Interpretation of volume kinetics in terms of pharmacokinetic principles / 대한마취과학회지

Volume kinetics is the pharmacokinetics of infusion fluids and describes the distribution and elimination of infused volume. Generally, pharmacokinetic parameters can be estimated by measuring the concentration of a drug. However, it is almost impossible to directly measure the concentration of fluids. Therefore, in volume kinetics, the disposition of fluids is indirectly quantified by measuring the hemoglobin concentration under the premise of no hemoglobin loss. If the hemoglobin concentration is repeatedly measured while administering the fluids, the dilution (relative change of the plasma volume) for each corresponding hemoglobin concentration can be obtained. The dilution is based on the concept of plasma volume expansion. The method of quantifying the drugs disposition with compartmental analysis has been equally applied to volume kinetics. The transfer of fluids between compartments is explained by first-order kinetics, and it is assumed that fluid is only removed from the central compartment. Population analysis can be used to identify covariates that can account for inter-individual variability in volume kinetic parameters. Body weight and mean blood pressure are well-known representative covariates of kinetic volume parameters. Using volume kinetic parameters, the volume expansion effects of crystalloid and colloid solutions can be understood more effectively, thereby facilitating appropriate fluid therapy. Although limitations exist in volume kinetics, its implications are important for clinicians when administering fluids.

Interpretation of volume kinetics in terms of pharmacokinetic principles / 대한마취과학회지

Volume kinetics is the pharmacokinetics of infusion fluids and describes the distribution and elimination of infused volume. Generally, pharmacokinetic parameters can be estimated by measuring the concentration of a drug. However, it is almost impossible to directly measure the concentration of fluids. Therefore, in volume kinetics, the disposition of fluids is indirectly quantified by measuring the hemoglobin concentration under the premise of no hemoglobin loss. If the hemoglobin concentration is repeatedly measured while administering the fluids, the dilution (relative change of the plasma volume) for each corresponding hemoglobin concentration can be obtained. The dilution is based on the concept of plasma volume expansion. The method of quantifying the drugs disposition with compartmental analysis has been equally applied to volume kinetics. The transfer of fluids between compartments is explained by first-order kinetics, and it is assumed that fluid is only removed from the central compartment. Population analysis can be used to identify covariates that can account for inter-individual variability in volume kinetic parameters. Body weight and mean blood pressure are well-known representative covariates of kinetic volume parameters. Using volume kinetic parameters, the volume expansion effects of crystalloid and colloid solutions can be understood more effectively, thereby facilitating appropriate fluid therapy. Although limitations exist in volume kinetics, its implications are important for clinicians when administering fluids.

Optimal effect-site concentration of remifentanil to prevent hemodynamic changes during nasotracheal intubation using a video laryngoscope

Background@#Nasotracheal intubation is the most commonly used method to secure the field of view when performing surgery on the oral cavity or neck. Like orotracheal intubation, nasotracheal intubation uses a laryngoscope. Hemodynamic change occurs due to the stimulation of the sympathetic nervous system. Recently, video laryngoscope with a camera attached to the end of the direct laryngoscope blade has been used to minimize this change. In this study, we investigated the optimal effect-site concentration (Ce) of remifentanil for minimizing hemodynamic responses during nasotracheal intubation with a video laryngoscope. @*Methods@#Twenty-one patients, aged between 19 and 60 years old, scheduled for elective surgery were included in this study. Anesthesia was induced by slowly injecting propofol. At the same time, remifentanil infusion was initiated at 3.0 ng/ml via target-controlled infusion (TCI). When remifentanil attained the preset Ce, nasotracheal intubation was performed using a video laryngoscope. The patient's blood pressure and heart rate were checked pre-induction, right before and after intubation, and 1 min after intubation. Hemodynamic stability was defined as an increase in systolic blood pressure and heart rate by 20% before and after nasotracheal intubation. The response of each patient determined the Ce of remifentanil for the next patient at an interval of 0.3 ng/ml. @*Results@#The Ce of remifentanil administered ranged from 2.4 to 3.6 ng/ml for the patients evaluated. The estimated optimal effective effect-site concentrations of remifentanil were 3.22 and 4.25 ng/ml, that were associated with a 50% and 95% probability of maintaining hemodynamic stability, respectively. @*Conclusion@#Nasotracheal intubation using a video laryngoscope can be successfully performed in a hemodynamically stable state by using the optimal remifentanil effect-site concentration (Ce50 , 3.22 ng/ml; Ce95 , 4.25 ng/ml).

