The effects of dexmedetomidine/remifentanil and midazolam/remifentanil on auditory-evoked potentials and electroencephalogram at light-to-moderate sedation levels in healthy subjects.

Avoidance of excessively deep sedation levels is problematic in intensive care patients. Electrophysiologic monitoring may offer an approach to solving this problem. Since electroencephalogram (EEG) responses to different sedation regimens vary, we assessed electrophysiologic responses to two sedative drug regimens in 10 healthy volunteers. Dexmedetomidine/remifentanil (dex/remi group) and midazolam/remifentanil (mida/remi group) were infused 7 days apart. Each combination of medications was given at stepwise intervals to reach Ramsay scores (RS) 2, 3, and 4. Resting EEG, bispectral index (BIS), and the N100 amplitudes of long-latency auditory-evoked potentials (ERP) were recorded at each level of sedation. During dex/remi, resting EEG was characterized by a recurrent high-power low-frequency pattern which became more pronounced at deeper levels of sedation. BIS Index decreased uniformly in only the dex/remi group (from 94 +/- 3 at baseline to 58 +/- 14 at RS 4) compared to the mida/remi group (from 94 +/- 2 to 76 +/- 10; P = 0.029 between groups). The ERP amplitudes decreased from 5.3 +/- 1.3 at baseline to 0.4 +/- 1.1 at RS 4 (P = 0.003) in only the mida/remi group. We conclude that ERPs in volunteers sedated with dex/remi, in contrast to mida/remi, indicate a cortical response to acoustic stimuli, even when sedation reaches deeper levels. Consequently, ERP can monitor sedation with midazolam but not with dexmedetomidine. The reverse is true for BIS.

P3 amplitude and time-on-task effects in distractible adolescents.

OBJECTIVE: The aim of our study was to examine the role of brain activity related to stimulus evaluation processes in distractibility by analyzing the P3 event-related potential. METHODS: We studied the P3 response to target stimuli at the beginning, in the middle, and at the end of a two-tone auditory oddball task in easily distractible (n = 16) and non-distractible (n = 16) adolescents. RESULTS: Easily distractible adolescents showed enhanced frontal and reduced parietal P3 amplitude across the blocks relative to non-distractible adolescents. Also, the usual decline in P3 amplitude at the end of the task was significantly larger in distractible than in non-distractible adolescents. CONCLUSIONS: These results suggests that the P3 effects are not limited to the neuropsychiatric disorders, and that increased distractibility may be characterized by reduced amount of resources allocated to the task with continued testing. SIGNIFICANCE: The results of this study contribute to elucidation of the functional basis of distractibility.

Cerebral signs of altered adaptability in females with acute psychosis.

In psychosis, behavior is not guided by sensory cues from surroundings. Novel, meaningful behaviors require intact integrative functions such as short-term memory and motor planning, as well as an optimized level of arousal. In this study, we monitored markers of automatic auditory processing in 15 female never-medicated psychotic patients. Fifty-eight channels of EEG were recorded simultaneously with sympathetic skin responses while arousing auditory stimuli were delivered. Neuropsychological tests concentrating on frontal lobe functions were also performed. Prominent neurophysiological and behavioral signs of increased cortical activation were observed in psychotic patients. This widespread disinhibition may attempt to compensate for the impairment of neuronal processing of sensory input from surroundings in the earliest stages of a psychotic illness.

Evidence of auditory processing during postoperative propofol sedation.

OBJECTIVES: Our aim was to characterize cerebral event-related responses, which index the detection of auditory stimuli during postoperative sedation. METHODS: We monitored auditory event-related potentials (ERPs) before and after elective cardiac operation in 29 patients. Sedation levels, induced with propofol, were evaluated clinically with Ramsay score (RS). RESULTS: During deep sedation (RS 6), patients could be categorized into 3 groups according to ERP responses evoked by a standard 'oddball' paradigm. In one group, there were no cortical responses indexing the detection of a sound (N100), another group showed clear responses, and the third group was characterized by a later P300a component which was taken to reflect orienting to a novel stimulus in adults who were awake. However, in deep sedation, P300a did not show behaviour characteristic to an orienting reaction. In moderate sedation (RS 4), all the patients showed a visible N100. Total sedative propofol dose, hemodynamics and the spontaneous electroencephalography (EEG) were not connected to the category of an individual's responses. CONCLUSIONS: The results of our study suggest that the detection and automatic auditory information processing function during postoperative sedation, and may signal the individual stages of awakening in a sensitive way. In addition, the findings suggest a deficit in sensory memory function during sedation.

Assessment of postoperative sedation level with spectral EEG parameters.

OBJECTIVES: Several sedation scores have been developed, but still a need exists for an objective method to monitor sedation level during intensive care. Our study presents a procedure for finding a combination of electroencephalogram (EEG) characteristics, which could be used in estimating sedation level. METHODS: We measured EEG in 29 cardiac surgical patients prior to and after the cardiac bypass grafting operation at different sedation levels. The clinical assessment of sedation levels was evaluated with the Ramsay Score. Spectral EEG parameters were computed and a linear model to predict postoperative sedation level was constructed by using principal component analysis and regression analysis. RESULTS: Sedation levels modified all computed spectral EEG parameters. The model based on optimal combination of EEG parameters predicted the observed Ramsay Score value with a prediction probability of 88%. CONCLUSIONS: This study suggests that a combination of spectral EEG parameters may discriminate between 3 sedation levels: awake, moderate sedation and deep sedation.

The effect of interruption to propofol sedation on auditory event-related potentials and electroencephalogram in intensive care patients.

