The effect of clonidine infusion on distribution of regional cerebral blood flow in volunteers.
BACKGROUND
Through their action on the locus coeruleus, alpha2-adrenoceptor agonists induce rapidly reversible sedation while partially preserving cognitive brain functions. Our goal in this observational study was to map brain regions whose activity is modified by clonidine infusion so as to better understand its loci of action, especially in relation to sedation.


METHODS
Six ASA I-II right-handed volunteers were recruited. Electroencephalogram (EEG) was monitored continuously. After a baseline H2(15)O activation scan, clonidine infusion was started at a rate ranging from 6 to 10 microg x kg(-1) x h(-1). A sequence of 11 similar scans was then performed at 8 min intervals. Plasma clonidine concentration was measured. Using statistical parametric mapping, we sought linear correlations between normalized regional cerebral blood flow (rCBF), an indicator of regional brain activity, and plasma clonidine concentration or spindle EEG activity.


RESULTS
Clonidine induced clinical sedation and EEG patterns (spindles) comparable to early stage nonrapid eye movement sleep. A significant negative linear correlation between clonidine concentration and rCBF or spindle activity was observed in the thalamus, prefrontal, orbital and parietal association cortex, posterior cingulate cortex, and precuneus.


CONCLUSIONS
The EEG patterns and decreases in rCBF of specific brain regions observed during clonidine-induced sedation are similar to those of early stage nonrapid eye movement sleep. Patterns of deactivated brain regions are also comparable to those observed during general anesthesia or vegetative state, reinforcing the hypothesis that alterations in the activity of a common network occur during these modified conscious states.
Bonhomme
Vincent
V
University Department of Anesthesia and Intensive Care Medicine, CHU de Liege and CHR de la Citadelle, 4000 Liege, Belgium. vincent.bonhomme@chu.ulg.ac.be
Maquet
Pierre
P
Phillips
Christophe
C
Plenevaux
Alain
A
Hans
Pol
P
Luxen
Andre
A
Lamy
Maurice
M
Laureys
Steven
S
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage* / Q000097:blood; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects*; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003000:Clonidine / Q000008:administration & dosage* / Q000097:blood; D003071:Cognition / Q000187:drug effects; D003243:Consciousness / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000097:blood; D007262:Infusions, Intravenous; D008297:Male; D049268:Positron-Emission Tomography; D012123:Pulmonary Ventilation / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D012107:Research Design; D013997:Time Factors
D000316:Adrenergic alpha-Agonists; D006993:Hypnotics and Sedatives; D003000:Clonidine