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Background: When an imbalance occurs between the demand and capacity for protein folding, unfolded proteins accumulate in the endoplasmic reticulum (ER) lumen and activate the unfolded protein response (UPR). In addition, unfolded proteins are cleared from the ER lumen for ubiquitination and subsequent cytosolic proteasomal degradation, which is termed as the ER-associated degradation (ERAD) pathway. This study focused on changes in the UPR and ERAD pathways induced by the repeated inhalation anesthetic exposure in Caenorhabditis elegans. Methods: Depending on repeated isoflurane exposure, C. elegans was classified into the control or isoflurane group. To evaluate the expression of a specific gene, RNA was extracted from adult worms in each group and real-time polymerase chain reaction was performed. Ubiquitinated protein levels were measured using western blotting, and behavioral changes were evaluated by chemotaxis assay using various mutant strains. Results: Isoflurane upregulated the expression of ire-1 and pek-1 whereas the expression of atf-6 was unaffected. The expression of both sel-1 and sel-11 was decreased by isoflurane exposure, possibly indicating the inhibition of retro-translocation. The expression of cdc-48.1 and cdc-48.2 was decreased and higher ubiquitinated protein levels were observed in the isoflurane group than in the control, suggesting that deubiquitination and degradation of misfolded proteins were interrupted. The chemotaxis indices of ire-1, pek-1, sel-1, and sel-11 mutants decreased significantly compared to N2, and they were not suppressed further even after the repeated isoflurane exposure. Conclusion: Repeated isoflurane exposure caused significant ER stress in C. elegans. Following the increase in UPR, the ERAD pathway was disrupted by repeated isoflurane exposure and ubiquitinated proteins was accumulated subsequently. UPR and ERAD pathways are potential modifiable neuroprotection targets against anesthesia-induced neurotoxicity.

Background Serine synthetic pathway plays an essential role in the development and function of the nervous system. This study investigated whether the serine synthetic pathway was affected by repeated volatile anesthetic exposure using C. elegans and its relationship with anesthesia-induced neurotoxicity. Methods Synchronized worms were divided into two groups: the control and isoflurane groups. Worms in the isoflurane group were exposed to isoflurane for 1 h at each larval stage. The chemotaxis index was evaluated when they reached the young adult-stage in both groups. Also, RNA was extracted from the young adult-worms, and the expressions of C31C9.2, F26H9.5, and Y62E10 A.13 were evaluated using real-time polymerase chain reaction in both groups. At the same time, the l -serine level was measured. After phosphoserine phosphatase inhibitor – glycerophosphorylcholine (GPC) – and l -serine were treated, the change of chemotaxis index was determined. Results In young adult worms exposed to isoflurane, the genetic expressions of C31C9.2, F26H9.5, and Y62E10 A.13 were decreased, and a significant decrease was shown in Y62E10 A.13. The serine level in worms was also lower in the isoflurane group than in the control group (5.13 ± 1.44 vs. 7.65 ± 0.81 pM, n = 5 in each group, p = 0.009). Exposure to GPC reduced the chemotaxis index to a similar degree as repeated isoflurane exposure (52.9% in GPC group vs 58.7% in the isoflurane group). The chemotaxis index (61.1%) was not decreased by repeated isoflurane anesthesia in GPC-treated worms. In this condition, the l -serine level was low similarly in both groups (5.22 ± 1.19 vs. 4.90 ± 1.36 pM, n = 5 in each group, p = 0.702). When l -serine was supplied to C. elegans, the deteriorated chemotaxis index by isoflurane exposure recovered (78.1% in the control group vs. 75.5% in the isoflurane group, p = 0.465). Conclusion Serine synthetic pathway was negatively affected in C. elegans by repeated isoflurane exposure. Y62E10 A.13, which corresponds to phosphoserine phosphatase, was mostly influenced, followed by low l -serine level. Supplementation with l -serine could restore the chemotaxis index.

Background The effort to improve tracheal intubation process is clinically valuable. We hypothesized that a preoperative brief exercise therapy would increase mouth opening and neck extension, enhancing intubation conditions during general anesthesia. Methods Patients undergoing general anesthesia were randomized into two groups. The exercise group performed the exercise regimen including masseter muscle massage and stretching of jaw and neck joints before anesthetic induction, while the control did not. Before (baseline) and after the intervention, we evaluated Mallampati score, mouth aperture size, and sternomental distance. After tracheal intubation, intubation difficulty scale with direct laryngoscope and oropharyngeal soft tissue injury were also evaluated. Results A total of 138 patients completed the analysis (control = 68, exercise = 70). Baseline characteristics did not differ between groups. At anesthetic induction, there was a significant difference in Mallampati score between the two groups (P = 0.039) and the incidence of Mallampati scores of 1 was higher in the exercise group (odds ratio [95% CI]: 2.1 [1.0–4.3], P = 0.043). Mouth opening after the intervention was greater in the exercise group than in the control group (estimated difference [95% CI]: − 2.4 [− 4.8 – -0.1], P = 0.042) and sternomental distance was similar between the two groups (estimated difference [95% CI]: − 3.7 [− 9.0–1.7, P = 0.175). The exercise group showed less soft tissue injuries (odds ratio [95% CI]: 0.2 [0.1–0.8], P = 0.009), however, intubation difficulty scale did not differ between the study groups (P = 0.112). Conclusions The brief pre-anesthetic exercise improved intubation conditions and enabled faster tracheal intubation with less injury to oropharyngeal soft tissue. Trial registration Clinical Research Information Service (registration number: KCT0002618), registered at December 28, 2017.

Background: Tranexamic acid (TXA) is the most widely used hemostatic agent in surgical patients. However, when used in a high dose, it could cause a seizure in the postoperative period. The exact effector mechanism behind the seizure triggering remains unknown. Therefore, the authors investigated the effects of TXA on the activity of glutamate transporter type 3 (excitatory amino acid transporter 3; EAAT3), which is the main neuronal glutamate transporter type. Methods: EAAT3 was expressed in Xenopus laevis oocytes through mRNA injection. Oocytes were incubated with diluted tranexamic acid for 72 h. Two-electrode voltage clamping was used to measure membrane currents before, during, and after applying 30 M L-glutamate. Responses were quantified by integrating the current traces and reported in microcoulombs (C). Results were presented as mean  SEM.Results: TXA (30 to 1,000 M) significantly decreased EAAT3 activity. Our kinetic study showed that Vmax was significantly decreased in the TXA group compared with the control group (1.1  0.1 vs. 1.4  0.1 C, n = 18–23, P = 0.043), but the Km did not significantly change (12.7  3.9 M for TXA vs. 12.8  3.8 for control, n = 18–23, P = 0.986).Conclusions: Our results suggest that TXA attenuates EAAT3 activity, which may explain its proconvulsant effect.

OBJECTIVES Patients with pancreatic cancer generally experience increasing pain as their disease progresses, making the titration of opioids difficult. This study aimed to determine a correlation between prescribed opioid doses and survival time in patients with unresectable pancreatic cancer. METHODS This retrospective observational cohort study in a tertiary care institution reviewed the medical records of patients diagnosed with unresectable pancreatic cancer and treated over a 10-year period. RESULTS We screened 1152 patients with unresectable pancreatic cancer, and 566 were eligible for inclusion in this study. There was a statistically significant negative correlation between initial opioid dose and survival time from initial opioid dose (correlation coefficient, -0.184; P < 0.01) and survival time from initial pancreatic cancer diagnosis (correlation coefficient, -0.177; P < 0.01). In addition, there were 0.8% and 0.6% increases in initial opioid dosage (morphine equivalent daily dose) and rate of increasing opioid dose (morphine equivalent daily dose per month), respectively, associated with the risk of early death (≤180 days, P < 0.05). CONCLUSIONS Correlations between patient survival, initial opioid dose, final opioid dose, and the rate of increase of opioid dosage could provide useful information for clinicians treating unresectable pancreatic cancer patients.

Background Opioid usage is reportedly increased in patients with advanced cancer and low total cholesterol (TC). The aim of this study was to determine the effects of preoperative serum TC levels on postoperative opioid usage in patients undergoing laparoscopic gastric cancer surgery. Methods We retrospectively analyzed the medical records of patients with gastric cancer who underwent laparoscopic gastrectomy at our institution between January 1, 2011 and July 31, 2017. We investigated the correlation between TC levels in the month before surgery and numeric rating scale (NRS) scores and opioid consumption on postoperative days (PODs) 0 to 3. The patients were stratified according to preoperative TC level (< 160 mg/dL, low; 160 to 199 mg/dL, medium; ≥ 200 mg/dL, high). Results TC and NRS scores (PODs 0, 1) for 1,919 eligible patients showed weak but significant positive coefficients (0.074 and 0.098 on POD 0 and POD 1, respectively, P < 0.01). After adjusting for confounders, there were no significant differences in postoperative NRS scores on PODs 0, 1, 2, or 3 or in oral morphine equivalents on PODs 0 to 3 according to TC level. Conclusion Preoperative serum TC levels have no effect on pain outcomes in the 3 days following laparoscopic gastric surgery.

