Attenuation of High-Frequency (50-200 Hz) Thalamocortical Electroencephalographic Rhythms by Isoflurane in Rats Is More Pronounced for the Thalamus Than for the Cortex.

BACKGROUND: Thalamocortical electroencephalographic rhythms in gamma (30-80 Hz) and high-gamma (80-200 Hz) ranges have been linked to arousal and conscious processes. We have recently shown that propofol causes a concentration-dependent attenuation of the power of thalamocortical rhythms in the 50 to 200 Hz range and that this effect is far more pronounced for the thalamus. To determine whether similar attenuation occurs with other anesthetics, we characterized the concentration-effect relationship of the inhaled anesthetic isoflurane on the spectral power of these rhythms. METHODS: Local field potentials were recorded from the barrel cortex and ventroposteromedial thalamic nucleus in 9 chronically instrumented rats to measure spectral power in the gamma/high-gamma range (30-200 Hz). Rats were placed in an airtight chamber and isoflurane was administered at 0.75%, 1.1%, and 1.5% concentrations. Spectral power was assessed during baseline, at the 3 isoflurane concentrations after 30 minutes for equilibration, and during recovery over 4 frequency bands (30-50, 51-75, 76-125, and 126-200 Hz). Unconsciousness was defined as sustained loss of righting reflex. Multiple linear regression was used to model the change in power (after logarithmic transformation) as a function of concentration and recording site. P values were corrected for multiple comparisons. RESULTS: Unconsciousness occurred at the 1.1% concentration in all animals. Isoflurane caused a robust (P ≤ 0.008) linear concentration-dependent attenuation of cortical and thalamic power in the 30 to 200 Hz range. The concentration-effect slope for the thalamus was steeper than for the cortex in the 51 to 75 Hz (P = 0.029) and 76 to 200 Hz (P < 0.001) ranges but not for the 30 to 50 Hz range (P = 0.320). Comparison with our previously published propofol data showed that slope for cortical power was steeper with isoflurane than with propofol for all frequency bands (P = 0.033). For thalamic power, the slope differences between isoflurane and propofol were not statistically significant (0.087 ≤ P ≤ 0.599). CONCLUSIONS: Isoflurane causes a concentration-dependent attenuation of the power of thalamocortical rhythms in the 30 to 200 Hz range, and this effect is more pronounced for the thalamus than for the cortex for frequencies >50 Hz. In comparison with propofol, isoflurane caused a greater attenuation in the cortex, but the effects on the thalamus were similar. Isoflurane and propofol cause common alterations of fast thalamocortical rhythms that may constitute an electrophysiologic signature of the anesthetized state.

Attenuation of high-frequency (50-200 Hz) thalamocortical EEG rhythms by propofol in rats is more pronounced for the thalamus than for the cortex.

BACKGROUND: Thalamocortical EEG rhythms in gamma (30-80 Hz) and high-gamma (80-200 Hz) ranges have been linked to arousal and conscious processes. To test the hypothesis that general anesthetics attenuate these rhythms, we characterized the concentration-effect relationship of propofol on the spectral power of these rhythms. In view of the ongoing debate about cortex versus thalamus as the primary site of anesthetic action for unconsciousness, we also compared the relative sensitivity of cortex and thalamus to this effect propofol. METHODS: Adult male Long-Evans rats were chronically implanted with electrodes in somatosensory (barrel) cortex and ventroposteromedial thalamus. Propofol was delivered by a computer-controlled infusion using real-time pharmacokinetic modeling to obtain the desired plasma concentration. Spectral power was assessed during baseline, at four stable propofol plasma-concentrations (0, 3,6,9,12 µg/ml) and during recovery over four frequency ranges (30-50, 51-75, 76-125, 126-200 Hz). Unconsciousness was defined as complete loss of righting reflex. Multiple regression was used to model the change of power (after logarithmic transformation) as a function of propofol concentration and recording site. RESULTS: Unconsciousness occurred at the 9 µg/ml concentration in all animals. Propofol caused a robust linear concentration-dependent attenuation of cortical power in the 76-200 Hz range and of thalamic power in the 30-200 Hz range. In all instances the concentration-effect slope for the thalamus was markedly steeper than for the cortex. Furthermore the lowest concentration causing unconsciousness significantly reduced cortical power in the 126-200 Hz range and thalamic power in the 30-200 Hz range. CONCLUSIONS: Propofol causes a concentration-dependent attenuation of the power of thalamocortical rhythms in the 30-200 Hz range and this effect is far more pronounced for the thalamus, where the attenuation provides a robust correlate of the hypnotic action of propofol [corrected].

