A comparison of propofol- and dexmedetomidine-induced electroencephalogram dynamics using spectral and coherence analysis.

BACKGROUND: Electroencephalogram patterns observed during sedation with dexmedetomidine appear similar to those observed during general anesthesia with propofol. This is evident with the occurrence of slow (0.1 to 1 Hz), delta (1 to 4 Hz), propofol-induced alpha (8 to 12 Hz), and dexmedetomidine-induced spindle (12 to 16 Hz) oscillations. However, these drugs have different molecular mechanisms and behavioral properties and are likely accompanied by distinguishing neural circuit dynamics. METHODS: The authors measured 64-channel electroencephalogram under dexmedetomidine (n = 9) and propofol (n = 8) in healthy volunteers, 18 to 36 yr of age. The authors administered dexmedetomidine with a 1-µg/kg loading bolus over 10 min, followed by a 0.7 µg kg h infusion. For propofol, the authors used a computer-controlled infusion to target the effect-site concentration gradually from 0 to 5 µg/ml. Volunteers listened to auditory stimuli and responded by button press to determine unconsciousness. The authors analyzed the electroencephalogram using multitaper spectral and coherence analysis. RESULTS: Dexmedetomidine was characterized by spindles with maximum power and coherence at approximately 13 Hz (mean ± SD; power, -10.8 ± 3.6 dB; coherence, 0.8 ± 0.08), whereas propofol was characterized with frontal alpha oscillations with peak frequency at approximately 11 Hz (power, 1.1 ± 4.5 dB; coherence, 0.9 ± 0.05). Notably, slow oscillation power during a general anesthetic state under propofol (power, 13.2 ± 2.4 dB) was much larger than during sedative states under both propofol (power, -2.5 ± 3.5 dB) and dexmedetomidine (power, -0.4 ± 3.1 dB). CONCLUSION: The results indicate that dexmedetomidine and propofol place patients into different brain states and suggest that propofol enables a deeper state of unconsciousness by inducing large-amplitude slow oscillations that produce prolonged states of neuronal silence.

Continuous positive airway pressure and ventilation are more effective with a nasal mask than a full face mask in unconscious subjects: a randomized controlled trial.

INTRODUCTION: Upper airway obstruction (UAO) is a major problem in unconscious subjects, making full face mask ventilation difficult. The mechanism of UAO in unconscious subjects shares many similarities with that of obstructive sleep apnea (OSA), especially the hypotonic upper airway seen during rapid eye movement sleep. Continuous positive airway pressure (CPAP) via nasal mask is more effective at maintaining airway patency than a full face mask in patients with OSA. We hypothesized that CPAP via nasal mask and ventilation (nCPAP) would be more effective than full face mask CPAP and ventilation (FmCPAP) for unconscious subjects, and we tested our hypothesis during induction of general anesthesia for elective surgery. METHODS: In total, 73 adult subjects requiring general anesthesia were randomly assigned to one of four groups: nCPAP P0, nCPAP P5, FmCPAP P0, and FmCPAP P5, where P0 and P5 represent positive end-expiratory pressure (PEEP) 0 and 5 cm H2O applied prior to induction. After apnea, ventilation was initiated with pressure control ventilation at a peak inspiratory pressure over PEEP (PIP/PEEP) of 20/0, then 20/5, and finally 20/10 cm H2O, each applied for 1 min. At each pressure setting, expired tidal volume (Vte) was calculated by using a plethysmograph device. RESULTS: The rate of effective tidal volume (Vte > estimated anatomical dead space) was higher (87.9% vs. 21.9%; P<0.01) and the median Vte was larger (6.9 vs. 0 mL/kg; P<0.01) with nCPAP than with FmCPAP. Application of CPAP prior to induction of general anesthesia did not affect Vte in either approach (nCPAP pre- vs. post-; 7.9 vs. 5.8 mL/kg, P = 0.07) (FmCPAP pre- vs. post-; 0 vs. 0 mL/kg, P = 0.11). CONCLUSIONS: nCPAP produced more effective tidal volume than FmCPAP in unconscious subjects. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01524614.

Electroencephalogram signatures of loss and recovery of consciousness from propofol.

Unconsciousness is a fundamental component of general anesthesia (GA), but anesthesiologists have no reliable ways to be certain that a patient is unconscious. To develop EEG signatures that track loss and recovery of consciousness under GA, we recorded high-density EEGs in humans during gradual induction of and emergence from unconsciousness with propofol. The subjects executed an auditory task at 4-s intervals consisting of interleaved verbal and click stimuli to identify loss and recovery of consciousness. During induction, subjects lost responsiveness to the less salient clicks before losing responsiveness to the more salient verbal stimuli; during emergence they recovered responsiveness to the verbal stimuli before recovering responsiveness to the clicks. The median frequency and bandwidth of the frontal EEG power tracked the probability of response to the verbal stimuli during the transitions in consciousness. Loss of consciousness was marked simultaneously by an increase in low-frequency EEG power (<1 Hz), the loss of spatially coherent occipital alpha oscillations (8-12 Hz), and the appearance of spatially coherent frontal alpha oscillations. These dynamics reversed with recovery of consciousness. The low-frequency phase modulated alpha amplitude in two distinct patterns. During profound unconsciousness, alpha amplitudes were maximal at low-frequency peaks, whereas during the transition into and out of unconsciousness, alpha amplitudes were maximal at low-frequency nadirs. This latter phase-amplitude relationship predicted recovery of consciousness. Our results provide insights into the mechanisms of propofol-induced unconsciousness, establish EEG signatures of this brain state that track transitions in consciousness precisely, and suggest strategies for monitoring the brain activity of patients receiving GA.

Tracking brain states under general anesthesia by using global coherence analysis.

Time and frequency domain analyses of scalp EEG recordings are widely used to track changes in brain states under general anesthesia. Although these analyses have suggested that different spatial patterns are associated with changes in the state of general anesthesia, the extent to which these patterns are spatially coordinated has not been systematically characterized. Global coherence, the ratio of the largest eigenvalue to the sum of the eigenvalues of the cross-spectral matrix at a given frequency and time, has been used to analyze the spatiotemporal dynamics of multivariate time-series. Using 64-lead EEG recorded from human subjects receiving computer-controlled infusions of the anesthetic propofol, we used surface Laplacian referencing combined with spectral and global coherence analyses to track the spatiotemporal dynamics of the brain's anesthetic state. During unconsciousness the spectrograms in the frontal leads showed increasing α (8-12 Hz) and δ power (0-4 Hz) and in the occipital leads δ power greater than α power. The global coherence detected strong coordinated α activity in the occipital leads in the awake state that shifted to the frontal leads during unconsciousness. It revealed a lack of coordinated δ activity during both the awake and unconscious states. Although strong frontal power during general anesthesia-induced unconsciousness--termed anteriorization--is well known, its possible association with strong α range global coherence suggests highly coordinated spatial activity. Our findings suggest that combined spectral and global coherence analyses may offer a new approach to tracking brain states under general anesthesia.