Alteration of coupling between brain and heart induced by sedation with propofol and midazolam

Abstract

For a comprehensive understanding of the nervous system, several previous studies have examined the network connections between the brain and the heart in diverse conditions. In this study, we identified coupling between the brain and the heart along the continuum of sedation levels, but not in discrete sedation levels (e.g., wakefulness, conscious sedation, and deep sedation). To identify coupling between the brain and the heart during sedation, we induced several depths of sedation using patient-controlled sedation with propofol and midazolam. We performed electroencephalogram (EEG) spectral analysis and extracted the instantaneous heart rate (HR) from the electrocardiogram (ECG). EEG spectral power dynamics and mean HR were compared along the continuum of sedation levels. We found that EEG sigma power was the parameter most sensitive to changes in the sedation level and was correlated with the mean HR under the effect of sedative agents. Moreover, we calculated the Granger causality (GC) value to quantify brain-heart coupling at each sedation level. Additionally, the GC analysis revealed noticeably different strengths and directions of causality among different sedation levels. In all the sedation levels, GC values from the brain to the heart (GC(b -> h)) were higher than GC values from the heart to the brain (GC(h -> b)). Moreover, the mean GC(b -> h) increased as the sedation became deeper, resulting in higher GC(b -> h) values in deep sedation (1.97 +/- 0.18 in propofol, 2.02 +/- 0.15 in midazolam) than in pre-sedation (1.71 +/- 0.13 in propofol, 1.75 +/- 0.11 in midazolam; p < 0.001). These results show that coupling between brain and heart activities becomes stronger as sedation becomes deeper, and that this coupling is more attributable to the brain-heart direction than to the heart-brain direction. These findings provide a better understanding of the relationship between the brain and the heart under specific conditions, namely, different sedation states.