Steady-state Anesthesia Research Articles

BNST GABAergic neurons modulate wakefulness over sleep and anesthesia

The neural circuits underlying sleep-wakefulness and general anesthesia have not been fully investigated. The GABAergic neurons in the bed nucleus of the stria terminalis (BNST) play a critical role in stress and fear that relied on heightened arousal. Nevertheless, it remains unclear whether BNST GABAergic neurons are involved in the regulation of sleep-wakefulness and anesthesia. Here, using in vivo fiber photometry combined with electroencephalography, electromyography, and video recordings, we found that BNST GABAergic neurons exhibited arousal-state-dependent alterations, with high activities in both wakefulness and rapid-eye movement sleep, but suppressed during anesthesia. Optogenetic activation of these neurons could initiate and maintain wakefulness, and even induce arousal from anesthesia. However, chronic lesion of BNST GABAergic neurons altered spontaneous sleep-wakefulness architecture during the dark phase, but not induction and emergence from anesthesia. Furthermore, we also discovered that the BNST-ventral tegmental area pathway might participate in promoting wakefulness and reanimation from steady-state anesthesia. Collectively, our study explores new elements in neural circuit mechanisms underlying sleep-wakefulness and anesthesia, which may contribute to a more comprehensive understanding of consciousness and the development of innovative anesthetics.

Permutation entropy is not an age-independent parameter for EEG-based anesthesia monitoring.

An optimized anesthesia monitoring using electroencephalographic (EEG) information in the elderly could help to reduce the incidence of postoperative complications. Processed EEG information that is available to the anesthesiologist is affected by the age-induced changes of the raw EEG. While most of these methods indicate a "more awake" patient with age, the permutation entropy (PeEn) has been proposed as an age-independent measure. In this article, we show that PeEn is also influenced by age, independent of parameter settings. We retrospectively analyzed the EEG of more than 300 patients, recorded during steady state anesthesia without stimulation, and calculated the PeEn for different embedding dimensions m that was applied to the EEG filtered to a wide variety of frequency ranges. We constructed linear models to evaluate the relationship between age and PeEn. To compare our results to published studies, we also performed a stepwise dichotomization and used non-parametric tests and effect sizes for pairwise comparisons. We found a significant influence of age on PeEn for all settings except for narrow band EEG activity. The analysis of the dichotomized data also revealed significant differences between old and young patients for the PeEn settings used in published studies. Based on our findings, we could show the influence of age on PeEn. This result was independent of parameter, sample rate, and filter settings. Hence, age should be taken into consideration when using PeEn to monitor patient EEG.

Increased Perirolandic Cortical Excitability May Facilitate Sensory Motor Mapping in Children (P13-1.003)

