It has been reported that anesthetics influence the autoregulation of brain vessels differently. Ketamine, an NMDA receptor antagonist, is used for analgesia as well as general anesthesia and is known to effect rCBF. In this study PET-measurements using 15O-butanol were done to quantify regional cerebral blood flow (rCBF) in detail during three levels of ketamine anesthesia. Eight healthy male volunteers aged 30 ± 3 yrs were examined. After bolus injections of 550 MBq of the freely diffusible rCBF tracer 15O-butanol each subject was scanned four times: during waking state (WS) and three different levels of ketamine application with dosages of 0.1, 0.38, and 1.5 mg S-ketamine per kg body weight. The three levels were antinociception (ANOC), analgesia (ANAL), and deep anesthesia (DA). 8 Hz flicker light was applied as reference stimulus in all scans. PET-scanning was done with a Siemens scanner HR+ in 3D mode for 101 sec per condition and was accompanied by continuous arterial blood sampling. In addition, pCO2, pSaO2, systolic blood pressure (SBP), and heart rate (HR) were monitored. Time-radioactivity data of the reconstructed PET-images (all corrections done) were obtained for whole cerebrum (WC), frontal (FC), anterior cingulate (ACC), parietal (PC), and visual (VC) cortex, thalamus (TH), and cerebellum (CB). Applying the one-tissue compartment model of CBF and corrections for delay and dispersion of the blood data, rCBF was determined by non-linear curve fitting. pCO2 did not decreased significantly from 41.0 ± 4.0 mmHg for WS to 37.9 ± 4.3 mmHg for DA. pSaO2 remained unchanged, whereas SBP and HR became significantly greater by 10% and 41%, respectively. During WS global cerebral CBF was 54.7 ± 4.6 ml/min/100 g and increased slightly to 59.1 ± 8.9 ml/min/100 g at ANOC. When ANAL and DA were reached, cerebral CBF changed considerably by 49% and 88% to finally 103 ± 23.8 ml/min/100 g. Cerebellar rCBF increased much less by 30% and 55% at ANAL and DA, respectively. Whereas rCBF of the different cortical areas became greater by less than 24% from WS to ANOC, it increased by at least 39% at ANAL and 81% at DA - except for VC. During DA the activation in VC caused by the visual stimulation did not only disappear, but rCBF of VC became 30% lower than the global cerebral CBF. The greatest changes were observed in FC and ACC: from 65.7 ± 7.6 to 146.7 ± 32.5 ml/min/100 g and from 60.0 ± 11.8 to 171.6 ± 44.6 ml/min/100 g, respectively. rCBF of PC and TH during DA was only 111.6 ± 34.1 and 128.5 ± 37.3 ml/min/100 g, respectively. This study reports detailed quantitative data on the effect of ketamine on rCBF which have not been available for humans until now. When the dosage of ketamine was increased to 0.37 mg/kg, so that the analgetic level was invoked, rCBF of all brain regions examined here except the visual cortex is significantly augmented with the greatest increases in the frontal and anterior cingulate cortex.