Quantitative analysis of the effect of fraction ofinspired oxygen on peripheral oxygen saturation inhealthy volunteers

Background@#The international organization for standardization (ISO) 80601-2-61 dictates that the accuracy ofa pulse oximeter should be assessed by a controlled desaturation study. We aimed to characterize the relationshipbetween the fraction of inspired oxygen (FiO2) and peripheral oxygen saturation (SpO2) using a turnover modelby retrospectively analyzing the data obtained from previous controlled desaturation studies. @*Materials and Methods@#Each volunteer was placed in a semi-Fowler’s position and connected to a breathingcircuit to administer the hypoxic gas mixture containing medical air, oxygen, nitrogen, and carbon dioxide.Volunteers were exposed to various levels of induced hypoxia over 70-100% arterial oxygen saturation (SaO2).The study period consisted of two rounds of hypoxia and the volunteers were maintained in room air betweeneach round. FiO2 and SpO2 were recorded continuously during the study period. A population pharmacodynamicanalysis was performed with the NONMEM VII level 4 (ICON Development Solutions, Ellicott City, MD,USA). @*Results@#In total, 2899 SpO2 data points obtained from 20 volunteers were used to determine the pharmacodynamiccharacteristics. The pharmacodynamic parameters were as follows: kout = 0.942 1/min, Imax = 0.802, IC50 =85.3%, γ = 27.3. @*Conclusion@#The changes in SpO2 due to decreases in FiO2 well explained by the turnover model with inhibitoryfunction as a sigmoidal model.

Performance of the MP570T pulse oximeter in volunteers participating in the controlled desaturation study: a comparison of seven probes

Background@#The performance of the pulse oximeter was evaluated based on the ISO 80601-2-61:2011 (E) guidelines. This study aimed to determine whether the various finger probes of the MP570T pulse oximeter (MEK-ICS Co., Ltd., Korea) would provide clinically reliable peripheral oxygen saturation (SpO2) readings over a range of 70100% arterial oxygen saturation (SaO2) during non-motion conditions. @*Methods@#Each volunteer (n = 12) was connected to a breathing circuit for the administration of a hypoxic gas mixture. For frequent blood sampling, an arterial cannula was placed in a radial artery. The following seven pulse oximeter probes were simultaneously attached to each volunteer’s fingers: (1) WA-100 reusable finger probe (MEDNIS Co., Ltd., Korea), (2) MDNA disposable finger probe (MEDNIS Co., Ltd.), (3) IS-1011 disposable finger probe (Insung Medical Co., Ltd., Korea), (4) CJ340NA disposable finger probe (CHUN JI IN Medical Co., Ltd., Korea), (5) NellcorTM OxiMax DS-100A reusable finger probe (Medtronic, USA), (6) NellcorTM OxiMax MAX-N disposable finger probe (Medtronic), and (7) OXI-PRO DA disposable finger probe (Bio-Protech Inc., Korea). @*Results@#A total of 275 SpO2-SaO2 pairs were included in the analysis. The accuracy of the root mean square (Arms) of each probe was 2.83%, 3.98%, 3.75%, 6.84%, 3.43%, 5.17%, and 3.84%, respectively. @*Conclusions@#The MP570T pulse oximeter with WA-100 reusable, MDNA disposable, IS-1011 disposable, NellcorTM OxiMax DS-100A reusable, and OXI-PRO DA disposable finger probes meets an acceptable standard of SpO2 accuracy under non-motion conditions.

Pharmacodynamic Analysis of the Influence of Propofol on Left Ventricular Long-Axis Systolic Performance in Cardiac Surgical Patients

