Do you believe that processed EEG helps to prevent intraoperative awareness? / 대한마취과학회지

No abstract available.

A Simulation Study of Propofol Effect-Site Concentration for Appropriate Sedation in Pediatric Patients Undergoing Brain MRI: Pharmacodynamic Analysis

PURPOSE: We aimed to establish the propofol effect-site concentration (Ce) for appropriate sedation by pharmacodynamic analysis and to determine the propofol Ce during occurrence of sedation-related side effects in pediatric patients undergoing brain magnetic resonance imaging (MRI). MATERIALS AND METHODS: In 50 pediatric patients scheduled for brain MRI, sedation was induced with 2.0 mg/kg propofol; additional propofol doses were 0.5–1 mg/kg. Propofol Ce was simulated by inputting the propofol administration profiles of patients into a pediatric compartmental model (Choi model). The relationship between propofol Ce and probabilities of sedation and recovery were analyzed using a sigmoidal Emax model. The simulated propofol Ce for sedation-related side effects was investigated. Population model parameters were estimated using the Nonlinear Mixed-Effects Modelling software. RESULTS: The mean values of propofol Ce₅₀ for sedation during the preparation, scanning, and recovery phases were 1.23, 0.43, and 0.39 µg/mL. The simulated propofol Ce values during oxygen desaturation (SpO₂<90%) (3 patients; 6%), hypotension (16 patients; 32%), and bradycardia (12 patients; 24%) were 3.01±0.04, 2.05±0.63, and 2.41±0.89 µg/mL, respectively. CONCLUSION: The required propofol Ce₅₀ for applying monitors during the preparation phase before the start of MRI was higher than the propofol Ce₅₀ required during the scanning phase. During low-intensity stimulation phases, such as scanning, propofol bolus dose should be strictly titrated not to exceed the propofol Ce that can lead to oxygen desaturation because of the relatively low propofol Ce (Ce₉₅, 1.43 µg/mL) required for sedation in most patients.

Brain and lung: dangerous crosstalk / 대한마취과학회지

No abstract available.

Pharmacodynamic Estimate of Propofol-Induced Sedation and Airway Obstruction Effects in Obstructive Sleep Apnea-Hypopnea Syndrome

PURPOSE: Sedatives must be carefully titrated for patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) as oversedation may lead to disastrous respiratory outcomes. This study aimed to investigate the relations between the effect-site concentration (Ce) of propofol and sedation and airway obstruction levels in patients with OSAHS. MATERIALS AND METHODS: In 25 patients with OSAHS, sedation was induced by 2% propofol using target-controlled infusion. Sedation and airway obstruction levels were assessed using the Observer's Assessment of Alertness/Sedation Scale and a four-category scale, respectively. The relationships between propofol Ce and sedation and airway obstruction were evaluated using a sigmoid Emax model. Pharmacodynamic modeling incorporating covariates was performed using the Nonlinear Mixed Effects Modeling VII software. RESULTS: Increased propofol Ce correlated with the depth of sedation and the severity of airway obstruction. Predicted Ce50(m) (Ce associated with 50% probability of an effect> or =m) for sedation scores (m> or =2, 3, 4, and 5) and airway-obstruction scores (m> or =2, 3, and 4) were 1.61, 1.78, 1.91, and 2.17 microg/mL and 1.53, 1.64, and 2.09 microg/mL, respectively. Including the apnea-hypopnea index (AHI) as a covariate in the analysis of Ce50(4) for airway obstruction significantly improved the performance of the basic model (p<0.05). CONCLUSION: The probability of each sedation and airway obstruction score was properly described using a sigmoid Emax model with a narrow therapeutic range of propofol Ce in OSAHS patients. Patients with high AHI values need close monitoring to ensure that airway patency is maintained during propofol sedation.

Pharmacokinetic and pharmacodynamic modeling in anesthetic field

Models are simplified descriptions of true biological processes. Pharmacokinetic/pharmacodynamic (PK/PD) modeling is a mathematical description on the relationship between pharmacokinetics and pharmacodynamics. The PK/PD modeling allows estimation of PK/PD parameters and it can establish dose-concentration-response relationships which describe and predict the effect-time courses of a drug. PK/PD modeling has recently emerged as a major tool in clinical pharmacology in order to optimize drug uses by designing rational dosage forms. Population analysis is used to estimate the variability in the population and also to establish guidelines for the individualization of drug dosage regimen. Non-linear mixed effect model is the basis of population approach. This approach permits the simultaneous analysis for all the data of the studied population, by using either PK or PD models to describe the typical trends (population means) and individual profiles. The target controlled infusion system is based on the population PK models which describe the inter-individual PK variability by individualizing the PK parameters according to the patient's covariate. The PK/PD modeling is highly useful for the development of drugs as well as for pharmacotherapy.