<h3>Objective:</h3> We are hereby describing a case of refractory pediatric epilepsy where resection of perirolandic seizure foci was performed successfully under neurophysiologic guidance. <h3>Background:</h3> Pediatric neurophysiologic sensory-motor mapping is frequently unsuccessful, due to inability to localize central sulcus (CS) and primary motor cortex (M1). These shortcomings result from poor somatosensory evoked potentials (SSEP) and high M1 depolarization thresholds respectively, both reflections of the immaturity of the central nervous system. <h3>Design/Methods:</h3> Case report <h3>Results:</h3> An 8-year-old boy with developmental delay, debilitating focal epilepsy and epileptic encephalopathy underwent phase 2 video EEG monitoring. The recordings showed seizures with early involvement of several depth electrodes located within the right parieto-frontal regions, and an early motor semiology involving the left arm. The patient underwent neurophysiologically guided resection of the seizure foci under general anesthesia. Pre-resection electrocorticography (ECoG) via a 64 contact grid showed abundant perirolandic epileptiform discharges (ED), maximal postcentrally. Cortical recordings of high amplitude median SSEP and a low depolarization threshold led to successful CS localization and identification of M1, respectively. A subdural strip electrode placed over the precentral gyrus and secured in position, allowed simultaneous ECoG and motor monitoring during the resection of the postcentral foci. Initially, ECoG showed near continuous runs of ED, unchanged by cortical electrical stimulation. Under steady state anesthesia, at a constant propofol infusion rate, this activity decreased in frequency and stopped altogether towards the end stages of the resection, as the M1 threshold increased by 7 mA. Post-resection fronto-parietal ECoG recordings were quiet. Post-operatively, the patient became seizure free, showed cognitive improvement and no motor deficits. <h3>Conclusions:</h3> Increased cortical excitability may lead to successful functional mapping in children. Under steady anesthetic conditions, increases in the M1 threshold during resection of nearby epileptic foci may be an early sign of decrease in the abnormal regional cortical excitability. <b>Disclosure:</b> Dr. Alzahrany has nothing to disclose. Dr. Simon has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Risk Management Foundation of the Harvard Institutions Incorporated. Dr. Simon has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for MCIC Vermont. Dr. Simon has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Aaronson, Rappaport, Feinstein&amp; Deutch. Dr. Simon has received publishing royalties from a publication relating to health care. Dr. Simon has received personal compensation in the range of $0-$499 for serving as a Speaker with American Clinical Neurophysiology Society . Dr. Simon has a non-compensated relationship as a Speaker with International Society of Intraoperative Neurophysiology that is relevant to AAN interests or activities. Dr. Simon has a non-compensated relationship as a Speaker with Brazilian Congress of Neurology that is relevant to AAN interests or activities.

Electroencephalographic Evidence for Individual Neural Inertia in Mice That Decreases With Time.

Previous studies have demonstrated that the brain has an intrinsic resistance to changes in arousal state. This resistance is most easily measured at the population level in the setting of general anesthesia and has been termed neural inertia. To date, no study has attempted to determine neural inertia in individuals. We hypothesize that individuals with markedly increased or decreased neural inertia might be at increased risk for complications related to state transitions, from awareness under anesthesia, to delayed emergence or confusion/impairment after emergence. Hence, an improved theoretical and practical understanding of neural inertia may have the potential to identify individuals at increased risk for these complications. This study was designed to explicitly measure neural inertia in individuals and empirically test the stochastic model of neural inertia using spectral analysis of the murine EEG. EEG was measured after induction of and emergence from isoflurane administered near the EC50 dose for loss of righting in genetically inbred mice on a timescale that minimizes pharmacokinetic confounds. Neural inertia was assessed by employing classifiers constructed using linear discriminant or supervised machine learning methods to determine if features of EEG spectra reliably demonstrate path dependence at steady-state anesthesia. We also report the existence of neural inertia at the individual level, as well as the population level, and that neural inertia decreases over time, providing direct empirical evidence supporting the predictions of the stochastic model of neural inertia.

Validation of a nasal SedLine® sensor placement: Going beyond the forehead when depth of anesthesia is important

IntroductionSince the inception of general anesthesia, the assessment of anesthetic depth has been challenging and a goal that anesthesiologists constantly strive for. Nowadays, an increasing number of monitors allow us to have a more specific assessment of depth of anesthesia. However, the conventional sensor-lead positioning on the forehead recommended by manufacturers may sometimes coincide with the surgical field thereby posing a clinical challenge. This study compares the conventional frontal placement on the forehead with an experimental nasal placement for the standard Masimo SedLine® EEG sensor in surgical neuromonitoring, analyzing and comparing numeric values (Patient State Index-PSi) and EEG waveform traces. MethodsAuthors performed a single-center, observational, prospective study enrolling 40 patients under a standardized anesthesia protocol. Three contiguous time periods (induction, steady-state anesthesia and awakening) were used to stratify data analysis so that within-patient correlations between nasal and frontal readings could be examined by time period independently. ResultsA total of 106,209 matched numeric values and 3,543 min of EEG data from each sensor’s positions were collected from 40 patients. Total average alignment between two sensor positions, keeping in mind that 5 PSi units were used as acceptable limit of agreement, was 83.01% and p-values associated with R2 correlation coefficients were statistically significant at 0.001 level. Steady-state anesthesia phase alignment (with full muscle-relaxation), which present 73% of all collected data, show a concordance within 5 PSi unit alignment in 95.77%. One hundred and twenty tracings from 40 patients were presented to two epileptologists and inter-rater agreement or reliability was achieved in 88% of EEG-traces’ analysis. ConclusionsThe current results suggest that SedLine® Brain Function Monitoring sensor is acceptable for clinical use when standard sensor position in the forehead is not possible. This allows for the possibility of utilization of the sensor whenever the forehead placement cannot be utilized.

