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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Detection of intraoperative awareness via auditory evoked potentials in an infant]. / 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.

Concurrent recording of AEP, SSEP and EEG parameters during anaesthesia: a factor analysis.

BACKGROUND: Spontaneous EEG, mid-latency auditory evoked potentials (AEP) and somatosensory evoked potentials (SSEP) have been used to monitor anaesthesia. This poses the question as to whether or not EEG, AEP and SSEP vary in parallel with varying conditions during surgical anaesthesia. METHODS: A total of 81 variables (31 EEG, 22 SSEP, 28 AEP) were simultaneously recorded in 48 surgical patients during anaesthesia. A total of 307 cases of the 81 variables in stable anaesthetic states were recorded. A factor analysis was performed for this data set. RESULTS: Sixteen variables were excluded because of multicollinearity. We extracted 13 factors with eigenvalues >1, representing 78.3% of the total variance, from the remaining 65 x 307 matrix. The first three factors represented 12%, 11% and 10% of the total variance. Factor 1 had only significant loadings from EEG variables, factor 2 only significant loadings from AEP variables and factor 3 only significant loadings from SSEP variables. CONCLUSION: EEG, AEP and SSEP measure different aspects of neural processing during anaesthesia. This gives rise to the hypothesis that simultaneous monitoring of these quantities may give additional information compared with the monitoring of each quantity alone.

[Unwanted wakefulness during general anesthesia]. / Unerwünschte Wachheit während Allgemeinanästhesie.

Intraoperative wakefulness ("awareness") is still a relevant problem. Different stages of wakefulness exist: conscious awareness with explicit recall of pain in 0.03% and with nonpainful explicit recall in 0.1-0.2% of all anesthesias; amnesic awareness or implicit recall may occur with unknown, even higher incidences. Sufficient analgesia minimizes possible painful perceptions. Opioids, benzodiazepines, and N(2)O alone or combined lead to the highest incidences of nonpainful intraoperative wakefulness. Volatile anesthetics, etomidate, barbiturates, and propofol in sufficient doses effectively block any sensory processing and therefore abolish intraoperative wakefulness. Intraoperative awareness with recall may lead to sustained impairment of the patients, in severe cases even to a post-traumatic stress disorder (PTSD). The observation of clinical signs does not reliably detect intraoperative wakefulness in all cases; monitoring of end-tidal gas concentrations, EEG, or evoked potentials may help in prevention. Active information is recommended only for patients at higher risk. Complaints about recall of intraoperative events should be taken seriously; in cases of sustained symptoms psychological help may be necessary.

Discrimination of anesthetic states using mid-latency auditory evoked potential and artificial neural networks.

This study was undertaken to determine whether artificial neural network (ANN) processing of mid-latency auditory evoked potentials (MLAEPs) can identify different anesthetic states during propofol anesthesia, and to determine those parameters that are most useful in the identification process. Twenty-one patients undergoing elective abdominal surgery were studied. To maintain general anesthesia, the patients received propofol (3-5 mgkg(-1) h(-1) intravenously). Epidural analgesia at the level of T4-5 blocked painful stimuli. MLAEP was recorded continuously with patients awake, during induction, during maintenance of general anesthesia, and during emergence until the patients were recovered from anesthesia. Latencies of the 5 MLAEP peaks and three peak to peak amplitudes were measured, along with hemodynamic parameters (heart rate, systolic, and diastolic arterial blood pressure). Four-layer ANNs were used to model the relationship between the parameters of the MLAEP and the four different states (awake, adequate anesthesia, during/before intraoperative movement, and emergence from anesthesia). The best identification accuracy was obtained using only the five latencies. The combination of five latencies and three amplitudes did not improve the identification accuracy. Use of the only the three hemodynamic parameters produced a much poorer identification. This study suggests that the MLAEP has useful information for identifying different anesthetic states, especially in its latencies. A nonlinear discrimination approach, such as the ANN, can effectively capture the relation between the MLAEP patterns and the different states of anesthesia.

