Effective therapeutic infusions produced by closed-loop feedback control of methohexital administration during total intravenous anesthesia with fentanyl

A combined pharmacokinetic and pharmacodynamic model of methohexital was used to establish and evaluate feedback control of methohexital delivery during total intravenous anesthesia with fentanyl in 11 surgical patients. The median frequency of the EEG power spectrum served as the pharmacodynamic variable constituting feedback. Based on previous investigations a median frequency from 2-3 Hz was chosen as the desired EEG set point. In addition to methohexital, patients were given a 10-min loading infusion of 0.5 mg of fentanyl followed by a constant-rate infusion of 0.22 mg/h. In agreement with an earlier similar study in volunteers given only methohexital and aiming at the same set point, identical distribution of EEG power was achieved in the current study. The decrease of median EEG frequency to 2-3 Hz was primarily induced by an increase in fractional power in the 0.5-2- Hz frequency band to 46 +/- 4%. The average requirement of methohexital during the first 2 h was 675 +/- 250 mg. The authors conclude that model-based feedback control of intravenous methohexital delivery can help establish and quantitate methohexital requirements during total intravenous anesthesia with fentanyl.     

Isoflurane, nitrous oxide, and fentanyl pharmacodynamic interactions in surgical patients as measured by effects on median power frequency

STUDY OBJECTIVE: To identify and quantify the simultaneous interactions of isoflurane, nitrous oxide (N2O), and fentanyl during surgical procedures. The slowing of the EEG to a median power frequency of 2 Hz to 3 Hz was chosen as the measure of pharmacodynamic drug effect. DESIGN: Prospective, randomized, open label. SETTING: Operating room of a university hospital. PATIENTS: 65 ASA physical status I and II patients undergoing gynecological laparatomies. INTERVENTIONS: 25 patients received no fentanyl. 20 patients received a loading dose of 100 micrograms fentanyl and a continuous infusion of 70 micrograms.h-1 fentanyl. Calculated effect compartment concentrations were 0.7 ng.ml-1 between the first and second hours after induction of anesthesia. Another 20 patients received a loading dose of 200 micrograms fentanyl and a continuous infusion of 150 micrograms.h-1 fentanyl; the respective effect compartment concentrations were 1.5 ng.ml-1. N2O was randomly administered in concentrations of 0, 20, 40, and 60 vol%; in the group that did not receive fentanyl, we additionally investigated 75 vol% N2O. Each patient received two different N2O concentrations, with each combination of N2O and fentanyl finally applied to ten patients. Isoflurane vaporizer settings were chosen so that the median power frequency was held between 2 Hz and 3 Hz. The type and degree of interaction among the three anesthetic drugs was analyzed based on a generalized isobole approach. MEASUREMENTS AND MAIN RESULTS: The interaction of isoflurane, N2O, and fentanyl is compatible with additivity. A model with regard to the relative potencies and age dependency is given by: [formula: see text] with C0,iso = 1.30 vol%, C0,N2O = 177 vol%, C0,fen = 10.6 ng.ml-1, and a = -0.0031 yr-1. where conc. = end-tidal or effect compartment concentrations. CONCLUSION: The potency of N2O and fentanyl to substitute isoflurane in maintaining a median power frequency of 2 Hz to 3 Hz during surgery is less than anticipated from minimum alveolar concentration studies.     

Spectral edge frequency of the electroencephalogram to monitor "depth" of anaesthesia with isoflurane or propofol

To determine threshold values, sensitivity and specificity of the spectral edge frequency (SEF) of the electroencephalogram (EEG) that indicate intraoperative movements, we studied 49 patients undergoing, elective laparotomy. Extradural analgesia was used in all patients. To maintain general anaesthesia, patients in group 1 (n = 23) received 0.4- 1.2 vol% isoflurane and patients in group 2 (n = 24) propofol 3-5 mg kg- 1 h-1 i.v. During operation and emergence from anaesthesia, spontaneous purposeful movements were documented. The EEG was recorded continuously in the awake state until the end of anaesthesia. Power spectral analysis calculated the SEF and power in the delta, theta, alpha and beta bands and the delta ratio. Adequate anaesthesia caused a statistically significant decrease in SEF from 16 to 12 Hz. Power in the beta band decreased and power in the theta band and total power increased compared with the awake state. Before and during movements observed in the intraoperative period or during emergence from general anaesthesia, SEF increased from 12 to 18 Hz, the power in beta band increased and theta power decreased compared with the state of adequate anaesthesia. A threshold value of SEF 14 Hz to predict movements during anaesthesia had a sensitivity of 72% and specificity of 82%.      

