Mid-latency Auditory Evoked Potentials Research Articles

Impact of Propofol on Midlatency Auditory-Evoked Potentials in Children

Kuhnle, G. E.*; Hornuss, C.†; Lenk, M.†; Salam, A. P.‡; Wiepcke, D.†; Edelmann-Gahr, V.†; Flake, G.†; Daunderer, M.†; Oberhauser, M.§; Müller, H.-H.∥; Feuerecker, M.† Author Information

Impact of propofol on mid-latency auditory-evoked potentials in children

Propofol is increasingly used in paediatric anaesthesia, but can be challenging to titrate accurately in this group. Mid-latency auditory-evoked potentials (MLAEPs) can be used to help titrate propofol. However, the effects of propofol on MLAEP in children are unclear. Therefore, we investigated the relationship between propofol and MLAEP in children undergoing anaesthesia. Fourteen healthy children aged 4-16 yr received anaesthesia for elective surgery. Before surgery, propofol was administered in three concentrations (3, 6, 9 µg ml(-1)) through a target-controlled infusion pump using Kataria and colleagues' model. MLAEPs were recorded 5 min after having reached each target propofol concentration at each respective concentration. Additionally, venous propofol blood concentrations were assayed at each measuring time point. Propofol increased all four MLAEP peak latencies (peaks Na, Pa, Nb, P1) in a dose-dependent manner. In addition, the differences in amplitudes were significantly smaller with increasing propofol target concentrations. The measured propofol plasma concentrations correlated positively with the latencies of the peaks Na, Pa, and Nb. Propofol affects MLAEP latencies and amplitudes in children in a dose-dependent manner. MLAEP measurement might therefore be a useful tool for monitoring depth of propofol anaesthesia in children.

Neurophysiology and Intraoperative Nociception

Neurophysiology and Intraoperative Nociception

Mid-Latency Auditory Evoked Potentials in 2 Meditative States

Mid-latency auditory evoked potentials (MLAEPs) were assessed in 60 participants during 4 mental states described in traditional yoga texts. These 4 mental states are random thinking, nonmeditative-focused thinking, meditative focusing, and meditation. Assessments were made before (5 minutes), during (20 minutes), and after (5 minutes) each of the 4 states, on 4 separate days. There were prolonged latencies of 2 MLAEPs components, the Na and Pa waves during meditation (P < .05, post hoc analyses following analysis of variance [ANOVA]), suggesting that auditory information transmission at the level of the medial geniculate and primary auditory cortex (ie, the neural generators corresponding to the Na and Pa waves) was delayed. Hence, meditation influenced MLAEPs, while meditative focusing did not.

Effects of increasing sevoflurane MAC levels on mid-latency auditory evoked potentials in infants, schoolchildren, and the elderly

Detection of mid-latency auditory evoked potentials (MLAEPs) is a technology to monitor central nervous structures. As seen in adults and children, general anaesthesia influences the MLAEP latencies. MLAEP detection seems to be a promising tool to assess different levels of anaesthesia depth in adults and children. MLAEPs were recorded in 10 infants (2 months-3 yr), 12 schoolchildren (6-14 yr), and 10 elderly (75-89 yr) under general anaesthesia with increasing concentrations of sevoflurane at steady state. In addition, MLAEPs were detected before and after the application of sufentanil. At all different ages, MLAEP latencies increased significantly with higher volume percentages of sevoflurane. These results were also detectable when MAC values of sevoflurane were compared with MLAEP peaks. An age-dependent effect could be displayed as elderly people need lower absolute sevoflurane concentrations to achieve the same MLAEP peak increase. Overall, the application of sufentanil under steady-state sevoflurane application at 1 MAC did not importantly affect the MLAEP latencies. MLAEP latencies increase at the influence of sevoflurane in a dose-dependent manner and in relation to age. These results imply that MLAEP detection is a reasonable tool for monitoring hypnotic effects at all ages. Further studies are required to standardize MLAEP alterations related to effects of medication used for general anaesthesia at all different ages.