Modeling of Recovery Profiles in Mentally Disabled and Intact Patients after Sevoflurane Anesthesia; A Pharmacodynamic Analysis

PURPOSE: Mentally disabled patients show different recovery profiles compared to normal patients after general anesthesia. However, the relationship of dose-recovery profiles of mentally disabled patients has never been compared to that of normal patients. MATERIALS AND METHODS: Twenty patients (10 mentally disabled patients and 10 mentally intact patients) scheduled to dental surgery under general anesthesia was recruited. Sevoflurane was administered to maintain anesthesia during dental treatment. At the end of the surgery, sevoflurane was discontinued. End-tidal sevoflurane and recovery of consciousness (ROC) were recorded after sevoflurane discontinuation. The pharmacodynamic relation between the probability of ROC and end-tidal sevoflurane concentration was analyzed using NONMEM software (version VII). RESULTS: End-tidal sevoflurane concentration associated with 50% probability of ROC (C50) and gamma value were lower in the mentally disabled patients (C50=0.37 vol %, gamma=16.5 in mentally intact patients, C50=0.19 vol %, gamma=4.58 in mentally disabled patients). Mentality was a significant covariate of C50 for ROC and gamma value to pharmacodynamic model. CONCLUSION: A sigmoid Emanx model explains the pharmacodynamic relationship between end-tidal sevoflurane concentration and ROC. Mentally disabled patients may recover slower from anesthesia at lower sevoflurane concentration at ROC an compared to normal patients.

Effect of Dexmedetomidine on the Corrected QT and Tp-e Intervals during Spinal Anesthesia

PURPOSE: The aim of this study is to evaluate the effect of dexmedetomidine on corrected QT (QTc) and Tp-e intervals in patients undergoing spinal anesthesia. MATERIALS AND METHODS: We studied 50 patients who were scheduled to undergo spinal anesthesia before orthopedic surgeries. Patients were allocated to receive either an infusion of dexmedetomidine or normal saline after spinal anesthesia. RESULTS: QTc intervals were significantly prolonged after spinal anesthesia, and the prolonged QTc interval returned to baseline values 10 minutes after either normal saline or dexmedetomidine administration in both groups. The QTc interval values after dexmedetomidine administration were significantly shorter compared to the QTc interval values just before dexmedetomidine administration. CONCLUSION: Dexmedetomidine could promote the return of a prolonged QTc interval induced by spinal anesthesia and might be helpful in patients who have a prolonged QTc interval.

Neurobiology, pharmacokinetics and pharmacodynamics of drug abuse

All drugs of abuse, like neural rewarding behaviors such as sex and eating, increase extra-cellular dopamine (DA) levels in the nucleus accumbens (NA), which is a part of the common reward mesolimbic pathway from the ventral tegmental area (VTA) to the NA. As addiction progresses from initial use to obsessive compulsive use, the neurobiology shifts from a DA-based behavioral system to a predominantly glutamate-based one, still relying on DA. A DA release in the prefrontal cortex (PFC) and amygdala in the relapse stimulates glutamate transmission between the PFC and amygdala and glutamate release in the pathway from the PFC to the NA core, constituting a "final common pathway" for drug-seeking behavior. Dysfunction of critical PFC structures results in drug craving and impaired decision making. Inhalation and smoking are the routes of administration that allow the most rapid delivery of drugs to the brain, while intravenous injection maximizes the bioavailability of a drug. The pharmacokinetic properties of a drug that dispose the user to increased self-administration include rapid absorption, rapid entry into the central nervous system, high bioavailability, short half-life, small volume of distribution, and high free drug clearance. The pharmacokinetic properties associated with drug dependence are a long half-life, low free drug clearance, and presence of the drug at high enough concentrations and for a sufficient time to permit tolerance to develop. Pharmacokinetics and pharmacodynamics play an important role in predicting the dependence and abuse potential of drugs.

