Higher nocturnal and awake oxygen saturations in children with sickle cell disease receiving hydroxyurea therapy

Abstract

Rationale: Obstructive sleep apnea and intermittent nocturnal oxygen desaturations are highly prevalent in children with sickle cell disease and have been reported to contribute to associated morbidity, including vasoocclusive disease. Hydroxyurea (HU) is increasingly used to treat children with sickle cell disease and has been shown to decrease the number and severity of vasoocclusive crises. Although there has been an increase in the use of HU, the impact of HU on the prevalence of obstructive sleep apnea and nocturnal hypoxia are not well documented.

Objectives: To evaluate whether the use of HU is associated with a decreased frequency of obstructive sleep apnea and higher nocturnal and awake oxygen saturations (SaO2) in children with sickle cell disease.

Methods: This was a retrospective, cross-sectional review of children with sickle cell disease referred to the sleep laboratory at the Hospital for Sick Children, Toronto, Canada. Polysomnogram data in children with sickle cell disease receiving HU therapy were compared with those not prescribed HU.

Measurements and main results: Children with sickle cell disease receiving HU therapy (HU group, n = 37) were matched with children not receiving HU (no-HU group, n = 104). Obstructive sleep apnea was diagnosed in 14 of 37 (38%) and 54 of 104 (52%) in the HU group and no-HU groups, respectively (P = 0.14). The median obstructive apnea-hypopnea index was 0.9 and 1.9 events/h in the HU group and the no-HU group, respectively (P = 0.28). The HU group compared with the no-HU group had a significantly higher median awake SaO2 (98.6 and 96.2%, respectively; P < 0.0001), a significantly higher median sleep SaO2 (98.4 and 96.1%, respectively; P < 0.001), and a significantly higher nadir SaO2 while asleep (91.4 and 85.0%, respectively; P = 0.0002).

Conclusions: In children with sickle cell disease, the use of HU was associated with an increase in awake and nocturnal SaO2, despite there being no difference in the frequency of obstructive sleep apnea and the severity of the obstructive apnea-hypopnea index. Improving nocturnal SaO2 may be an important mechanism of action of HU therapy. The use of HU to improve nocturnal saturations across the severity spectrum of sickle cell disease may be beneficial in decreasing morbidities related to sickle cell disease.

Keywords: hydroxyurea; nocturnal oxygen saturations; obstructive sleep apnea.