The sensory thalamus and cerebral motor cortex are affected concurrently during induction of anesthesia with propofol: a case series with intracranial electroencephalogram recordings.

PURPOSE: Brain imaging studies suggest that loss of consciousness induced by general anesthetics is associated with impairment of thalamic function. There is, however, limited information on the time course of these changes. We recently obtained intracranial electroencephalogram (EEG) recordings from the ventroposterolateral (VPL) nucleus of the thalamus and from the motor cortex during induction of anesthesia in three patients to study the time course of the alterations of cortical and thalamic function. CLINICAL FEATURES: The patients were American Society of Anesthesiologists physical status I-II males aged 33-57 yr with intractable central pain caused by brachial plexus injury (patient 1 and 2) or insular infarct (patient 3). Anesthesia was induced with propofol (2.5-3.1 mg·kg(-1) over 30-45 sec) followed, after loss of consciousness, by rocuronium for tracheal intubation. The data retained for analysis are from one minute before the start of propofol to 110 sec later during ventilation of the patients' lungs before tracheal intubation. Spectral analysis was used to measure absolute EEG power. Propofol caused significant increases of cortical and thalamic power in the delta to beta frequency bands (1-30 Hz). These increases of cortical and thalamic power occurred either concomitantly or within seconds of each other. Propofol also caused a decrease in cortical and thalamic high-gamma (62-200 Hz) power that also followed a similar time course. CONCLUSION: We conclude that induction of anesthesia with propofol in these patients was associated with concurrent alterations of cortical and sensory thalamic activity.

Cortical processing of complex auditory stimuli during alterations of consciousness with the general anesthetic propofol.

BACKGROUND: The extent to which complex auditory stimuli are processed and differentiated during general anesthesia is unknown. The authors used blood oxygenation level-dependent functional magnetic resonance imaging to examine the processing words (10 per period; compared with scrambled words) and nonspeech human vocal sounds (10 per period; compared with environmental sounds) during propofol anesthesia. METHODS: Seven healthy subjects were tested. Propofol was given by a computer-controlled pump to obtain stable plasma concentrations. Data were acquired during awake baseline, sedation (propofol concentration in arterial plasma: 0.64 +/- 0.13 microg/ml; mean +/- SD), general anesthesia (4.62 +/- 0.57 microg/ml), and recovery. Subjects were asked to memorize the words. RESULTS: During all periods including anesthesia, the sounds conditions combined elicited significantly greater activations than silence bilaterally in primary auditory cortices (Heschl gyrus) and adjacent regions within the planum temporale. During sedation and anesthesia, however, the magnitude of the activations was reduced by 40-50% (P < 0.05). Furthermore, anesthesia abolished voice-specific activations seen bilaterally in the superior temporal sulcus during the other periods as well as word-specific activations bilaterally in the Heschl gyrus, planum temporale, and superior temporal gyrus. However, scrambled words paradoxically elicited significantly more activation than normal words bilaterally in planum temporale during anesthesia. Recognition the next day occurred only for words presented during baseline plus recovery and was correlated (P < 0.01) with activity in right and left planum temporale. CONCLUSIONS: The authors conclude that during anesthesia, the primary and association auditory cortices remain responsive to complex auditory stimuli, but in a nonspecific way such that the ability for higher-level analysis is lost.

