Assessment of cerebral oxygenation using near infra-red spectroscopy in obstructive sleep apnoea and chronic obstructive pulmonary disease
This thesis describes a set of studies of the use of near infrared spectroscopy to measure cerebral oxygenation in obstructive sleep apnea (OSA) and chronic hypoxia. Cerebral oxygenation depends on cerebral blood flow and arterial oxygen saturation. The hypothesis underlying these studies was whether measurement of cerebral oxygenation using near infra-red spectroscopy (MRS) gives additional valid information compared to measuring arterial oxygen saturation alone. We also hypothesized that this technique could be used to assess overnight cerebral oxygenation in sleep studies. Our first validation study in 13 subjects with significant OS A showed that the fall in cerebral tissue saturation (measured as tissue oxygenation index, TO I) during sleep apnoea is related to arterial saturation (Sa02) (p=0.012), apnoea duration (p=0.001) and sleep stage (p<0.001) in a multiple regression in 1036 apnoeas. We also demonstrated changes in cerebral blood volume (range 0.41 - 0.09 ml/lOOg) and cytochrome oxidase oxidation state (range 0.48 - 0.13uM) occurring during apnoeas in 8 of these subjects. In a second validation study in 8 subjects we demonstrated correlations between changes in TOI and both arterial saturation (p=0.001), apnoea duration (p=0.001) and cerebral blood flow velocity (p=0.012) measured using carotid Doppler. We derived area under the curve (AUC) measures and dip rates for TOI and Sa02 during overnight studies and compared them to conventional polysomnographic measures, showing significant correlations of pretreatment apnoea hypopnoea index (AHI) with dip rates for both TOI and Sa02. AUC TOI correlations with pretreatment AHI were weak. Mean AUC for TOI was 339.4 (161-675) and mean AUC for Sa02 was 308.5 (89-944). Mean 4% Sa02 dip rate was 32.6 (1.5-90.6) and mean 4% TOI dip rate was 24 (0.1-95.7). Pilot studies were also carried out on 11 subjects with chronic obstructive pulmonary disease (COPD) during oxygen challenge. Calculated cerebral blood volume measurements varied from 1.51 ml/lOOg to 3.65 ml/lOOg. Changes in TOI in response to supplementary oxygen in patients with COPD and chronic hypoxia are related to both cerebral blood volume (p=0.001) and arterial saturation (p=0.001). The most important new findings in these studies are that cerebral blood flow changes appear to exacerbate rather than compensate for arterial hypoxia during sleep apnoea, and so it is plausible that TOI measurement (which picks up both Sa02 and cerebral blood flow velocity (CBFV) changes) may be more closely related to changes in neuropsychological function than pulse oximetry. The changes in cerebral oxygenation are profound enough to affect intracerebral redox state measured as cytochrome oxidase oxidation. Pilot work in COPD patients suggests that changes in cerebral blood volume affecting cerebral oxygenation occur during supplementary oxygen administration. NIRS provides a non-invasive method of measuring cerebral oxygenation suitable for use in sleep studies, and during oxygen administration.