Byung Moon Choi

The directionality and functional organization of frontoparietal connectivity during consciousness and anesthesia in humans

Frontoparietal connectivity has been suggested to be important in conscious processing and its interruption is thought to be one mechanism of general anesthesia. Data in animals demonstrate that feedforward processing of information may persist during the anesthetized state, while feedback processing is inhibited. We investigated the directionality and functional organization of frontoparietal connectivity in 10 human subjects anesthetized with propofol on two separate occasions. Multichannel electroencephalography and a computational method of assessing directed functional connectivity were employed. We demonstrate that directed feedback connectivity is diminished with loss of consciousness and returns with responsiveness to verbal command. We also applied the Dendrogram classification method to assess the global organization of directed functional connectivity during consciousness and anesthesia. We demonstrate a state-specific hierarchy and subject-specific subhierarchy in functional organization. These data support the hypothesis that specific states of human consciousness are defined by specific states of frontoparietal connectivity.

Propofol induction reduces the capacity for neural information integration: implications for the mechanism of consciousness and general anesthesia.

The cognitive unbinding paradigm suggests that the synthesis of neural information is attenuated by general anesthesia. Here, we analyzed the functional organization of brain activities in the conscious and anesthetized states, based on functional segregation and integration. Electroencephalography (EEG) recordings were obtained from 14 subjects undergoing induction of general anesthesia with propofol. We quantified changes in mean information integration capacity in each band of the EEG. After induction with propofol, mean information integration capacity was reduced most prominently in the gamma band of the EEG (p=.0001). Furthermore, we demonstrate that loss of consciousness is reflected by the breakdown of the spatiotemporal organization of gamma waves. We conclude that induction of general anesthesia with propofol reduces the capacity for information integration in the brain. These data directly support the information integration theory of consciousness and the cognitive unbinding paradigm of general anesthesia.

Pharmacokinetics and pharmacodynamics of propofol microemulsion and lipid emulsion after an intravenous bolus and variable rate infusion.

Background:The aim of this trial was to evaluate the induction and recovery characteristics of microemulsion propofol (Aquafol; Daewon Pharmaceutical Co., Ltd., Seoul, Korea). Pharmacokinetics, pharmacodynamics, and safety profile were investigated. Lipid emulsion propofol (Diprivan®; AstraZeneca, London, United Kingdom) was used as a comparator. Methods:Thirty-one healthy volunteers aged 20–79 yr were given an intravenous bolus of propofol 2 mg/kg, followed by variable rate infusion for 60 min. Each volunteer was studied twice with different formulations at an interval of 1 week. Arterial concentrations of propofol were measured, and Bispectral Index was used as a surrogate measure of propofol effect. The induction and recovery characteristics including bioequivalence were evaluated by noncompartmental analysis. The pharmacokinetics and pharmacodynamics were investigated using a population approach with mixed effects modeling. The rate, severity, and causal relation of adverse events were analyzed. Results:Both formulations were bioequivalent. The observed time to peak effect after a bolus of both formulations was 1.5 min. Plasma concentration of propofol at loss of consciousness, time to loss of consciousness after a bolus, and time to recovery of consciousness after discontinuation of infusion did not show significant differences. The population pharmacokinetics and pharmacodynamics revealed a variety of differences between two formulations. Aquafol showed similar safety profile to Diprivan®. Conclusions:The efficacy and safety of Aquafol were not different from those of Diprivan® within the dose range in this study.