[Depth of anesthesia, awareness and EEG]. / Messung der Narkosetiefe, Awareness und EEG.

Inapparent adverse intraoperative wakefulness is still a relevant problem in modern anaesthetic routine. It can be associated with serious negative effects on the postoperative recovery of the patients. Several different procedures have been developed to monitor and therefore avoid intraoperative situations of wakefulness during general anaesthesia. The most promising methods are the PRST-score, calculated from changes in the blood pressure, heart rate, sweating and tear production, the so-called isolated forearm technique, spontaneous EEG and its derived parameters such as spectral edge frequencies or BIS and finally mid-latency auditory evoked potentials. The observation of clinical autonomic signs, even including the calculation of the PRST-score does not seem to be valid enough to indicate or predict intraoperative wakefulness. The isolated forearm technique can be regarded as the most reliable tool to detect intraoperative wakefulness, but it can only be applied for a very limited period of time. The processed EEG with the median frequency, spectral edge frequency or bispectral index are important scientific tools to quantify central anaesthetic effects especially to develop pharmacodynamic-pharmacokinetic models of anaesthetic action. But they seem to be less suitable to indicate situations of intraoperative wakefulness or awareness. The mid-latency auditory evoked potentials are depressed dose-dependently by a series of anaesthetic agents, which correlate with the occurrence of situations of intraoperative wakefulness and awareness. There is a hierarchical correlation between certain values of the MLAEP and intraoperative wakefulness defined by purposeful movements, amnesic awareness with only implicit recall and conscious awareness with explicit recall. For some of the most commonly used anaesthetics reasonable threshold values of the MLAEP for the different states of consciousness have already been determined. Future studies in broad patient populations with all of the different routinely used anesthetics and procedures will have to finally identify the importance of the recording of mid-latency auditory evoked potentials as a routine method to assess the depth of anaesthesia.

Power spectral analysis of the electroencephalogram during increasing end-expiratory concentrations of isoflurane, desflurane and sevoflurane.

We studied the effects of increasing end-expiratory concentrations of isoflurane (0.3, 0.6, 0.9, 1.2 vol.%) (n = 12 patients), desflurane (1.5, 3.0, 4.5, 6.0 vol.%) (n = 12 patients) and sevoflurane (0.5, 1.0, 1.5, 2.0 vol.%) (n = 12 patients) on power spectral analysis of the electroencephalogram (EEG). Spectral edge frequency (SEF), total power (TP) and relative power in the delta, theta, alpha and beta band were calculated. EEG changes were very similar within the three groups. SEF decreased, TP and relative power in the delta and theta band increased, power in the beta band decreased in a dose-dependent fashion with comparable regression lines. This indicates that MAC equivalent administration of isoflurane, desflurane and sevoflurane in clinically applied dose ranges is associated with equipotent EEG suppression.

[Sevoflurane and the nervous system]. / Sevofluran und Nervensystem.

During sevoflurane anaesthesia cerebral blood flow is preserved or slightly decreased. Cerebral oxygen consumption is reduced to 50% under 1 MAC sevoflurane. Autoregulation of cerebral blood flow and responsiveness of cerebral blood flow to changes in Pa CO2 are widely preserved. Sevoflurane produces a dose dependent increase in intracranial pressure and a decrease in cerebrovascular resistance that can not be observed under hypocapnic conditions. Central stimulus processing, the electroencephalogram and sensory evoked potentials are suppressed under sevoflurane in a dose dependent fashion. The electrophysiological data indicate that intraoperative awareness phenomena should be suppressed with sevoflurane 1.5-2.0 vol.%. Recovery of cognitive and psychomotor functions seems to be faster and more complete after sevoflurane than after isoflurane anaesthesia. In inducing seizure like EEG or muscle activity, sevoflurane seems to be comparable with isoflurane. There is no limitation of sevoflurane use in patients with concomitant psychiatric or neurological diseases, and sevoflurane may be valuable addition in neurosurgery or carotid surgery.

Midlatency auditory evoked potentials predict movements during anesthesia with isoflurane or propofol.

