The clinical experiment to develop the brain protection protocol in cerebral ischemia using compressed spectral array

Objective：The clinical experiment to establish the cerebral protection protocol for hemodynamically vulnerable patients from ischemic insult during surgery is presented. Methods：The experiment divided in two parts, one is to analyze the effect of intravenous anesthetics and inhalation anesthetics on EEG activity in neurologically intact 81 patients. The others is to develop the stepwise cerebral protection protocol during aneurysm surgery which required temporary clipping, carotid endarterectomy and extracranial intracranial arterial bypass surgery in 61 patients. The cerebral protection protocol included the use of intraoperative compressed spectral array(CSA) monitoring, induced hypertension, thiopental induced burst suppression and moderate hypothermia. Results：With the efforts of brain protection protocol, 59 of the 61 patients recovered without any newly developed neurological deficit from the surgery. One patient had carotid stenosis with multiple untreated aneurysms, and therefore, induced hypertension was not applied. This patient developed significant postoperative neurological deficits correlated well with the CSA changes. In one patient who has cerebral aneurysm, thiopental bolus injection was used. This patient has reduction of EEG activity during temporary clipping and developed the relatively well correlated neurologic deficit postoperatively. Among 28 carotid endarterectomy cases, three patients has definite reduction of EEG activities within 7 to 15 seconds of interval carotid artery(ICA) test clamping before endarterectomy. But, these patients recovered from surgery without any neurological deficit inspite of 28 to 35 minutes ICA clamping with the effort of thiopental induced burst suppression, induced hypertension and moderate hypothermia. Conclusion：Cerebral protection protocol under CSA monitoring could prevent ischemic insults from circulatory disruption on vulnerable ischemic hemisphere.ope

Identification of an amino acid defining the distinct properties of murine β1 and β3 subunit containing GABAA receptors

Abstract: Murine γ‐aminobutyric acid (GABA) type A homomeric receptors made of β1 subunits are profoundly different, when expressed in Xenopus oocytes, from β3 homomeric receptors. Application of the intravenous general anesthetic pentobarbital, etomidate, or propofol to β3 homomeric receptors allows current flow. In contrast, β1 homomers do not respond to any of these agents. Through construction of chimeric β1/β3 receptors, we identified a single amino acid that determines the pharmacological difference between the two β subunits. When the serine residue present in the wild‐type nonresponsive β1 subunit is replaced by an asparagine found in the same position in the β3 subunit, the resulting point‐mutated β1S265N forms receptors responsive to intravenous general anesthetics, like the wild‐type β3 subunits. Conversely, after mutation of the wild‐type β3 to β3N265S, the homomeric receptor loses its ability to respond to these same general anesthetics. Wild‐type‐to‐mutant titration experiments showed that the nonresponsive phenotype is dominant: A single nonresponsive residue within a pentameric receptor is sufficient to render the receptor nonresponsive. In α1βx or α1βxγ2 heteromeric receptors, the same residue manifests as a partial determinant of the degree of potentiation of the GABA‐induced current by some general anesthetics. The location of this amino acid at the extracellular end of the second transmembrane segment, its influence in both homomeric and heteromeric receptor function, and its dominant behavior suggest that this residue of the β subunit is involved in an allosteric modulation of the receptor.ope

Comparison of ramosetron and ondansetron for the treatment of established postoperative nausea and vomiting after laparoscopic surgery: a prospective, randomized, double-blinded multicenter trial