相同MAC浓度的安氟醚和异氟醚对脑电图功率谱的影响

２４例 ２０～５０岁、ＡＳＡⅠ级、行择期外科手术的患者，随机分成两组：安氟醚组和异氟醚组。不用术前药，麻醉诱导以静脉硫喷妥钠５ｍｇ／ｋｇ、阿曲库胺０．６～０．７ｍｇ／ｋｇ。单纯吸入安氟醚或异氟醚维持全麻。气管插管后控制呼吸，维持呼气末二氧化碳分压（ＰＥＴＣＯ２）４．２７。４．９３ｈｐａ。以ＴＯＦ监测肌松，间断给予阿曲库胺 １０～１５ｍｇ，维持Ｔ４／Ｔ１＜２５％。采用 ＦＰ１－Ａ１、ＦＰ２－Ａ２双导联监护脑电，验证呼气末麻醉药浓度在 ０． ５、０．８、１． ０、１． ３和 １．５ ＭＡＣ时的脑电功率谱、９５％边缘频率（ＳＥＦ）和中心频率（ＭＰＦ）改变。结果发现，随ＭＡＣ增加脑电功率谱表现出波增加，α和β波减少，而ＳＥＦ、ＭＰＦ值随ＭＡＣ增加而减少的改变呈负性线性关系，ｒ＝－０．９５。提示脑电功率谱、ＳＥＦ和ＭＰＦ在评价全麻深度上有一定意义。     

Human auditory steady-state response during general anesthesia

The 40-Hz auditory steady-state evoked response (ASSR) is a sinusoidal electrical response of the brain to periodically presented auditory stimuli. It was recorded during anesthesia in 10 elective surgical patients to evaluate its usefulness as a measure of the level of consciousness. The anesthetic agents used were thiopental, fentanyl, and isoflurane with or without nitrous oxide. Recordings were carried out during the period before induction and during induction, surgical anesthesia, emergence, and recovery from anesthesia. The level of consciousness was measured with an auditory stimulus detection task. The electroencephalogram (EEG) was also recorded for comparison with the ASSR. The following indices were analyzed: total EEG power, relative power in the beta, alpha, theta, and delta frequency bands, and the median and spectral edge frequency. The amplitude of the ASSR was reduced significantly at the end of the induction period and decreased below noise levels during surgical anesthesia. It increased significantly during emergence and recovery. The amplitude during recovery remained significantly smaller than the preinduction values. The changes of the ASSR paralleled those of the level of consciousness. The EEG measurements were distorted by the presence of muscle artifacts that were prominent during emergence and recovery. The amplitude of the ASSR appears to provide a more reliable indicator of the level of consciousness than the EEG.     

Induction of anesthesia with small doses of sufentanil or fentanyl: dose versus EEG response, speed of onset, and thiopental requirement

The purpose of this study was to examine the dose versus EEG response relationship, the speed of onset, and the thiopental requirement for induction of anesthesia with small doses of sufentanil and fentanyl. The power spectrum of the electroencephalogram (EEG) was used to quantify the effect of the opioids. Eight male surgical patients, 52-80 yr old, were randomly divided into eight groups of ten to receive fentanyl, 5, 7, 10, or 13 micrograms/kg, or sufentanil, 0.5, 0.7, 1.0, or 1.3 micrograms/kg. The opioid was given iv over 1 min at a constant rate of infusion. Three to four minutes after the start of the opioid dose, thiopental was given iv in 25 mg increments every 30 s until the patient was unconscious. Power in the 1-3 Hz band reached maximum levels in less than 4 min after the start of opioid administration. At fentanyl doses of 7.0 micrograms/kg or less, or sufentanil doses of 1.0 micrograms/kg or less, the EEG effects did not increase in proportion to the dose of opioid. There was not a significant difference in the maximum power achieved in the 1-3 Hz band for sufentanil, 0.5, 0.7 and 1.0, and fentanyl, 5 and 7 micrograms/kg. Doses of fentanyl, 10 or 13 micrograms/kg, or sufentanil, 1.3 micrograms/kg were substantially more effective; the maximum power increased significantly between 7 and 10 micrograms/kg of fentanyl and 1.0 and 1.3 micrograms/kg of sufentanil (P less than 0.0001). The potency of sufentanil and fentanyl were compared by super-imposing, the dose versus response (power) curves. The potency ratio was 1:8 (sufentanil:fentanyl).(ABSTRACT TRUNCATED AT 250 WORDS)     