A comparison between target-controlled and manually controlled propofol infusions in patients undergoing routine surgical procedures

Previous studies have shown that target-controlled infusion (TCI) was associated with increased propofol consumption as compared with manually controlled infusion (MCI). However, most studies lacked an objective measurement of anaesthetic depth. We compared TCI and MCI with regard to propofol dose requirement while monitoring depth of anaesthesia with bispectral index (BIS) and midlatency auditory-evoked potentials (MLAEPs). Fifty ASA 1 or 2 patients undergoing elective ENT surgery were randomly allocated to the TCI group (n = 25)or the MCI group (n = 25). BIS, MLAEPs, haemodynamic parameters and propofol plasma concentration were determined at various stages before, during and after anaesthesia. During anaesthesia, BIS values were always maintained between 40 and 60. Anaesthesia significantly increased latency of Pa and Nb compared with when patients were awake (P < 0.01). After extubation, the latency of Pa and Nb significantly decreased and basically returned to baseline level. BIS and latency of both Pa and Nb did not differ between groups.Also, the propofol induction dose (mean WSD: TCI, 2.09 +/- 0.36 mg kg(-1); MCI, 2.06 +/- 0.16 mg kg(-1) and total dose (TCI, 5.57 +/- 0.96 mg kg(-1) h(-1); MCI, 5.79 +/- 0.87 mg kg(-1) h(-1) and measured plasma propofol concentration during anaesthesia did not differ between groups. At 15 min after intubation, the mean predicted plasma concentration (2.2 +/- 0.2 microg ml(-1)) differed significantly from the measured plasma concentration (2.8 +/- 1.2 microg ml(-1)). No correlation was observed between predicted and measured propofol plasma concentrations.

Bilateral measurement of bispectral index and mid-latency auditory evoked potentials in patients with unilateral brain lesions

Purpose The impact of intracranial lesions on the results of bispectral index (BIS) and mid-latency auditory evoked potentials (MLAEP) remains unclear. We tested the hypothesis that MLAEP (latencies of wave Pa and wave Nb) obtained bilaterally from patients with unilateral brain lesions result in less bias than BIS values obtained from both sides. Patients Twenty patients with unilateral supratentorial lesions were included in the study. Materials and Methods Bispectral index and MLAEP were measured bilaterally using the BIS and AEP modules of the Monitor S/5 (GE, Helsinki, Finland). Significance of the difference in the number of patients with a clinically relevant bias (more than 10%) of BIS and MLAEP was calculated by Fisher exact test. Results Bispectral index was significantly in more patients different on the side of the lesion than latencies of wave Pa and Nb (18 patients for BIS, 1 patient for Pa, 3 patients for Nb, P < .0001). Mean bias was −18.8 ± 25.7 for BIS, 1.5 ± 3.4 milliseconds for wave Pa, and −1.5 ± 6.1 milliseconds for wave Nb (data given as mean ± SD). Conclusions Mid-latency auditory evoked potentials are less biased by intracranial lesions than BIS and seem to be superior to BIS for the monitoring of patients with intracranial lesions.

Changes in Midlatency Auditory Evoked Potentials following Two Yoga-Based Relaxation Techniques

Practicing meditation while focusing on a sound or a symbol influenced midlatency auditory evoked potentials (MLAEPs). Cyclic meditation (CM) is a technique combining yoga postures with meditation while supine, which has influenced the P300 event-related potential. The effects of CM on MLAEPs have not been previously studied. The MLAEPs were studied before and after the practice of CM compared to an equal duration of supine rest (SR) in 47 male volunteers (group mean age 26.5 +/- 4.4 years), recorded from the vertex referenced to linked earlobes. The sessions were one day apart and subjects were randomly assigned to each session. The Pa wave peak latency and Nb wave peak latency significantly increased following CM compared to before CM (repeated measures ANOVA, post-hoc analysis with least significant difference, p<0.05). There was a significant increase in the peak amplitude of the Nb wave (p<0.05) compared to before CM. Post SR there was a significant increase in the peak latency of the Na wave (p<0.05) compared to before SR. In conclusion following CM the latencies of neural generators corresponding to cortical areas is prolonged, whereas following SR a similar change occurs at mesencephalic-diencephalic levels.

