The mechanisms through which general anaesthetics, an extremely diverse group of drugs, cause reversible loss of consciousness have been a long-standing mystery. Gradually, a relatively small number of important molecular targets have emerged, and how these drugs act at the molecular level is becoming clearer. Finding the link between these molecular studies and anaesthetic-induced loss of consciousness presents an enormous challenge, but comparisons with the features of natural sleep are helping us to understand how these drugs work and the neuronal pathways that they affect. Recent work suggests that the thalamus and the neuronal networks that regulate its activity are the key to understanding how anaesthetics cause loss of consciousness.

General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal

Little is known about the effect of anesthetic management on long-term outcomes. We designed a prospective observational study of adult patients undergoing major noncardiac surgery with general anesthesia to determine if mortality in the first year after surgery is associated with demographic, preop

Anesthetic management and one-year mortality after noncardiac surgery.

BackgroundThe 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 seda

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

Background:The purpose of this investigation was to describe the pharmacodynamic interaction between propofol and remifentanil for probability of no response to shaking and shouting, probability of no response to laryngoscopy, Bispectral Index (BIS), and electroencephalographic approximate entropy (

Pharmacodynamic interaction between propofol and remifentanil regarding hypnosis, tolerance of laryngoscopy, bispectral index, and electroencephalographic approximate entropy.

Two defining effects of inhaled anesthetics (immobility in the face of noxious stimulation, and absence of memory) correlate with the end-tidal concentrations of the anesthetics. Such defining effects are characterized as MAC (the concentration producing immobility in 50% of patients subjected to a

Age, minimum alveolar anesthetic concentration, and minimum alveolar anesthetic concentration-awake.

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 Minimum Alveolar Concentration (MAC) of Sevoflurane in Humans

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.

Influence of age on hypnotic requirement, bispectral index, and 95% spectral edge frequency associated with sedation induced by sevoflurane.

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.

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

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 Conclusions sevoflurane anesthesia.

Auditory evoked potential index predicts the depth of sedation and movement in response to skin incision during sevoflurane anesthesia.

UNLABELLED We compared the ease of passage through the glottis of two different tubes and two different sizes of tracheal tube exchanger (TE) during introducer-guided tracheal intubation. One tube was a polyvinyl chloride tube with a standard bevel, and the other was a newly designed tube with a hemispherical bevel. The outer diameters (OD) of the two TEs were 2.5 and 5.0 mm. After the standard induction of anesthesia, followed by vecuronium-induced paralysis, a TE was inserted into the trachea with a direct laryngoscope. By using the introducer as a guide, the tracheal tube was inserted into the trachea. The difficulty in passing the tube was assessed by a blinded observer and graded with a four-point scale. The newly designed tube was inserted more smoothly than was the conventional tube when the 2.5-mm-OD TE was used (P < 0.01). In situations such as those occurring after one-lung anesthesia, when use of a thicker TE is not applicable, this newly designed taper-tipped tube may be considered as an adjunct to oral tracheal tube exchange, using a thinner (smaller-OD) TE as the guide for tracheal intubation. IMPLICATIONS In situations such as after one-lung anesthesia, when use of a thicker tube exchanger (TE) is not applicable, a newly designed taper-tipped tube with the leading edge in the midline may be considered as an adjunct to an oral tracheal tube exchange, using a thinner TE as the guide for tracheal intubation.

Takasumi Katoh

Papers

The Minimum Alveolar Concentration (MAC) of Sevoflurane in Humans

Influence of age on hypnotic requirement, bispectral index, and 95% spectral edge frequency associated with sedation induced by sevoflurane.

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

Auditory evoked potential index predicts the depth of sedation and movement in response to skin incision during sevoflurane anesthesia.

The effects of tracheal tube tip design and tube thickness on laryngeal pass ability during oral tube exchange with an introducer.