EEGs during high-dose fentanyl-, sufentanil-, or morphine-oxygen anesthesia

In 49 patients undergoing open-heart surgery we compared the electroencephalographic (EEG) effects of high-dose morphine, fentanyl, or sufentanil with O2, using two computerized analysis and display techniques: a period analysis (the Klein method) and an aperiodic analysis (the Neurometrics monitor). During fentanyl or sufentanil anesthesia, both techniques revealed a general decrease in frequency, shown by the aperiodic analysis primarily as a marked increase in the very low frequency range: an increase in the 1-Hz bin (TP1, in muv2) from 2.80 X 10(4) +/- 3.20 X 10(4) (SD) to 45.1 X 10(4) +/- 27.2 X 10(4) for fentanyl and from 3.11 X 10(4) +/- 2.83 X 10(4) to 52.8 X 10(4) for sufentanil. The cumulative percent power at 3 Hz (CP3) increased from 27.2 +/- 6.8 to 83.0 +/- 11.0 for fentanyl and from 22.7 +/- 5.2 to 85.1 +/- 10.4 for sufentanil, while the frequency at 90% cumulative percent power (F90, in Hz) decreased from 17.8 +/- 2.9 to 7.9 +/- 2.8 for fentanyl and 16.4 +/- 5.2 to 5.6 +/- 4.3 for sufentanil. The changes with morphine were less obvious, with some attenuation of high-frequency power shown by the Klein method, and an increase from 24.1 +/- 8.6 to 59.3 +/- 20.7 with CP3, but no change in TP1. Low-frequency power with the period analysis and TP1 with the aperiodic analysis decreased between laryngoscopy and the incisions with fentanyl and sufentanil.(ABSTRACT TRUNCATED AT 250 WORDS)     

The midlatency auditory evoked potentials predict responsiveness to verbal commands in patients emerging from anesthesia with xenon, isoflurane, and sevoflurane but not with nitrous oxide

BACKGROUND: It has recently been demonstrated that the approximately 40-Hz spectral power of the midlatency auditory evoked potential (MLAEP) correlates well with wakefulness during desflurane or propofol anesthesia. The aim of this study was to characterize how other inhalational anesthetics affects the MLAEP as the patients regain responsiveness to simple verbal command during emergence from anesthesia. METHODS: Sixty patients were randomly assigned to receive xenon, isoflurane, sevoflurane, or nitrous oxide (N2O) supplemented with epidural anesthesia. During emergence, the concentration of an anesthetic was decreased in 0.1-minimum alveolar concentration (MAC) decrements from 0.8 MAC or from 70% in the case of N2O, and each new concentration was maintained for 15 min. Every 5 min during each equilibration period, the MLAEP was recorded and the patients were asked to open their eyes and squeeze and release the investigator's hand. This process was repeated until the first response to either of these commands was observed. RESULTS: Thirteen patients were excluded because of technical reasons. The preanesthetic MLAEP showed a periodic waveform, where the Na-Pa-Nb complex was the most prominent component contributing to the high energy around 29-39 Hz in the power spectrum. Emergence from xenon, isoflurane, and sevoflurane anesthesia produced similar changes in the MLAEP. The spectral power for the frequency 29 Hz or greater was severely suppressed at 0.8 MAC but significantly recovered between the concentration only 0.1 MAC higher that permitting the first response to command and that associated with the first response. In contrast, N2O hardly affected the MLAEPs, even at the concentrations producing unresponsiveness. Two patients did not lose responsiveness even at the highest concentration tested (70%). CONCLUSIONS: The MLAEP is closely associated with responsiveness to verbal command during emergence from anesthesia with xenon, isoflurane, and sevoflurane but not with N2O.     