A brief cardiac arrest due to saline irrigation during surgery for infratentorial cerebellar tumor / 대한마취과학회지

No abstract available.

A brief cardiac arrest due to saline irrigation during surgery for infratentorial cerebellar tumor / 대한마취과학회지

No abstract available.

Conversion of orotracheal to nasotracheal intubation using a fiberoptic bronchoscope in a patient with intraoral hematoma / 대한마취과학회지

No abstract available.

Heart rate variability predicts the extent of corrected QT interval prolongation after tracheal intubation

BACKGROUND: Corrected QT (QTc) interval can be modulated by sympathetic and parasympathetic balance. Tracheal intubation causes significant prolongation of the QTc interval due to sympathetic stimulation. This study was designed to elucidate the relationship between baseline autonomic nervous system activity and QTc prolongation after endotracheal intubation using heart rate variability (HRV). METHODS: Sixty-six healthy patients were included and the baseline HRV data were recorded for 5 min before anesthesia. Power spectrum densities were calculated for low frequencies (LF, 0.04-0.15 Hz) and high frequencies (HF, 0.15-0.4 Hz), defined as either LF's or HF's relative part of the total power. Anesthesia was induced with sevoflurane and vecuronium was given. The QTc interval, heart rate (HR) and mean arterial pressure (MAP) were measured before induction (baseline), before laryngoscopy (pre-intubation) and immediately after the intubation (post-intubation). RESULTS: The QTc interval change at post-intubation from baseline (DeltaQTc) showed a significant negative correlation with the HF (r = 0.34, P = 0.006) and positive correlation with LF/HF ratio (r = 0.37, P = 0.005). Patients were retrospectively divided into low-HF/LF (2.5, n = 22). The DeltaQTc was statistically higher in the high-LF/HF group compared to that in the low-LF/HF group (P = 0.048). The HR and MAP at baseline, pre-intubation and post-intubation were not different between two groups. CONCLUSIONS: The QTc interval prolongation after endotracheal intubation is influenced by baseline autonomic conditions and can be exaggerated in patients with activated sympathetic activity or depressed parasympathetic activity.

Association between opioid receptor gene polymorphism and postoperative pain response in Koreans

BACKGROUND: The objective of this study was to investigate the association between A118G single nucleotide polymorphism (SNP) of human micro-opioid receptor (OPRM1) gene and the postoperative pain response in Korean patients undergoing thyroidectomy. METHODS: Fifty two adult patients undergoing thyroidectomy were enrolled in this study. Their blood samples were genotyped for the A118G polymorphism. Pain intensity was assessed by a verbal numerical rating scale (VNRS) at postanesthesia care unit, postoperative 6, 24, and 48 hours. Mechanical pain threshold was assessed using electronic von Frey preoperatively and repeated at postoperative 24 and 48 hours on the forearm and periincisional regions. RESULTS: Of the 50 patients, 23 patients were A118 homozygous (AA), 19 patients were heterozygous (AG), and 8 patients were 118G homozygous (GG). The VNRS score was higher in patients with GG genotype than other genotypes at PACU (P < 0.05). Mechanical pain thresholds on the forearm and periincisional area were decreased at postoperative 24 and 48 hours from the preoperative values in all genotypes (P < 0.05). However, the changes in pain thresholds were similar among the genotypes. CONCLUSIONS: A118G SNP of OPRM1 gene is associated with inter-individual difference in immediate postoperative pain score in Korean population.

The effect of beta1-adrenergic receptor gene polymorphism on prolongation of corrected QT interval during endotracheal intubation under sevoflurane anesthesia / 대한마취과학회지