The time-course and RNA interference of TNF-α, IL-6, and IL-1β expression on neuropathic pain induced by L5 spinal nerve transection in rats

Background The objective of this study was to investigate the time-course of the expression of TNF-α, IL-6, and IL-1β after L5 spinal nerve transection (SNT), and to determine the effect of small interfering RNA (siRNA) targeting these cytokines on neuropathic pain. Methods Rats received control siRNA (CON group, n = 80) or a cocktail of siRNAs targeting these cytokines (COCK group, n = 70). The siRNAs were given via intrathecal catheter 1 d prior to SNT, on the operation day, and 1, 2 and 3 d postoperatively. Behavioral tests and levels of the cytokine mRNAs and proteins as well as glial cell activity were following the L5 SNT. Results In the CON group, TNF-α and IL-1β mRNA levels increased immediately after SNT and remained high for 6 d, while IL-6 transcripts only began to increase after 12 h. TNF-α and IL-1β mRNA levels in the COCK group were lower than in the CON group at all time points (P < 0.05). In the behavioral tests, allodynia and hyperalgesia were significantly lower in the COCK group from 2 d after SNT (P < 0.05). Conclusions The time courses of TNF-α, IL-6 and IL-1β mRNA expression after L5 SNT differ. RNA interference may be a method of reducing the development of mechanical allodynia and hyperalgesia in response to nerve injury.

The optimal concentration of siRNA for gene silencing in primary cultured astrocytes and microglial cells of rats.

Background Small interfering RNAs (siRNAs) have been used to knockdown specific gene expression in various cells. Astrocytes and microglial cells play a key role in fundamental central nervous system functions and in chronic neuroinflammation. The aims of this study were to determine the optimal concentration of siRNA demonstrating efficient transfection and inhibition of gene expression via RNA interference (RNAi) and lower cytotoxicity, in primary cultured astrocytes and microglial cells of rats. Methods Astrocytes and microglial cells were isolated from the cerebral cortices of 2-day-old rats. Both the cells were transfected using transfection reagent (Lipofectamine™ 2000), and fluorescein-labeled double-stranded RNA (dsRNA) or siRNA targeting green fluorescent protein. Transfection efficiency and cytotoxicity of dsRNA, and the degrees of RNAi induced by siRNA in these cells, were evaluated at various concentrations of RNA. Results Transfection efficiencies of dsRNA in both astrocytes and microglial cells were significantly higher (P < 0.05) at the concentrations of 20, 40, and 80 nM than at the concentrations of 0, 5, and 10 nM. There were no significant cytotoxicities within the applied concentrations of dsRNA (0-80 nM). The degrees of RNAi induced by siRNA were significantly higher (P < 0.05) at the concentrations of 5, 10, 20, 40, 80 nM, and 20, 40, 80 nM in astrocytes and microglial cells, respectively, compared with the control (0 nM). Conclusions The siRNA concentration of 20 nM may be appropriate to induce RNAi in both astrocytes and microglial cells, while demonstrating low cytotoxicity, high transfection efficiency, and effective RNAi.

A new therapeutic option for postoperative pain management with oxycodone HCI injection

Fentanyl is the most commonly used opioid analgesic in intravenous patient-controlled analgesia (IV PCA) in Korea. IV oxycodone was approved for postoperative IV PCA by the Ministry of Food and Drug Safety of Korea in 2013. The approved dosage regimen for postoperative pain relief with IV oxycodone is IV bolus loading of 2 mg followed by PCA composed of demand boluses of 1 mg and no background infusion with an oxycodone concentration of 1 mg/ml. However, a simulation study indicated that the minimum effective analgesic concentration (MEAC, as indicated by relief of pain by administering rescue analgesics) of oxycodone was reached most quickly with a higher loading dose of 0.1 mg/kg and IV PCA with background infusion. Oxycodone is a therapeutic option as an analgesic for postoperative pain management. It is necessary to reduce the analgesic dose of oxycodone in elderly patients because metabolic clearance decreases with age.