The Midlatency Auditory Evoked Potentials Predict Responsiveness to Verbal Commands in Patients Emerging from Anesthesia with Xenon, Isoflurane, and Sevoflurane but Not with Nitrous Oxide

Background: It has recently been demonstrated that the approximately 40-Hz spectral power of the midlatency auditory evoked potential (MLAEP) correlates well with wakefulness during desflurane or propofol anesthesia. The aim of this study was to characterize how other inhalational anesthetics affects the MLAEP as the patients regain responsiveness to simple verbal command during emergence from anesthesia.

Methods: Sixty patients were randomly assigned to receive xenon, isoflurane, sevoflurane, or nitrous oxide (N2O) supplemented with epidural anesthesia. During emergence, the concentration of an anesthetic was decreased in 0.1-minimum alveolar concentration (MAC) decrements from 0.8 MAC or from 70% in the case of N2O, and each new concentration was maintained for 15 min. Every 5 min during each equilibration period, the MLAEP was recorded and the patients were asked to open their eyes and squeeze and release the investigator's hand. This process was repeated until the first response to either of these commands was observed.

Results: Thirteen patients were excluded because of technical reasons. The preanesthetic MLAEP showed a periodic waveform, where the Na-Pa-Nb complex was the most prominent component contributing to the high energy around 29-39 Hz in the power spectrum. Emergence from xenon, isoflurane, and sevoflurane anesthesia produced similar changes in the MLAEP. The spectral power for the frequency 29 Hz or greater was severely suppressed at 0.8 MAC but significantly recovered between the concentration only 0.1 MAC higher that permitting the first response to command and that associated with the first response. In contrast, N2O hardly affected the MLAEPs, even at the concentrations producing unresponsiveness. Two patients did not lose responsiveness even at the highest concentration tested (70%).     

Changes in the EEG power spectrum after midazolam anaesthesia combined with racemic or S – (+) ketamine

Changes in the EEG power spectrum were studied in 50 patients (ASA status I or II), receiving either 2 mg·kg^-1 of racemic ketamine or 1 mg kg^-1 of S – (+) ketamine in a randomized and double-blind manner after prior administration of 0.1 mg·kg^-1 of midazolam. The patients receiving intramuscular premedication with midazolam about 45 minutes prior to induction of anaesthesia showed, in a deliberately quiet environment and mostly in the early morning, a delta dominated EEG (56% delta power) with a reduced alpha peak (17% alpha power) and an average median of 4 Hz as the baseline findings of the EEG power spectrum. The intravenous administration of midazolam led to activation of the lower beta range (13–18 Hz) and the subsequent injection of ketamine caused an increase in activity in the fast beta range (21–30 Hz), both being accompanied by a reduction of delta power from 56% to 40%. Correspondingly, an increase in the median frequency was noted. Causing nearly the same changes in EEG, S – (+) ketamine was confirmed to be twice as potent as racemic ketamine.     

Electroencephalographic change during induction of high-dose fentanyl anesthesia--evaluation by LIFESCAN EEG monitor]

The relation between the patient's consciousness level and the change in electroencephalographic (EEG) activity during general anesthesia has not been well understood. In the present study, we evaluated such relationship quantitatively during the induction of high-dose fentanyl anesthesia in adult open-heart cases. There are significant increase in delta activity and significant decrease in alpha and beta activity in response to the induction of anesthesia. The loss of consciousness coincided with the sharp reduction in delta ratio and edge frequency (80%). Such reduction was more prominent in delta ratio than in edge frequency. These findings suggest that delta ratio could indicate the consciousness level during the induction of high-dose fentanyl anesthesia. Further study is needed to clarify the EEG response during inhalation and intravenous anesthesia in relation to EEG activity.     