BACKGROUND: Propofol induced a decline in the left ventricular (LV) systolic performance in non-cardiac surgery. We tested the hypothesis that propofol decreased the LV contractile function by dose dependent manner in cardiac surgery patients. METHODS: Anesthesia was maintained with target-controlled infusions of propofol and remifentanil in cardiac surgery patients. With a fixed effect-site concentration (Ce) of remifentanil (20 ng/mL) after sternotomy, the Ce of propofol was adjusted to maintain a Bispectral index of 40–60 (Ce1). Mitral annular Doppler tissue image tracings and other echocardiographic variables, including end-diastolic and end-systolic volumes, stroke volume, and mitral inflow pulse wave Doppler profile at Ce1, were recorded using transesophageal echocardiography. Echocardiographic recordings were repeated after the Ce-values of propofol were doubled and tripled at 10-minute intervals (defined as Ce2 and Ce3, respectively). Serial changes in echocardiographic variables for each Ce of propofol were assessed using generalized linear mixed effect modeling. The pharmacodynamic relationship between the Ce of propofol and peak systolic mitral annular velocity (Sm) was analyzed by logistic regression using non-linear mixed effect modeling (NONMEM). RESULTS: Means of Ce1, Ce2, and Ce3 were 0.8, 1.6, and 2.4 μg/mL, respectively, and their means of Sm (95% confidence interval) were 9.7 (9.3–10.2), 8.7 (8.2–9.1), and 7.5 cm/sec (7.0–8.0), respectively (P < 0.01). Ce values of propofol and Sm showed a significant inter-correlation and predictability (intercept, 10.8; slope–1.0 in generalized mixed linear modeling; P < 0.01). Ce values producing 10% and 20% decline of Sm with 50%-probability were 1.4 and 2.1 μg/mL, respectively. CONCLUSION: Propofol reduces LV systolic long-axis performance in a dose-dependent manner. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01826149

Accuracy assessment of a PION TCI pump based on international standards

BACKGROUND: Inaccuracies associated with target-controlled infusion (TCI) delivery systems are attributable to both software and hardware issues, as well as pharmacokinetic variability. However, little is known about the inaccuracy of the syringe pump operating in TCI mode. This study aimed to evaluate the accuracy of the TCI pump based on international standards.METHODS: A test apparatus for accuracy evaluation of a syringe pump (PION TCI®, Bionet Co. Ltd.) was designed to apply the gravimetric method. Pump accuracy was evaluated in terms of deviation defined by the following equation: infusion rate deviation (%) = (Rate(mea) − Rate(est)) / Rate(est) × 100, where Rate(mea) is the infusion rate (ml/h) as measured by the gravimetric system, and Rate(est) is the infusion rate (ml/h) as estimated by the pump. An infusion rate representing TCI mode was determined from previous clinical trial data which evaluated the predictive performance of the pharmacokinetic model. The PION TCI pump used in that clinical trial was used to evaluate accuracy of the syringe pump. The distribution of infusion rates obtained from the clinical trial was calculated, and the median value of the distribution was determined as the representative value.RESULTS: The representative infusion rate representing TCI mode was 31 ml/h, at which the infusion rate deviation was 4.5 ± 1.6%.CONCLUSIONS: The inaccuracy of the syringe pump contributing to TCI system inaccuracy is insignificant.

Optimal effective-site concentration of remifentanil for sedation during plate removal of maxilla

BACKGROUND: Removal of the plate following Le Fort I osteotomy and BSSO (bilateral sagittal split osteotomy) is a common procedure. However, patients who undergo plate removal experience intense pain and discomfort. This study investigated the half-maximal effective concentration (Ce50 ) of remifentanil in the prevention of plate removal pain under sedation using dexmedetomidine. METHODS: The study evaluated 18 patients, between 18 and 35 years of age, scheduled for elective surgery. Remifentanil infusion was initiated after sedation using dexmedetomidine, and started at a dose of 1.5 ng/mL on the first patient via target-controlled infusion (TCI). Patients received a loading dose of 1.0 µg/kg dexmedetomidine over 10 min, followed by a maintenance dose of 0.7 µg/kg/h. When the surgeon removed the plate, the patient Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score was observed. RESULTS: The Ce of remifentanil ranged from 0.9 to 2.1 ng/mL for the patients evaluated. The estimated effect-site concentrations of remifentanil associated with a 50% and 95% probability of reaching MOAA/S score of 3 were 1.28 and 2.51 ng/mL, respectively. CONCLUSIONS: Plate removal of maxilla can be successfully performed without any pain or adverse effects by using the optimal remifentanil effect-site concentration (Ce50 , 1.28 ng/mL; Ce95 , 2.51 ng/mL) combined with sedation using dexmedetomidine.

Investigation into memory formation according to the level of hypnotic depth using process dissociation

BACKGROUND: Process dissociation procedure has been used to evaluate explicit and implicit memories. Two process-dissociation measurement models are described. METHODS: This prospective study evaluated intraoperative memory formation in Korean patients undergoing elective surgery under general anesthesia and its relation to the depth of hypnotic state. A total of 270 patients enrolled were randomly assigned to three groups based on Bispectral Index (BIS) values in the following ranges: 30 to 40, BIS 40 to 50, and BIS 50 to 60 according to the level of hypnotic depth induced by propofol or sevoflurane during the presentation of wordlists. When the level of hypnotic depth was maintained at the target BIS range, words were played for 15 minutes via headphones to patients. Within 24 hours after the word presentation, memory was assessed using an auditory word stem completion test. The probability of explicit and implicit memory was calculated using original and extended measurement models. Brice interviews were performed within 1 and 24 hours after surgery. RESULTS: A total of 119 patients who did not deviate from the target BIS range were included in the analysis. The 95% confidence interval (CI) of the probability of occurrence of implicit memory evaluated by the original model did not include zero. However, when the extension model was used, 0 was included in the 95% CI. Explicit memory evaluated via Brice interviews did not occur in any group. CONCLUSIONS: When BIS was maintained in the range of 30 to 60 during surgery, no explicit or implicit memory was observed.