EEG under anesthesia—Feature extraction with TESPAR

We investigated the problem of automatic depth of anesthesia (DOA) estimation from electroencephalogram (EEG) recordings. We employed Time Encoded Signal Processing And Recognition (TESPAR), a time-domain signal processing technique, in combination with multi-layer perceptrons to identify DOA levels. The presented system learns to discriminate between five DOA classes assessed by human experts whose judgements were based on EEG mid-latency auditory evoked potentials (MLAEPs) and clinical observations. We found that our system closely mimicked the behavior of the human expert, thus proving the utility of the method. Further analyses on the features extracted by our technique indicated that information related to DOA is mostly distributed across frequency bands and that the presence of high frequencies (>80 Hz), which reflect mostly muscle activity, is beneficial for DOA detection.

A Comparison of Auditory Evoked Potentials Derived From a Monitor Integrated Module Versus Standard Technique

Measurement of brain stem auditory evoked potentials (BAEP) and midlatency auditory evoked potentials (MLAEP) using a new monitor integrated module was compared with an established device. The aim of this study was to evaluate if the new system could replace the more inconvenient established technique. MLAEP and BAEP were obtained from 19 anesthetized male patients using the AEP-Module for Monitor S/5 [GE, Helsinki, Finland (S/5)] and Neuropack 4 mini [Nihon Kohden, Tokyo, Japan (Neuropack)]. Significance of different results was calculated by paired t test. Bias was estimated by Bland-Altman statistics. Latencies of BAEP were significantly shorter and amplitudes of BAEP were significantly higher for Neuropack. Mean latencies of MLAEP (Pa and Nb) were not significantly different (Pa 44.1+/-4.4 ms vs. 41.9+/-5.4 ms/Nb 66.4+/-5.6 ms vs. 62.8+/-6.5 ms), but methods are not interchangeable owing to great variability (Pa -13.16 to 8.94 ms, Nb -19.15 to 11.79 ms). BAEP recorded by S/5 cannot be used for diagnostic interpretation using generally accepted normal values, but can be used for examining changes during the monitoring period. Mean values of Pa and Nb were not significantly different, but values of the S/5 varied above and below the values of Neuropack such that the measurements could not be used for diagnostic interpretation. However, this did not reduce their usefulness for determining adequate hypnosis.

Bispectral Index and Middle Latency Auditory Evoked Potentials in Children Younger Than Two-Years-Old

We analyzed the values of the bispectral index (BIS) and midlatency auditory evoked potentials (MLAEP) and their correlation with the modified Ramsay score (RS) during wakefulness and natural sleep in healthy children without pharmacological sedation. Fifty-three healthy children younger than 2-yr-old were studied. Children were evaluated simultaneously using the modified RS, the BIS, and MLAEPs. Each patient was studied only once. The correlation and agreement were studied. The correlation among the three methods was determined using the Spearman Rank Correlation test and the agreement among the methods was assessed using by Cohen's Kappa test. There was a moderate-to-good correlation (r) among the three methods (P = 0.01): BIS and MLAEP (r = 0.574), BIS and RS (r = -0.504), and MLAEP and RS (r = -0.624). However, the level of agreement (kappa) was only poor to fair: BIS and MLAEP (kappa = 0.392), BIS and RS (kappa = 0.270), and MLAEP and RS (kappa = 0.409). All the correlations were lower in children between 1 and 6 mo-of-age. When the children were asleep (RS: 3-5), the BIS values were higher in children younger than 1 mo-of-age than in children older than 6 mo-of-age (P after Bonferroni correction = 0.028). The BIS, MLAEP, and RS have a good correlation in children younger than 2 yr not receiving pharmacological sedation, though the level of agreement was poor.

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.