Effects of clonidine on narcotic requirements and hemodynamic response during induction of fentanyl anesthesia and endotracheal intubation

The effects of clonidine, a centrally acting alpha 2-adrenergic receptor agonist, on depth of fentanyl anesthesia and on cardiovascular response to laryngoscopy and intubation were studied. Twenty-four patients undergoing aortocoronary bypass surgery (ACBS) with a history of arterial hypertension, coronary artery disease (NYHA class 3-4), and well-preserved left ventricular function were assigned randomly to either Group 1 (n = 12), who received standard premedication, or Group 2 (n = 12), who received clonidine 5 micrograms X kg-1 po in addition to standard premedication 90 min before estimated induction time. Depth of anesthesia was assessed by on-line aperiodic computerized analysis of the electroencephalogram (Lifescan EEG Monitor). Fentanyl was administered in 250-micrograms increments to shift the EEG to the 0.5-3-Hz frequency range (delta activity) in all subjects. In both groups, the anesthetic regimen effectively prevented hyperdynamic cardiovascular responses to laryngoscopy and intubation. No significant differences in measured or derived hemodynamic variables were observed between the two groups during the awake control period, except for stroke volume index (SVI), which was significantly greater in Group 1, 44 +/- 9 ml X beat-1 X m-2 compared with Group 2, 35 +/- 3.3 ml X beat-1 X m-2 (P less than 0.05). By contrast, fentanyl requirements in Group 2 were significantly reduced by 45% when compared with Group 1, i.e., from 110 +/- 23 to 61 +/- 19 micrograms X kg-1 (P less than 0.001). The authors conclude that at a similar anesthetic depth, as assessed by the EEG shift into the lower frequency range (0.5-3 Hz), a markedly reduced fentanyl dose effectively prevented the hyperdynamic cardiovascular response to laryngoscopy and intubation in the group of patients premedicated with clonidine. This is likely explained by the known synergistic inhibitory action of opiates and alpha 2-adrenoceptor agonists on central sympathetic outflow.     

Influence of changes in arterial carbon dioxide tension on the electroencephalogram and posterior tibial nerve somatosensory cortical evoked potentials during alfentanil/nitrous oxide anesthesia

The effects of variation of arterial CO2 tension (PaCO2) on the electroencephalogram (EEG) and posterior tibial nerve somatosensory cortical evoked potentials (PTN-SCEP) during opioid/N2O anesthesia have not been well documented. We studied the effects of hypocapnia (PaCO2 approximately 23 mmHg) and hypercapnia (PaCO2 approximately 50 mmHg) during steady-state alfentanil/N2O anesthesia in 16 patients. EEG and PTN-SCEP were recorded continuously, while PaCO2 was altered in 15-min intervals by varying the inspired CO2 concentration. Hypocapnia caused significant increases in power in the delta, theta, and beta bands (P less than 0.01), with the greatest increase observed in the alpha band. Relative power increased in the alpha band but remained unchanged in the delta, theta, and beta bands. Median frequency and 95% spectral edge frequency were unaltered during hypocapnia. In contrast, hypercapnia caused a significant decrease of power in the alpha and beta bands, whereas delta and theta power remained unchanged. This was reflected in a significant decrease of the 95% spectral edge frequency, from 8.9 (6.7-11.6) to 7.0 (5.6-8.6) Hz. All EEG parameters returned to normal upon restoration of normocapnia. There was a significant negative correlation between power in the alpha band and end-tidal CO2 in all patients (r = 0.47 to -0.89). PTN-SCEP latencies and amplitudes were not significantly different from control values during hypocapnia and hypercapnia. It is concluded that variations in PaCO2 within the limits 20-50 mmHg produce substantial changes in the EEG power spectrum, especially in the alpha band (8-12 Hz), but do not alter PTN-SCEP.     

小剂量麻醉药物用于神经外科患者早期苏醒的随机前瞻性研究

背景开颅术后为尽早观察神经系统的并发症，使患者从麻醉状态中迅速苏醒至关重要。然而快通道技术常常会伴有体循环高血压，后者有潜在诱发颅内血肿的风险。尽管到目前为止巳研究了很多种药物，但用麻醉药物缓解苏醒期高血压的研究不多。本研究拟观察在关颅阶段应用小剂量麻醉药物能否有助于患者早期苏醒并减轻血流动力学反应。方法在150例血压正常行小脑幕上肿瘤切除术患者中，评价3种苏醒方法的效果，这些患者均采用异氟烷标准麻醉。患者随机分为3组，关闭硬脑膜时分别给予小剂量丙泊酚（3mg·kg^-1·h^-1），芬太尼（1．5μg·kg^-1·h^-1），异氟烷（呼气末浓度为0．2％）直至开始缝皮。头部包扎结束时停止使用氧化亚氮。结果中位苏醒时间丙泊酚组为6分钟，芬太尼组为4分钟，异氟烷组为5分钟（P=0．008）。与拔管时和拔管后相比，患者拔管前更容易出现高血压（P=0．009）。3组间比较，芬太尼组拔管前和总体艾司洛尔使用率较低（P=0．01）。手术前脑显像显示严重的大脑中线偏移是苏醒期高血压的独立危险因素。结论关颅时的疼痛可能是交感刺激引起苏醒期高血压的重要原因。关颅时给予小剂量芬太尼比丙泊酚、异氟烷对神经外科患者早期苏醒更具有优势，而且是预防手术后早期高血压最有效的方法。     

