Takasumi Katoh

Electroencephalographic derivatives as a tool for predicting the depth of sedation and anesthesia induced by sevoflurane

Background The electroencephalogram (EEG) has been evaluated as a tool for measuring depth of anesthesia, but the use of the EEG monitoring is still controversial. The current study was designed to evaluate the accuracy of three EEG parameters and anesthetic concentration for predicting depth of sedation and anesthesia during sevoflurane anesthesia. Methods One low and one high equilibrated concentration ranging from 0.2–1.8% were assigned randomly and administered consecutively to 69 patients. The bispectral index (BIS; version 3.2), 95% spectral edge frequency (SEF), and median power frequency (MPF) were obtained from a bipolar frontomastoid (Fp1‐A1, Fp2‐A2) montage using an EEG monitor. Sedation was assessed using the responsiveness portion of the observers assessment of alertness‐sedation scale. In the second phase of the study, the 47 patients who were scheduled to have skin incisions were observed for purposeful movement in response to skin incision at sevoflurane concentrations between 1.6% and 2.4%. The relation among BIS, 95% SEF, MPF, sevoflurane concentration, sedation score, and movement or no movement after skin incision, was determined. Prediction probability values for EEG parameters and sevoflurane concentration to predict depth of sedation and anesthesia were also calculated. Results The BIS and sevoflurane concentration correlated closely with the sedation score. Both 95% SEF and MPF changed significantly but biphasically with increasing sedation. The prediction probability values for BIS and sevoflurane concentration were 0.966 and 0.945, respectively, indicating a high predictive performance for depth of sedation. No EEG parameters predicted movement after skin incision better than chance alone. Conclusions Parameters derived from EEG, such as BIS, and 95% SEF are reliable guides to the depth of sedation, but not to the adequacy of anesthesia level for preventing movement during sevoflurane anesthesia.

The minimum alveolar concentration (MAC) of sevoflurane in humans

Forty surgical patients were divided into two groups and anesthetized with either sevoflurane and oxygen or sevoflurane, oxygen, and nitrous oxide. The minimum alveolar concentration (MAC) for sevoflurane required to prevent movement in response to surgical incision in healthy patients was 1.71 ± 0.07% (SE). The AD95 (anesthetic ED95) that prevented 95% of patients from moving was 2.07%. The addition of 63.5% end-tidal nitrous oxide allowed a reduction in the alveolar sevoflurane concentration to 0.66 ± 0.06% (SE). The reduction in sevoflurane MAC was 61.4%. The AD95 for sevoflurane with 63.5% end-tidal nitrous oxide was 0.94%.

The Effects of Fentanyl on Sevoflurane Requirements for Loss of Consciousness and Skin Incision

Background Fentanyl produces a minimal reduction in the minimum alveolar concentration of sevoflurane to prevent response to a verbal command in 50% of patients (MACawake) at low but analgesic plasma concentrations. The reduction in MACawake, however, is still unknown at higher fentanyl concentrations. The reduction in the MAC of sevoflurane by fentanyl has not been described accurately. The purpose of this study was to determine the MACawake and MAC reduction of sevoflurane by fentanyl. Methods Ninety‐two patients were randomly allocated to seven fentanyl concentration groups (target plasma concentrations of 0, 1, 1.5, 3, 6, 10, and 14 ng/ml). Responses to verbal command were observed for MACawake assessment at predetermined sevoflurane concentrations. Thereafter, in patients whose target fentanyl concentration was 0 to 10 ng/ml, responses to skin incision were observed for MAC assessment at new steady‐state sevoflurane concentrations. The reduction in the MACawake and MAC of sevoflurane by the measured fentanyl concentration was calculated. Results There was an initial steep reduction in the MAC of sevoflurane by fentanyl, with 3 ng/ml resulting in a 59% MAC reduction. A ceiling effect was observed, with 10 ng/ml providing only a further 17% reduction in MAC. The initial reduction in MACawake was not as steep as that in MAC. Fentanyl reduced MACawake by approximately 24% at a plasma concentration of 3 ng/ml. Although the reduction curve of MACawake was parabolic, no manifest ceiling effect was observed at concentrations administered in the present study. Conclusions The reduction in sevoflurane requirements for loss of consciousness and skin incision by fentanyl was determined. Fentanyl reduced both requirements, but the mode of the reduction was not comparable.