Background The conversion of epidural labor analgesia (ELA) to epidural surgical anesthesia (ESA) for intrapartum cesarean section (CS) often fails, resulting in intraoperative pain. Spinal anesthesia (SA) can provide a denser sensory block than ESA. The purpose of this prospective, non-blinded, parallel-arm, randomized trial was to compare the rate of pain-free surgery between ESA and SA following ELA for intrapartum CS. Methods Both groups received continuous epidural infusions for labor pain at a rate of 10 ml/h. In the ESA group (n = 163), ESA was performed with 17 ml of 2% lidocaine mixed with 100 µg fentanyl, 1 : 200,000 epinephrine, and 2 mEq bicarbonate. In the SA group (n = 160), SA was induced with 10 mg of 0.5% hyperbaric bupivacaine and 15 µg fentanyl. We investigated the failure rate of achieving pain-free surgery and the incidence of complications between the two groups. Results The failure rate of achieving pain-free surgery was higher in the ESA group than the SA group (15.3% vs. 2.5%, P < 0.001). There was no statistical difference between the two groups in the rate of conversion to general anesthesia; however, the rate of analgesic requirement was higher in the ESA group than in the SA group (12.9% vs. 1.3%, P < 0.001). The incidence of high block, nausea, vomiting, hypotension, and shivering and Apgar scores were comparable between the two groups. Conclusions SA after ELA can lower the failure rate of pain-free surgery during intrapartum CS compared to ESA after ELA.

Background Cholesterol plays an important role in the action of opioid analgesics, but its association with postoperative pain has not been clarified. Our study examined the association of pre- and postoperative total serum cholesterol (TSC), and change between the pre- and postoperative TSC levels with postoperative pain outcomes in patients with non-small cell lung cancer (NSCLC) who underwent video-assisted thoracoscopic surgery (VATS) lobectomy. Methods We retrospectively reviewed medical records of patients with NSCLC who underwent VATS lobectomy at the Seoul National University Bundang Hospital in South Korea. We sought to determine the association between preoperative TSC, TSC on postoperative day (POD) 0–1, and pre- and postoperative changes in TSC by comparing numeric rating scale (NRS) scores on POD 0, 1, and 2 and total morphine equivalent consumption on POD 0–2. Multivariate linear regression analyses were used, and P < 0.05 was considered statistically significant. Results A total of 1,720 patients with NSCLC who underwent VATS lobectomy were included in the analysis. The change in TSC, preoperative TSC, and postoperative TSC showed no associations with morphine equivalent consumption on POD 0–2 (P > 0.05). In addition, the changes in TSC, preoperative TSC, and postoperative TSC were not associated with postoperative NRS pain score on POD 0, 1, and 2 (P > 0.05). Conclusions Our results indicated that no significant association was observed between pre- and postoperative TSC level and postoperative pain outcome after VATS lobectomy of the lung.

†† Background: This prospective, randomized, double-blind study was undertaken to compare prophylactic nicardipine infusion with esmolol infusion to determine their effects on the control of hemodynamic response during emergence from total intravenous anesthesia (TIVA) with propofol and remifentanil. Methods: One hundred and thirty two patients undergoing thyroidectomy were divided randomly into 3 groups. About 10 minutes before the end of surgery, propofol was stopped in all the patients and nicardipine group (n = 44) received a continuous infusion of 2 μg/kg/min nicardipine during emergence from TIVA, esmolol group (n = 44) received 250μg/kg/min esmolol, and placebo group received 10−14 ml/hr of isotonic saline until 15 min after transfer to a postanesthesia care unit (PACU). Hemodynamic profiles were measured every minute throughout the study period. Results: MBP was significantly lower in the nicardipine group than in the esmolol group (P ＜ 0.05) from 10 min after PACU transfer until 10 min after study drug infusion stop. On the other hand, HR was significantly lower in the esmolol group than in the nicardipine group from 6 min after drug infusion. Conclusions: Nicardipine infusion attenuated blood pressure increases more effectively than esmolol infusion during emergence from TIVA. (Korean J Anesthesiol 2009; 57: 597∼603)

This retrospective study evaluated the association between maximum clot firmness of FIBTEM (MCFFIB) and blood loss, and determined a cutoff value of MCFFIB that may predict massive bleeding in total hip replacement arthroplasty (THRA). Seventy-two adult patients undergoing THRA for avascular necrosis of the femoral head or degenerative arthritis of the hip were included. Patients' medical records were reviewed to collect pre and postoperative laboratory data, as well as the amount of intra and postoperative blood loss (IBL and PBL). Each pre and postoperative fibrinogen level had a significant correlation with the pre and postoperative MCFFIB, respectively (ρ = 0.289, P = 0.014 and ρ = 0.286, P = 0.015). IBL had significant correlations with pre and postoperative MCFFIB (ρ = -0.305, P = 0.010 and ρ = -0.297, P = 0.013, respectively), and PBL also showed significant correlations with the pre and postoperative MCFFIB (ρ = -0.471, P < 0.001 and ρ = -0.475, P < 0.001, respectively). A respective pre or postoperative MCFFI cutoff value of 16 mm or less or 10 mm or less showed the highest sensitivity and specificity for predicting IBL 1000 ml or above or PBL 400 ml or above. Postoperative transfusion was performed more frequently in patients showing postoperative MCFFIB 10 mm or less (31 vs. 3.3%, P = 0.005). MCFFIB correlated well with the amount of IBL or PBL. In addition, a particular value of pre or postoperative MCFFIB could offer the predictive standard for massive bleeding in THRA.

Background In addition to propofol, dexmedetomidine is a suitable alternative for intraoperative sedation in procedures requiring regional anesthesia. To date, however, little is known about the influences of each drug on upper airway patency. Accordingly, the authors investigated differences between dexmedetomidine and propofol sedation in the occurrence of upper airway obstruction and requirements for airway intervention in patients with mild obstructive sleep apnea. Methods Patients with an apnea/hypopnea index of 5–14/h according to Watch-PAT 200 analysis were enrolled in this study. Spinal anesthesia was routinely performed for surgery. Intraoperative sedation was initiated using either dexmedetomidine or propofol infusion at a level of modified observer’s assessment of alertness/sedation scale 3. The primary outcome was the proportion of patients exhibiting signs of upper airway obstruction. A sign of upper airway obstruction was defined as no detection of end-tidal carbon dioxide for at least 10 s despite respiratory efforts. Results A total of 50 patients were included in the final analysis (dexmedetomidine [n = 26]; propofol [n = 24]). During the intraoperative sedation period, there was a significantly lower proportion of patients exhibiting signs of upper airway obstruction in the dexmedetomidine group than in the propofol group (11.5% vs. 41.7%, P = 0.035). An artificial airway was inserted in 1 patients (3.8%) and 5 patient (20.8%) in the dexmedetomidine and propofol groups, respectively (P = 0.093). Conclusion Dexmedetomidine sedation was associated with a lower incidence of upper airway obstruction than propofol sedation in patients with mild obstructive sleep apnea. Trial registration number Clinical trials.gov (NCT02993718): Retrospectively registered.

Background The relationship between statin use and incidence of postoperative delirium (POD) is controversial. We investigated the association between perioperative statin use and occurrence of delirium after total knee arthroplasty (TKA) under spinal anesthesia. Methods We retrospectively reviewed the electronic medical records of patients who underwent TKA under spinal anesthesia at single tertiary care hospital between January 2005 and October 2017. POD incidence was recorded for patients who received statins continuously from 1 month before surgery until discharge and for patients who did not receive any statins. Univariable and multivariable logistic regression analyses were conducted to investigate an association between occurrence of POD and perioperative statin use. Results In total, 6,020 procedures were included, and 992 (16.4%) were associated with perioperative statin use. POD was confirmed for 304 (5.0%) procedures. The statin group showed a 1.7% significant lower incidence ( P =0.017) of POD (35/992, 3.5%) than the no-statin group (1,420/5,028, 5.4%). In multivariable logistic regression analysis, the POD incidence in the statin group was 34% lower than that in the no statin group [odds ratio (OR), 0.66; 95% confidence interval (CI), 0.45–0.97; P = 0.036] Moreover, the POD incidence was decreased by 37% (OR, 0.63; 95% CI, 0.40–0.99; P = 0.047), and 79% (OR, 0.21; 95% CI, 0.05-0.88; P = 0.033) respectively, when atorvastatin and simvastatin were administered. Conclusions Continuous perioperative statin use may be associated with a significantly lower risk of delirium after TKA under spinal anesthesia; simvastatin was the most effective statin for POD prevention.

This study was conducted to evaluate the effect of scalp blocks using levobupivacaine on recovery profiles including postoperative pain, patient-controlled analgesia (PCA) consumption, postoperative nausea and vomiting (PONV), and other adverse events in patients undergoing frontoparietal craniotomy for aneurysm clipping.Fifty-two patients scheduled for elective frontoparietal craniotomy for unruptured aneurysm clipping were enrolled. After surgery, scalp blocks were performed using normal saline (group C, n = 26) or 0.75% levobupivacaine (group L, n = 26). Postoperative pain scores and PCA consumption were recorded for 72 hours after recovery of consciousness. The time from patient recovery to the first use of PCA drug and rescue analgesics, the requirement for vasoactive agents, and adverse effects related to PCA and local anesthetics also were recorded.Postoperative pain scores and PCA consumption in group L were lower than in group C (P.05). The time intervals from patient recovery to the first use of PCA drug (P.001) and rescue analgesics (P = .038) was longer in group L than in group C. Additionally, less antihypertensive agent was required (P = .017), and PONV occurred less frequently (P = .039) in group L than in group C.Scalp blocks with 0.75% levobupivacaine improved recovery profiles in that it effectively lowered postoperative pain and PCA consumption without severe adverse events and also reduced the requirement for a postoperative antihypertensive agent and the incidence of PONV in patients who underwent frontoparietal craniotomy for aneurysm clipping.

