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A comparison of GABA-ergic (propofol) and non-GABA-ergic (dexmedetomidine) sedation on visual and motor cortical oscillations, using magnetoencephalography.

ABSTRACT: Studying changes in cortical oscillations can help elucidate the mechanistic link between receptor physiology and the clinical effects of anaesthetic drugs. Propofol, a GABA-ergic drug produces divergent effects on visual cortical activity: increasing induced gamma-band responses (GBR) while decreasing evoked responses. Dexmedetomidine, an α2- adrenergic agonist, differs from GABA-ergic sedatives both mechanistically and clinically as it allows easy arousability from deep sedation with less cognitive side-effects. Here we use magnetoencephalography (MEG) to characterize and compare the effects of GABA-ergic (propofol) and non-GABA-ergic (dexmedetomidine) sedation, on visual and motor cortical oscillations. Sixteen male participants received target-controlled infusions of propofol and dexmedetomidine, producing mild-sedation, in a placebo-controlled, cross-over study. MEG data was collected during a combined visuomotor task. The key findings were that propofol significantly enhanced visual stimulus induced GBR (44% increase in amplitude) while dexmedetomidine decreased it (40%). Propofol also decreased the amplitudes of the Mv100 (visual M100) (27%) and Mv150 (52%) visual evoked fields (VEF), whilst dexmedetomidine had no effect on these. During the motor task, neither drug had any significant effect on movement related gamma synchrony (MRGS), movement related beta de-synchronisation (MRBD) or Mm100 (movement-related M100) movement-related evoked fields (MEF), although dexmedetomidine slowed the Mm300. Dexmedetomidine increased (92%) post-movement beta synchronisation/rebound (PMBR) power while propofol reduced it (70%, statistically non- significant). Overall, dexmedetomidine and propofol, at equi-sedative doses, produce contrasting effects on visual induced GBR, VEF, PMBR and MEF. These findings provide a mechanistic link between the known receptor physiology of these sedative drugs with their known clinical effects and may be used to explore mechanisms of other anaesthetic drugs on human consciousness.

SUBMITTER: Saxena N

PROVIDER: S-EPMC9227747 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundGuidelines currently recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation. Differences exist between these sedatives in arousability, immunity, and inflammation. Whether they affect outcomes differentially in mechanically ventilated adults with sepsis undergoing light sedation is unknown.MethodsIn a multicenter, double-blind trial, we randomly assigned mechanically ventilated adults with sepsis to receive dexmedetomidine (0.2 to 1.5 μg per kilogram of body weight per hour) or propofol (5 to 50 μg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation-Sedation Scale (RASS, on which scores range from -5 [unresponsive] to +4 [combative]). The primary end point was days alive without delirium or coma during the 14-day intervention period. Secondary end points were ventilator-free days at 28 days, death at 90 days, and age-adjusted total score on the Telephone Interview for Cognitive Status questionnaire (TICS-T; scores range from 0 to 100, with a mean of 50±10 and lower scores indicating worse cognition) at 6 months.ResultsOf 432 patients who underwent randomization, 422 were assigned to receive a trial drug and were included in the analyses - 214 patients received dexmedetomidine at a median dose of 0.27 μg per kilogram per hour, and 208 received propofol at a median dose of 10.21 μg per kilogram per minute. The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was -2.0 (interquartile range, -3.0 to -1.0). We found no difference between dexmedetomidine and propofol in the number of days alive without delirium or coma (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval [CI], 0.74 to 1.26), ventilator-free days (adjusted median, 23.7 vs. 24.0 days; odds ratio, 0.98; 95% CI, 0.63 to 1.51), death at 90 days (38% vs. 39%; hazard ratio, 1.06; 95% CI, 0.74 to 1.52), or TICS-T score at 6 months (adjusted median score, 40.9 vs. 41.4; odds ratio, 0.94; 95% CI, 0.66 to 1.33). Safety end points were similar in the two groups.ConclusionsAmong mechanically ventilated adults with sepsis who were being treated with recommended light-sedation approaches, outcomes in patients who received dexmedetomidine did not differ from outcomes in those who received propofol. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01739933.).