Auditory-evoked potentials in bispectral index-guided anaesthesia for cardiac surgery

Background and objective: Midlatency auditory-evoked potentials, as measures of the anaesthetic state, were evaluated at similar levels of bispectral index in cardiac surgical patients maintained with either propofol or isoflurane anaesthesia. Methods: Twenty-four patients were randomly allocated to anaesthesia with propofol (n = 12) or isoflurane (n = 12). Bispectral index was maintained below 60 during surgery. Auditory-evoked potentials were collected before induction of anaesthesia, 10 min after intubation, 30 min after sternotomy, during cardiopulmonary bypass at the time of cross-clamping of the aorta and during stable mild hypothermia, after de-clamping of the aorta, and after the operation. Results: At the pre-determined time points, bispectral index values showed comparable depth of hypnosis in both groups. The latency of the Nb component of midlatency auditory-evoked potentials was significantly increased in the isoflurane group after intubation (P < 0.001) and that of both the Nb and the Pa components after sternotomy (P < 0.001) compared with the propofol group. No differences between the groups were detected with respect to haemodynamic variables. No patient reported recall of intraoperative events. Conclusion: After intubation and surgical stimulation, when bispectral index was at a constant level, there was a difference in the Nb and Pa components of the midlatency auditory-evoked potentials between the two anaesthetic regimens, indicating a distinction in the state of anaesthesia. Our results suggest that the parallel use of these two electrophysiological methods can show differences in the components of anaesthesia between various anaesthesia methods in cardiac surgical patients.

Is naso-gastric tube insertion necessary to reduce the risk of gastric injury at subcostal laparoscopic insufflation? A pilot study

Midlatency auditory-evoked potentials, as measures of the anaesthetic state, were evaluated at similar levels of bispectral index in cardiac surgical patients maintained with either propofol or isoflurane anaesthesia. Twenty-four patients were randomly allocated to anaesthesia with propofol (n = 12) or isoflurane (n = 12). Bispectral index was maintained below 60 during surgery. Auditory-evoked potentials were collected before induction of anaesthesia, 10 min after intubation, 30 min after sternotomy, during cardiopulmonary bypass at the time of cross-clamping of the aorta and during stable mild hypothermia, after de-clamping of the aorta, and after the operation. At the pre-determined time points, bispectral index values showed comparable depth of hypnosis in both groups. The latency of the Nb component of midlatency auditory-evoked potentials was significantly increased in the isoflurane group after intubation (P < 0.001) and that of both the Nb and the Pa components after sternotomy (P < 0.001) compared with the propofol group. No differences between the groups were detected with respect to haemodynamic variables. No patient reported recall of intraoperative events. After intubation and surgical stimulation, when bispectral index was at a constant level, there was a difference in the Nb and Pa components of the midlatency auditory-evoked potentials between the two anaesthetic regimens, indicating a distinction in the state of anaesthesia. Our results suggest that the parallel use of these two electrophysiological methods can show differences in the components of anaesthesia between various anaesthesia methods in cardiac surgical patients.

Objective response detection technique in frequency-domain for reflecting changes in MLAEP

The mid-latency auditory evoked potential (MLAEP) occurs within the interval 10–100 ms post-stimulus and exhibits morphological changes due to coma, general anaesthesia and neurological and psychiatric diseases. This work evaluates an objective response detection technique in the frequency domain, the magnitude squared coherence ( κ ˆ 2 ( f ) ) , in reflecting MLAEPs changes in amplitude and latencies. Both simulation and EEG data were used in this investigation. The EEG during auditory stimulation in 10 volunteers under propofol-induced anaesthesia was acquired. Based on the null hypothesis of non-existing response, critical values have been derived in order to detect the auditory response. The alternative hypothesis was used to infer about maximal-response frequencies as well as to derive confidence intervals for the estimated values of κ ˆ 2 ( f ) during anaesthesia. Changes in both simulated and real MLAEPs could be tracked by κ ˆ 2 ( f ) , even for low SNR. High degree of cortical activation occurred predominantly between 30 and 90 Hz. This finding could be related to the sensory-originated phase-locked oscillation in the gamma band (30–70 Hz). Hence, for applications where changes on MLAEPs should be assessed, the use of κ ˆ 2 ( f ) as an objective statistical response detection technique is worth to be applied.