This study aimed to evaluate the effect of riluzole on the activity of excitatory amino acid transporter type 3 (EAAT3), a neuronal glutamate transporter, and to investigate the role of protein kinase C (PKC) in this effect. EAAT3 expression was induced in Xenopus oocytes by injecting EAAT3 mRNA. Using the two-electrode voltage clamping method, membrane currents were recorded before, during, and after applying l-glutamate (30 μM) in the absence and presence of prior incubation with riluzole (0.3-100 μM). To study the effect of PKC on the riluzole-induced change in EAAT3 activity, oocytes were preincubated with 100 μM phorbol-12-myristate-13-acetate (PMA), a PKC activator, or PKC inhibitors (2 µM staurosporine and 100 µM chelerythrine) before the recording. Responses were quantified by integrating current traces and are reported in microCoulombs (μC). Riluzole reduced EAAT3 activity in a concentration-dependent manner (0.3-100 μM). Treatment of oocytes with PMA significantly increased the baseline and riluzole-reduced EAAT activity (P0.05). In addition, treatment of oocytes with PKC inhibitors reduced basal transporter currents, but did not show a further significant decrease in the riluzole-reduced EAAT3 activity. These results suggest that riluzole reduces EAAT3 activity through PKC inhibition.

Magnesium sulfate has been used in preeclampsia patients in order to prevent seizure. It is also used for the treatment of arrhythmia and asthma and as an anesthetic adjunct in patients undergoing surgery for pheochromocytoma. However, its potentiating effects on perioperative analgesia and muscle relaxation have drawn attention recently. These characteristics of magnesium (anesthetic- and analgesic-sparing effect) enable anesthesiologists to reduce the use of anesthetics during surgery and the use of analgesics after surgery. Magnesium sulfate has a high therapeutic index and cost-effectiveness. Considering these diverse characteristics useful for anesthesia, appropriate use of magnesium sulfate would improve surgical outcome and patients' satisfaction.

Caffeine has been known to trigger seizures, however, the precise mechanism about the proconvulsive effect of caffeine remains unclear. Glutamate transporters play an important role to maintain the homeostasis of glutamate concentration in the brain tissue. Especially, dysfunction of excitatory amino acid transporter type 3 (EAAT3) can lead to seizures. We investigated the effects of caffeine on the activity of EAAT3 and the involvement of protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K). Rat EAAT3 was expressed in Xenopus oocytes by injecting EAAT3 mRNA. l- Glutamate (30 μM)-induced inward currents were recorded via the two-electrode voltage clamp method. Caffeine decreased EAAT3 activity in a dose-dependent manner. Caffeine (30 μM for 3 min) significantly reduced V max , but did not alter K m value of EAAT3 for glutamate. When preincubated oocytes with phorbol-12-myristate-13-acetate (PMA, a PKC activator) were exposed to caffeine, PMA-induced increase in EAAT3 activity was abolished. Two PKC inhibitors (chelerythrine and staurosporine) significantly reduced basal EAAT3 activity. Whereas, there were no significant differences among the PKC inhibitors, caffeine, and PKC inhibitors + caffeine groups. In similarly fashion, wortmannin (a PI3K inhibitor) significantly decreased EAAT3 activity, however no statistical differences were observed among the wortmannin, caffeine, and wortmannin + caffeine groups. Our results demonstrate that caffeine attenuates EAAT3 activity and this reducing effect of caffeine seems to be mediated by PKC and PI3K.

Postoperative sore throat (POST) is a common complaint after general anesthesia, especially following thyroidectomy.We examined the effect of adjusting the endotracheal tube cuff pressure during thyroidectomy on the incidence of airway complications. Ninety patients scheduled for elective thyroidectomy were randomized into two groups: control (group A, n = 45) and experimental (group B, n = 45). All patients underwent total intravenous anesthesia with propofol and remifentanil. In group A, the cuff pressure was set to 25 cm H2O initially and then monitored continuously without adjustment during thyroidectomy. In group B, the cuff pressure was maintained at approximately 25 cm H2O throughout the operation. The incidences and the severity of POST, hoarseness, dysphagia, and cough were recorded at 2 and 24 h postoperatively.Cuff pressures in group A changed significantly over time (P 0.05) and were higher than those of group B during thyroidectomy (P 0.05). The incidences of POST were lower in group B than in group A at 2 and 24 h postoperatively (P 0.05), and there was a significant difference in the severity of POST at 2 h postoperatively between the two groups. There were no differences in the incidences of hoarseness, dysphagia, and cough between the two study groups (P 0.05). Adjusting the endotracheal cuff pressure during thyroidectomy decreased the incidence and degree of POST.Intraoperative monitoring and adjustment of the cuff pressure can reduce POST in patients undergoing thyroidectomy.

Study objective We evaluated the effect of magnesium sulfate—an enhancer of neuromuscular blockade—on onset and duration of low dose of rocuronium, and on operating conditions during laryngeal microsurgery. Design Randomized, prospective, double-blinded study. Patients Eighty-four patients scheduled for elective laryngeal microsurgery. Interventions Patients were randomly allocated to receive different doses of rocuronium: 0.6 mg/kg (group C, n=28), 0.45 mg/kg (group LR, n=28), or 0.45 mg/kg plus magnesium sulfate 30 mg/kg (group LM, n=28). Measurements We measured the onset time and duration of action of rocuronium, and evaluated the surgeon's satisfaction with the operating conditions. Main results Group LR showed significantly delayed onset time (group C: 87±22 seconds, group LR: 127±47 seconds, and group LM: 89±32 seconds; P =.001) and maximal suppression than did other groups (group C: 102±30 seconds, group LR: 155±66 seconds, and group LM: 105±36 seconds; P =.002). Duration of action of rocuronium was significantly longer in group C than in other groups (group C: 39±7 minutes, group LR: 28±8 minutes, group LRM: 31±8 minutes; P P =.002), surgeon's satisfaction ( P =.005), and sore throat ( P =.035) were significantly worse in group LR. Conclusions Magnesium sulfate 30 mg/kg accelerated the onset and improved operating conditions of low-dose rocuronium without prolongation of action.

Background Sevoflurane is widely used in paediatric anaesthesia but frequently causes emergence agitation (EA). This study evaluated whether limiting the sevoflurane concentration by combining remifentanil with sevoflurane reduced the incidence of EA. Methods Eighty-four preschool children scheduled for adenotonsillectomy were randomly assigned to either the remifentanil or sevoflurane group. In the remifentanil group, anaesthesia was induced with thiopental, rocuronium, and 1% sevoflurane. It was maintained with 1% sevoflurane, 60% nitrous oxide in oxygen, and a continuous infusion of remifentanil. For the sevoflurane group, anaesthesia was induced with thiopental, rocuronium, and 8% sevoflurane, and was maintained with 2–3% sevoflurane. Both groups received ketorolac 1 mg/kg and dexamethasone 0.15 mg/kg. EA was measured using the paediatric anaesthesia emergence delirium (PAED) scale and a four-point EA scale in the post-anaesthesia care unit. Results The scores on the PAED scales were significantly lower in the remifentanil group than in the sevoflurane group [median (interquartile range); 6 (4.25–10.25) vs. 11 (7.75–14.0), P = 0.007], and the proportion of patients with PAED scores ≥ 10 was significantly lower in the remifentanil group than in the sevoflurane group [15 (35.7%) vs. 27 (64.2%), P = 0.009]. The incidence of EA evaluated using the four-point scale was also lower in the remifentanil group [11 (26.1%) vs. 21 (50%), respectively, P = 0.025]. Conclusion The incidence of EA was lower in children undergoing adenotonsillectomy who received a lower concentration of sevoflurane combined with remifentanil than in those given a higher concentration of sevoflurane without remifentanil.