Comparison of the clinical performance of the modified Marsh model for propofol between underweight and normal-weight patients with Crohn's disease / 대한마취과학회지

BACKGROUND: The aim of this retrospective study was to compare the clinical performance of the modified Marsh model for propofol between underweight and normal-weight patients with Crohn's disease. METHODS: The medical records of 50 patients who underwent elective surgery for Crohn's disease were reviewed retrospectively. Propofol and remifentanil were administered using target effect-site concentration (Ce)-controlled infusion with the modified Marsh and Minto models. Target Ce values of propofol were adjusted within a range of 2.5–3 µg/ml to maintain a bispectral index (BIS) value of less than 60 during anesthesia maintenance. Dosages of anesthetic agents administered during surgery were compared between underweight and normal-weight patients. The infusion profiles of patients were applied as inputs to calculate the Ce values in the Schnider model. RESULTS: The total midazolam and remifentanil dosages required for underweight patients were higher than those required for normal-weight patients to maintain BIS values at less than 60 within a target propofol Ce range of 2.5–3 µg/ml. Simulation results suggested that the Schnider model may be an appropriate pharmacokinetic model for target-controlled infusion in underweight patients, as the clearance was consistently higher in the Schnider model than the modified Marsh model, particularly in underweight patients. CONCLUSIONS: The modified Marsh model might cause inadvertent propofol underdosing in underweight patients. Future studies are necessary to compare the predictive performance of the modified Marsh and Schnider pharmacokinetic models in underweight patients.

Predictive performance of target controlled infusion of propofol-MCT/LCT using the modified Marsh and Schnider models: a simulation study

BACKGROUND: Only two pharmacokinetic models of propofol are commercially available in the category of target controlled infusion (TCI) pumps: the modified Marsh and Schnider models. Both models were developed using propofol-LCT (long chain triglyceride). Depending on the excipient, the pharmacokinetic properties of fast-acting drugs, such as propofol, vary. Hence, it is necessary to evaluate the predictive performances of both models using propofol-MCT (medium chain triglyceride)/LCT, which is frequently used in clinical practice. METHODS: This was a computer simulation study, using data collected in the previous clinical analysis used to evaluate the predictive performance of a pharmacokinetic model of propofol-MCT/LCT. The infusion profiles for each patient were applied as inputs to both models. Simulations were performed using TCI software, and the simulated plasma concentrations of both models were calculated. RESULTS: In total, 217 plasma samples, obtained from 35 patients, were used to determine the predictive performance. The pooled median (95% CI) biases and inaccuracies were 9.6 (−1.7 to 15.4) and 32.1 (22.6–38.2) respectively, for the modified Marsh model, and −5.9 (−8.9 to −0.7) and 26.3 (21.7–27.8) respectively, for the Schnider model. CONCLUSIONS: Although the pooled bias and inaccuracy of the Schnider models were clinically acceptable (< 10–20% and approximately 20–30%, respectively), the Schnider model consistently produced negatively biased predictions. Conversely, even though the pooled inaccuracy of the modified Marsh model failed to meet this criterion, the value did not deviate significantly from the standard. Therefore, it is reasonable to conclude that both TCI models can be used for propofol-MCT/LCT.

Unexpected anesthetic leakage from a damaged O-ring on the Selectatec back bar: A case report

The Selectatec mounting system was devised to provide easy and quick on-site fitting of various vaporizers for the anesthetic machine. However, a quick changing system for the vaporizer can also damage the O-ring due to friction between the vaporizer and the Selectatec back bar. We herein report a case of an unexpected anesthetic gas leakage from a damaged O-ring on the Selectatec back bar, which resulted from exchanging the vaporizers between two operations. In cases using the Datex Ohmeda machine, it is not easy to detect leakages from the vaporizers because of the location of the check valve near to the fresh gas outlet. This complicates the use of the positive pressure leakage test to detect a low pressure system leakage on the Selectatec back bar. We recommend the preanesthetic negative pressure or low-flow leakage test to detect a low pressure leakage when exchanging vaporizers on the Selectatec system.

