Linear transformation of the encoding mechanism for light intensity underlies the paradoxical enhancement of cortical visual responses by sevoflurane.

KEY POINTS: The mechanisms of action of anaesthetics on the living brain are still poorly understood. In this respect, the analysis of the differential effects of anaesthetics on spontaneous and sensory-evoked cortical activity might provide important and novel cues. Here we show that the anaesthetic sevoflurane strongly silences the brain but potentiates in a dose- and frequency-dependent manner the cortical visual response. Such enhancement arises from a linear scaling by sevoflurane of the power-law relation between light intensity and the cortical response. The fingerprint of sevoflurane action suggests that circuit silencing can boost linearly synaptic responsiveness presumably by scaling the number of responding units and/or their correlation following a sensory stimulation. ABSTRACT: General anaesthetics, which are expected to silence brain activity, often spare sensory responses. To evaluate differential effects of anaesthetics on spontaneous and sensory-evoked cortical activity, we characterized their modulation by sevoflurane and propofol. Power spectra and the bust-suppression ratio from EEG data were used to evaluate anaesthesia depth. ON and OFF cortical responses were elicited by light pulses of variable intensity, duration and frequency, during light and deep states of anaesthesia. Both anaesthetics reduced spontaneous cortical activity but sevoflurane greatly enhanced while propofol diminished the ON visual response. Interestingly, the large potentiation of the ON visual response by sevoflurane was found to represent a linear scaling of the encoding mechanism for light intensity. To the contrary, the OFF cortical visual response was depressed by both anaesthetics. The selective depression of the OFF component by sevoflurane could be converted into a robust potentiation by the pharmacological blockade of the ON pathway, suggesting that the temporal order of ON and OFF responses leads to a depression of the latter. This hypothesis agrees with the finding that the enhancement of the ON response was converted into a depression by increasing the frequency of light-pulse stimulation from 0.1 to 1 Hz. Overall, our results support the view that inactivity-dependent modulation of cortical circuits produces an increase in their responsiveness. Among the implications of our findings, the silencing of cortical circuits can boost linearly the cortical responsiveness but with negative impact on their frequency transfer and with a loss of the information content of the sensory signal.

Intrinsic positive end-expiratory pressure during ventilation through small endotracheal tubes during general anesthesia: incidence, mechanism, and predictive factors.

STUDY OBJECTIVE: To assess the safety of mechanical ventilation and effectiveness of extrinsic positive end-expiratory pressure (PEEP) (PEEPe) in improving peripheral oxygen saturation (SpO2) during direct microlaryngeal laser surgery; to assess the incidence, amount, and nature (dynamic hyperinflation or airflow obstruction) of ensuing intrinsic PEEP (PEEPi); and to find a surrogate PEEPi indicator. DESIGN: Quasiexperimental. SETTING: S. Raffaele Hospital (Milano), November 2009 to December 2010. PATIENTS: Fifty-two adults scheduled for direct microlaryngeal laser surgery. Exclusion criterion is pregnancy. INTERVENTIONS: Twenty-one percent O2 mechanical ventilation through 4.5- to 5.5-mm internal diameter endotracheal tubes; in 29 patients, after measurement of PEEPi, an identical amount of PEEPe was added; and PEEPi. MEASUREMENTS: SpO2, peak (Pawpeak) and plateau (Pawplateau) airway pressure, and end-expiratory carbon dioxide were measured every 5 minutes. Respiratory compliance (Crs) was computed. PEEPi was measured (end-expiratory occlusion method). MAIN RESULTS: PEEPi ≥5 cm H2O occurred in 14 patients (27%) after intubation, in 16 (30%) at the beginning, and in 14 (27.3%) at the end of surgery. Thirty-one patients (59.4%) exhibited PEEPi ≥5 cm H2O on at least 1 time point. PEEPi at the beginning of surgery was positively correlated with Pawplateau, Crs, tidal volume, and body mass index. Body mass index was the only predictor for the occurrence of PEEPi ≥5 cm H2O. At the beginning of surgery, the Pawplateau receiver operating characteristic curve predicting PEEPi ≥5 cm H2O had area under the receiver operating characteristic curve of 0.85; best cutoff value of 15.5 cm H2O (sensitivity, 88.9%; specificity, 75%; correctly classified cases, 86.1%). When PEEPe was applied, in 23 cases (82.1%), total PEEP equaled PEEPe+ PEEPi; in 3 (10.7%), it was lower; and in 2 (7.1%), it was higher. Application of PEEPe increased SpO2 (P< .05) and Crs (P< .05). CONCLUSIONS: During ventilation through small endotracheal tubes, PEEPi (mostly due to dynamic hyperinflation) is common. Hemodynamic complications, barotrauma, and O2 desaturation (reversible with PEEPe) are rare. Pawplateau provided by ventilators is useful in suspecting and monitoring the occurrence of PEEPi and allows detection of lung overdistension as PEEPe is applied.