Laryngoscopy and tracheal intubation (LTI) after induction of general anesthesia often cause hypertension and tachycardia. Labetalol and nicardipine have been used to prevent and treat acute cardiovascular responses to LTI.The goal of this study was to compare the preventive and therapeutic effects of labetalol 0.4 mg/kg IV and nicardipine 20 μg/kg IV on hypertensive responses to LTI during induction of general anesthesia.Patients undergoing general anesthesia were randomly allocated to 4 groups. In part I (prevention), 80 patients were randomized to receive either 0.4 mg/kg of labetalol (n = 40) or 20 μg/kg of nicardipine (n = 40) 4 minutes before LTI. In part II (treatment), patients were randomized to receive 0.4 mg/kg of labetalol (n = 40) or 20 μg/kg of nicardipine (n = 40) after LTI if hypertension occurred. The number of additional study drug doses required by patients with hypertension (parts I and II) and time to return to normotension (part II) were recorded. Mean arterial pressure and heart rate were monitored, and rate-pressure product was calculated. Adverse events were also monitored.A total of 130 patients (72 patients in part I and 58 patients in part II) were included in the analysis. In parts I and II, the number of patients who required additional doses of the study drug because of persistent hypertension was lower in the nicardipine groups than in the labetalol groups (P0.05). Mean arterial pressure was lower and heart rate was significantly higher over time in the nicardipine groups compared with the labetalol groups (P0.05) in parts I and II. In part II, time to return to normotension was shorter in the nicardipine treatment group than in the labetalol treatment group (61 [21] vs 130 [46] seconds; P = 0.01). No statistical differences were observed in the incidence of adverse events except for tachycardia in part I (2 cases in the labetalol prevention group vs 18 cases in the nicardipine prevention group; P = 0.01).Patients who received nicardipine were less likely to require additional doses for either the prevention or treatment of hypertensive responses to LTI and responded to the study drug more rapidly than patients who received labetalol for the treatment of hypertensive responses to LTI. However, labetalol was associated with a lower incidence of tachycardia and less of an increase in rate-pressure product when used for the prevention of hypertension during LTI.

Background Remifentanil is known to cause bradycardia and hypotension, as well as the decreases of cardiac output (CO). We hypothesized that hemodynamic suppression by remifentanil would affect the onset time of rocuronium. This study investigated whether the onset of rocuronium was influenced by the drug-administration sequence during induction of anesthesia with target-controlled infusion of propofol and remifentanil. Methods Healthy adult patients (n = 126) undergoing elective surgery under general anesthesia were randomized into two groups according to drug-administration sequence. In Remi-Pro-Rocu group (n = 62), remifentanil was infused first, followed by propofol. Then, rocuronium was administered lastly. In Pro-Rocu-Remi group (n = 64), propofol, rocuronium, and remifentanil were given in that order. As a primary outcome, the onset time of rocuronium was measured. Mean arterial pressure (MAP), heart rate (HR), CO, and stroke volume were recorded before anesthesia (T1), at injection of rocuronium (T2), immediately before and after intubation (T3 and T4). Results In Remi-Pro-Roc group, the onset of rocuronium was delayed significantly compared with Pro-Rocu-Remi group [median (interquartile range); 130 (105–150) vs. 90 (71–100) s, P

Background: Dexmedetomidine has a sedative analgesic property without respiratory depression. This study evaluated the efficacy of dexmedetomidine as an appropriate sedative drug for monitored anesthesia care (MAC) in outpatients undergoing cataract surgery on both eyes compared with combination of propofol and alfentanil. Methods : Thirty-one eligible patients were randomly divided into two groups on the first operation day. Dexmedetomidine was administered in group D at 0.6 μg/kg/h, and propofol and alfentanil was infused concomitantly in group P at a rate of 2 mg/kg/h and 20 μg/kg/h, respectively. Sedation was titrated at Ramsay sedation score 3. Iowa satisfaction with anesthesia scale (ISAS) of the patients was evaluated postoperatively. Systolic blood pressure (SBP), heart rate (HR), respiration rate (RR), and peripheral oxygen saturation (SpO2) were recorded throughout the surgery. For the second operation, the group assignments were exchanged. Results: Postoperative ISAS was 50.3 (6.2) in group D and 42.7 (8.7) in group P, which was statistically significant (P < 0.001). SBP was significantly lower in group D compared with group P from the beginning of the operation. HR, RR, and SpO2 were comparable between the two groups. There were 8 cases (25.8%) of hypertension in group P, and 1 case (3.2%) in group D (P < 0.05). In contrast, 1 case (3.2%) of hypotension and 1 case (3.2%) of bradycardia occurred in group D. Conclusions: Compared with the combined use of propofol and alfentanil, dexmedetomidine could be used appropriately for MAC in cataract surgery with better satisfaction from the patients and a more stable cardiovascular state. (Korean J Anesthesiol 2011; 61: 453-459)

BACKGROUND: The authors examined the impact of parenteral iron and recombinant human erythropoietin-β (rHuEPO-β) administered in the bilateral total knee replacement arthroplasty (TKRA), on postoperative anemia and transfusion requirements in iron-deficient patients. STUDY DESIGN AND METHODS: A total of 108 iron-deficient patients were randomly assigned to two groups: Group C (control) or Group IE (200 mg of iron sucrose intravenously over 1 hr and 3000 IU of rHuEPO-β subcutaneously during the operation and during the postoperative period if the hemoglobin [Hb] level was 70-80 g/L). One or 2 units of blood were transfused to patients in both groups according to postoperative Hb level (between 60 and 70 g/L or betweeen 50 and 60 g/L, respectively). Perioperative laboratory and clinical outcomes (Hb, iron variables, postoperative bleeding amount, and number of units of RBCs transfused and incidences) were documented. RESULTS: Although preoperative Hb and the amount of postoperative bleeding were comparable in the two groups, Hb levels at 1, 2, and 3 days and at 2 and 6 weeks postoperation were significantly higher in Group IE. Furthermore, the transfusion rate was significantly lower in Group IE (20.4% vs. 53.7%, p = 0.011) and the mean number of red blood cell units transfused was markedly lower in Group IE (0.2 ± 0.5 vs. 0.8 ± 0.8, p = 0.005). Postoperative iron, ferritin, and transferrin saturation levels were significantly higher in Group IE. CONCLUSIONS: Treatment with parenteral iron and low-dose rHuEPO-β in bilateral TKRA effectively attenuated anemia and decreased transfusion requirements in iron-deficient patients.

Glucocorticoids can increase the extracellular concentrations of glutamate, the major excitatory neurotransmitter. We investigated the effects of corticosterone on the activity of a glutamate transporter, excitatory amino acid carrier 1 (EAAC1; also called excitatory amino acid transporter type 3 [EAAT3]), and the roles of protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) in regulating these effects. Rat EAAC1 was expressed in Xenopus oocytes by injecting mRNA. L-Glutamate (30 μM)-induced membrane currents were measured using the two-electrode voltage clamp technique. Exposure of these oocytes to corticosterone (0.01-1 μM) for 72 h decreased EAAC1 activity in a dose-dependent fashion, and this inhibition was incubation time-dependent. Corticosterone (0.01 μM for 72 h) significantly decreased the V(max), but not the K(m), of EAAC1 for glutamate. Furthermore, pretreatment of oocytes with staurosporine, a PKC inhibitor, significantly decreased EAAC1 activity (1.00±0.06 to 0.70±0.05 μC; P

To determine the effect-site target concentration (C(et)) of remifentanil that provides optimal conditions for patients and operators during cataract surgery during monitored anesthesia care using a target controlled infusion (TCI) of propofol and remifentanil.Prospective, randomized, double-blinded study.Operating room and postoperative recovery area of a university-affiliated hospital.66 adult, ASA physical status I, II, and III patients undergoing cataract surgery.Group I received C(et) of remifentanil 0.5 ng/mL; Group 2 received C(et) of remifentanil one ng/mL; and Group 3 received C(et) of remifentanil 1.5 ng/mL. After giving TCI propofol (C(et); one μg/mL)-remifentanil, an ophthalmologist administered topical anesthesia.Intraoperative hemodynamics, pain scores, sedation scores, patient satisfaction scores, and operators' satisfaction scores regarding surgical conditions were recorded. No statistical differences in heart rate or mean blood pressure were detected among the three groups during surgery. Pain scores (Group 1: 31.9 ± 17.9 vs. Group 2: 11.8 ± 7.7 and Group 3: 11.8 ± 7.7; P0.05) were higher and patient satisfaction scores (Group 1: 4.7 ± 0.8 vs. Group 2: 5.4 ± 0.4 and Group 3: 5.5 ± 0.4; P0.05) were lower in Group 1 than Groups 2 and 3. On the other hand, surgeon satisfaction was lowest in Group 3 (Group 3: 2.9 ± 1.3 vs. Group 1: 4.7 ± 0.4 and Group 2: 4.6 ± 0.7; P0.05) due to ocular movement.C(et) values of remifentanil and propofol of one ng/mL and one μg/mL, respectively, appear to provide optimal conditions for patients and operators during cataract surgery using monitored anesthesia care with TCI.

Propofol-based total intravenous anesthesia (TIVA) has been reported to improve long-term outcome following cancer surgery, when compared with inhalation agents. However, such investigational reports are still controversial, and no studies have been conducted in relation to non-small cell lung cancer (NSCLC) surgery. The present study aimed to compare the favorable effects of TIVA versus inhalation agents on recurrence-free survival and overall survival after curative resection of NSCLC. This retrospective cohort study examined medical records of the patients who were diagnosed with NSCLC and underwent curative resection at Seoul National University Bundang Hospital from August 2003 to July 2012. The primary outcome included the comparison of postoperative overall survival and recurrence-free survival in both groups. To balance the 2 groups for analysis, a propensity matching method was used, and stratified Cox proportional hazard models were used for statistical analysis. This study included 943 cases of NSCLC for final analysis, and the cases were divided into the TIVA group (n = 749) and inhalation group (n = 194). Propensity matching produced 196 patients in each group. The final analysis revealed no significant difference in the hazard ratio (HR) for recurrence between the TIVA and inhalation groups ( P = .233). The HR for death between the 2 groups was not significantly different either ( P = .551). In this study, we found no benefit of propofol-based TIVA for long-term oncologic outcome after NSCLC surgery, relative to inhalation agents.

