Spoken words are processed during dexmedetomidine-induced unresponsiveness.

BACKGROUND: Studying the effects of anaesthetic drugs on the processing of semantic stimuli could yield insights into how brain functions change in the transition from wakefulness to unresponsiveness. Here, we explored the N400 event-related potential during dexmedetomidine- and propofol-induced unresponsiveness. METHODS: Forty-seven healthy subjects were randomised to receive either dexmedetomidine (n=23) or propofol (n=24) in this open-label parallel-group study. Loss of responsiveness was achieved by stepwise increments of pseudo-steady-state plasma concentrations, and presumed loss of consciousness was induced using 1.5 times the concentration required for loss of responsiveness. Pre-recorded spoken sentences ending either with an expected (congruous) or an unexpected (incongruous) word were presented during unresponsiveness. The resulting electroencephalogram data were analysed for the presence of the N400 component, and for the N400 effect defined as the difference between the N400 components elicited by congruous and incongruous stimuli, in the time window 300-600 ms post-stimulus. Recognition of the presented stimuli was tested after recovery of responsiveness. RESULTS: The N400 effect was not observed during dexmedetomidine- or propofol-induced unresponsiveness. The N400 component, however, persisted during dexmedetomidine administration. The N400 component elicited by congruous stimuli during unresponsiveness in the dexmedetomidine group resembled the large component evoked by incongruous stimuli at the awake baseline. After recovery, no recognition of the stimuli heard during unresponsiveness occurred. CONCLUSIONS: Dexmedetomidine and propofol disrupt the discrimination of congruous and incongruous spoken sentences, and recognition memory at loss of responsiveness. However, the processing of words is partially preserved during dexmedetomidine-induced unresponsiveness. CLINICAL TRIAL REGISTRATION: NCT01889004.

Electroencephalogram reactivity to verbal command after dexmedetomidine, propofol and sevoflurane-induced unresponsiveness.

Although electroencephalogram reactivity (i.e. transient changes in electrical brain activity following external stimulus) might be useful in depth-of-anaesthesia monitoring, it has not been systematically examined with different anaesthetics at doses titrated to unresponsiveness. Three 10-subject groups of healthy volunteers received dexmedetomidine, propofol or sevoflurane in escalating pseudo-steady-state concentrations at 10-min intervals until they did not open their eyes to command. The electroencephalogram was continuously recorded and spectral variables were calculated with short-time Fourier transform and time-varying autoregressive modelling. Electroencephalogram reactivity was most prominent in the midfrontal derivations (termed F3 and F4). During drug-induced unresponsiveness, electroencephalogram reactivity was still present in all drug groups. Dexmedetomidine, propofol and sevoflurane induced distinct suppression patterns on the electroencephalogram reactivity at the same clinical endpoint (unresponsiveness). Reactivity was best maintained with propofol, while only minimally preserved with dexmedetomidine and sevoflurane. Thus, it may be difficult to harness reactivity for depth-of-anaesthesia monitoring.

Wide inter-individual variability of bispectral index and spectral entropy at loss of consciousness during increasing concentrations of dexmedetomidine, propofol, and sevoflurane.

BACKGROUND: The bispectral index (BIS) and the spectral entropy (state entropy, SE, and response entropy, RE) are depth-of-anaesthesia monitors derived from EEG and have been developed to measure the effects of anaesthetics on the cerebral cortex. We studied whether they can differentiate consciousness from unconsciousness during increasing doses of three different anaesthetic agents. METHODS: Thirty healthy male volunteers aged 19-30 yr were recruited and divided into three 10-volunteer groups to receive either dexmedetomidine, propofol, or sevoflurane in escalating concentrations at 10 min intervals until loss of consciousness (LOC) was reached. Consciousness was tested at 5 min intervals and after drug discontinuation at 1 min intervals by requesting the subjects to open their eyes. LOC was defined as unresponsiveness to the request and pre-LOC as the last meaningful response. The first meaningful response to the request after drug discontinuation was defined as regaining of consciousness (ROC). For the statistical analysis, pre-LOC and ROC values were pooled to represent the responsive state while LOC values represented the unresponsive state. Prediction probability (P(K)) was estimated with the jack-knife method. RESULTS: The lowest mean values for BIS, SE, and RE were recorded at LOC with all three drugs. The P(K) values were low for dexmedetomidine (BIS 0.62, SE 0.58, RE 0.59), propofol (BIS 0.73, SE 0.72, RE 0.72), and sevoflurane (BIS 0.70, SE 0.52, RE 0.62). CONCLUSIONS: Because of wide inter-individual variability, BIS and entropy were not able to reliably differentiate consciousness from unconsciousness during and after stepwise increasing concentrations of dexmedetomidine, propofol, and sevoflurane.

Analysis of heart rate variability dynamics during propofol and dexmedetomidine anesthesia.

It has been observed that heart rate variability (HRV) diminishes during anesthesia, but the exact mechanisms causing it are not completely understood. The aim of this paper was to study the dynamics of HRV during low dose propofol (N=9) and dexmedetomidine (N=8) anesthesia by using state-of-the-art time-varying methods, and thereby ultimately try to improve the safety of anesthesia. The time-varying spectrum is estimated by using a Kalman smoother approach. The results show that there is an overall increase in HRV and decrease in heart rate prior to loss of consciousness. For dexmedetomidine these changes are more considerable than for propofol. For dexmedetomidine the variability also seems to start decreasing right after loss of consciousness, whereas for propofol HRV continues increasing.

Kalman smoother based time-varying spectrum estimation of EEG during single agent propofol anesthesia.

A time-varying parametric spectrum estimation method for analyzing EEG dynamics is presented. EEG signals are first modeled as a time-varying auto-regressive stochastic process and the model parameters are estimated recursively with a Kalman smoother algorithm. Time-varying spectrum estimates are then obtained from the estimated parameters. The proposed method was applied to measurements collected during low dose propofol anesthesia. The method was able to detect changes of event related (de)synchronization type elicited by verbal command.