Background: Postoperative nausea and vomiting (PONV) is a common complication after surgery, which increases physical and psychological discomfort and delays recovery. The aim of this study was to test the hypothesis that ramosetron is comparable to ondansetron for the treatment of established PONV after laparoscopic surgery using a prospective, randomized, double-blinded, noninferiority study. Methods: Patients who had at least two risk factors of PONV and underwent laparoscopic surgery under general anesthesia were assessed for eligibility. Patients who developed PONV within the first 2 h after anesthesia received ondansetron (4 mg) or ramosetron (0.3 mg) intravenously in a randomized double-blind manner. Patients were then observed for 24 h after drug administration. The incidence of nausea and vomiting, severity of nausea, rescue antiemetic necessity, and adverse effects at 0-2 or 2-24 h after drug administration was evaluated. The primary endpoint was the rate of patients exhibiting a complete response, defined as no emesis and no further rescue antiemetic medication for 24 h after drug administration. Results: Among the 583 patients, 210 (36.0%) developed PONV and were randomized to either the ondansetron (n=105) or ramosetron (n=105) group. Patient's characteristics were similar between the groups. The complete response rate was 44.1% in the ondansetron group and 52.9% in the ramosetron group after 24 h of initial antiemetic administration. The incidence of adverse events was not different between the groups. Conclusion: We found evidence to support the noninferiority of ramosetron (0.3 mg) compared to ondansetron (4 mg) for the treatment of established PONV in moderate to high-risk patients undergoing laparoscopic surgery.ope

Proper Target Concentration of Fentanyl during Endotracheal Intubation with a CACI (Computer Assisted Continuous Infusion) in Patients Undergoing Coronary Artery Bypass Graft Surgery

BACKGROUND: The computer-assisted continuous infusion (CACI) system was developed to more rapidly attain and to maintain stable effect-site fentanyl concentrations as compared with the intermittent injection method. The CACI system allows the anesthesiologist to control effect-site fentanyl concentrations during various surgical stimuli during cardiac anesthesia. This system can rapidly control the depth of anesthesia and compensate for the disadvantages of IV anesthesia. Early patient recovery also enables early tracheal extubation, which is an important component of the "fast track" cardiac surgery pathway. In this study, the use of a target-controlled infusion of low-dose propofol was combined with the target-controlled infusion of fentanyl for patients undergoing coronary artery bypass graft surgery. The purpose of this study was to evaluate the proper effect-site concentration of fentanyl for the tracheal intubation of patients undergoing coronary artery bypass graft surgery. METHODS: Fifty patients scheduled for elective coronary artery bypass graft surgery were included, and randomly allocated to group L (effect-site fentanyl concentration = 5 ng/ml, n = 25) or group H (effect-site fentanyl concentration = 7.5 ng/ml, n = 25). Anesthesia was induced and maintained by the computer-controlled infusions of propofol and fentanyl. Hemodynamics and other variables were recorded preinduction, and before and 1 minute after intubation. RESULTS: The two groups were compared with regard to demographic and perioperative data. The two groups were similar demographically, and no significant differences was found in any hemodynamic parameter at any time between the two groups. CONCLUSIONS: Both fentanyl regimens provided stable hemodynamics and adequate anesthesia in patients during endotracheal intubation. It is reasonable to say that the lower dose of fentanyl (5 ng/ml) may be the better choice, because it provides the same level of anesthesia during endotracheal intubation during coronary artery bypass graft surgery.ope

Amino acid residues involved in agonist binding and its linking to channel gating, proximal to transmembrane domain of 5-HT3A receptor for halothane modulation

BACKGROUND: The 5-hydroxytryptamine type 3 (5-HT3) receptor is a member of the Cys-loop superfamily of ligand-gated ion channels (LGICs) and modulated by pharmacologic relevant concentrations of volatile anesthetics or n-alcohols like most receptors of LGICs. The goal of this study was to reveal whether the site-directed single mutations of E-106, F-107 and R-222 in 5-HT3 receptor may affect the anesthetic modulation of halothane known as positive modulator. METHODS: The wild-type and mutant receptors, E106D, F107Y, R222F, R222V, were expressed in Xenopus Laevis oocytes and receptor function was assessed using two electrode voltage clamp techniques. RESULTS: E106D, F107Y, R222F, R222V mutant 5-HT3A receptors were functionally expressed. F107Y mutant 5-HT3A receptors displayed decreased sensitivity to 5-HT compared to the wild type 5-HT3A receptor (P < 0.05). Halothane showed positive modulation in both wild and F107Y mutant 5-HT3A receptors but F107Y mutant 5-HT3 receptor showed greater enhancing modulation comparing to wild-type receptor. Meanwhile, R222F and R222V mutant 5-HT3 receptor lost positive modulation with 1 and 2 MAC of halothane. Most interestingly, positive modulation by halothane was converted into negative modulation in E106D mutant 5-HT3A receptor. CONCLUSIONS: The present study implicate the amino acid residues known for agonist binding and linking agonist binding to channel gating might also have important role for anesthetic modulation in 5-HT3A receptorope

