (46.1% [6.6%] vs 41.2% [7.6%]; P< 0.025). Hb concentration (9.6 [1.4] g/dL vs 8.5 [1.2] g/dL; P< 0.027), hematocrit (28% [3%] vs 24% [4%]; P < 0.028), and mean corpuscular volume (102% [7%] vs 89% [8%]; P < 0.027) also were significantly higher in the HU group compared with controls. In 8 patients with SCD and VOC (6 men, 2 women; mean [SD] age, 28 [5] years), single-dose HU, either alone or in combination with inhaled oxygen, did not significantly affect cerebral oxygenation, and SpO(2) failed to correlate with rSO(2) index in these patients. The results of this open-label pilot study in patients with SCD suggest that the low cerebral oxygenation in these patients is significantly improved but not normalized with long-term HU treatment. A single dose of HU, either alone or in combination with inhaled oxygen, did not appear to influence cerebral oxygenation in patients with VOC.