To determine threshold values, sensitivity, and specificity of midlatency auditory evoked potentials (MLAEP) for prediction of spontaneous intraoperative movements, 40 patients undergoing elective laparotomy were studied. Continuous epidural analgesia was used in all patients. To maintain general anesthesia, the patients in Group 1 (n = 20) received isoflurane (0.4-1.2 vol%), and the patients in Group 2 (n = 20) received propofol (3-5 mg x kg(-1) x h(-1) intravenously). Spontaneous movements were documented intraoperatively. Auditory evoked potentials were recorded continuously until the end of anesthesia. Latencies of the peaks V, Na, Pa, Nb, and P1 (ms) and amplitudes Na/Pa, Pa/Nb, and Nb/P1 (microV) were measured. Changes of MLAEP latencies and amplitudes during anesthesia were similar in both groups. Anesthesia led to statistically significant increases in the latencies of Na, Pa, Nb, and P1 and decreases in the amplitudes of Na/Pa, Pa/Nb, and Nb/P1 compared with the awake state. Before and during spontaneous movement observed intraoperatively or during emergence from anesthesia, the latencies of the peaks Na, Pa, Nb, and P1 decreased, and the amplitudes Na/Pa, Pa/Nb, Nb/P1 increased significantly. A threshold value of 60 ms of Nb proved to be most predictive of movement during anesthesia. MLAEP recording seems to be a promising method to monitor the level of anesthesia as defined by spontaneous movement during anesthesia.

Midlatency auditory evoked potentials and motor signs of wakefulness during anaesthesia with midazolam.

We have studied midlatency auditory evoked potentials (MLAEP) and motor signs of wakefulness during anaesthesia with midazolam in 10 patients undergoing elective laparotomy under continuous extradural analgesia. Anaesthesia was induced with midazolam 0.3 mg kg-1 and maintained with midazolam 0.3-0.9 mg kg-1 h-1. Motor signs of wakefulness were documented as spontaneous movements and movements after simple commands (open eyes or move arms). MLAEP were recorded continuously awake, and during anaesthesia until the end of anaesthesia. Latencies of the peaks V, Na, Pa, Nb and P1 (ms) and amplitudes of the peaks Na/Pa, Pa/Nb and Nb/P1 (microV) were measured. Twenty-five movements were observed during anaesthesia; 15 movements in six patients were in response to commands. In two patients supplementary isoflurane was given. Latencies of the MLAEP peaks Pa, Nb and P1 increased slightly during anaesthesia. Amplitudes for Na/Pa, Pa/Nb and Nb/P1 did not change significantly. The high incidence of motor signs of wakefulness associated with preserved MLAEP indicated a high level of cortical neural activity and none of the MLAEP variables predicted movement during anaesthesia with midazolam.

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%.

[Monitoring intraoperative awareness. Vegetative signs, isolated forearm technique, electroencephalogram, and acute evoked potentials]. / Monitoring intraoperativer Wachzustände. Vegetative Zeichen, isolierte Unterarmtechnik, Elektroenzephalogramm und akustisch evozierte Potentiale.