Correlation of the A-Line™ ARX index with acoustically evoked potential amplitude

Automated indices derived from mid-latency auditory evoked potentials (MLAEP) have been proposed for monitoring the state of anaesthesia. The A-Line ARX index (AAI) has been implemented in the A-Line monitor (Danmeter, V1.4). Several studies have reported variable and, in awake patients, sometimes surprisingly low AAI values. The purpose of this study was to reproduce these findings under steady-state conditions and to investigate their causes. Ten awake unmedicated volunteers were studied under steady-state conditions. For each subject, the raw EEG and the AAI were recorded with an A-Line monitor (V1.4) during three separate sessions of 45.0 (1.6) min duration each. MATLAB (Mathworks) routines were used to derive MLAEP responses from EEG data and to calculate maximal MLAEP amplitudes. The AAI values ranged from 15 to 99, while 11.4% fell below levels which, according to the manufacturer, indicate an anaesthetic depth suitable for surgery. Inter-individual and intra-individual variation was observed despite stable recording conditions. The amplitudes of the MLAEP varied from 0.8 to 42.0 microV. The MLAEP amplitude exceeded 2 microV in 75.3% of readings. The Spearman's rank correlation coefficient between the MLAEP amplitude and the AAI value was r=0.89 (P<0.0001). The version of the A-Line monitor used in this study does not exclude contaminated MLAEP signals. Previous publications involving this version of the A-Line monitor (as opposed to the newer A-Line/2 monitor series) should be reassessed in the light of these findings. Before exclusively MLAEP-based monitors can be evaluated as suitable monitors of depth of anaesthesia, it is essential to ensure that inbuilt validity tests eliminate contaminated MLAEP signals.

Detektion intraoperativer Wachheit bei einem Kleinkind mit akustisch evozierten Potenzialen

Intraoperative wakefulness is not only limited to adults and can also be found at a similar percentage (0.8%) in paediatric anaesthesia. For prevention of awareness neurophysiologic methods like auditory evoked potentials might be helpful. We report a case of a 2-year-old boy receiving balanced anaesthesia with sevoflurane and alfentanil. Midlatency auditory evoked potentials (MLAEPs) were recorded continuously before, during and after the surgical procedure. During the surgical procedure sevoflurane was withdrawn unintentionally. After a short period of time the boy started coughing and moved his legs, which was interpreted as insufficient analgesia. Several boli of alfentanil did not lead to the expected clinical effect on the depth of anaesthesia. After a recheck of the anaesthetic ventilator the error was determined and delivery of the volatile anaesthetic restored. The postoperative evaluation of the MLAEPs revealed the inadequate suppression of auditory processing during this incident with latencies comparable to the awake state. After reapplication of sevoflurane the MLAEPs were almost completely suppressed demonstrating adequate anesthetic depth. Exemplarily this case suggests that MLAEPs could be used to detect intraoperative awareness also in paediatric anaesthesia. Investigations to prove the validity and reproducibility of MLAEPs in children will be necessary.

Comparison of auditory evoked potential parameters for predicting clinically anaesthetized state

Most of the research efforts to monitor the depth of anaesthesia using the mid-latency auditory evoked potential (MLAEP) signal in humans are based on the detection of the amplitudes and latencies of the signal peaks. Attempts have also been made to combine different time-domain and frequency-domain parameters. A comparison of different parameters is required to identify those which best discriminate the awake state from the anaesthetized state. Although the sensitivity of MLAEP signal peaks is appreciable in awake and light anaesthesia states, it is reduced considerably at the moderate anaesthesia level, rendering this method unsuitable for predicting the surgical stage of anaesthesia. To overcome this problem, a numerically derived quantity--the morphology index--was used which does not require location of the peaks of the signal, but, at the same time, reflects the changes in both the latency and amplitude of the peaks. AEPs were recorded in the hospital for 18 patients during various states, i.e. awake, induction, unconscious and after regaining consciousness from halothane anaesthesia. The peak latencies, amplitudes, morphology index and peak power frequency (PPF) were calculated. The sensitivity and specificity of PPF (89% and 95%, respectively) were found to be better than those for Pa and Nb peak amplitudes, their latencies and the morphology index. In addition, PPF showed minimum inter-patient variation. The mean value (standard deviation) of this parameter was 26.9 (0.67) during the awake state, decreased to 17.1 (1.2) during the anaesthetized state, and increased again to 26.1 (0.93) when the patients regained full consciousness. PPF is the best of the four studied MLAEP parameters for the clinical characterization of the anaesthetized state during surgery.