Significance of Brain Protection and Neurophysiological Monitoring in Carotid Endarterectomy

We present our results of carotid endarterectomy performed in 12 patients(bilateral in 2 patients) under prospective brain protection-monitoring protocol during the past two years. The protocol consists of induced hypertension, mild hypothermia, and pentothal burst suppression under bipolar two-channel compressed spectral array(CSA) monitoring. Eleven of the 12 patients recovered without any new deficit from the surgery, and this result was expected as their CSA monitoring showed no significant changes. One patient had multiple untreated aneurysms, and therefore, hypertension was not applied. This patient developed significant postoperative neurological deficits correlated well with the CSA changes. One of the major advantages of CSA monitoring is that dosage of thiopental sodium for burst suppression, that varied greatly from 1,016mg to 3,220mg, could be titrated on each patient based upon the CSA findings. Another important benefit of our brain protection-monitoring protocol is that unnecessary shunting procedure could be avoided. In conclusion, brain protection under CSA monitoring could prevent dangerous ischemic insults from circulatory disruption on already vulnerable ischemic hemisphere in patients requiring carotid endarterectomy.ope

A retrospective analysis of prolonged propofol-remifentanil anesthesia in the neurosurgical patients

BACKGROUND: A rare, but fatal, propofol infusion syndrome has been reported in critically ill patients after prolonged use of propofol (more than 24-48 hours). But there are few reports on the clinical characteristics of prolonged anesthesia (more than 10 hours) using propofol, especially in the neurosurgical patients. METHODS: A retrospective study was conducted to find intra-and post-anesthetic characteristics (up to 7 postoperative days) and long-term outcomes (more than 1 and half years) in the neurosurgical patients who needed prolonged propofol-remifentanil anesthesia. Data were collected via medical records and descriptive analysis was conducted. RESULTS: Thirty one neurosurgical patients underwent 34 operations using propofol-remifentanil anesthesia for more than 10 hours from November 2005 to January 2007. Mean duration of anesthesia and surgery was 936 +/- 279 and 805 +/- 283 min, respectively. Propofol and remifentanil were administered with a mean infusion rate of 7.2 +/- 1.8 mg/kg/h and 8.6 +/- 2.4microg/kg/h, respectively. Vasopressors were used in six cases during anesthetic management. Intraoperative hypotension occurred in two patients. Even though hepatic, cardiac, and renal enzymes elevated transiently in some patients during postanesthetic course, any significant lactic acidosis did not occur in them. Two patients died of sepsis and GI bleeding thereafter. Median days of hospital admission and stay at neurosurgical care unit were 36.5 days and 8 days. CONCLUSIONS: A retrospective analysis of the prolonged propofol and remifentanil anesthesia for 34 neurosurgical cases did not show any morbidities and mortalities related to intravenous anesthetics.ope

Effect of charcoal filter on the emergence from sevoflurane anesthesia in a semi-closed rebreathing circuit