BACKGROUND: The extracellular glutamate concentration is tightly controlled by excitatory amino acid transporters (EAATs). EAAT4 is the predominant EAAT in the cerebellar Purkinje cells. Purkinje cells play a critical role in motor coordination and may be an important target for ethanol to cause motor impairments. We designed this study to determine the effects of chronic ethanol exposure on the activity of EAAT4 and evaluate the involvement of protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) in these effects. METHODS: EAAT4 was expressed in Xenopus oocytes following injection of EAAT4 mRNA. Oocytes were incubated with ethanol-containing solution for 24 to 96 hours. Membrane currents induced by l-aspartate were recorded using 2-electrode voltage clamps. Responses were quantified by integration of the current trace and reported in microCoulombs (microC). RESULTS: Ethanol dose- and time-dependently reduced EAAT4 activity. EAAT4 activity after a 96-hour exposure was significantly decreased compared to the control values at all concentrations tested (10 to 100 mM). Ethanol (50 mM) significantly decreased the Vmax (2.2 +/- 0.2 microC for control vs. 1.6 +/- 0.2 microC for ethanol, n = 18, p < 0.05) of EAAT4 for L-aspartate. Preincubation of ethanol-treated (50 mM for 96 hours) oocytes with phorbol-12-myrisate-13-acetate (100 nM for 10 minutes) abolished the ethanol-induced decrease in EAAT4 activity. While staurosporine (2 microM for 1 hour) or chelerythrine (100 microM for 1 hour) significantly decreased EAAT4 activity, no difference was observed in EAAT4 activity among the staurosporine, ethanol, or ethanol plus staurosporine groups. Similarly, EAAT4 activity did not differ among the chelerythrine, ethanol, or ethanol plus chelerythrine groups. Pretreatment of the oocytes with wortmannin (1 microM for 1 hour) also significantly decreased EAAT4 activity. However, no difference was observed in the wortmannin, ethanol, or ethanol plus wortmannin groups. CONCLUSIONS: The results of this study suggest that chronic ethanol exposure decreases EAAT4 activity and that PKC and PI3K may be involved in these effects. These effects of ethanol on EAAT4 may cause an increase in peri-Purkinje cellular glutamate concentration, and may be involved in cerebellar dysfunction and motor impairment after chronic ethanol ingestion.

We evaluated changes in rotational thromboelastometry (ROTEM(®) ) parameters and clinical outcomes in patients undergoing total hip replacement arthroplasty, with concomitant infusions of tranexamic acid and of 6% hydroxyethyl starch 130/0.4. Fifty-five patients were randomly assigned to either the tranexamic acid (n = 29) or the control (n = 26) group. Hydroxyethyl starch was administered in the range of 10-15 ml.kg(-1) during the operation in both groups. In the control group, the clot formation time and maximum clot firmness of APTEM showed significant differences when compared with those of EXTEM at one hour postoperatively, suggestive of fibrinolysis. In the tranexamic acid group, there was no significant difference between each postoperative EXTEM and APTEM parameter. In the tranexamic acid and control group, postoperative blood loss was 308 ml (210-420 [106-745]) and 488 ml (375-620 [170-910], p = 0.002), respectively, and total blood loss was 1168 ml (922-1470 [663-2107]) and 1563 ml (1276-1708 [887-1494], p = 0.003). Haemoglobin concentration was higher in the tranexamic acid group on the second postoperative day (10.5 (9.4-12.1 [7.9-14.0]) vs. 9.6 (8.9-10.5[7.3-16.0]) g.dl(-1) , p = 0.027). In patients undergoing total hip replacement arthroplasty, postoperative fibrinolysis aggravated by hydroxyethyl starch was attenuated by co-administration of 10 mg.kg(-1) tranexamic acid, which may have led to less postoperative blood loss.

Glutamate transporters (excitatory amino acid transporters, EAAT) regulate extracellular concentrations of glutamate, a major excitatory neurotransmitter. We reported that acute ethanol exposure increases the activity of a major neuronal EAAT, EAAT3. This effect is consistent with the general inhibitory effect of acute alcohol toxicity in the central nervous system (CNS). However, chronic ethanol exposure has CNS presentations different from acute alcohol toxicity. We hypothesize that chronic ethanol exposure will affect the EAAT3 activity differently from acute ethanol exposure.EAAT3 was expressed in Xenopus oocytes by injection of EAAT3 mRNA. Oocytes were incubated with diluted ethanol for 24-96 hr. Using two-electrode voltage clamp, membrane currents were recorded after the application of L-glutamate. Responses were quantified by integration of the current trace and reported as microCoulombs (microC).Ethanol (10-100 mM) reduced EAAT3 activity in a time-dependent and reversible manner. After a 96 hr-incubation, the activity was significantly decreased compared to the control values at any concentrations tested in this study. Kinetic study demonstrated that a 96 hr-exposure to 50 mM ethanol significantly decreased Vmax (3.6 +/- 0.3 for control versus 2.6 +/- 0.3 microC for ethanol, n = 20, p0.05) but had no effect on Km (57.6 +/- 12.8 for control versus 51.8 +/- 16.3 microM for ethanol, n = 20, p0.05) of EAAT3 for glutamate. When ethanol (50 mM for 96 hr)-treated oocytes were incubated with phorbol-12-myrisate-13-acetate (50 or 100 nM for 10 min), ethanol-induced decrease in EAAT3 activity was abolished. Preincubation of the oocytes with 100 microM chelerythrine significantly decreased EAAT3 activity (1.00 +/- 0.08 for control versus 0.51 +/- 0.09 microC for chelerythrine group, n = 18-20, p0.05). However, there was no statistical difference among the chelerythrine, ethanol, or chelerythrine plus ethanol groups. Likewise, staurosporine (2 microM for 1 hr) significantly decreased EAAT3 activity and there was no statistical difference among the staurosporine, ethanol, or staurosporine plus ethanol groups.Our results show that chronic ethanol exposure decreases EAAT3 activity at clinically relevant concentrations and that this effect may be protein kinase C-dependent. Such an effect could be a neuroadaptive mechanism to overcome the inhibitory effect of ethanol on the excitatory neurotransmission.

Background Hydroxyethyl starch (HES) solutions are used as plasma expanders for correcting hypovolemia, but can lead to impaired coagulation. We evaluated the changes in hematological and hemostatic profiles with three types of HES. Methods Patients were randomized to receive volume replacement with 10% pentastarch 260/0.45 in 0.9% saline (Group-PEN, n = 25), 6% tetrastarch 130/0.4 in 0.9% saline (Group-TETS, n = 25), or 6% tetrastarch 130/0.4 in a balanced electrolyte solution (Group-TETB, n = 25). Coagulation was assessed using rotational thromboelastometry (ROTEM®) and other laboratory tests were performed, including measurements of hematological and hemostatic parameters and electrolytes. Results Post-operative ROTEM® parameters changed toward hypocoagulable states in all groups. The post-operative parameters of EXTEM and FIBTEM were more impaired in Group-PEN than in Group-TETB. The percentage change in INTEM clot formation time (P = 0.004) and α-angle (P = 0.003) were smaller in Group-TETS and Group-TETB than in Group-PEN. The percentage change in the FIBTEM maximum clot firmness was greatest in Group-PEN (P = 0.011). The international normalized ratio of prothrombin time (P < 0.001) and the activated partial thromboplastin time (P < 0.001) were significantly prolonged in Group-PEN compared to those of Group-TETB. Conclusions The 6% HES 130/0.4 in a balanced electrolyte solution seemed to have less of an impact on blood coagulation than the 10% HES 260/0.45. No differences in hemostatic profile were observed between the balanced electrolyte and saline-based 6% HES 130/0.4.

Desflurane is a volatile anaesthetic agent with neuroprotective properties. Excitatory amino-acid carrier 1 (EAAC1) may be neuroprotective by taking up glutamate and cysteine. Therefore, the effects of desflurane on EAAC1 activity were investigated in this study. EAAC1 was expressed in Xenopus laevis oocytes. Two-electrode voltage-clamping technique was used to record membrane currents upon exposure to l -glutamate (30 μM) in the presence or absence of desflurane (0.4, 1.0, 2.0, 2.6, or 3.2 mM). Currents were also measured in oocytes pre-exposed to a protein kinase C (PKC) activator (50 nM phorbol-12-myristate-13-acetate, PMA), PKC inhibitors (1 μM staurosporine or 50 μM chelerythrine), or phosphatidylinositol-3-kinase (PI3K) inhibitors (5 μM wortmannin or 10 μM LY294002). Desflurane significantly increased EAAC1 activity. The EC50 of desflurane for increasing the EAAC1 response was 0.75 mM. A kinetic study showed that desflurane significantly increased the Vmax but had no effect on the Km of the EAAC1 response for glutamate. Treatment of oocytes with desflurane plus PMA significantly increased the transporter currents compared to the control, but did not further increase the response compared to either agent alone. Staurosporine attenuated desflurane-enhanced transporter currents without decreasing the basal activity; chelerythrine did not decrease either. In addition, pretreatment of oocytes with two PI3K inhibitors (wortmannin or LY294002) significantly reduced desflurane-enhanced EAAC1 activity without decreasing basal activity. Our results suggest that desflurane increases EAAC1 activity via PKC or PI3K. This enhanced EAAC1 activity may be a mechanism for the neuroprotective effect of desflurane.