BACKGROUND: The hemodynamic responses to endotracheal intubation are associated with sympathoadrenal activity. Polymorphisms in the beta1-adrenergic receptor (beta1AR) gene can alter the pathophysiology of specific diseases. The aim of this study is to investigate whether the Ser49Gly and Arg389Gly polymorphism of the beta1AR gene have different cardiovascular responses during endotracheal intubation under sevoflurane anesthesia. METHODS: Ninety-one healthy patients undergoing general anesthesia were enrolled. Patients underwent slow inhalation induction of anesthesia using sevoflurane in 100% oxygen. Vecuronium 0.15 mg/kg was given for muscle relaxation. Endotracheal intubation was performed by an anesthesiologist. The mean arterial pressure (MAP), heart rate (HR), and the corrected QT (QTc) interval were measured before induction, before laryngoscopy, and immediately after tracheal intubation. Genomic DNA was isolated from the patients' peripheral blood and then evaluated for the beta1AR-49 and beta1AR-389 genes using an allele-specific polymerase chain reaction method. RESULTS: No differences were found in the baseline values of MAP, HR, and the QTc interval among beta1AR-49 and beta1AR-389, respectively. In the case of beta1AR-49, the QTc interval change immediately after tracheal intubation was significantly greater in Ser/Ser genotypes than in Ser/Gly genotypes. No differences were observed immediately after tracheal intubation in MAP and HR for beta1AR-49 and beta1AR-389. CONCLUSIONS: We found an association between the Ser49 homozygote gene of beta1AR-49 polymorphism and increased QTc prolongation during endotracheal intubation with sevoflurane anesthesia. Thus, beta1AR-49 polymorphism may be useful in predicting the risk of arrhythmia during endotracheal intubation in patients with long QT syndrome.

Facial paralysis after spine surgery : A case report

diopathic facial nerve paralysis after surgery is not common but has clinical significance. We report a case of facial nerve paralysis in the immediate postanesthetic period after cervical spine surgery. A 41-year-old man with cervical herniated disc was scheduled for cervical laminectomy. After uneventful surgery, he suffered from left facial numbness and weakness. Imaging study and audiogram couldn't reveal any anatomic abnormality except Thornwaldt cyst. Conservative treatment with steroids and antivirals resolved his symptoms until 16th day after surgery.

The Expression of the Ca++ Channel alpha2delta Subunit and TRPM8 in the Dorsal Root Ganglion of Sympathetically Maintained Pain and Sympathetic Independent Pain Rat Models / 대한통증학회지

BACKGROUND: Peripheral nerve injury induces up-regulation of the calcium channel alpha2delta (alpha2delta) subunit and TRPM8 in the dorsal root ganglion (DRG) which might contribute to allodynia development. We investigated the expression of the alpha2delta subunit and TRPM8 in the DRG of sympathetically maintained pain (SMP) and sympathetic independent pain (SIP) rat model. METHODS: For the SMP model, the L5 and L6 spinal nerves were ligated tightly distal to the DRG. For the SIP model, the tibial and sural nerves were transected, while the common peroneal nerve was spared. After a 7 day postoperative period, tactile and cold allodynia were assessed using von Frey filaments and acetone drops, respectively. Expression of the alpha2delta subunit and TRPM8 in the L5 and L6 DRG were subsequently examined by a Western blot. RESULTS: There were no significant differences between the two models for the thresholds of tactile and cold allodynia. Expression of the alpha2delta subunit in the ipsilateral DRG to the injury was increased as determined on a Western blot as compared to that in the contralateral or sham-operated DRG of the SMP model, but there was no difference in expression seen with the use of the SIP model. There was no difference in the expression of TRPM8 in the ipsilateral DRG to the injury and the contralateral or sham-operated DRG of either model. CONCLUSIONS: Up-regulation of the alpha2delta subunit in injured DRG may play a role that contributes to tactile allodynia development in SMP, but not TRPM8 to cold allodynia after peripheral nerve injury.

Rocuronium Dosage Producing the Ceiling Effect on Onset Time in Young Male Patients / 대한마취과학회지

BACKGROUND: Rocuronium is considered a good candidate for rapid-sequence induction of anesthesia. Increased dose of rocuronium shortens the onset time but prolongs the duration of action. However, the ceiling effect of onset time appears when larger doses are used.Clinical trials have not shown the exact dose of ceiling effect. We performed this study to find dose producing the ceiling effect of onset time. METHODS: One hundred forty young male adults were randomized to oneof seven doses of rocuronium:0.6, 0.7, 0.8, 0.9, 1.0, 1.1 or 1.2 mg/kg.Anesthesia was induced with IV thiopental sodium and maintained with sevoflurane after tracheal intubation. Neuromuscular block was monitored with acceleromyography using single twitch.The onset time, the recovery of single twitch to 10% and also the changes in hemodynamics were checked. RESULTS: A dose of up to 1.0 mg/kg shortens the onset time but no further decrement was seen with doses larger than 1.0 mg/kg.The recovery time was prolonged as doses were increased but there were no differences in the hemodynamics. CONCLUSIONS: This study showed that in young male adults under IV induction with thiopental sodium, the ceiling effect of onset time appeared with rocuronium doses in excess of 1.0 mg/kg.

