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Anesthesiology. 2015 Jan;122(1):140-9. doi: 10.1097/ALN.0000000000000510.

Disruption of cortical connectivity during remifentanil administration is associated with cognitive impairment but not with analgesia.

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From the Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark (A.K.-R. S.S.O., C.G., L.P.M., A.M.D.); The Multidisciplinary Pain Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark (G.P.K.); Section of Palliative Medicine, Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark (G.P.K., P.S.); Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (L.L.C.); Department of Electrical and Computer Engineering, McMaster University, Hamilton, Ontario, Canada (A.K.-R.); and Center for Sensory-Motor Interactions (SMI), Department of Health Science and Technology, Aalborg University, Aalborg, Denmark (A.M.D.).



The authors investigated the effect of remifentanil administration on resting electroencephalography functional connectivity and its relationship to cognitive function and analgesia in healthy volunteers.


Twenty-one healthy male adult subjects were enrolled in this placebo-controlled double-blind cross-over study. For each subject, 2.5 min of multichannel electroencephalography recording, a cognitive test of sustained attention (continuous reaction time), and experimental pain scores to bone-pressure and heat stimuli were collected before and after infusion of remifentanil or placebo. A coherence matrix was calculated from the electroencephalogram, and three graph-theoretical measures (characteristic path-length, mean clustering coefficient, and relative small-worldness) were extracted to characterize the overall cortical network properties.


Compared to placebo, most graph-theoretical measures were significantly altered by remifentanil at the alpha and low beta range (8 to 18 Hz; all P < 0.001). Taken together, these alterations were characterized by an increase in the characteristic path-length (alpha 17% and low beta range 24%) and corresponding decrements in mean clustering coefficient (low beta range -25%) and relative small-worldness (alpha -17% and low beta range -42%). Changes in characteristic path-lengths after remifentanil infusion were correlated to the continuous reaction time index (r = -0.57; P = 0.009), while no significant correlations between graph-theoretical measures and experimental pain tests were seen.


Remifentanil disrupts the functional connectivity network properties of the electroencephalogram. The findings give new insight into how opioids interfere with the normal brain functions and have the potential to be biomarkers for the sedative effects of opioids in different clinical settings.

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