BackgroundThe precise mechanism and optimal measure of anesthetic-induced unconsciousness has yet to be elucidated. Preferential inhibition of feedback connectivity from frontal to parietal brain networks is one potential neurophysiologic correlate, but has only been demonstrated in animals or under limited conditions in healthy volunteers.Methods and FindingsWe recruited eighteen patients presenting for surgery under general anesthesia; electroencephalography of the frontal and parietal regions was acquired during (i) baseline consciousness, (ii) anesthetic induction with propofol or sevoflurane, (iii) general anesthesia, (iv) recovery of consciousness, and (v) post-recovery states. We used two measures of effective connectivity, evolutional map approach and symbolic transfer entropy, to analyze causal interactions of the frontal and parietal regions. The dominant feedback connectivity of the baseline conscious state was inhibited after anesthetic induction and during general anesthesia, resulting in reduced asymmetry of feedback and feedforward connections in the frontoparietal network. Dominant feedback connectivity returned when patients recovered from anesthesia. Both analytic techniques and both classes of anesthetics demonstrated similar results in this heterogeneous population of surgical patients.ConclusionsThe disruption of dominant feedback connectivity in the frontoparietal network is a common neurophysiologic correlate of general anesthesia across two anesthetic classes and two analytic measures. This study represents a key translational step from the underlying cognitive neuroscience of consciousness to more sophisticated monitoring of anesthetic effects in human surgical patients.

A5 as an early variable of clot firmness is effective in detecting critically low PLT and Fib. A5 can therefore be a reliable fast index guiding transfusion therapy in hypocoagulable patients undergoing LDLT.

Summary Reducing blood loss is beneficial in living liver donor hepatectomy. Although it has been suggested that maintaining a low central venous pressure is important, it is known that low stroke volume variation may be associated with increased blood loss. Therefore, we compared the effect on blood loss of 40 patients randomly assigned to a high stroke volume variation group (maintaining 10–20% of stroke volume variation) vs 38 patients in a control group (maintaining < 10% stroke volume variation) during living‐donor right hepatectomy. Mean (SD) blood loss during donor hepatectomy was significantly lower in the high stroke volume variation group than in the control group: 476 (131) ml vs 836 (341) ml, respectively (p < 0.001). Blood pressure and peri‐operative laboratory values did not differ between the two groups. However, in the high stroke volume variation group, central venous pressure values were also significantly lower. We were unable to disentangle the effects of stroke volume variation and central venous pressure, but our results confirm that the two together appear beneficial.

We examined the antiallodynic interaction between gabapentin and adenosine A1 receptor agonist, N6-(2-phenylisopropyl)-adenosine R-(-)isomer (R-PIA), in a rat model of nerve ligation injury. Rats were prepared with ligation of left L5-6 spinal nerves and intrathecal catheter implantation for drug administration. Mechanical allodynia was measured by applying von Frey filaments. Gabapentin and R-PIA were administered to obtain the dose-response curve and the 50% effective dose (ED50). Fractions of ED50s were administered concurrently to establish the ED50 of the drug combination. The drug interaction between gabapentin and R-PIA was analyzed using the isobolographic method. Adenosine A1 receptor antagonist was administered intrathecally to examine the reversal of the antiallodynic effect. Locomotor function changes were evaluated by rotarod testing. Intrathecal gabapentin and R-PIA and their combination produced a dose-dependent antagonism against mechanical allodynia without severe side effects. Intrathecal gabapentin synergistically enhanced the antiallodynic effect of R-PIA when coadministered. There were no significant changes in rotarod performance time, except gabapentin 300 μg. In the combination group, the maximal antiallodynic effect was reversed by A1 adenosine receptor antagonist. These results suggest that activation of adenosine A1 receptors at the spinal level is required for the synergistic interaction on the mechanical allodynia.

Background: Studies investigating the correlation between spinal adenosine A1 receptors and vincristine-induced peripheral neuropathy (VIPN) are limited. This study explored the role of intrathecal N6-(2-phenylisopropyl)-adenosine R-(-)isomer (R-PIA) in the rat model of VIPN. Methods: Vincristine (100 μg/kg) was intraperitoneally administered for 10 days (two 5-day cycles with a 2-day pause) and VIPN was induced in rats. Pain was assessed by evaluating mechanical hyperalgesia, mechanical dynamic allodynia, thermal hyperalgesia, cold allodynia, and mechanical static allodynia. Biochemically, tumor necrosis factor-alpha (TNF-α) level and myeloperoxidase (MPO) activity were measured in the tissue from beneath the sciatic nerve.Results: Vincristine administration resulted in the development of cold allodynia, mechanical hyperalgesia, thermal hyperalgesia, mechanical dynamic allodynia, and mechanical static allodynia. Intrathecally administered R-PIA (1.0 and 3.0 μg/10 μl) reversed vincristine-induced neuropathic pain (cold and mechanical static allodynia). The attenuating effect peaked 15 min after intrathecal administration of R-PIA after which it decreased until 180 min. However, pretreatment with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10 μg/10 μl) 15 min before intrathecal R-PIA administration significantly attenuated the antiallodynic effect of R-PIA. This antiallodynic effect of intrathecal R-PIA may be mediated through adenosine A1 receptors in the spinal cord. Intrathecally administered R-PIA also attenuated vincristine-induced increases in TNF-α level and MPO activity. However, pretreatment with intrathecal DPCPX significantly reversed this attenuation.Conclusions: These results suggest that intrathecally administered R-PIA attenuates cold and mechanical static allodynia in a rat model of VIPN, partially due to its anti-inflammatory actions.

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Background : Licorice, a core traditional herbal medicine, is frequently coadministered with the conventional medications in Korea. Several reports suggested that the licorice treatment induced the cytochrome P450 (CYP) in rats, especially for CYP3A isoform. However, no report has been addressed to the effect of licorice on midazolam, CYP3A substrate, in human. This study was performed to evaluate the effect of licorice on the disposition and pharmacodynamic effects of midazolam in human. Methods : One gram of freeze dried water extract of licorice (extraction ratio ; 25%) or placebo were orally administered divided in two times to 10 healthy male subjects for 7 days as one blind randomized crossover manner with 2 weeks washout. On the day after completion of 7 days pretreatment, multiple blood samples were drawn and urine was collected for 24 hours after oral dose of 7.5 mg midazolam. Psychomotor performance tests including digit span test and digit symbol substitution test were conducted for 4 hours after midazolam administration on each phase of midazolam treatment and before pretreatment of placebo or licorice extract. The plasma concentration of midazolam and 1-hydroxymidazolam were determined with using HPLC and pharmacokinetic parameters were estimated by noncompartmental method. Results : After 1 week treatment of licorice extract, the plasma clearance of midazolam was significantly increased (1.15+0.50 vs 1.59+0.81 L/min, p<0.05) and the half-life was shortened (2.07+0.74 vs 1.34+0.60 hr, p<0.05) compared to those obtained after placebo treatment. Mean AUC of midazolam was decreased from 102.13+28.84 ng/ml•hr to 85.06+48.51 ng/ml•hr after licorice treatment, but not significantly different (p=0.11). There was no significant changes in AUC and urinary amount of 1-hydroxymidazolam by licorice pretreatment. The changes in the score of psychomotor performance tests (DST and DSST) measured after midazolam dosing were not significantly different between placebo and licorice pretreatment. Conclusions : Licorice water extract seems to affect the disposition of midazolam in human, but it is suggested that the CYP3A4 induction is not the major mechanism of the interaction. Further studies are remained to evaluate the mechanism of the pharmacokineitc interaction between midazolam and licorice water extract.

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