This study was designed to investigate whether stepwise tapering of remifentanil at the end of surgery could decrease postoperative pain scores and requirements of rescue analgesics after remifentanil-desflurane anesthesia in patients with thyroidectomy. Sixty two patients undergoing thyroidectomy under general anesthesia were randomly allocated into two groups. All patients were anesthetised with desflurane and high-dose remifentanil. Remifentnail was infused at the rate of 0.3 μg/kg/min until the end of surgery in patients of the control group (group A) whereas remifentanil was tapered gradually from 0.3 to 0.1 μg/kg/min until the end of surgery for at least 30 minutes in patients with group B. Pain scores (0–100 numerical rating scale, NRS), rescue analgesic requirements and adverse events were assessed at 30 min, 2 h, 6 h, 12 h, and 24 h after operation. There was a significant decrease in pain scores at 30 min (20 [0–80] vs. 50 [0–100], P = 0.002) and 2 h (30 [10–60] vs. 40 [20–80], P = 0.018) after surgery in group B compared with group A. In addition, rescue analgesics are less required in group B than in group A postoperatively (2 [1-3] vs. 3 [2,3], P = 0.039). There were no significant differences in adverse events between the two groups. Tapering of remifentanil at the end of surgery decreased postoperative pain scores immediately after thyroidectomy with desflurane and high-dose remifentanil anesthesia. Clinical Research information Service (CRiS, registration number KCT0000589 ).

The purpose of this study was to evaluate the effect of ondansetron on excitatory amino acid transporter type 3 (EAAT3) and to elucidate the roles of protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) in the effect. EAAT3 was expressed in Xenopus oocytes following the injection of rat EAAT3 mRNAs. Using the two-electrode voltage clamping method, the inward currents induced by l -glutamate were measured for 1 min in the presence and absence of ondansetron (1–1000 μM). Different concentrations of l -glutamate (3–300 μM) were used to determine the kinetic characteristics of EAAT3. To identify the involvement of PKC and PI3K in the effect, oocytes were exposed to a PKC activator and to PKC inhibitors and PI3K inhibitors, and l -glutamate-induced currents were recorded. Ondansetron decreased EAAT3 activity in a dose-dependent manner. In a kinetic study, ondansetron (10 μM for 3 min) reduced V max , but not K m compared with the control group. The PKC activator abolished the ondansetron-induced decrease in EAAT3 activity. The PKC inhibitors (staurosporine and chelerythrine) and ondansetron had not additive or synergistic effects on EAAT3 activity. The PI3K inhibitors (wortmannin and LY294002) decreased the EAAT3 response, although there were no differences among the groups comprising ondansetron, PI3K inhibitors, and PI3K inhibitors plus ondansetron. Our results demonstrate that ondansetron attenuates EAAT3 activity and this effect seems to be mediated by PKC and PI3K.

Dexmedetomidine, an α2 adrenergic agonist, has neuroprotective and anticonvulsant properties in addition to its sedative and anxiolytic effects. We hypothesized that dexmedetomidine would increase the activity of excitatory amino acid transporter type 3 (EAAT3) and that this effect would involve protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K), two protein kinases known to regulate EAAT3 activity. EAAT3 was expressed in Xenopus oocytes by injecting its mRNA. Two-electrode voltage clamping was used to record membrane currents before, during, and after application of 30 μM l-glutamate in the presence of 0.1-30 nM dexmedetomidine. Dexmedetomidine-treated oocytes were also exposed to a PKC activator (phorbol-12-myristate-13-acetate [PMA]), PKC inhibitors (chelerythrine, staurosporine, and calphostin C), and PI3K inhibitors (wortmannin and LY294002) before current measurement. Dexmedetomidine application resulted in a concentration-dependent increase in the EAAT3 activity in response to l-glutamate. The kinetic study showed that dexmedetomidine significantly increased the Vmax without changing Km. Treatment of oocytes with PMA significantly increased transporter currents compared with controls, but treatment with dexmedetomidine plus PMA did not further increase the response compared with PMA or dexmedetomidine alone. In addition, pre-treatment of oocytes with PKC inhibitors and PI3K inhibitors significantly abolished the dexmedetomidine-enhanced EAAT3 activity. These results suggest that dexmedetomidine increases the activity of EAAT3 expressed in Xenopus oocytes. PKC and PI3K seem to mediate this effect. These findings may explain the neuroprotective and anticonvulsant effects of dexmedetomidine.

Nicotine, the main ingredient of tobacco, elicits seizures in animal models and cigarette smoking is regarded as a behavioral risk factor associated with epilepsy or seizures. In the hippocampus, the origin of nicotine-induced seizures, most glutamate uptake could be performed primarily by excitatory amino acid transporter type 3 (EAAT3). An association between temporal lobe epilepsy and EAAT3 downregulation has been reported. Therefore, we hypothesized that nicotine may elicit seizures through the attenuation of EAAT3 activity. We investigated chronic nicotine exposure (72 h) cause reduction of the activity of EAAT3 in a Xenopus oocyte expression system using a two-electrode voltage clamp. The roles of protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) were also determined. Nicotine (0.001-1 μM) resulted in a time- and dose-dependent decrease in EAAT3 activity with maximal inhibition at nicotine concentrations of 0.03 μM or higher and at an exposure time of 72 h. Vmax on the glutamate response was significantly reduced in the nicotine group (0.03 μM for 72 h), but the Km value of EAAT3 for glutamate was not altered. When nicotine-exposed oocytes (0.03 μM for 72 h) were pretreated with phorbol-12-myristate-13-acetate (PMA, a PKC activator), the nicotine-induced reduction in EAAT3 activity was abolished. PKC inhibitors (staurosporine, chelerythrine, and calphostin C) significantly reduced basal EAAT3 activity, but there were no significant differences among the PKC inhibitors, nicotine, and PKC inhibitors+nicotine groups. Similar response patterns were observed among PI3K inhibitors (wortmannin and LY294002), nicotine, and PI3K inhibitors+nicotine. In conclusion, this study suggests that nicotine decreases EAAT3 activity, and that this inhibition seems to be dependent on PKC and PI3K. Our results may provide an additional mechanism for nicotine-induced seizure.

The adverse effects of spinal anesthesia (SA) include arterial hypotension and bradycardia. The aim of this study was to compare the effects of 2 type 3 serotonin receptor antagonists in SA-induced adverse effects. Specifically, we assessed whether ramosetron was more effective than ondansetron in reducing SA-induced decreases in blood pressure (BP) and heart rate (HR).A total of 117 patients undergoing orthopedic surgery and receiving SA were intravenously administered 0.3 mg of ramosetron (n = 39, group R), 4 mg of ondansetron (n = 39, group O4), or 8 mg of ondansetron (n = 39, group O8). Systolic BP (SBP), diastolic BP (DBP), mean BP (MBP), HR, and the lowest SBP, DBP, MBP, and HR values were measured preoperatively (baseline) and intraoperatively. The incidence of postoperative nausea and vomiting, the need for rescue antiemetics, the amount of patient-controlled analgesia consumption, and pain score in the first 48 hours after surgery were determined.Baseline values did not significantly differ among the 3 groups. After SA, SBP, DBP, MBP, and HR were lower than their baseline values in all 3 groups. The differences between the baseline and the lowest values were significantly less in group R than in groups O4 and O8 with respect to SBP (P0.001), DBP (P = 0.001), and MBP (P0.001) less in group R than in group O4 with respect to HR (P = 0.032). Intergroup differences were not significant for postoperative nausea and vomiting, the need for rescue antiemetics, patient-controlled analgesia consumption, or pain score.The administration of ramosetron (0.3 mg) significantly attenuated the SA-induced decrease in BP compared with 4 or 8 mg of ondansetron and HR compared with 4 mg of ondansetron.

Many anti-epileptics cause resistance to non-depolarizing neuromuscular blocking agents, but this has not been reported for valproic acid (VPA). We hypothesized that VPA would increase the rocuronium requirement and that magnesium sulphate (MgSO(4)) may reduce this increase.Fifty-five patients undergoing cerebrovascular surgeries were studied. Subjects were allocated into three groups at a 1:1:1 ratio: Groups VM, VC, and C. Groups VM and VC were given VPA premedication; Group C was not. A rocuronium injection (0.6 mg kg(-1) i.v.) was administered to Group VM, followed by MgSO(4) as a 50 mg kg(-1) i.v. bolus and 15 mg kg(-1) h(-1) infusion. The same volume of 0.9% saline was administered to the other groups. Supplementary rocuronium (0.15 mg kg(-1)) was given whenever the train-of-four count reached 2. Rocuronium requirements (primary outcome), mean arterial pressure (MAP), heart rate (HR), nausea, vomiting, shivering, and use of anti-emetics and nicardipine were compared.Group VC showed the highest rocuronium requirement [mg kg(-1) h(-1): 0.47 (0.08) vs 0.33 (0.12) (Group C), 0.31 (0.07) (Group VM); P0.001]. MAP, intraoperative HR, nausea, vomiting, shivering, and use of anti-emetics and nicardipine were not significantly different among the groups. Postoperative HR was lower in Group VM than in Group VC.VPA increased the rocuronium requirement, and MgSO(4) infusion attenuated this increase.