INTRODUCTION: In this observational pilot study we evaluated the electroencephalogram (EEG) and auditory event-related potentials (ERPs) before and after discontinuation of propofol sedation in neurologically intact intensive care patients. METHODS: Nineteen intensive care unit patients received a propofol infusion in accordance with a sedation protocol. The EEG signal and the ERPs were measured at the frontal region (Fz) and central region (Cz), both during propofol sedation and after cessation of infusion when the sedative effects had subsided. The EEG signal was subjected to power spectral estimation, and the total root mean squared power and spectral edge frequency 95% were computed. For ERPs, we used an oddball paradigm to obtain the N100 and the mismatch negativity components. RESULTS: Despite considerable individual variability, the root mean squared power at Cz and Fz (P = 0.004 and P = 0.005, respectively) and the amplitude of the N100 component in response to the standard stimulus at Fz (P = 0.022) increased significantly after interruption to sedation. The amplitude of the N100 component (at Cz and Fz) was the only parameter that differed between sedation levels during propofol sedation (deep versus moderate versus light sedation: P = 0.016 and P = 0.008 for Cz and Fz, respectively). None of the computed parameters correlated with duration of propofol infusion. CONCLUSION: Our findings suggest that use of ERPs, especially the N100 potential, may help to differentiate between levels of sedation. Thus, they may represent a useful complement to clinical sedation scales in the monitoring of sedation status over time in a heterogeneous group of neurologically intact intensive care patients.

Midlatency auditory-evoked potentials in the assessment of sedation in cardiac surgery patients.

OBJECTIVES: Midlatency auditory-evoked potentials (MLAEPs) may provide an objective measure of depth of sedation. The aim of this study was to evaluate MLAEPs for measuring sedation in cardiac surgery patients. DESIGN: Prospective study. SETTING: Intensive care unit of a university hospital. PARTICIPANTS: Twenty-two patients scheduled for elective coronary artery bypass grafting. INTERVENTIONS: MLAEPs were obtained at 5 time points: the day before surgery (baseline), 1 hour before surgery, after premedication, postoperatively during deep (Ramsay 6) and moderate (Ramsay 4) sedation, and the day after surgery. MEASUREMENTS AND MAIN RESULTS: The latency of the Nb MLAEP component increased from 44 ms (38-60 ms; median, range) at baseline to 49 ms (41-64 ms) after premedication (p = 0.03) and further to 63 ms (48-80 ms) during deep sedation after surgery (P < 0.01). Although a decreasing clinical level of sedation after rewarming was not associated with a significant change in Nb latency (61 ms [42-78 ms]), the MLAEP NaPa amplitude increased from 0.9 muV (0.4-1.6 microV) to 1.3 muV (0.8-3.9 microV; p = 0.01). Nb latency remained increased the day after surgery (49 ms [37-71 ms]) as compared with baseline (p < 0.01). CONCLUSIONS: MLAEP latencies can reflect subtle changes in auditory perception, while amplitudes seem to change with transition between deep levels of sedation.

N100 auditory potential and electroencephalogram discriminate propofol-induced sedation levels.

OBJECTIVE: In the present study, we evaluated the electroencephalogram (EEG) and auditory N100 potential (N100) before and during propofol-induced sedation. The aim was to test whether using EEG and N100 the level of sedation may be evaluated. METHODS: Twenty-nine cardiac surgery patients were studied. The EEG signal and the N100 potential were recorded at awake one day before the cardiac operation and two times after the operation, when the clinical level of postoperative propofol sedation was considered deep (Ramsay Score 6) and moderate (Ramsay Score 4). Discriminant analysis was used to select those spectral EEG and/or N100 variables which would predict the correct level of sedation best. The final classification was based on canonical discriminant functions and Mahalanobis' distance. RESULTS: The spectral EEG variables (slow/fast-ratio, delta, and beta2 powers) predicted the correct level of sedation with 81% (canonical discriminant functions) and 80% (Mahalanobis' distance) accuracy. Similarly, the N100 (amplitude, latency, and the first principal component) predicted the correct level of sedation with 91% and 92% accuracy, and the combination of the EEG and N100 with 96% and 93% accuracy. CONCLUSIONS: Our findings suggest that the combined use of EEG and N100 may help to differentiate the propofol-induced sedation levels, and thus be a useful compliment to clinical sedation scales.

Measuring depth of sedation with auditory evoked potentials during controlled infusion of propofol and remifentanil in healthy volunteers.

Avoiding excessively deep levels of sedation is a major problem in intensive care patients. We studied whether clinically relevant levels of sedation can be objectively assessed using long latency auditory evoked potentials. We measured the auditory evoked potentials at 100 ms after the stimulus (N100) in 10 healthy volunteers during stepwise increasing, clinically relevant levels of sedation (Ramsay score [RS] 2-4). The volunteers were studied on three separate occasions and received an infusion of either propofol or a combination of propofol and remifentanil. Effects of remifentanil infusion alone were tested during target controlled infusion (target plasma concentrations: 1, 2, and 3 ng/mL). Remifentanil did not affect evoked potential amplitudes and latencies. During both propofol-induced and propofol/remifentanil-induced sedation, the N100 amplitude decreased similarly without an effect on the latencies as the level of sedation increased from Ramsay score 2 to Ramsay score 4 (P < 0.01). At the same clinical level of sedation, propofol plasma concentrations were larger when sedation was achieved by propofol alone (propofol versus propofol/remifentanil, RS 3: 2.12 mug/mL +/- 0.51 versus 1.32 +/- 0.43, P < 0.01; RS 4: 3.37 +/- 0.47 versus 1.86 +/- 0.34, P < 0.01). Our results suggest that long latency auditory evoked potentials provide an objective electrophysiological analog to the clinical assessment of sedation independent of the sedation regime used.