Characteristics of electroencephalogram signatures in sedated patients induced by various anesthetic agents

Devices that monitor the depth of hypnosis based on the electroencephalogram (EEG) have long been commercialized, and clinicians use these to titrate the dosage of hypnotic agents. However, these have not yet been accepted as standard monitoring devices for anesthesiology. The primary reason is that the use of these monitoring devices does not completely prevent awareness during surgery, and the development of these devices has not taken into account the neurophysiological mechanisms of hypnotic agents, thus making it possible to show different levels of unconsciousness in the same brain status. An alternative is to monitor EEGs that are not signal processed with numerical values presented by these monitoring devices. Several studies have reported that power spectral analysis alone can distinguish the effects of different hypnotic agents on consciousness changes. This paper introduces the basic concept of power spectral analysis and introduces the EEG characteristics of various hypnotic agents that are used in sedation.

An overview of pharmacodynamic drug interaction with isobole and response surface model in anesthesia

Drug interaction is the principal concept of anesthetic practice. Typically, drug interactions are divided into three categories i.e., additive, synergistic, or infra-additive interactions. Pharmacodynamic drug interactions are typically described using mathematical models. The traditional model is an isobole, which is an iso-effect curve that shows dose or concentration combinations that result in equal effect. Response surface model is a pharmacodynamic tool that describes all isoboles and concentration effect curves for a given endpoint in one equation. In summarizing concentration-effect relationships, the response surface model allows anesthesiologists the versatility to work with precise and safe drug interactions. The aim of this review is to provide the reader with principal concepts of the isobole and response surface model and evaluate characteristics of most commonly used models, including 4 response surface models i.e., the Greco model, reduced Greco model, Minto model, and the Hierarchy model. In addition, the concept of population analysis using nonlinear mixed effects modeling is introduced.

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

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 / 대한마취과학회지

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.

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

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. Hartmann's solution (H group, n = 28), Voluven(R) (V group, n = 34), and Hextend(R) (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 Hartmann's solution showed better performance than the other models.

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

BACKGROUND: The objective of this study was to investigate the time-course of the expression of TNF-alpha, IL-6, and IL-1beta 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-alpha and IL-1beta mRNA levels increased immediately after SNT and remained high for 6 d, while IL-6 transcripts only began to increase after 12 h. TNF-alpha and IL-1beta 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-alpha, IL-6 and IL-1beta 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.

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

This article was inadvertently omitted Acknowledgments section for grant support.

Temporal linear mode complexity as a surrogate measure of the anesthetic drug effects during sevoflurane anesthesia / 대한마취과학회지

BACKGROUND: The aims of this study were to compare the stability, correlation with end-tidal sevoflurane, and area below the effect (AUCeffect) vs. time curves of temporal linear mode complexity (TLMC) and approximate entropy (ApEn) during sevoflurane anesthesia. Another study goal was to characterize the time course of the effects of sevoflurane. METHODS: Electroencephalogram (EEG) parame1ter stability was evaluated using the coefficients of variation (CV) of the median baseline (E0), maximal (Emax), and individual median E0 - Emax values. Correlations between sevoflurane concentration and EEG parameters were tested. AUCeffect vs. time curves of TLMC and ApEn were calculated to quantitate any decrease in central nervous system activities. A sigmoid Emax model was used for pharmacodynamic modeling. RESULTS: TLMC and ApEn demonstrated CVs of 8.36 and 7.35 (for E0) and 19.61 and 13.45 (Emax), respectively. The CVs of the individual median E0 - Emax values were 65.16 for TLMC and 59.97 for ApEn. The Spearman correlation coefficient was -0.3103 for TLMC and -0.3410 for ApEn (P < 0.001 for both parameters). The median AUCeffect value was 338.9 for TLMC and 246.5 for ApEn (P = 0.457). The final pharmacodynamic parameters estimated by sigmoid Emax models were described as follows; E0: 0.614, 0.617, Emax: 0.334, 0.287, Ce50: 5.48, 5.07 vol%, gamma: 1.88, 2.01, ke0: 0.306, 0.236 min (TLMC, ApEn). CONCLUSIONS: TLMC is comparable to ApEn according to the univariate EEG descriptors of the effects of sevoflurane. A sigmoid Emax model well described the pharmacodynamics of sevoflurane for TLMC and ApEn.