Prolonged (more than ten hours) neuromuscular blockade after cardiac surgery: report of two cases.

PURPOSE: We examine two cases of prolonged neuromuscular blockade (NMB) after cardiac surgery. To the best of our knowledge, these are the first reported cases of complete paralysis lasting more than ten hours after surgery. CLINICAL FEATURES: We attribute the extended durations of NMB (more than ten hours) to high doses of NMB drugs in combination with magnesium sulphate and moderate renal failure. Advanced age, hepatic disease, aminoglycoside exposure, hypocalcemia, and possible interaction between rocuronium and pancuronium may have played minor roles. CONCLUSION: We should avoid administering large doses of NMB agents, even in the context of planned postoperative ventilation. If NMB is not monitored intraoperatively in patients who are at risk of prolonged NMB, then train-of-four response should be measured in the intensive care unit. Adequate sedation should be provided until proper recovery of neuromuscular function is documented.

Human auditory steady-state responses: the effects of recording technique and state of arousal.

UNLABELLED: There is some controversy in the literature about whether auditory steady-state responses (ASSRs) can be reliably recorded in all subjects and whether these responses consistently decrease in amplitude during drowsiness. In 10 subjects, 40-Hz ASSRs became significantly different from background electroencephalogram activity with a probability of P < 0.01 and an average time of 22 s (range, 2-92 s), provided that the responses were analyzed with time-domain averaging rather than spectral averaging. In a second experiment with 10 subjects, 40-Hz ASSRs recorded between the vertex and posterior neck consistently decreased in amplitude during drowsiness and sleep. Findings that the ASSR may occasionally increase during drowsiness may be explained by postauricular muscle responses recorded from a mastoid reference. These may occur during drowsiness in association with rolling-eye movements. ASSRs recorded between the vertex and posterior neck are not distorted by these reflexes. These findings combine with previous literature on the effects of general anesthetics on the ASSR to confirm that the ASSR is a valid option for monitoring the hypnotic effects of general anesthetics. IMPLICATIONS: Auditory steady-state responses to stimuli presented at rates near 40 Hz can be used to monitor anesthesia. These responses can be quickly and reliably recorded during both sleep and wakefulness, provided that appropriate averaging techniques are used.

Effects of isoflurane on auditory middle latency (MLRs) and steady-state (SSRs) responses recorded from the temporal cortex of the rat.

Auditory steady-state responses (SSRs) are believed to result from superimposition of middle latency responses (MLRs) evoked by individual stimuli during repetitive stimulation. Our previous studies showed that besides linear addition of MLRs, other phenomena, mainly related to the adaptive properties of neural sources, interact in a complex way to generate the SSRs recorded from the temporal cortex of awake rats. The aim of this study was to evaluate the effects of the inhalational general anesthetic, isoflurane, on MLRs and SSRs at several repetition rates (30-60 Hz) recorded from the temporal cortex of rats. Auditory evoked potentials were obtained by means of epidural electrodes in the awake condition and during anesthesia at three isoflurane concentrations (0.38, 0.76 and 1.13 vol.% in oxygen). MLR latency significantly increased during anesthesia in a concentration-dependent manner, while MLR amplitude, even when significantly attenuated with respect to the mean awake baseline value, failed to correlate with isoflurane concentration. SSRs decreased in amplitude and increased in phase during anesthesia in a concentration-dependent manner and the anesthetic-induced decrease of SSR amplitude appeared to be higher than the corresponding MLR attenuation. SSR prediction curves synthesized by linear addition of MLRs failed to predict SSRs in both amplitude and phase. Moreover, phase discrepancies proved to be higher during anesthesia. Our results suggest that MLRs and SSRs recorded from the temporal cortex of the rat exhibit differential sensitivity to isoflurane and that isoflurane could enhance the role of rate-dependent effects in SSR generation.