Estrogen, a neuroactive sex hormone in the brain, enhances neuronal excitability and increases seizures. Glutamate transporters help in limiting the excitatory neurotransmission by uptaking glutamate from the synapses. We investigated the effects of 17β-estradiol on the activity of a glutamate transporter, excitatory amino acid transporter 3 (EAAT3), in Xenopus oocytes. EAAT3 was expressed in Xenopus oocytes by injection of rat EAAT3 mRNA. l -Glutamate (30 μM)-induced membrane currents mediated by EAAT3 were measured using the two-electrode voltage clamp technique. 17β-Estradiol reduced EAAT3 activity in a concentration- and time-dependent manner. 17β-Estradiol (10 nM for 72 h) significantly decreased Vmax but had no effect on Km of EAAT3 for glutamate. When 17β-estradiol treated oocytes were incubated with phorbol-12-myrisate-13-acetate, a protein kinase C (PKC) activator, 17β-estradiol-induced decrease in EAAT3 activity was abolished. Furthermore, in pretreatment of oocytes with chelerythrine or staurosporine, two PKC inhibitors, EAAT3 activity was significantly decreased. However, there was no statistical difference among the 17β-estradiol, PKC inhibitor, or 17β-estradiol plus PKC inhibitor groups. Likewise, wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, significantly reduced basal EAAT3 activity, but the activity did not differ among the 17β-estradiol, wortmannin, or 17β-estradiol plus wortmannin groups. Estradiol receptor inhibitor, fulvestrant, did not change the reduced EAAT3 activity by 17β-estradiol. Our results suggest that 17β-estradiol decreases EAAT3 activity. PKC and PI3K seem to be involved in this effect, possibly not via estradiol receptors.

In a randomized, double-blind, prospective study, we have evaluated the effect of i.v. infusion of magnesium sulphate during spinal anaesthesia on postoperative analgesia and postoperative analgesic requirements.Forty patients undergoing total hip replacement arthroplasty under spinal anaesthesia were included. After the induction of spinal anaesthesia, the magnesium group (Group M) received magnesium sulphate 50 mg kg(-1) for 15 min and then 15 mg kg(-1) h(-1) by continuous i.v. infusion until the end of surgery. The saline group (Group S) received the same volume of isotonic saline over the same period. After surgery, a patient-controlled analgesia (PCA) device containing morphine and ketorolac was provided for the patients. Postoperative pain scores, PCA consumption, and the incidences of shivering, postoperative nausea, and vomiting were evaluated immediately after surgery, and at 30 min, 4, 24, and 48 h after surgery. Serum magnesium concentrations were checked before the induction of anaesthesia, immediately after surgery, and at 1 and 24 h after surgery.Postoperative pain scores were significantly lower in Group M at 4, 24, and 48 h after surgery (P0.05). Cumulative postoperative PCA consumptions were also significantly lower in Group M at 4, 24, and 48 h after surgery (P0.05). Postoperative magnesium concentrations were higher in Group M (P0.05 at 4, 24, and 48 h after surgery), but no side-effects associated with hypermagnesemia were observed. Haemodynamic variables and the incidences of shivering, nausea, and vomiting were similar in the two groups.I.V. magnesium sulphate administration during spinal anaesthesia improves postoperative analgesia.

Glutamate is a major excitatory neurotransmitter in the central nervous system. Glutamate transporters play a critical role in maintaining extracellular glutamate concentrations. We investigated the effects of ethanol on a neuronal glutamate transporter, excitatory amino acid transporter type 3 (EAAT3), and the role of protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3 K) in mediating these effects.EAAT3 was expressed in Xenopus oocytes by injection of EAAT3 messenger RNA. By using a two-electrode voltage clamp, membrane currents were recorded after the application of l-glutamate. Responses were quantified by integration of the current trace and reported as microcoulombs. Data are mean +/- SEM.Ethanol enhanced EAAT3 activity in a concentration-dependent manner. At 25, 50, 100, and 200 mM of ethanol, the responses were significantly increased compared with control values. Kinetic study demonstrated that ethanol (50 mM) significantly increased Vmax (3.48 +/- 0.2 microC for control versus 4.16 +/- 0.24 microC for ethanol; n = 19; p0.05) without a significant change in the Km (65.6 +/- 11.1 microM for control versus 55.8 +/- 9.6 microM for ethanol; n = 19; p0.05) of EAAT3 for glutamate. Preincubation of the oocytes with phorbol-12-myristate-13-acetate (PMA) significantly increased EAAT3 activity (0.98 +/- 0.08 muC for control versus 1.28 +/- 0.09 microC for ethanol; n = 19; p0.05). However, there was no statistical difference among the responses of EAAT3 to PMA, ethanol, or PMA plus ethanol. Although the PKC inhibitors chelerythrine and staurosporine did not decrease the basal EAAT3 activity, they abolished the enhancement of EAAT3 activity by ethanol. Pretreatment with wortmannin, a PI3 K inhibitor, also abolished the ethanol-enhanced EAAT3 activity.These results suggest that acute ethanol exposure increases EAAT3 activity at clinically relevant concentrations and that PKC and PI3 K may be involved in mediating these ethanol effects.

The number of patients with spinal cord injury (SCI) has increased recently due to the development of medical management and rehabilitation. As the survival rates of females with SCI are increasing, the number of parturient females with SCI is also rising [1]. Autonomic dysreflexia (ADR) is the most serious complication in parturient females with SCI above the T10 level, because uterine contractions and labor pain cannot be detected by the patients themselves. Early fetal and uterine monitoring with adequate labor analgesia is essential to prevent ADR [2]. Parturient females with SCI should be assessed by a multidisciplinary team that includes an obstetric anesthesiologist, obstetrician, and neurologist, and an intrapartum care plan should be established early to avoid labor-induced ADR [3]. We herein present a case of a parturient female with SCI at the level of T6 who was admitted for early labor analgesia but in whom normal delivery failed; an emergency cesarean section was successfully performed under epidural anesthesia. A 36-year-old, 148 cm, 49 kg, primigravida and primipara parturient female was admitted at 34 + 2 weeks' gestation for delivery. She had been paraplegic with muscular atrophy due to T6 damage after suffering from poliomyelitis when she was 5 years old. Partial sensation remained below T10. She reported no previous experience of ADR. Uterine contraction and labor pain are known to potentially induce ADR; in addition, her uterine contractions were thought to be insufficient for vaginal delivery. Thus, she was admitted for careful observation of her uterine contractions and for induction of labor. No blood test abnormalities were noted at the time of admission, but cardiomegaly was evident on a chest X-ray. Pulmonary function testing showed a moderate restrictive pattern (FVC, 55%; FEV1, 63%; FEV1/FVC, 90%), but the results of her arterial blood gas analysis were within the normal range. A sinus rhythm was present on the electrocardiogram (ECG), and mild mitral/atrial regurgitation with normal systolic function (ejection fraction, 68%) and a graft valve was observed on echocardiography. The cardiologist stated that according to her cardiac function, she might be at low risk for delivery, and if a hypertensive event occurred due to ADR, it could be controlled with nitroglycerine, nicardipine, and nitroprusside. At the time of admission, her vital signs were stable (blood pressure, 90-106/50-65 mmHg; heart rate, 77-88 /min; respiratory rate, 20 /min; body temperature, 35.8℃). Upon admission, her cervical dilatation was 3 to 4 cm and effacement was 50%. A continuous fetal heart rate and labor monitoring were maintained, but there was no progression for 6 days after admission. On the seventh day after admission, the amniotic membrane ruptured and the uterus contracted for 5 to 6 min cycles. Epidural labor analgesia was planned, and an epidural catheter was inserted through the L4-5 interspace upon feeling a loss of resistance. An injection of 0.75% ropivacaine (10 ml, 75 mg), fentanyl (200 µg), and normal saline (87 ml) (total amount, 100 ml) was administered as a bolus dose after a test dose, and a patient-controlled analgesia pump for continuous infusion was connected with the remainder (90 ml) of the mixture at a flow rate of 10 ml/h. A radial arterial catheter was placed, and continuous monitoring of her blood pressure, ECG, and pulse oximetry was performed. About 2 h later, an oxytocin infusion was started to induce labor. Her cervix was fully effaced 4 h after the oxytocin infusion was begun, and her blood pressure and heart rate became elevated slightly to 154/104 mmHg and 82 /min, respectively. ADR was suspected, and a continuous infusion of nitroglycerine was started from 0.4 µg/kg/min and tapered for 2 h. About 3 h after full cervical effacement, failure of descent was diagnosed and an emergent cesarean section was planned. The patient was transferred to the operating room without premedication, and standard monitoring was begun, including ECG, pulse oximetry, and continuous invasive blood pressure measurement. A facial mask with a reserve bag was fitted to the patient with a fresh gas flow of 6 L/min of 100% oxygen. Seven milliliters of 0.75% (52.5 mg) ropivacaine was injected via an epidural catheter, and her level of sensory block was determined at T6 using an alcohol swab and pinprick test. During the emergency cesarean section, the vital signs of the patient were stable (blood pressure, 127/84 mmHg; heart rate, 100 /min; oxygen saturation, 100%). After placental extraction, 30 IU of oxytocin was administered and titrated according to her blood pressure and uterine contractions. Her level of sensory block was determined to be at T6 using an alcohol swab after the surgery, and there were no hemodynamic abnormalities during the cesarean section. Hemodynamic monitoring was continued in the recovery room, and the epidural catheter was removed 1 h after the surgery. Postoperative pain control was achieved using an intravenous NSAID. ADR is initiated by noxious stimuli below the lesion. Such noxious stimuli may include bowel or bladder distension, pelvic examination, uterine contraction, or pain [2]. The impulse is then transmitted to the spinothalamic tract and posterior columns. Sympathetic spinal reflexes are propagated, and the inhibitory outflow from the hypothalamus increases. However, the inhibitory outflow cannot be transmitted in patients with SCI, and this unregulated sympathetic activity leads to severe hypertension [3]. It is important to avoid trigger factors, especially during pregnancy. For example, urinary catheterization or pelvic examination using a speculum should be performed under topical anesthesia, and a proper bowel regimen should be applied if the patient complains of constipation or bowel distension [1]. Hypertension is also a sign of pre-eclampsia; therefore, distinguishing ADR from preeclampsia is important for appropriate treatment. In cases of ADR, hypertension and other symptoms are synchronous with uterine contraction, but the symptoms in patients with pre-eclampsia are independent of uterine contractions. In addition, an elevated LFT may be seen in patients with pre-eclampsia, in contrast to the normal LFT of patients with ADR [1]. Epidural catheterization should be established early in labor and maintained during the postoperative period for adequate pain control. Achievement of a T10 sensory level or higher should be attempted [2]. Despite the lack of sensation, epidural catheterization for continuous analgesia is considered to be the most effective method of preventing ADR during labor [4]. In the present patient, the epidural catheter was removed in the recovery room to prevent catheter infection because decubitus ulcers were present near the insertion site of the epidural catheter, and methicillin-resistant Staphylococcus aureus was cultured from the sore.