Age-related cerebrovascular carbon dioxide reactivity in children with ventricular septal defect younger than 3years.

Impaired cerebrovascular reactivity to carbon dioxide was proposed to contribute to neurological morbidity in children undergoing cardiac surgery. The objective of this study was to assess carbon dioxide reactivity and regional cerebral oxygen saturation in children younger than 3years. This study enrolled children younger than 3years undergoing ventricular septal defect repair. The cohort was divided into three age groups: younger than 6months, 6-12months, and 12-36months. Under steady-state anesthesia, carbon dioxide reactivity was calculated by measuring changes in middle cerebral artery blood flow velocity using transcranial Doppler sonography. Regional cerebral oxygen saturation changes were measured by near-infrared spectroscopy while endtidal carbon dioxide pressure was adjusted from 30 to 45mmHg. Carbon dioxide reactivity showed a statistically significant increasing relationship with age (younger than 6months group: 4.42%±2.73%, 6-12months group: 5.86%±1.91%, 12-36months group: 7.58%±1.49%; P<.001). Regional cerebral oxygen saturation showed a statistically significant increasing relationship with age (younger than 6months group: 65%±6%, 6-12months group: 68%±5%, 12-36months group: 70%±5%; P=.027). Regional cerebral oxygen saturation showed a statistically significant increasing relationship with endtidal carbon dioxide pressure in all children (P<.001). Abnormal carbon dioxide reactivity is prevalent in children younger than 3years and the degree varies according to age.

Sevoflurane sparing effect of dexmedetomidine in patients undergoing laparoscopic cholecystectomy: A randomized controlled trial.

Background and Aims:Sevoflurane is an excellent but expensive anesthetic agent for laparoscopic cholecystectomy. To decrease sevoflurane consumption during surgery adjuvants like dexmedetomidine may be used. Dexmedetomidine is a recently introduced drug which alleviates the stress response of surgery, produces sedation and analgesia. We aimed to evaluate sevoflurane sparing effect of dexmedetomidine in patients undergoing laparoscopic cholecystectomy under entropy-guided general anesthesia (GA).Material and Methods:In this prospective randomized control study, 100 American Society of Anesthesiologists physical status I–II adult surgical patients scheduled to undergo laparoscopic cholecystectomy were enrolled. Patients were randomly divided into two groups (n = 50). In dexmedetomidine group, patients received intravenous (IV) dexmedetomidine 0.5 μg/kg over 10 min before induction followed by 0.5 μg/kg/h infusion while in control group, patients received the same volume of normal saline.Results:Sevoflurane consumption was 41% lower in dexmedetomidine group as compared to control group (7.1 [1.6] vs. 12.1 [1.9] ml, P <0.001). A 40% reduction was observed in induction dose of propofol (83.0 [19.1] vs. 127.6 [24.8] mg, P <0.001). Mean Riker sedation-agitation score, visual analog score for pain and Aldrete's score were significantly lower in dexmedetomidine group as compared to control group. None of the patients experienced any significant side effects.Conclusion:A 41% reduction in sevoflurane consumption was observed in patients receiving IV dexmedetomidine as an adjuvant in patients undergoing laparoscopic cholecystectomy under GA.

Effects of single-shot and steady-state propofol anaesthesia on rocuronium dose-response relationship: a randomised trial.