The Effect of Fentanyl on Sevoflurane Requirements for Somatic and Sympathetic Responses to Surgical Incision

BACKGROUND Fentanyl produces a reduction in the minimum alveolar concentration (MAC) of isoflurane and desflurane needed to blockade adrenergic response (BAR) to surgical incision in 50% of patients (MAC-BAR). MAC-BAR of sevoflurane and the reduction in MAC-BAR of sevoflurane by fentanyl have not been described previously. The purpose of this study was to determine the MAC and MAC-BAR reduction of sevoflurane by fentanyl with and without nitrous oxide (N2O). METHODS Two hundred twenty-six patients were randomly assigned to one of two groups: a sevoflurane group and a sevoflurane/N2O group. Patients in each group were randomly assigned to one of five different fentanyl concentration subgroups. Patients were anesthetized with sevoflurane and fentanyl in the sevoflurane group and with sevoflurane, fentanyl, and N2O (66 vol%) in the sevoflurane/N2O group. Somatic and sympathetic responses to surgical incision were observed for MAC and MAC-BAR assessment at predetermined concentrations of sevoflurane. RESULTS Fentanyl produced an initial steep reduction in the MAC and MAC-BAR of sevoflurane, with 3 ng/ml resulting in a 61% reduction in MAC and an 83% reduction in MAC-BAR. A ceiling effect was observed for MAC and MAC-BAR, with 6 ng/ml fentanyl providing only an additional 13% and 9% reduction in MAC and MAC-BAR, respectively. In the presence of 66 vol% N2O, MAC and MAC-BAR of sevoflurane were reduced with increasing concentrations of fentanyL A ceiling effect was not observed for reduction in MAC and MAC-BAR in the presence of N2O. CONCLUSIONS MAC and MAC-BAR decreased similarly with increasing concentrations of fentanyl in plasma, showing an initial steep reduction followed by a ceiling effect. In the presence of N2O, MAC and MAC-BAR decreased similarly but did not exhibit a ceiling effect.

Influence of Age on Hypnotic Requirement, Bispectral Index, and 95% Spectral Edge Frequency Associated with Sedation Induced by Sevoflurane

Background Aging is associated with a reduction in anesthetic requirements. The effects of age on the electroencephalographic response to inhalational anesthesia have not been well documented. The objective of the present study was to determine the influence of age on hypnotic requirement and electroencephalographic derivatives such as bispectral index and 95% spectral edge frequency associated with sedation induced by sevoflurane. Methods Ninety-six patients were randomly allocated into one of three age groups A, B, and C, ranging in age from 18–39 yr, 40–64 yr, and 65–85 yr, respectively. Patients in each group were sedated with sevoflurane at two predetermined concentrations ranging between 0.45% and 0.85%. The relationship between sevoflurane concentration and response to a verbal command, as well as the relationships between response and bispectral index and 95% spectral edge frequency, was determined. Results Multiple regression analysis showed that end-tidal sevoflurane concentration and age significantly affected both bispectral index and 95% spectral edge frequency. ED50 values of sevoflurane concentration for loss of consciousness, defined as no response to verbal command, were different between groups A and C: 0.72 (95% confidence interval: 0.68–0.75) versus 0.59 (95% confidence interval: 0.56–0.62). However, the same effective values of bispectral index and 95% spectral edge frequency at this same clinical end point did not differ. Conclusions Increasing age reduced sevoflurane requirements to suppress responses to a verbal command but did not change bispectral index and 95% spectral edge frequency associated with this end point, and in a population with a wide age range, bispectral index would predict depth of sedation better than end-tidal sevoflurane concentration.

The effects of prolonged low-flow sevoflurane anesthesia on renal and hepatic function.

UNLABELLED We assessed the effects of prolonged low-flow sevoflurane anesthesia on renal and hepatic functions by comparing high-flow sevoflurane with low-flow isoflurane anesthesia. Thirty patients scheduled for surgery of > or =10 h in duration randomly received either low-flow (1 L/min) sevoflurane anesthesia (n = 10), high-flow (6-10 L/min) sevoflurane anesthesia (n = 10), or low-flow (1 L/min) isoflurane anesthesia (n = 10). We measured the circuit concentrations of Compound A and serum fluoride. Renal function was assessed by blood urea nitrogen, serum creatinine, creatinine clearance, and urinary excretion of glucose, albumin, protein, and N:-acetyl-beta-D-glucosaminidase. The hepatic function was assessed by serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase, and total bilirubin. Compound A exposure was 277 +/- 120 (135-478) ppm-h (mean +/- SD [range]) in the low-flow sevoflurane anesthesia. The maximum concentration of serum fluoride was 53.6 +/- 5.3 (43.4-59.3) micromol/L for the low-flow sevoflurane anesthesia, 47.1 +/- 21.2 (21.4-82.3) micromol/L for the high-flow sevoflurane anesthesia, and 7.4 +/- 3.2 (3.2-14.0) micromol/L for the low-flow isoflurane anesthesia. Blood urea nitrogen and serum creatinine were within the normal range, and creatinine clearance did not decrease throughout the study period in any group. Urinary excretion of glucose, albumin, protein, and N:-acetyl-beta-D-glucosaminidase increased after anesthesia in all groups, but no significant differences were seen among the three groups at any time point after anesthesia. Lactate dehydrogenase and alkaline phosphatase on postanesthesia Day 1 were higher in the high-flow sevoflurane group than in the low-flow sevoflurane group. However, there were no significant differences in any other hepatic function tests among the groups. We conclude that prolonged low-flow sevoflurane anesthesia has the same effect on renal and hepatic functions as high-flow sevoflurane and low-flow isoflurane anesthesia. IMPLICATIONS During low-flow sevoflurane anesthesia, intake of Compound A reached 277 +/- 120 ppm-h, but the effect on the kidney and the liver was the same in high-flow sevoflurane and low-flow isoflurane anesthesia.