Auditory functional magnetic resonance in awake (nonsedated) and propofol-sedated children.

BACKGROUND: Functional Magnetic Resonance Imaging (fMRI) is often used in preoperative assessment before epilepsy surgery, tumor or cavernous malformation resection, or cochlear implantation. As it requires complete immobility, sedation is needed for uncooperative patients. OBJECTIVE: The aim of this study was to compare the fMRI cortical activation pattern after auditory stimuli in propofol-sedated 5- to 8-year-old children with that of similarly aged nonsedated children. METHODS: When possible, children underwent MRI without sedation, otherwise it was induced with i.v. propofol 2 mg·kg(-1) and maintained with i.v. propofol 4-5 mg·kg(-1) ·h(-1) . Following diagnostic MRI, fMRi was carried out, randomly alternating two passive listening tasks (a fairy-tale and nonsense syllables). RESULTS: We studied 14 awake and 15 sedated children. During the fairy-tale task, the nonsedated children's blood-oxygen-level-dependent (BOLD) signal was bilaterally present in the posterior superior temporal gyrus (STG), Wernicke's area, and Broca's area. Sedated children showed similar activation, with lesser extension to Wernicke's area, and no activation in Broca's area. During the syllable task, the nonsedated children's BOLD signal was bilaterally observed in the STG and Wernicke's area, in Broca's area with leftward asymmetry, and in the premotor area. In sedated children, cortical activation was present in the STG, but not in the frontal lobes. BOLD signal change areas in sedated children were less extended than in nonsedated children during both the fairy-tale and syllable tasks. Modeling the temporal derivative during both the fairy-tale and syllable tasks, nonsedated children showed no response while sedated children did. CONCLUSIONS: After auditory stimuli, propofol-sedated 5- to 8-year-old children exhibit an fMRI cortical activation pattern which is different from that in similarly aged nonsedated children.

Feasibility of standard mechanical ventilation with low FiO2 and small endotracheal tubes during laser microlaryngeal surgery.

BACKGROUND: No technique can be considered as a gold standard for ventilation during direct laser CO2 laryngeal microsurgery. We evaluated the feasibility of standard ventilation with laser-safe endotracheal tubes (ETTs) and inspired O2 fraction (FiO2) = 0.21 during direct microlaryngoscopy. METHODS: During total intravenous anesthesia, standard mechanical normoventilation was set with FiO2 = 0.21 and 50 mm Hg peak inspiratory pressure limit. If SpO2 was <90% for >2 minutes, FiO2 was increased to 0.3; after 4 minutes it was increased to 0.4; after another 4 minutes, positive end-expiratory pressure (PEEP) could be set at 5 cm H2O; and after another 4 minutes, surgery was stopped if SpO2 remained <90%. RESULTS: We studied 111 consecutive direct microlaryngoscopies on different patients. Four patients (3.6%) suffered minor intraoperative desaturation. Barotrauma was not observed, PEEP was never applied, and surgery was never stopped. Body mass index was independently predictive of the occurrence of intraoperative desaturation. CONCLUSIONS: Standard mechanical ventilation with FiO2 = 0.21 through laser-safe ETTs is feasible during direct microlaryngoscopy.

Functional magnetic resonance imaging (fMRI) in children sedated with propofol or midazolam.

Magnetic resonance imaging (MRI) requires patient immobility and children generally need to be sedated. The ideal sedative agent for functional MRI (fMRI) should only minimally hamper the neurophysiologic effect of the administered sensorial stimulation. This study compares the effect of propofol and midazolam on the fMRI auditory activation pattern in children. Fourteen children in the 3 to 7 year age group without neurologic or auditory deficits were randomly assigned to receive propofol or midazolam for sedation during auditory fMRI. Two patients in the midazolam group were excluded due to positive baseline MRIs. The children were stimulated using a passive listening task. The fMRI signal was modeled using various functions (hemodynamic response function, temporal derivative, and dispersion derivative) to check for the differing temporal characteristics of the signal between the groups. Patients in the propofol group showed activation only in the primary auditory cortex and exhibited a pattern more similar to that of nonsedated adults. Patients in the midazolam group exhibited a more complex pattern, presenting activation areas other than the primary auditory cortex; a delay in the functional response and higher duration variability were also observed. Our sample sizes are too small to derive a conclusive inference. Our preliminary study encourages the hypothesis that propofol is preferable to midazolam to maintain sedation in 3 to 7-year-old children during auditory fMRI because it facilitates the elicitation of a more focused auditory cortical activation pattern with less temporal and spatial dispersion.