Similar to volatile anaesthetics, propofol may influence neuromuscular transmission. We hypothesised that the administration of propofol influenced the potency of rocuronium depending on the duration of the administration. After consent, patients scheduled for elective surgery randomly received rocuronium either after induction of anaesthesia with propofol (2min of propofol, n=36) or after 30min of propofol infusion (30min of propofol, n=36). Remifentanil was given in both groups. Neuromuscular monitoring was performed by calibrated electromyography. The dose-response relationship of rocuronium was determined with a single-bolus technique (0.07, 0.1, 0.15, 0.2, 0.3 and 0.45mg/kg rocuronium). The primary endpoints were the ED50 and ED95 of rocuronium after 2 and 30min propofol. Data are presented as means with (95% confidence interval). The trial is registered with the Eudra-CT: 2009-012815-16. A total of 72 patients were included. Time to maximal neuromuscular blockade was significantly shorter in patients after 30min of propofol [3.3min (2.9-3.7)] compared with patients anaesthetised with 2min of propofol [4.6min (4.0-5.2)]. After 30min of propofol, the slope of the dose-response curve was significantly steeper (30min of propofol: 4.34 [3.62-5.05]; 2min of propofol: [3.34 (2.72-3.96)], resulting in lower ED95 values of rocuronium (30min of propofol: 0.287mg/kg [0.221-0.368]; 2min of propofol [0.391mg/kg (0.296-0.520)]. The ED50 were not different between groups. The potency of rocuronium was significantly enhanced after propofol infusion for 30min. Estimates of potency those are usually determined during steady-state anaesthesia might underestimate rocuronium requirements for endotracheal intubation at the time of induction.

The effect of ketamine and rocuronium on the quantium consciousness index (qCON) during steady-state anesthesia with propofol and remifentanil

The effect of ketamine and rocuronium on the quantium consciousness index (qCON) during steady-state anesthesia with propofol and remifentanil

A Response Surface Model Approach for Continuous Measures of Hypnotic and Analgesic Effect during Sevoflurane–Remifentanil Interaction

The authors studied the interaction between sevoflurane and remifentanil on bispectral index (BIS), state entropy (SE), response entropy (RE), Composite Variability Index, and Surgical Pleth Index, by using a response surface methodology. The authors also studied the influence of stimulation on this interaction. Forty patients received combined concentrations of remifentanil (0 to 12 ng/ml) and sevoflurane (0.5 to 3.5 vol%) according to a crisscross design (160 concentration pairs). During pseudo-steady-state anesthesia, the pharmacodynamic measures were obtained before and after a series of noxious and nonnoxious stimulations. For the "prestimulation" and "poststimulation" BIS, SE, RE, Composite Variability Index, and Surgical Pleth Index, interaction models were applied to find the best fit, by using NONMEM 7.2.0. (Icon Development Solutions, Hanover, MD). The authors found an additive interaction between sevoflurane and remifentanil on BIS, SE, and RE. For Composite Variability Index, a moderate synergism was found. The comparison of pre- and poststimulation data revealed a shift of C50SEVO for BIS, SE, and RE, with a consistent increase of 0.3 vol%. The Surgical Pleth Index data did not result in plausible parameter estimates, neither before nor after stimulation. By combining pre- and poststimulation data, interaction models for BIS, SE, and RE demonstrate a consistent influence of "stimulation" on the pharmacodynamic relationship between sevoflurane and remifentanil. Significant population variability exists for Composite Variability Index and Surgical Pleth Index.