The vasovagal response is characterized by an inappropriate combination of bradycardia and paradoxical vasodilation. During a general or neuraxial anesthesia-induced sympathectomy, a sudden vagal activation and/or an acute reduction in sympathetic tone can cause serious vasovagal responses. Neuraxial anesthesia for Cesarean section may trigger vasovagal response, due to multiple risk factors; high neuraxial block, sudden hemorrhage, aortocarval compression, peritoneal manipulation, and emotional stress. A 39-year-old pregnant woman, at 38 weeks of gestation with episodes of non-sustained ventricular arrhythmia and newly developed vasovagal syncope during pregnancy, was scheduled to undergo a spinal anesthesia for an elective Cesarean section. Immediately after the placental expulsion, a sudden severe bradycardia, followed by a cardiac arrest occurred. The patient fully recovered after prompt cardiopulmonary resuscitation with chest compression, manual ventilation with oxygen, rapid injection of epinephrine and hydration. This case illustrates a serious potential risk of vasovagal response superimposed on neuraxial anesthesia, during a Cesarean section, especially during placental expulsion.

Background We investigated the effects of a magnesium sulfate pretreatment on intubating conditions and cardiovascular responses during rapid sequence tracheal intubation (RSI) in this double-blind randomized study. Methods Adult patients (n = 154) were randomly allocated to a rocuronium-0.6, rocuronium-0.9, or magnesium group. The magnesium group was pretreated with 50 mg/kg MgSO4, and the other two groups received the same volume of isotonic saline. Anesthesia was induced with alfentanil, propofol, and either 0.6 mg/kg (rocuronium-0.6 and magnesium groups) or 0.9 mg/kg (rocuronium-0.9 group) rocuronium. An anesthesiologist, blinded to the group assignments, performed RSI and assessed the intubating conditions. Systolic arterial pressure (SAP) and heart rate (HR) were recorded before the magnesium sulfate or normal saline was administered, before anesthesia induction, before intubation, and every minute after intubation for 5 min. Results Airway features were similar among the three groups. The intubating conditions were improved significantly in the magnesium group (P < 0.001) compared with the other two groups. Significant increases in SAP at 1 min after intubation were observed in the rocuronium-0.6 and -0.9 groups when compared with the magnesium group (P < 0.05). HR was comparable among the three groups (P > 0.05). No hypertensive episode occurred during the immediate post-intubation period in the magnesium group (P = 0.001), and tachycardia occurred most frequently in the rocuronium-0.6 group (P < 0.05). Conclusions MgSO4 administered prior to RSI using alfentanil, propofol, and rocuronium may improve intubating conditions and prevent post-intubation hypertension.

Guillain-Barré syndrome is an acute inflammatory demyelinating polyradiculopathy characterized by progressive motor weakness, areflexia, and ascending paralysis. Guillain-Barré syndrome is extremely rare in pregnant patients, and there are no established guidelines for delivery or safest anesthetic methods. We report a Cesarean delivery in the case of a 32-year old woman who was diagnosed with Guillain-Barré syndrome 18 weeks into gestation. Tracheostomy was performed due to progressive respiratory muscle weakness and respiratory failure, and ventilator support was required in the intensive care unit. The respiratory difficulty was exacerbated by the growth of the fetus, necessitating emergency Cesarean delivery. The delivery was successfully performed under general anesthesia, and the patient recovered without neurological sequelae.

Kennedy’s disease is a rare lower motor neuron disease affecting the limbs and bulbar musculature. Regional anesthesia is generally the recommended anesthetic technique in patients with Kennedy’s disease because of bulbar involvement and airway clearing disturbance. We administered general anesthesia in a patient with Kennedy’s disease who was undergoing a laparoscopic cholecystectomy. We closely monitored the degree of neuromuscular blockade throughout the operation and injected atracurium on demand. There was no exacerbation of neurologic signs or symptoms postoperatively. Therefore, we report the successful administration of general anesthesia for laparoscopic cholecystectomy in a patient with Kennedy’s disease.

Background: Etomidate frequently causes myoclonus. Since the myoclonus is caused by a transient disequilibrium due to etomidate exposure in the CNS, we hypothesized that a slow rate of injection of the drug may decrease the incidence of myoclonus. We conducted a prospective randomized study to compare the effect of two different types of the etomidate injection rate on the incidence and severity of myoclonus. Methods: Fifty patients were randomly assigned to the fast-injection group (group F) or slow-injection group (group S): Group F patients received etomidate (0.3 mg/kg) over ten seconds. The same dose was administered over two minutes for group S patients. The response to the injection of etomidate was grade d on a four-point scale in a blinded manner. The time to loss of consciousness (LOC) was also recorded. Results: The incidence of myoclonus was significantly lower (P ＜ 0.001) in group S patients; 84% and 28% in group F and group S patients, respectively. The myoclonus was also significantly less severe in group S patients (P ＜ 0.001). The time to LOC was significantly longer in group S patients (106 ± 22 sec) than that of group F patients (49 ± 18 sec, P ＜ 0.001). Conclusions: With same dose, a slower rate of injection resulted in a lower incidence of myoclonus and can effectively reduce myoclonus without the use of a pretreatment agent. (Korean J Anesthesiol 2008; 55: 305～7)

Background Prophylactic fluid preloading before spinal anesthesia has been a routine procedure to prevent maternal hypotension during cesarean delivery. Unlike colloid, timing of infusion of crystalloid may be important because of its short stay in intravascular space. We hypothesized that crystalloid loading just after intrathecal injection compared to preload would be more effective in preventing maternal hypotension. Methods In this prospective controlled study, sixty parturients were randomized to receive 15 ml/kg of crystalloid before (preload group) or after (coload group) intrathecal drug injection for spinal anesthesia. Hypotension was defined if systolic arterial pressure decreased below 80% of baseline and ephedrine was administered to treat hypotension. The incidence of hypotension and the total dose of ephedrine were checked. Blood pressure, heart rate and nausea before childbirth were assessed. Neonatal outcomes were evaluated with Apgar scores and umbilical blood gas analysis. Results The incidence of hypotension was lower in the coload group compared to the preload group (53% vs. 83%, P = 0.026). The blood pressure showed the bigger drop during spinal anesthesia in the preload group (34 ± 13 vs. 25 ± 10 mmHg, P = 0.002) and smaller dose of ephedrine was required in the coload group (7.5 [0–30] vs. 15 [0–40] mg, P = 0.015). The incidence of nausea was also lower in the coload group (27% vs. 60%, P = 0.019). Neonatal outcome measures were comparable between two groups. Conclusions In case of using crystalloids for cesarean delivery, coload is more effective than preload for the prevention of maternal hypotension after spinal anesthesia. Trial registration Clinical Research Information Service KCT0000324 (Jan 12th, 2012)