The Measured Value And Clinical Value Of Minimal Alveolar Concentration Of Sevoflurane For Inducing Isoelectric Electroencephalogram.

Background:Minimal alveolar concentration (MAC) was introduced to compare the potencies of inhalation anesthetic agents. Sevoflurane is a commonly used inhalation anesthesia agent today. Its effects on motor response (MAC), adrenergic reflexes (MACBAR) to nociceptive stimulation, and eye opening to verbal command (MACawake) in50%of subjects have been widely investigated. However, the relation between concentration of sevoflurane and different EEG states is relatively unstudied.EEG burst suppression and isoelectric EEG are frequently observed in deep general anesthesia. Previous studies have demonstrated that burst suppression or isoelectric EEG can be purposely induced by anesthetic agents to protect the brain during neurosurgery or cardio-surgery. Although still a controversial issue, low EEG-derived indices might be associated with adverse outcomes after cardiac and non-cardiac surgery. Understanding the relation between concentrations of volatile anesthetics and abnormal EEG states including burst suppression or isoelectric EEG might help practitioners avoid excessively deep anesthesia in vulnerable patients, or achieve transient burst suppression or isoelectric EEG when desired. Hence, this study aimed to determine the MAC of sevoflurane inducing isoelectric EEG (MACie) and burst suppression EEG (MACbs) in50%of middle-aged adults.Most volatile anesthetics, acting principally through enhancement of gamma-amino-butyric acid (GABA) action, induce a typical dose-dependent increase in frontal slow wave activity. As a N-methyl-D-aspartate (NMDA) receptor antagonist, nitrous oxide has quite different electroencephalographic effects compared to the inductive general anesthetics, and is associated with suppression of power in frontal slow wave activity and enhancement of high frequency EEG activity. Nitrous oxide has an additive effect on volatile anesthetics for preventing movement and hemodynamic response to surgical incision, but that may not translate to an additive suppression of brain electrical activities. In this prospective, randomized, subjects and outcome assessor blinded, parallel group, up-down sequential allocation study, we aimed to study the effects of nitrous oxide on MACie of sevoflurane.Previous studies showed that the burst suppression and isoelectric EEG induced by propofol may protect the brain from injury. However, it is not clear whether sevoflurane have the similar effect. We studied the cerebral blood flow and cerebral metabolic rate during burst suppression and isoelectric EEG, and investigated the Serum concentrations of s100β protein, postoperative delirium and postoperative cognitive dysfunction, to give some reference for clinical application.Methods and Results1. Minimal alveolar concentration of sevoflurane for inducing isoelectric electroencephalogramMethods:We included31middle-aged subjects;30subjects finished the study protocol and received sevoflurane at preselected concentrations according to a modified Dixon’up-and-down’design starting at1.7%with0.2%steps size. General anesthesia was induced and maintained with sevoflurane; tracheal intubation was facilitated with cisatracurium. After a period of30min before skin incision, the state of isoelectric EEG was considered as significant when a burst suppression ratio of100%lasted for.1min. The hemodynamic responses to skin incision and the vasopressor requirement to maintain stable hemodynamic status were also analyzed according to the EEG state.Results:MACie was3.5%(95%confidence interval,3.4-3.7%) in middle-aged subjects. When compared with subjects not in isoelectric EEG state, subjects in isoelectric EEG state received more phenylephrine to maintain stable hemodynamics (10of10compared with7of20subjects, P=0.001) and experienced less sympathetic responses to skin incision (1of10compared with11of20subjects, P=0.024).2. Nitrous oxide increases Minimal alveolar concentration of sevoflurane for inducing isoelectric electroencephalogramMethods:In this prospective, randomized, double-blind, parallel group, up-down sequential allocation study, ASA I and Ⅱ patients were included and received sevoflurane induction. After intubation, seventy-six patients were simply randomized to one of two groups receiving sevoflurane with either40%oxygen in air mixture (group S) or60%N2O in oxygen mixture (group SN). The MACie in group SN (MACieSN) and group S (MACieS) were determined separately by the Dixon method starting at2.5%with0.2%step size of expired fraction of sevoflurane. The subsequent doses of sevoflurane were determined by the presence or absence of isoelectric electroencephalogram in the previous patient in the same group. Meanwhile, the hemodynamic responses to skin incision of the two groups were also analyzed.Results:The MACieSN (3.9±0.4%) was significantly higher than MACieS (3.5±0.2%)(P=0.007). There is a statistically significant elevation of overall mean arterial pressure and more increase of heart rate in the group S than in the group SN (P=0.031and P=0.008, respectively).3. Burst suppression and isoelectric encephalogram induced by sevoflurane: metabolic suppression and postoperative cognition studiesMethods:In this prospective, randomized, double-blind study, ASA I and II patients were included and simply randomized to one of two groups receiving sevoflurane maintain with depth of anesthesia at either Narcotrend F0-1(group F) or Narcotrend EO-2(group E). After30minutes stablization, blood samples were obtained from the jugular venous bulb catheter and radial artery for measurement of cerebral arteriovenous oxygen difference across the cerebral vessels (Ca-jvO2). Then the Doppler sonography was used to measured blood flow of the extra cranial internal carotid artery and vertebral artery to calculate cerebral blood flow volume of the two groups. Serum concentrations of s100β protein were measured before surgery and after24,48and72h. Meanwhile, Postoperative delirium (POD) was diagnosed with the use of the Confusion Assessment Method in ICU (CAM-ICU). Postoperative Cognitive dysfunction (POCD) was assessed with the use of the Mini-Mental State Examination (MMSE) before surgery and7days after surgery.Results:There was a significant decrease in Ca-jvO2with increasing depth of anesthesia.1.69+0.77vs.3.38+0.93(P<0.001). There were no significant differences in mean blood flow of the extracranial internal carotid artery and vertebral artery. There were no significant differences between two groups on serum concentrations of s100(3protein, the incidence of POD and POCD.ConclusionsMACie for sevoflurane was-2.1times MAC for immobilization in middle-aged adults. Sevoflurane-induced isoelectric EEG state is associated with significant cardiovascular depression but reduced hemodynamic responses to skin incision.The addition of60%N2O increases MACie of sevoflurane and blunts adrenergic response to skin incision under sevoflurane anesthesia. The burst suppression and isoelectric encephalogram induced by sevoflurane had a significant effect on cerebral metabolic suppression, with no significant cerebral blood flow changes. No serum markers of cerebral injury or postoperative cognitive alteration were detected with burst suppression and isoelectric encephalogram.