Auditory Evoked Potential Index Predicts the Depth of Sedation and Movement in Response to Skin Incision during Sevoflurane Anesthesia

Background The auditory evoked potential (AEP) index, which is a single numerical parameter derived from the AEP in real time and which describes the underlying morphology of the AEP, has been studied as a monitor of anesthetic depth. The current study was designed to evaluate the accuracy of AEPindex for predicting depth of sedation and anesthesia during sevoflurane anesthesia. Methods In the first phase of the study, a single end-tidal sevoflurane concentration ranging from 0.5 to 0.9% was assigned randomly and administered to each of 50 patients. The AEPindex and the Bispectral Index (BIS) were obtained simultaneously. Sedation was assessed using the responsiveness portion of the observer’s assessment of alertness–sedation scale. In the second phase of the study, 10 additional patients were included, and the 60 patients who were scheduled to have skin incisions were observed for movement in response to skin incision at the end-tidal sevoflurane concentrations between 1.6 and 2.6%. The relation among AEPindex, BIS, sevoflurane concentration, sedation score, and movement or absence of movement after skin incision was determined. Prediction probability values for AEPindex, BIS, and sevoflurane concentration to predict depth of sedation and anesthesia were also calculated. Results The AEPindex, BIS, and sevoflurane concentration correlated closely with the sedation score. The prediction probability values for AEPindex, BIS, and sevoflurane concentration for sedation score were 0.820, 0.805, and 0.870, respectively, indicating a high predictive performance for depth of sedation. AEPindex and sevoflurane concentration successfully predicted movement after skin (prediction probability = 0.910 and 0.857, respectively), whereas BIS could not (prediction probability = 0.537). Conclusions Auditory evoked potential index can be a guide to the depth of sedation and movement in response to skin incision during sevoflurane anesthesia.

Cerebral Awakening Concentration of Sevoflurane and Isoflurane Predicted During Slow and Fast Alveolar Washout

We studied 49 patients of ASA physical status I to determine cerebral anesthetic concentration on awakening calculated with end-tidal anesthetic concentration, when the end-tidal concentration decreased spontaneously. We also attempted to explain the difference in the average of the bracketing alveolar anesthetic concentration that allows and prevents the response to verbal command during recovery from anesthesia (MAC-Awake) between slow and fast alveolar washout by comparing the cerebral anesthetic concentrations with MAC-Awake determined by fast and slow washout. Slow washout was obtained by decreasing anesthetic concentrations in predetermined steps of 15 min, assuming equilibration between brain and alveolar partial pressures. Fast alveolar washout was obtained by discontinuation of the inhaled anesthetic, which had been maintained at 0.5 minimum alveolar anesthetic concentration (MAC) for at least 15 min. MAC-Awake values for sevoflurane and isoflurane obtained by slow washout were 0.34 ± 0.05 and 0.31 ± 0.05 (mean ± SD), respectively, when MAC-Awake was expressed as a ratio to age-adjusted MAC. MAC-Awake values obtained by fast washout (0.22 ± 0.07 MAC for sevoflurane, 0.22 ± 0.05 MAC for isoflurane) were significantly smaller than those obtained by slow washout. Anesthetic concentrations in the brain at first eye opening calculated with end-tidal concentrations during fast alveolar washout (0.34 ± 0.08 MAC for sevoflurane, 0.30 ± 0.08 MAC for isoflurane) were nearly equal to MAC-Awake obtained by slow alveolar washout. The difference in MAC-Awake between fast and slow alveolar washout could be explained by arterial-to-cerebral and end-tidal-to-arterial anesthetic differences.