Effect of head rotation during surgery in the prone position on regional cerebral oxygen saturation

Near-infrared spectroscopy (NIRS) has been used to study regional cerebral blood oxygen saturation (rScO2) in patients in the prone position. We aimed to test the hypothesis that head rotation more than 45° would affect the rScO2. A prospective, controlled, single cohort study. University Hospital specialising in spinal surgery. Fifty-two patients undergoing spinal surgery in prone position were enrolled and 48 completed the study. NIRS sensors were attached to each side of the forehead. Measurements were conducted during steady-state anaesthesia with the head in the neutral position, rotated left, rotated right and returned to the neutral position. Each series consisted of three measurements: resting on the head support, during head lift (to relieve pressure on the tissue at the sensors) and returned to rest on the head support. The differences in rScO2 between the neutral and the turned head positions. For both left and right sensors, the median differences in rScO2 between neutral and left or right positions were between 0 and -1 with the head up (P = 0.14 to 0.84). The median differences with the head down were between 3.8 and -0.8, with a significant difference for the left sensor when turned left (P < 0.01) and for the right sensor (P = 0.006) when turned right. Ten patients showed reductions of more than 10 in rScO2 in the rotated (and lifted) positions. When the head was lifted from the head support, the rScO2 was -0.5 to 3.75 units higher, but there was high variability between patients. We recommend the neutral head position for prone patients.TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01760369.

Awareness during anaesthesia

The study by Pandit and colleagues 1 emphasises the discrepancy between the oft-quoted 1–2:1000 incidence of ‘awareness during anaesthesia’ and its extraordinary rarity in the clinical experience of most UK anaesthetists. Pandit et al. categorised awareness into that occurring: (i) after induction but before surgery; (ii) during surgery; and (iii) after surgery but before full recovery. Many regard awareness in stages 1 and 3 as the risky periods of anaesthesia because they are non-steady states, but arousal due to stimulation at these stages is ameliorated by attention to the basic rules of administering general anaesthesia, supplementation with local anaesthesia and powerful analgesia, not by using a monitoring device that in our hands had poor sensitivity to opioid effects. Arousal during stage 2 may occur during steady-state anaesthesia when there is an unrecognised and insufficient dose of anaesthetic and analgesic drugs administered. Is there a role for monitoring here? Gratifyingly, this distressing state seems to be rare, although the incidence of 1–2:1000 is often quoted. Pandit et al. recorded the prevalence of patients who complained of pain and were intent on a formal complaint or litigation as about 1:100 000. This observation is not new and is consistent with a similarly low incidence of awareness (1:80–90 000 anaesthetics) that we reported 2 from hospitals in the Cambridge region between 1993 and 1999. The incidence is very low; it means that almost 100 000 patients would need to be monitored to pick up one case of this type of awareness. This state seems to be the tip of the iceberg, but how far below the surface should we go to explore the large spectrum of explicit recall? Electroencephalography can be used to identify changes in consciousness during propofol anaesthesia 3, but is a research tool, not yet available for widespread clinical use. Instead, more research should be performed to explore consciousness and memory during anaesthesia, such as that performed in Cambridge 2 and Northwick Park 4, which emphasised the powerful inhibitory effects of sub-MAC doses of general anaesthesia on working memory – and therefore subsequent recall – as well as pain perception in seemingly fully conscious subjects. The veracity of what is recalled must also be questioned. If there is no immediate postoperative record of the awareness events, how can the later recall of this event be verified as exact? Anecdotally, during a depth of anaesthesia study, a patient recalled precisely the events that had occurred after accidental discontinuation of general anaesthesia mid-procedure, except that contemporaneous video records showed that none of the recalled events had actually occurred. The rarity of painful awareness during anaesthesia should re-assure patients and confirm the high level of clinical competence of UK anaesthetists, despite their historical rejection of monitoring every patient using electroencephalographic or isolated forearm monitoring techniques. Now is not the time, if ever, for the National Institute for Health and Clinical Excellence to consider mandating such monitoring.