Clinical and psychological characteristics of propofol abusers in Korea: a survey of propofol abuse in 38, non-healthcare professionals

Background The aim of this study is to investigate the characteristics of propofol abuse based on the results of a survey analysis of abusers among non-healthcare professionals in Korea. Methods Thirty-eight propofol abusers were questioned between October and December 2010, and were enrolled and voluntarily participated in a structured survey consisting of an interview and completing a previously prepared questionnaire. The questionnaire was divided into three distinct parts: part 1 dealt with the history of propofol abuse; part 2 highlighted the problems caused by propofol abuse; and part 3 enquired regarding demographics of abusers. Results Thirty-one (81.6%) of the 38 interviewees abused propofol for more than one year. During the last 12 months, 34 (89.0%) received propofol at two or three times a week. The minimum and maximum amounts of propofol (median, range) administered each time were 500 (100, 1000) and 2000 (500, 4000) mg, respectively. Stress relief and the maintenance of a sense of well-being were quoted the most important reasons for the first-time administration of propofol and its subsequent abuse, respectively. The majority of abusers (36.0, 97.3%) reported a sense of pleasure or euphoria at the time of their propofol injection. Withdrawal symptoms occurred in five abusers (13.2%). Thirteen (36.1%) reported disruptions in their work life. None of the respondents had previously admitted to and or reported abuse of any other controlled substances. Conclusions These results provided reference data for the regulation of propofol in Korea as a controlled substance and may also be of interest to international agencies in other countries.

Corrigendum: The time-course and RNA interference of TNF-α, IL-6, and IL-1β expression on neuropathic pain induced by L5 spinal nerve transection in rats (Korean J Anesthesiol 2015 April 68(2): 159-169)

[This corrects the article on p. 159 in vol. 68, PMID: 25844135.].

Meningitis after a combined spinal epidural anesthesia − A case report −

The incidence of post-dural puncture meningitis is very low. A 44-year-old patient developed a fever (38degrees C, headache, neck stiffness, nausea, and vomiting after combined spinal epidural (CSE) anesthesia and surgery for closed reduction and internal fixation (CRIF) with intramedullary (IM) nailing, tibia, Rt. With a preliminary diagnosis of bacterial meningitis, empiric broad spectrum antimicrobial treatment was immediately started after cerebrospinal fluid (CSF) sampling. The CSF was clear and revealed a white blood cell count, protein, glucose, and pressure of 146/micrometer, 225 mg/dl, 48 mg/dl (serum 151 mg/dl), and 26 cmH2O, respectively. The CSF stain and culture were negative. Considering the injection of preventive antibiotics before CSE anesthesia, partially treated bacterial meningitis was suspected. Four weeks later, clinical symptoms had improved before the patient was discharged.

The predictive performance of infusion strategy nomogram based on a fluid kinetic model

Background In a previous study, fluid kinetic models were applied to describe the volume expansion of the fluid space by administration of crystalloid and colloid solutions. However, validation of the models were not performed, it is necessary to evaluate the predictive performance of these models in another population. Methods Ninety five consenting patients undergoing elective spinal surgery under general anesthesia were enrolled in this study. These patients were randomly assigned to three fluid groups i.e. Hartmanns solution (H group, n = 28), Voluven® (V group, n = 34), and Hextend® (X group, n = 33). After completion of their preparation for surgery, the patients received a loading and maintenance volume of each fluid predetermined by nomograms based on fluid pharmacokinetic models during the 60-minute use of an infusion pump. Arterial samples were obtained at preset intervals of 0, 10, 20, and 30 min after fluid administration. The predictive performances of the fluid kinetic modes were evaluated using the fractional change of arterial hemoglobin. The relationship between blood-volume dilution and target dilution of body fluid space was also evaluated using regression analysis. Results A total of 194 hemoglobin measurements were used. The bias and inaccuracy of these models were -2.69 and 35.62 for the H group, -1.53 and 43.21 for the V group, and 9.05 and 41.82 for the X group, respectively. The blood-volume dilution and target dilution of body-fluid space showed a significant linear relationship in each group (P < 0.05). Conclusions Based on the inaccuracy of predictive performance, the fluid-kinetic model for Hartmanns solution showed better performance than the other models.