In the present study, we used positron emission tomography to investigate changes in regional cerebral blood flow (rCBF) during a general anesthetic infusion set to produce a gradual transition from the awake state to unconsciousness. Five right-handed human volunteers participated in the study. They were given propofol with a computer-controlled infusion pump to achieve three stable levels of plasma concentrations corresponding to mild sedation, deep sedation, and unconsciousness, the latter defined as unresponsiveness to verbal commands. During awake baseline and each of the three levels of sedation, two scans were acquired after injection of an H215O bolus. Global as well as regional CBF were determined and correlated with propofol concentrations. In addition, blood flow changes in the thalamus were correlated with those of the entire scanned volume to determine areas of coordinated changes. In addition to a generalized decrease in global CBF, large regional decreases in CBF occurred bilaterally in the medial thalamus, the cuneus and precuneus, and the posterior cingulate, orbitofrontal, and right angular gyri. Furthermore, a significant covariation between the thalamic and midbrain blood flow changes was observed, suggesting a close functional relationship between the two structures. We suggest that, at the concentrations attained, propofol preferentially decreases rCBF in brain regions previously implicated in the regulation of arousal, performance of associative functions, and autonomic control. Our data support the hypothesis that anesthetics induce behavioral changes via a preferential, concentration-dependent effect on specific neuronal networks rather than through a nonspecific, generalized effect on the brain.

This work evaluated kinetic analysis methods for estimation of the receptor availability of the muscarinic receptor using dynamic positron emission tomography (PET) studies with [N-(11)C-methyl]-benztropine. The study also investigated the effect of propofol on central muscarinic receptor availability during general anesthesia. Six volunteers were scanned three times, once for baseline while awake, once during unconsciousness, and once after recovery to conscious level. An irreversible two-tissue compartment model was used to estimate the [N-(11)C-methyl]-benztropine specific binding rate constant k(3), a measure of muscarinic receptor availability. Two different estimation methods were used: 1) optimization with positivity constraints on all the parameters; 2) optimization with additional constraints determined from a one-tissue compartment fit to the cerebellum. In regions with low to middle muscarinic receptor density, the k(3) values from method (2) had lower standard errors than that for method (1) and gave a higher correlation with the density of muscarinic receptors measured in human tissue by in vitro studies (r(2) of 0.98 for Method 2 and r(2) of 0.72 for Method 1). But the k(3) values determined by Method 2 had higher errors for regions with high muscarinic receptor density compared to Method 1. For both methods the mean k(3) values during unconsciousness were generally lower than those during awake for most regions evaluated. Therefore, the method with additional constraints derived from the cerebellum (Method 2) was deemed superior for regions with low to middle muscarinic receptor density, while the method with positivity constraint is the better choice in the regions with high muscarinic receptor density. Our results also suggest the existence of propofol-related reductions in muscarinic receptor availability.

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Introduction. The purpose of the study was to determine the hemodynamic effects and conditions of ventilation and tracheal intubation after paralysis with either rocuronium (R) or vecuronium (V) during induction of anesthesia with moderate dose fentanyl. Patients and Methods. After IRB approval and written consent, 20 patients undergoing coronary artery surgery were randomized to receive, in a blinded fashion, ILI mg/kg (n= IlL or V, 015 mg/kg (n = 9). Premedication was with Iorazepam. Anesthesia was induced with an infusion of fentanyl, 0. I ug/kg/min, followed by a bolus of 15 ug/kg. The muscle relaxant was given 90 sec after the fentanyl induction, and the trachea was intubated 90 sec later. Ease of bag-mask ventilation was evaluated every 15 seconds before and after the relaxant. Tracheal intubating conditions were evaluated according to jaw relaxation, status of vocal cords, and cough/buck response. Train of four monitoring of the facial nerve-orbicularis oculis muscle was done. Data were compared between groups with Student's t test and the Cochran-ManteI-Haenzel test. A p value < 0.05 was considered significant. Results. Demographics and hemodynamics were similar between groups. Compared with V, patients receiving R were easier to ventilate, had faster loss of TOF, and better overall intubating conditions (Table) Discussion. During conditions of the study, R produced similar hemodynamics and better conditions for bag-mask ventilation and tracheal intubation compared with V.