Gender differences in cerebrovascular reactivity to carbon dioxide during sevoflurane anesthesia in children: preliminary findings

Cerebrovascular reactivity to carbon dioxide (CO(2) R) is affected by age, gender and anesthetic agents. While gender differences in CO(2) R are described in adults, there are no such data in children. To examine the gender differences in CO(2) R in children during sevoflurane anesthesia. Five girls and five boys <15 years of age and ASA physical status I, undergoing general anesthesia for elective surgery were enrolled. Under steady-state anesthesia with <1.0 MAC sevoflurane, middle cerebral artery blood flow velocity changes were monitored using Transcranial Doppler ultrasound while endtidal carbon dioxide (EtCO(2)) was adjusted from 40 to 30 mmHg (hypocapnia) and then from 40 to 50 mmHg (hypercapnia). CO(2)R was calculated between EtCO(2) ranges 30-40 and 40-50 mmHg. Cerebrovascular resistance (eCVR) was estimated as MAP/Vmca and the change in eCVR (ΔeCVR) between EtCO(2) 30 and 40 mmHg and between EtCO(2) 40 and 50 mmHg was calculated. There was no gender difference in CO(2)R. However, both CO(2)R and ΔeCVR were lower in the EtCO(2) 40-50 mmHg range compared to EtCO(2) 30-40 mmHg range only in girls (P = 0.01 and P = 0.01, respectively). Vmca increased significantly with increase in CO(2) (P < 0.001) for both boys and girls. The coefficient of nonlinear correlation (r) between Vmca and EtCO(2) was 0.88 in girls vs 0.66 in boys. While there were no gender differences in CO(2)R within the individual EtCO(2) ranges examined, girls but not boys had a significantly lower CO(2)R and ΔeCVR in the higher EtCO(2) range during <1.0 MAC sevoflurane anesthesia.

High-intensity transient signals during laparoscopic surgery in children

Laparoscopic interventions in children gain increasing popularity. Pneumoperitoneum as applied during laparoscopic surgery can induce gas emboli formation, but it is unclear whether this is associated with cerebral embolic events. To investigate the hypothesis that pneumoperitoneum causes cerebral emboli in children, the number and intensity of high-intensity transient signals (HITS) detected using transcranial Doppler ultrasonography were assessed before and after induction of pneumoperitoneum. Twenty children were monitored during laparoscopic surgery. General anaesthesia was performed using sevoflurane and sufentanil or alfentanil. Pressure-controlled ventilation was adapted to maintain end-tidal Pco(2) (Pe'(co(2))) between 4.7 and 6.0 kPa. Baseline measurement of HITS rate, cerebral blood flow velocity, and mean arterial pressure (MAP) were recorded during steady-state anaesthesia before skin incision and during pneumoperitoneum with intra-abdominal pressure of 1.6-2.0 kPa applied using CO(2). In 14 children (70%), HITS were detected during baseline and pneumoperitoneum. Three additional children (15%) developed HITS during pneumoperitoneum only and another three children (15%) presented no HITS during the investigation period. MAP and cerebral blood flow velocity increased with pneumoperitoneum. HITS are present in 70% of paediatric surgical patients under balanced anaesthesia before surgical interventions. Pneumoperitoneum further increased the occurrence of HITS.

Comparison of Anesthetic Depth Indexes Based on Thalamocortical Local Field Potentials in Rats

Local field potentials may allow a more precise analysis of the brain electrical activity than the electroencephalogram. In this study, local field potentials were recorded in the thalamocortical axis of rats to (i) compare the performance of several indexes of anesthetic depth and (ii) investigate the existence of thalamocortical correlated or disrupted activity during isoflurane steady-state anesthesia. Five rats chronically implanted with microelectrodes were used to record local field potentials in the primary somatosensory cortex and ventroposterolateral thalamic nuclei at six periods: before induction of anesthesia; in the last 5 min of randomized 20-min steady-state end-tidal 0.8, 1.1, 1.4, and 1.7% isoflurane concentrations; and after recovery. The approximate entropy, the index of consciousness, the spectral edge frequency, and the permutation entropy were estimated using epochs of 8 s. A correction factor for burst suppression was applied to the spectral edge frequency and to the permutation entropy. The correlation between the derived indexes and the end-tidal isoflurane was calculated and compared for the two studied brain regions indexes. Coherence analysis was also performed. The burst suppression-corrected permutation entropy showed the highest correlation with the end-tidal isoflurane concentration, and a high coherence was obtained between the two studied areas. The permutation entropy corrected with the classic burst suppression ratio is a promising alternative to other indexes of anesthetic depth. Furthermore, high coherence level of activity exists between the somatosensory cortical and thalamic regions, even at deep isoflurane stages.