Several methods have been developed to quantify central anaesthetic effects and monitor awareness during general anaesthesia. The most important of these are the PRST score, calculated from changes in blood pressure, heart rate, sweating, and tear production, the isolated forearm technique, where the patient is allowed to move during surgery, the processed electroencephalogram (EEG) and the derived parameters median frequency (MF) and spectral-edge frequency (SEF), and mid-latency auditory evoked potentials (MLAEP). In clinical practice, the application of individual doses of anaesthetics is generally guided by autonomic vegetative clinical signs such as changes in blood pressure, heart rate, sweating, and tear production, quantified as the PRST score. Unfortunately, these parameters are not very reliable with regard to predicting the suppression of consciousness and awareness, especially when high-dose opioids are used in patients with cardiovascular medications and a variety of accompanying diseases. The PRST score probably indicates mainly the autonomic responses to painful stimuli, and seems to be useful in guiding the individual use of analgesics. The isolated forearm technique is a useful test of the patient's responsiveness during general anaesthesia, and thus an instrument for investigating the incidence of awareness during different anaesthetic regimens and when muscle relaxants are employed. A disadvantage is that it can only be used for 20 to 30 min because of pressure-induced nerve blocks or lesions. It can not be employed when long-term relaxation is necessary and consciousness and awareness are to be monitored continuously. The processed EEG and the derived parameters MF and SEF are important scientific tools to quantify central effects of many anaesthetics and opioid analgesics that allow the development of pharmacodynamic-pharmacokinetic models of anaesthetic action. MF has proven to be useful in monitoring closed-loop feedback of intravenous drug administration. Unfortunately, until now there have been no clinical studies that document the usefulness of MF or SEF with regard to predicting intraoperative arousal or awareness. To the contrary, some experimental data failed to predict imminent arousal and response to surgical incision or verbal commands by MF or SEF. Therefore, the EEG seems to be of limited value for monitoring awareness, consciousness, or memory formation during anaesthesia. MLAEP are suppressed in a dose-dependent fashion by many general anaesthetics and correlate with wakefulness, awareness, and explicit and implicit memory during anaesthesia and seem to be a promising method of monitoring awareness during anaesthesia. Nevertheless, future studies will have to determine threshold values for the different MLAEP parameters for intraoperative awareness and explicit and implicit recall of intraoperatively presented information for the different commonly used anaesthetics. Only then will it be possible to determine the usefulness of the method in clinical practice.

[Intraoperative awareness and auditory evoked potentials]. / Intraoperative Wachheit und akustisch evozierte Potentiale.

Midlatency auditory evoked potentials (MLAEP) are suppressed dose-dependently during anaesthesia with a variety of general anaesthetics. Therefore, MLAEP have been proposed to measure depth of anaesthesia and to indicate intraoperative awareness. Several studies give evidence of a close relationship between MLAEP and motor signs of wakefulness, intraoperative awareness, and explicit and implicit memory functions during general anaesthesia. Summarising these data, one may conclude that there is a close hierarchical relation between cognitive function, memory and wakefulness during anaesthesia, and MLAEP latencies. A short Nb latency below 45 ms is consistent with conscious awareness and unimpaired memory function with explicit recall and adequate response to commands. When Nb latency increases to 45-50 ms, it may be associated with conscious awareness. Patients still respond to commands, but memory formation is impaired and explicit recall is lost. A further increase of Nb latencies seems to be consistent with unconscious awareness, characterised by implicit memory of intraoperative events; 60 ms seems to be the threshold value for motor signs of wakefulness during anaesthesia. With a further increase of MLAEP latency during anaesthesia, conscious awareness and memory formation, explicit and implicit recall, response to commands, and spontaneous purposeful movements during anaesthesia are blocked. The new volatile anaesthetic sevoflurane leads to a dose-dependent increase in MLAEP peak latencies and a decrease in MLAEP amplitudes. At about 1.5 vol.% end-expiratory sevoflurane concentration, MLAEP are significantly suppressed and Nb latency is in the range of 68-80 ms. Therefore, from the present data and those from the literature, one may expect that sevoflurane at concentrations greater than 1.5 vol.% for general anaesthesia would be able to suppress awareness phenomena such as purposeful movements, auditory perception, intraoperative wakefulness and awareness, memory formation, and explicit and implicit recall of intraoperative events.

[Awareness during general anesthesia. Definition, incidence, clinical relevance, causes, avoidance and medicolegal aspects]. / Wachzustände whrend Allgemeinanästhesie. Definition, Häufigkeit, klinische Relevanz, ursachen, Vermeidung und medikolegale Aspekte.