Closed-loop feedback control of methohexital anesthesia by quantitative EEG analysis in humans

A combined pharmacokinetic and pharmacodynamic model of methohexital was used to establish and evaluate feedback control of methohexital anesthesia in 13 volunteers. The median frequency of the EEG power spectrum served as the pharmacodynamic variable constituting feedback. Median frequency values from 2-3 Hz were chosen as the desired EEG level (set-point). In 11 volunteers, the feedback system succeeded in maintaining a satisfactory depth of anesthesia (i.e., unresponsiveness to verbal commands and tactile stimuli). During feedback control, 75% of all measured median frequency values were in the preset range of 2-3 Hz. This distribution of median frequency was obtained by applying random stimulation (six different acoustic and tactile stimuli) to the volunteers approximately every 1.5 min. The decrease of median frequency from baseline to anesthetic values was primarily induced by increasing the fractional power in the frequency band of 0.5-2 Hz from 12.6 +/- 4.5% (mean +/- SD) to 46.0 +/- 2.5%. The median time to recovery (as defined by opening eyes on command) after cessation of the feedback control period was 20.6 min (10.7-44.5 min) when median EEG frequency was 5.2 Hz (4.7-8.4 Hz). The average requirement of methohexital (mean +/- SD) during the 2 h was 1.02 +/- 0.16 g. It is concluded that pharmacokinetic-pharmacodynamic models of intravenous anesthetics established previously may be used to form a suitable background for model-based feedback control of anesthesia by quantitative EEG analysis. This approach gives a possible solution to the problem of adapting pharmacokinetic and pharmacodynamic data to individuals when using population mean data as starting values for drug therapy.     

Mechanism of anesthesia: view from the EEG during anesthesia

It is widely known that electroencephalogram (EEG) shows dramatic changes with increase of the concentration of anesthetic. It is considered that volatile anesthetics (i. e. isoflurane, sevoflurane), barbiturates, propofol show anesthetic effect by potentiating GABAA receptor. Changing patterns of EEG by these anesthetics are quite similar. In light anesthetic level, high frequency with low amplitude waves are dominant. With increase of anesthetic concentration, waves in alpha range (8-13 Hz) become dominant. In deeper levels, powers in alpha range then become smaller and theta or delta powers become dominant. With further deeper levels, EEG waveform changes into specific pattern so-called "burst and suppression", and finally it becomes flat. The author considers that prominent alpha power indicates adequate anesthetic level. However this is not always the required condition for adequate anesthesia, because alpha power never becomes larger in some patients even when the anesthetic level was judged as adequate by concentration dependent changing patterns of EEG. As EEG changes in relation to the concentration of anesthetic, it seems to be correlated with the level of consciousness. But EEG patterns during anesthesia are mainly determined by the condition of thalamic neurons, and it would merely indicate the level of hypnosis indirectly.     

Reversal of high-dose fentanyl anesthesia by naloxone

The EEG, respiratory and hemodynamic responses to postoperative reversal by naloxone of high-dose fentanyl anesthesia were studied in 20 patients (17 cardiac and 3 non-cardiac surgeries). In power spectrum analysis of EEG, power of delta band markedly decreased after naloxone drip infusion. Respiratory and hemodynamic responses were minimum, but increase in HR by 6.4 +/- 9.2 bpm, increase in diastolic BP by 5.3 +/- 9.6 mmHg, and decrease in CVP by 1.9 +/- 2.9 mmHg were statistically significant. Emergence of pain was also minimum and severe side effect was not observed. Reversal of high-dose fentanyl anesthesia by naloxone can reduce the incidence of postoperative respiratory depression and enables early extubation.     