PURPOSE: A charcoal filter attached within the anesthetic circuit has been shown to efficiently adsorb halothane or isoflurane, thus hastening anesthetic recovery in low or minimal flow system. This study was intended to demonstrate whether the charcoal filter enhances the recovery time from sevoflurane anesthesia using a semi-closed circuit system. MATERIALS AND METHODS: Thirty healthy patients scheduled for elective surgery under sevoflurane anesthesia were randomly assigned to the charcoal filter or control group. Upon completion of surgery, the end-tidal concentration of sevoflurane was maintained at 2.0 vol%. A charcoal filter was attached to the expiratory limb of the breathing circuit of charcoal filter group subjects. After sevoflurane was discontinued, ventilation was controlled with the same minute volume as the intra-operative period at a fresh gas flow rate of 5 L·min⁻¹ with 100% O₂. The elimination kinetics of sevoflurane from end-tidal concentration, Bispectral index and times of eye opening and extubation were obtained. RESULTS: The exponential time constant (τ) of alveolar sevoflurane concentration in the charcoal filter group was significantly shorter than that in the control group (1.7±0.5 vs. 2.5±1.1 min, p=0.008). The charcoal filter hastened rapid eye opening (11.1±3.8 vs. 14.8±3.0 min, p=0.007) and extubation (11.9±3.9 vs. 15.3±3.2 min, p=0.014), compared to the control group. CONCLUSION: A charcoal filter enhances the recovery from sevoflurane anesthesia with a semi-closed rebreathing circuit.ope

Effect of a single dose of esmolol on the bispectral index to endotracheal intubation during desflurane anesthesia

BACKGROUND: In this prospective, randomized, double-blind, placebo-controlled trial, we investigated the effect of a single dose of esmolol on the bispectral index (BIS) to endotracheal intubation during desflurane anesthesia. METHODS: After induction of anesthesia, 60 patients were mask-ventilated with desflurane (end-tidal 1 minimum alveolar concentration) for 5 min and then received either normal saline, esmolol 0.5 or 1 mg/kg, 1 min prior to intubation (control, esmolol-0.5 and esmolol-1 groups, n = 20/group). BIS, mean arterial pressure, and heart rate were measured prior to anesthesia induction and esmolol administration, immediately preceding intubation (time point 0), and every minute for 5 min after intubation (time point 1 to 5). At time point 0, 1 and 5, 5 ml of arterial blood was taken to measure plasma concentrations of norepinephrine and epinephrine. RESULTS: BIS increased significantly at 1 min after intubation when compared with pre-intubation values in all groups. Both mean arterial pressure and heart rate increased significantly 1 min after intubation when compared with preintubation values for all groups. Plasma epinephrine concentrations did not increase significantly after tracheal intubation in any of the groups. Norepinephrine increased at 1 min after intubation when compared with the preintubation values in the esmolol groups (P < 0.05). CONCLUSIONS: A single bolus of esmolol was unable to blunt the increase in BIS to endotracheal intubation during desflurane anesthesia.ope

Effect of ginsenosides on the desflurane modulation in the recombinant serotonin type 3A receptor expressed in Xenopus laevis oocytes.

BACKGROUND: Postoperative nausea and vomiting (PONV) is the most frequent and discomforting side effect following general anesthesia. Most volatile anesthetics have a potent effect on serotonin (5-hydroxydtryptamine, 5-HT) type 3 receptor mediating PONV, and their antagonists have been currently used effectively to prevent and/or reduce the incidence and severity of PONV. The authors reported previously that ginsenosides have inhibitory effect on 5-HT3A receptor. In this study we intended to elucidate the inhibitory effect of ginsenosides on the potentiated 5-HT3A receptor by desflurane. METHODS: After in vitro transcription of the recombinant mouse 5-HT3A receptor in the Xenopus laevis oocyte, we examined the effects of ginsenosides (g-Rb1, g-Rg1, g-Rd, g-Rg2) as well as ginsenoside metabolite, compound K on the modulation of desflurane by measuring currents flowing through 5-HT3A receptor using two-electrode voltage clamp technique. RESULTS: Although normalized inhibitory responses of ginsenosides were same regardless of desflurane, some ginsenosides such as g-Rd, g-Rg2, and g-Rg1 showed potential inhibition to the enhanced 5-HT induced current of 5-HT3A receptor by desflurane. CONCLUSIONS: Although ginsenosides have substantial inhibitory effect on 5-HT3A receptor, the effects of ginsenoside on potentiation by desflurane of 5-HT induced current via recombinant 5HT3A receptor may depend on the types of ginsenoside, which suggesting that ginsenoside might have an antagonistic action to nausea and vomiting associated with volatile anestheticsope