The possibility that a patient during general anaesthesia is aware of the operation going on and aware of severe pain that might be remembered postoperatively must be very alarming to patients and anaesthetists alike. Furthermore, there is experimental evidence showing that conscious recall of intraoperative events is only the tip of an iceberg; it seems very probable that there is even a higher incidence of unconscious perception during general anaesthesia. Therefore, the following stages of intraoperative awareness must be distinguished: (1) conscious awareness with explicit recall and with severe pain; (2) conscious awareness with explicit recall but no complaints of pains; (3) conscious awareness without explicit recall and possible implicit recall; (4) subconscious awareness without explicit recall and possible implicit recall; (5) no awareness. The incidence of conscious awareness with explicit recall and severe pain has been estimated at less frequent than 1/3000 general anaesthetics. Conscious awareness with explicit recall but no complaints of pain has been reported in the literature with an incidence of 05-2%. With 7-72%, conscious awareness without explicit recall and possible implicit recall shows a very wide range of variation and its occurrence probably depends on the anaesthetic drugs used. Subconscious awareness with possible implicit recall has an incidence of up to 80%, but there are many methodological problems in demonstrating implicit memory of intraoperative events. Reports of intraoperative awareness do not come exclusively from cardiac surgery and obstetrics, but also from all other operative specialties. Postoperatively, patients who experience intraoperative awareness may develop a so-called post-traumatic stress syndrome. Symptoms involve re-experiencing the event awake or in dreams, sleep disturbances, depression, avoidance of stimuli associated with the event. The probability of the development of the post-traumatic stress syndrome seems to coincide with the experience of severe pain. When a patient complains of intraoperative awareness postoperatively the anaesthesiologist should discuss the event frankly with the patient. When the symptoms of the post-traumatic stress syndrome persist a psychotherapy should follow. Causes for intraoperative awareness may be: equipment failure, too-light anaesthesia, e.g. for a caesarean section or for emergency surgery in severely injured or polytraumatized patients, during cardiac surgery, bronchoscopy of difficult intubation. There is interindividual variability in anaesthetic effect; for example, chronic drug or alcohol abuse or overweight may make increased anaesthetic doses necessary. They are at risk for intraoperative awareness. Some general anaesthetics or anaesthetic procedures, e.g. the combination of a relaxant and N2O, opioid mono-anaesthetics, or opioids combined with benzodiazepines, seem to involve a higher risk of intraoperative awareness than do volatile anaesthetics. The bases of litigation are medical malpractice, breach of contract by the anaesthesiologist or lack of informed consent from the patient. Therefore, patients who are at risk of intraoperative awareness should be given detailed information on this special risk before the operation.

Anesthesia with increasing doses of sufentanil and midlatency auditory evoked potentials in humans.

Our interest focused on the question whether sufentanil differs from alfentanil, fentanyl, and morphine with regard on its effects on midlatency auditory evoked potentials (MLAEP). Therefore, we studied MLAEP during general anesthesia with increasing doses of sufentanil in 16 patients scheduled for elective major urologic surgery. Anesthesia was induced with sufentanil (1 microgram/kg every 7 min to a total dose of 3 micrograms/kg). In 8 of 16 patients, further incremental doses of sufentanil were given to a total dose of 5 micrograms/kg. Auditory evoked potentials were recorded before and 5 min after every sufentanil dose on vertex (positive) and mastoids on both sides (negative). Latencies of the peaks V, Na, Pa, Nb, and P1 (ms), and amplitudes Na/Pa, Pa/Nb, and Nb/P1 (microV) were measured. In the awake state, MLAEP had high peak-to-peak amplitudes and a periodic waveform. During general anesthesia the brainstem response V was stable to increasing doses of sufentanil. There was a marked statistically significant increase in latency and decrease in amplitude of Nb and P1 after 1-2 micrograms/kg sufentanil, which remained stable under further sufentanil application. In contrast, the early cortical potentials Na and Pa increased only slightly in latencies. This increase was statistically significant at 4 micrograms/kg for Na and at 3 and 4 micrograms/kg for Pa. For the amplitudes Na/Pa and Pa/Nb there was only a slight and statistically insignificant reduction. After the largest dose of sufentanil (3-5 micrograms/kg) Na and Pa showed a similar pattern as in awake patients. We conclude that sufentanil does not differ essentially from alfentanil, fentanyl, and morphine with regard on its effects on MLAEP.