Nocturnal hypoxaemia and central-nervous-system events in sickle-cell disease

Background Central-nervous-system (CNS) events, including strokes, transien t ischaemic attacks, and seizures are common in sickle-cell disease. Stroke can be predicted by high velocities in the internal-carotid or middle-cere bral arteries on transcranial doppler ultrasonography. We tested the hypoth esis that nocturnal hypoxaemia can predict CNS events better than clinical or haematological features, or transcranial doppler sonography. Methods We screened 95 hospital-based patients with sickle-cell disease (me dian age 7.7 years [range 1.0-23.1]), but without previous stroke, with tra nscranial doppler and overnight pulse oximetry. Follow-up continued for a m edian of 6.01(0.11-8.54) years. Findings 19 patients had CNS events (six ischaemic and one haemorrhagic str oke, eight transient ischaemic attacks, and four seizures). Mean overnight oxygen saturation ([SaO(2)] hazard ratio 0.82 per 1% increase [95% CI 0.71- 0.93]; p=0.003) and higher internat-carotid or middle-cerebral artery veloc ity (1.02 for every increase of 1 cm/s [1.004-1.03]; p=0.009) were independ ently associated with time to CNS event. After accounting for mean SaO(2), artery velocity, and haemoglobinopathy, high haemoglobin concentration was also associated with an increased risk of CNS event (1.7 per g/dL, [1.18-2. 43]; p=0.004). Dips suggestive of obstructive sleep apnoea did not predict CNS events, and adenotonsillectomy seemed to have no effect, although the C I were wide and clinically important effects cannot be excluded. Interpretation Screening for, and appropriate management of, nocturnal hypo xaemia might be a safe and effective alternative to prophylactic blood tran sfusion for primary prevention of CNS events in sickle-cell disease.