Ketamine has no effect on bispectral index during stable propofol–remifentanil anaesthesia

Ketamine 0.15-1 mg kg(-1) decreases postoperative morphine consumption, but 0.5 mg kg(-1) is associated with an increase in the bispectral index (BIS) values that can lead to an overdose of hypnotic agents. The purpose of our investigation was to study the effect of ketamine 0.2 mg kg(-1) administered over a 5 min period on the BIS during stable target-controlled infusion (TCI) propofol-remifentanil general anaesthesia. Thirty ASA I or II patients undergoing abdominal laparoscopic surgery were included in this double-blind, randomized study. Anaesthesia was induced and maintained with a TCI of propofol and remifentanil. After 5 min of steady-state anaesthesia (BIS at 40) without surgical stimulation, patients received either an infusion of ketamine 0.2 mg kg(-1) or normal saline. The test drug was infused over 5 min. Standard parameters and BIS values were recorded every minute until 15 min post-infusion. The baseline mean (sd) value for the BIS was 37 (6.5) for the ketamine group and 39 (8.2) for the placebo group. The highest mean BIS value during the recording period was 41.5 (8.7) for the ketamine group and 40.1 (8.9) for the placebo group. BIS values were not statistically different between the groups (P=0.62); there was no significant change over time (P=0.65) with no group-time interaction (P=0.55). Under stable propofol and remifentanil TCI anaesthesia, a slow bolus infusion of ketamine 0.2 mg kg(-1) administered over a 5 min period did not increase the BIS value over the next 15 min.

Bispectral Index, Entropy, and Quantitative Electroencephalogram during Single-agent Xenon Anesthesia

The aim was to evaluate the performance of anesthesia depth monitors, Bispectral Index (BIS) and Entropy, during single-agent xenon anesthesia in 17 healthy subjects. After mask induction with xenon and intubation, anesthesia was continued with xenon only. BIS, State Entropy and Response Entropy, and electroencephalogram were monitored throughout induction, steady-state anesthesia, and emergence. The performance of BIS, State Entropy, and Response Entropy were evaluated with prediction probability, sensitivity, and specificity analyses. The power spectrum of the raw electroencephalogram signal was calculated. The mean (SD) xenon concentration during anesthesia was 66.4% (2.4%). BIS, State Entropy, and Response Entropy demonstrated low prediction probability values at loss of response (0.455, 0.656, and 0.619) but 1 min after that the values were high (0.804, 0.941, and 0.929). Thereafter, equally good performance was demonstrated for all indices. At emergence, the prediction probability values to distinguish between steady-state anesthesia and return of response for BIS, State Entropy, and Response Entropy were 0.988, 0.892, and 0.992. No statistical differences between the performances of the monitors were observed. Quantitative electroencephalogram analyses showed generalized increase in total power (P < 0.001), delta (P < 0.001) and theta activity (P < 0.001), and increased alpha activity (P = 0.003) in the frontal brain regions. Electroencephalogram-derived depth of sedation indices BIS and Entropy showed a delay to detect loss of response during induction of xenon anesthesia. Both monitors performed well in distinguishing between conscious and unconscious states during steady-state anesthesia. Xenon-induced changes in electroencephalogram closely resemble those induced by propofol.