Effect of halothane, isoflurane and fentanyl on spectral components of heart rate variability

We have examined the effect of isoflurane, halothane and fentanylon heart rate variability (HRV) using power spectral analysis(PSA). Forty patients were allocated randomly to receive oneof four anaesthetic techniques. Anaesthesia was induced withpropofol 2 mg kg^–1 and all patients breathed a mixtureof 66% nitrous oxide in oxygen. Twenty of these spontaneouslybreathing patients received 1.5% isoflurane and 20 received0.75% halothane. Ten patients in each of these groups receivedfentanyl 1 µg kg^–1 before induction. PSA was performedon 5-min segments of beat-to-beat R-R interval data taken beforeand 5 min after induction. No significant difference was observedin time domain or spectral HRV measures between inhalation agents.Fentanyl was associated with significantly slower heart rates,although no difference was observed in the power spectrum ofthose receiving fentanyl. Analysis of pooled data from the 40subjects showed that mean heart rate was unchanged and heartrate SD was decreased, as were total and individual powers inthree frequency bands of the HRV spectrum (low 0.02–0.08Hz, mid 0.08–0.15 Hz and high 0.15–0.45 Hz). A significantdecrease in the ratio of high power to (low+mid) power indicateda shift towards sympatholysis with anaesthesia. However, a significantlygreater depression of mid frequency components in comparisonwith low or high frequencies suggests that anaesthesia selectivelydepressed components of the HRV mechanism, independent of ageneral effect on autonomic tone.     

Acoustic evoked potentials of medium latency and intraoperative wakefulness during anesthesia maintenance using propofol, isoflurane and flunitrazepam/fentanyl

Auditory evoked potentials have been used as an indicator of awareness. During combined local and general anesthesia clinical signs of adequate anesthesia are difficult to evaluate. In the present study we combined peridural analgesia with three techniques of general anesthesia. Intraoperative wakefulness was documented and correlated with cardiocirculatory parameters as well as with mid-latency auditory evoked potentials (MLAEP). METHODS. After institutional approval and informed consent 30 patients undergoing elective laparotomy were studied as follows: first, continuous peridural analgesia was instituted in all patients to block painful sensation of surgical stimuli and the anesthetic level was maintained at T5. Then general anesthesia was induced with propofol 2.5 mg/kg i.v. (group I, n = 10), thiopental 5 mg/kg i.v. (group II, n = 10), or etomidate 0.2 mg/kg i.v. (group III, n = 10) and maintained with propofol 3-5 mg/kg per hour i.v. (group I), isoflurane 0.4-0.8 vol.-% (group II), or flunitrazepam 0.005-0.01 mg/kg i.v. and fentanyl 0.0025-0.005 mg/kg i.v. bolus injections every 20-30 min (group III). Heart rate and arterial pressure were registered continuously. Purposeful movements of the limbs, eye-opening, or other movements as well as coughing were documented as signs of intraoperative wakefulness. AEP were recorded in the awake state, after induction, and during maintenance of general anesthesia. Latencies of the peaks V, Na, and Pa were measured. By fast-Fourier transformation corresponding power-spectra were calculated to analyze the energy content of the AEP frequency components. RESULTS. Intraoperative wakefulness occurred statistically significantly more often in the patients of group III than in those of groups I and II. There was no correlation between wakefulness and cardiocirculatory parameters. Latencies of peaks V, Na, and Pa in the awake patients were in the normal range; the corresponding power-spectra had their major energy content in the 30-40-Hz range. After induction of general anesthesia with propofol, thiopentone, and etomidate as well as during maintenance of general anesthesia with propofol and isoflurane peak latencies of Na and Pa increased, frequencies in the 30-40 Hz range became suppressed, and MLAEP energy maxima shifted to the low-frequency range. In contrast, during maintenance of general anesthesia with flunitrazepam/fentanyl peak latencies of Na and Pa returned to awake values and frequencies in the range of 30 Hz regained energy dominance in the corresponding power-spectra. CONCLUSIONS. The maintenance of MLAEP and the primary cortical complex Na/Pa correlates with the incidence of motor signs of wakefulness. During the combination of regional and general anesthesia, isoflurane and propofol seem to provide better suppression of intraoperative wakefulness than bolus injections of flunitrazepam/fentanyl.