A comparison of sevoflurane with halothane, enflurane, and isoflurane on bronchoconstriction caused by histamine

This study was conducted to assess the effect of sevoflurane on lung resistance and compliance, and its responsiveness to histamine. We studied eight dogs to compare the effect of sevoflurane, isoflurane, enflurane, and halothane on bronchoconstriction caused by histamine. Baseline values of pulmonary resistance (RL) and dynamic pulmonary compliance (Cdyn) were measured prior to administration of histamine. Histamine (2, 4, and 8 μg · kg−1) were administered iv, and the values of RL and Cdyn at the time of peak effect were recorded. Under 1 or 2 MAC anaesthesia, sevoflurane as well as the other three anaesthetics had no bronchoactive effects. The four anaesthetics, including sevoflurane, demonstrated inhibitory effect on increases in RL and decreases in Cdyn caused by histamine. At 1 MAC anaesthesia, % changes in RL caused by 2, 4, or 8 μg · kg−1 of histamine were 38 ± 11, 85 ± 21, or 132 ± 24% (mean ± SE) for halothane, and 65 ± 11, 132 ± 15, or 172 ± 19% for sevoflurane, respectively. Sevoflurane was less effective than halothane in preventing increases in RL. In preventing decreases in Cdyn, sevoflurane was less effective than halothane only at 8 μg · kg−1 of histamine under 1 and 2 MAC anaesthesia. There was no difference in attenuating effect on changes in RL and Cdyn between sevoflurane and isoflurane or enflurane. We concluded that sevoflurane was less potent than halothane in attenuating changes in RL and Cdyn in response to iv histamine.RésuméCette étude a été réalisée dans le but d’évaluer les effets du sévoflurane sur la résistance et la compliance pulmonaires en réponse à l’histamine. Les effets du sévoflurane, de l’isoflurane, de l’enflurane et de l’halothane sur la bronchoconstriction induite par l’histamine sont comparés sur huit chiens. Avant l’administration d’histamine, on mesure les valeurs initiales de la résistance (RL) et de la compliance dynamique (Cdyn) pulmonaires. L’histamine (2, 4, 8 μg · kg−1) est administrée par la voie veineuse et les valeurs maximales de la RL et de la Cdyn sont enregistrées. Les quatre anesthésiques, dont le sévoflurane inhibent l’augmentation de la RL et la diminution de la Cdyn provoquées par l’histamine. A MAC 1 d’anesthésie, les pourcentages de changement de RL produits par 2, 4, ou 8 μg · kg−1 d’histamine sont respectivement de 38 ± 11, 85 ± 21, ou 132 ± 24% (moyenne + SD) pour l’halothane, et de 65 ± 11, 132 ± 15, ou 172 ± 19% pour le sévoflurane. Le sévoflurane est moins efficace que l’halothane pour prévenir les augmentations de RL. Le sévoflurane est moins efficace pour prevenir la diminution de Cdyn mais seulement à 8 μg · kg−1 d’histamine sous anesthésie à MAC 1 et 2. Le sévoflurane, l’halothane et l’isoflurane ne sont pas de différents pour amortir les changements de RL et Cdyn. Nous concluons que le sévoflurane est moins puissant que l’halothane pour diminuer la réponse à l’histamine de la RL et de la Cdyn.

Propofol concentration required for endotracheal intubation with a laryngoscope or fiberscope and its interaction with fentanyl.

The administration of fentanyl with propofol reduces the blood concentration of propofol required to achieve adequate anesthesia for tracheal intubation.However, different intubation procedures have variable intensities of noxious stimulation and may require different levels of anesthesia. The goal of this study was to determine the propofol blood concentration at which 50% of patients did not respond to stimulation (Cp50) for laryngoscopy, intubation with a laryngoscope, insertion of a slotted oral-pharyngeal airway (Ovassapian airway), and intubation with a fiberscope when administered in conjunction with fentanyl. Patients undergoing elective surgery were given varying amounts of propofol or propofol with fentanyl, and their responses to the four procedures listed above were assessed. These experiments demonstrated that the propofol concentration required for intubation with a laryngoscope was similar to that for intubation with a fiberscope, and that the required level was reduced by fentanyl. Hemodynamic responses to intubation were lower with a fiberscope than with a laryngoscope. We conclude that almost the same concentrations of propofol or fentanyl are necessary for suppressing both of the somatic responses to tracheal intubation with a fiberscope or a laryngoscope. Hemodynamic responses were attenuated more during intubation with a fiberscope. Implications: The propofol blood concentrations at which 50% of patients did not respond to stimulation for laryngoscopy, tracheal intubation with a laryngoscope, and tracheal intubation with a fiberscope were 10.9, 19.6, and 19.9 micro g/mL, respectively. These were reduced by fentanyl. Hemodynamic responses to intubation were less with a fiberscope than with a laryngoscope. (Anesth Analg 1998;86:872-9)