Midlatency auditory evoked potentials in children: effect of age and general anaesthesia

Midlatency auditory evoked potentials (MLAEP) are a promising tool for monitoring suppression of sensory processing during anaesthesia and might help to avoid awareness. MLAEP in children are different to those in adults and the exact changes during general anaesthesia are unknown. In 49 children of age between 2 and 12 yr, MLAEP were recorded before anaesthesia, during tracheal intubation, at steady-state balanced anaesthesia, and after extubation. MLAEP were recordable in all children in the awake (premedicated) state with latencies but not amplitudes dependent on children's age. MLAEP latencies significantly increased during tracheal intubation and steady-state anaesthesia. Changes in amplitudes were inconsistent. All MLAEP variables returned to near baseline values after extubation. The results of this study imply that MLAEP can successfully be recorded during anaesthesia in children above the age of 2 yr. Further studies are necessary before MLAEP might be applicable for monitoring purposes in paediatric anaesthesia.

New parameters of skin conductance compared with bispectral index® monitoring to assess emergence from total intravenous anaesthesia

Arousal after total i.v. anaesthesia (TIVA) has been reported to be detectable by monitoring the number of fluctuations per second (NFSC), a parameter of skin conductance (SC). However, compared with monitoring of the bispectral index (BIS), the predictive probability of NFSC was significantly lower. The aim of this study was to determine the value of the two new, not yet published parameters of SC, area under the curve (AUC) methods A and B, for monitoring emergence from TIVA compared with monitoring of NFSC and BIS. Twenty-five patients undergoing surgery were investigated. NFSC, AUC A, AUC B, BIS, and haemodynamic parameters (mean arterial pressure and heart rate) were recorded simultaneously. The performance of the monitoring devices in distinguishing between the clinical states 'steady-state anaesthesia', 'first clinical reaction', and 'extubation' were compared using the method of prediction probability (Pk) calculation. BIS showed the best performance in distinguishing between 'steady-state anaesthesia' vs 'first reaction' (Pk BIS 0.95; NFSC 0.73; AUC A 0.54; AUC B 0.62) and 'steady-state anaesthesia' vs 'extubation' (Pk BIS 0.99; NFSC 0.73; AUC A 0.71; AUC B 0.67). However, the time from first BIS>60/SC>0 to a first clinical reaction was significantly shorter for BIS (median BIS((R)) 180 s; NFSC 780 s; AUC A 750 s; AUC B 690 s; P < 0.001). AUC A and AUC B did not improve accuracy of SC monitoring in patients waking after TIVA.

Cardiovascular parameters continue to change after achieving constant effect site drug concentration

There is a good correlation between the calculated effect site concentration and the depth of anaesthesia. Propofol is known to depress the cardiovascular system but the relationship between the effect site concentration and cardiovascular depression has not been extensively studied. A previous study by Kazama et al. showed that the maximal cardiovascular depression (using systolic blood pressure only) would happen some 8 min after peak plasma propofol concentrations [1]. We wished to investigate this further while using effect site concentration target-controlled infusions (TCI) of total intravenous anaesthesia (TIVA). Local Research Ethics Committee approval was given and informed consent obtained from 20 patients of ASA physical status 1–2 due to undergo elective day surgery. They were then anaesthetised using a standard effect site concentration TIVA technique. From the time of attaining a steady state effect site concentration of both propofol and remifentanil ([ES]ss) we measured Bispectral Index, heart rate, blood pressure and cardiac index every minute for 25 min. Any alterations were then mathematically modelled in a nonlinear regression model to calculate when they reached a steady plateau with 95% certainty. These are shown in Table 1. We have shown that the time to maximal cardiovascular depression occurs well after that previously claimed [1]. The depression of cardiovascular parameters is most profound in the vasodilatation that is well known with propofol, reflected in the drop in mean arterial pressure. The reduction in heart rate is also significant but reflex mechanisms of increasing the stroke volume ensures that the measured cardiac index changes less. These results show that after achieving steady state concentrations of anaesthetic agents the cardiovascular system depresses further with a maximal time of depression ∼78 min after achieving calculated steady state anaesthesia. Papers using patients at ‘steady state’ anaesthesia must either have a comparable control arm to the experiment or wait for 78 min until the cardiovascular systems achieve a steady plateau.