The Analgesic Effects of Intrathecal Pregabalin in Rat Formalin Tests: Comparison between Pre- and Post-treatment / 대한마취과학회지

BACKGROUND: Pregabalin is an analog of gamma aminobutyric acid, and selectively interacts with the alpha-2-delta subunit of the voltage dependent calcium channels. The aims of this study were to investigate the analgesic effects of intrathecal pregabalin in rat formalin tests and to compare between the pre-treatment and post-treatment group. METHODS: All experimental animals were randomly divided into pre- and post-treatment groups. In pre-treatment groups, pregabalin (0.003g, 0.01g, 0.03g, 0.1g, n = 6 at each group) was administered through the intrathecal catheter 10 min prior to formalin injection. In post-treatment groups, pregabalin (0.01g, 0.03g, 0.1g, 0.3g, n = 6 at each group) was administered through the catheter 10 min after formalin injection. Formalin (50 ml, 5%) was injected in the left hind paw. We counted the number of flinching as a pain behavior for 60 min to quantify the nociceptive response. RESULTS: The withdrawal responses which were represented by flinching count, were decreased dose dependently in the phase 2, in all groups (pre-treatment and post-treatment group), while there were less analgesic effects and ceiling effects in the phase 1. There was more significant decreasing flinching number in the pre-treatment group than that in the post-treatment group. CONCLUSIONS: Intrathecal pregabalin has preemptive analgesic effect and may be useful in the management of inflammation induced hyperalgesia.

Antiallodynic Effect of Pregabalin in Rat Models of Sympathetically Maintained and Sympathetic Independent Neuropathic Pain

Pregabalin binds to the voltage-dependent calcium channel alphadelta subunit and modulates the release of neurotransmitters, resulting in analgesic effects on neuropathic pain. Neuropathic pain has both sympathetically maintained pain (SMP) and sympathetic independent pain (SIP) components. We studied the antiallodynic effects of pregabalin on tactile allodynia (TA) and cold allodynia (CA) in SMP-and SIP-dominant neuropathic pain models. Allodynia was induced by ligation of the L5 & L6 spinal nerves (SMP model) or by transection of the tibial and sural nerves (SIP model) in rats. For intrathecal drug administration, a PE-10 catheter was implanted through the atlantooccipital membrane to the lumbar enlargement. Pregabalin was administered either intraperitoneally (IP) or intrathecally (IT) and dosed up incrementally until an antiallodynic effect without sedation or motor impairment was apparent. TA was assessed using von Frey filaments, and CA was assessed using acetone drops. IP-administered pregabalin dose-dependently attenuated TA in both models and CA in the SMP model, but not CA in the SIP model. IT-administered pregabalin dose-dependently attenuated both TA and CA in both models. However, the dose response curve of IT-administered pregabalin in SMP was shifted to left from that of SIP and the ED50 of IT-administered pregabalin for CA in SMP was about 900 times less than that in SIP. These findings suggest that pregabalin exerts its antiallodynic effect mainly by acting at the spinal cord, and that IT-administered pregabalin has more potent antiallodynic effects in SMP. The alphadeltasubunit might be less involved in the CA in SIP.

Changes in Ionized and Total Magnesium Concentration during Spinal Surgery / 대한마취과학회지

BACKGROUND: The incidence of postoperative hypomagnesemia in patients undergoing spinal surgery has been reported to be 70%. Ionized magnesium is considered to be the biologically active form, but until the early 1990s, only the total magnesium concentration could be measured. Currently, the ionized magnesium concentration as well as total magnesium concentration can be assessed due in part to the development of a selective electrode. The aim of this study was to more fully characterize the changes in the total and ionized magnesium concentrations in patients undergoing elective spinal fusion surgery. METHODS: The total and ionized magnesium, creatinine, albumin, urinary magnesium concentration, hematocrit, total amount of fluid administration, transfusion, blood loss, and urine output were evaluated both preoperatively and postoperatively in each patient. RESULTS: The total and ionized magnesium concentrations decreased from 0.783 mM/L and 0.529 mM/L preoperatively to 0.717 mM/L and 0.511 mM/L during the postoperative period, respectively. CONCLUSIONS: The incidence of total hypomagnesemia during spinal surgery was 15% but the incidence of ionized hypomagnesemia was only 3%.