Modulation of the Sleep State–Dependent P50 Midlatency Auditory-Evoked Potential by Electric Stimulation of Acupuncture Points

Bray PA, Mamiya N, Fann AV, Gellman H, Skinner RD, Garcia-Rill EE. Modulation of the sleep state–dependent P50 midlatency auditory-evoked potential by electric stimulation of acupuncture points. Objective To determine if the P50 midlatency auditory evoked potential, a sleep state–dependent waveform thought to be generated by the reticular activating system, is modulated after surface stimulation of acupuncture points (ie, electroacupuncture). Design P50 potential recordings were carried out before, during, and after electroacupuncture. Setting A clinical research center. Participants Eighty healthy subjects ages 25 to 55 were recorded in 7 investigations. Interventions Stimulation of 3 specific acupuncture points (Pericardium 6, Heart 3, Liver 3) was compared with no stimulation or with stimulation of control points (Gall Bladder 34, Large Intestine 11, Small Intestine 3). We compared different frequencies of stimulation (5, 60, 100Hz), unilateral versus bilateral stimulation, and the effects of repeated episodes of stimulation. Main Outcome Measures P50 auditory evoked potential latency, amplitude (measure of level of arousal), and habituation (measure of sensory gait) at interstimulus interval of 250ms. Results Electroacupuncture at specific points decreased P50 potential amplitude versus electroacupuncture at control points ( P=.006) or versus no stimulation ( P<.001). The optimal effective frequency was 5Hz ( P<.05 at 5Hz, P>.05 at 60 and 100Hz), and unilateral electroacupuncture was not as effective as bilateral electroacupuncture ( P=.007). Repeated episodes of bilateral electroacupuncture showed additive effects ( P<.05). There were no differences in responsiveness across sexes ( P=.79), and electroacupuncture did not affect P50 potential habituation ( P>.05). Conclusions Electroacupuncture may be effectively used to decrease arousal levels, perhaps as adjunct therapy for disorders of hypervigilance.

New Composite Index Based on Midlatency Auditory Evoked Potential and Electroencephalographic Parameters to Optimize Correlation with Propofol Effect Site Concentration

This study investigates the accuracy of a composite index, the A-Line(R) auditory evoked potentials index version 1.6 (AAI1.6; Danmeter A/S, Odense, Denmark), as a measure of cerebral anesthetic drug effect in a model for predicting a calculated effect site concentration of propofol (CePROP). The AAI1.6 algorithm extracts information from the midlatency auditory evoked potentials, the spontaneous electroencephalographic activity, and the detection of burst suppression. The former version of this monitor, the A-Line auditory evoked potential index version 1.5, is only based on fast extracted midlatency auditory evoked potential information. After institutional ethics committee approval (University Hospital, Ghent, Belgium), informed consent was obtained from 13 patients (10 women, 3 men) with an American Society of Anesthesiologists physical status of I, aged 18-65 yr, who were scheduled to undergo ambulatory gynecologic or urologic surgery. The authors evaluated for Bispectral Index, A-Line auditory evoked potential index, version 1.5, AAI1.6 scaled from 0 to 100 and AAI1.6 scaled from 0 to 60, the interpatient stability at baseline, the detection of burst suppression, prediction probability, and correlation with CePROP, during a constant infusion of 1% propofol at 300 ml/h. The authors developed pharmacodynamic models relating the predicted CePROP to each measure of cerebral anesthetic drug effect. Bispectral Index had the lowest interindividual baseline variability. No significant difference was found with prediction probability analysis for all measures. Comparisons for correlation were performed for all indices. The AAI1.6 scaled to 60 had a significantly higher correlation with CePROP compared with all other measures. The AAI1.6 scaled to 100 had a significant higher correlation with CePROP compared with the A-Line auditory evoked potential index version 1.5 (P < 0.05) The authors found that the application of AAI1.6 has a better correlation with a calculated CePROP compared with a solitary fast extracting midlatency auditory evoked potential measure. Whether this improvement in pharmacodynamic tracing is accompanied by an improved clinical performance should be investigated using clinical endpoints.