Project description:Objective: Compare the duration of mechanical ventilation between patients receiving sedation with continuous infusions of propofol alone or combination with the use of dexmedetomidine and propofol. Design: Retrospective, propensity matched (1:1) cohort study, employing eight variables chosen a priori for matching. Timing of exposure to dexmedetomidine initiation was incorporated into a matching algorithm. Setting: Level 1, university-based, 32-bed, adult, mixed trauma and surgical intensive care unit (SICU). Continuous sedation was delivered according to a protocol methodology with daily sedation vacation and spontaneous breathing trials. Choice of sedation agent was physician directed. Patients: Between 2010 and 2014, 149 SICU patients receiving mechanical ventilation for >24 h received dexmedetomidine with propofol. Propensity matching resulted in 143 pair cohorts. Interventions: Dexmedetomidine with propofol or propofol alone. Measurements and Main Results: There was no statistical difference in SICU length of stay (LOS), with a median absolute difference of 5.3 h for propofol alone group (p = 0.43). The SICU mortality was not statistically different (RR = 1.002, p = 0.88). Examining a 14-day period post-treatment with dexmedetomidine, on any given day (excluding days 1 and 14), dexmedetomidine with propofol-treated patients had a 0.5% to 22.5% greater likelihood of being delirious (CAM-ICU positive). In addition, dexmedetomidine with propofol-treated patients had a 4.5% to 18.8% higher likelihood of being above the target sedation score (more agitated) compared to propofol-alone patients. Conclusions: In this propensity matched cohort study, adjunct use of dexmedetomidine to propofol did not show a statistically significant reduction with respect to mechanical ventilation (MV) duration, SICU LOS, or SICU mortality, despite a trend toward receiving fewer hours of propofol. There was no evidence that dexmedetomidine with propofol improved sedation scores or reduced delirium.

Project description:IntroductionDexmedetomidine was shown in two European randomized double-blind double-dummy trials (PRODEX and MIDEX) to be non-inferior to propofol and midazolam in maintaining target sedation levels in mechanically ventilated intensive care unit (ICU) patients. Additionally, dexmedetomidine shortened the time to extubation versus both standard sedatives, suggesting that it may reduce ICU resource needs and thus lower ICU costs. Considering resource utilization data from these two trials, we performed a secondary, cost-minimization analysis assessing the economics of dexmedetomidine versus standard care sedation.MethodsThe total ICU costs associated with each study sedative were calculated on the basis of total study sedative consumption and the number of days patients remained intubated, required non-invasive ventilation, or required ICU care without mechanical ventilation. The daily unit costs for these three consecutive ICU periods were set to decline toward discharge, reflecting the observed reduction in mean daily Therapeutic Intervention Scoring System (TISS) points between the periods. A number of additional sensitivity analyses were performed, including one in which the total ICU costs were based on the cumulative sum of daily TISS points over the ICU period, and two further scenarios, with declining direct variable daily costs only.ResultsBased on pooled data from both trials, sedation with dexmedetomidine resulted in lower total ICU costs than using the standard sedatives, with a difference of €2,656 in the median (interquartile range) total ICU costs-€11,864 (€7,070 to €23,457) versus €14,520 (€7,871 to €26,254)-and €1,649 in the mean total ICU costs. The median (mean) total ICU costs with dexmedetomidine compared with those of propofol or midazolam were €1,292 (€747) and €3,573 (€2,536) lower, respectively. The result was robust, indicating lower costs with dexmedetomidine in all sensitivity analyses, including those in which only direct variable ICU costs were considered. The likelihood of dexmedetomidine resulting in lower total ICU costs compared with pooled standard care was 91.0% (72.4% versus propofol and 98.0% versus midazolam).ConclusionsFrom an economic point of view, dexmedetomidine appears to be a preferable option compared with standard sedatives for providing light to moderate ICU sedation exceeding 24 hours. The savings potential results primarily from shorter time to extubation.Trial registrationClinicalTrials.gov NCT00479661 (PRODEX), NCT00481312 (MIDEX).

Project description:Visual snow refers to the persistent visual experience of static in the whole visual field of both eyes. It is often reported by patients with migraine and co-occurs with conditions such as tinnitus and tremor. The underlying pathophysiology of the condition is poorly understood. Previously, we hypothesized that visual snow syndrome may be characterized by disruptions to rhythmical activity within the visual system. To test this, data from 18 patients diagnosed with visual snow syndrome, and 16 matched controls, were acquired using magnetoencephalography. Participants were presented with visual grating stimuli, known to elicit decreases in alpha-band (8-13 Hz) power and increases in gamma-band power (40-70 Hz). Data were mapped to source-space using a beamformer. Across both groups, decreased alpha power and increased gamma power localized to early visual cortex. Data from the primary visual cortex were compared between groups. No differences were found in either alpha or gamma peak frequency or the magnitude of alpha power, p > 0.05. However, compared with controls, our visual snow syndrome cohort displayed significantly increased primary visual cortex gamma power, p = 0.035. This new electromagnetic finding concurs with previous functional MRI and PET findings, suggesting that in visual snow syndrome, the visual cortex is hyperexcitable. The coupling of alpha-phase to gamma amplitude within the primary visual cortex was also quantified. Compared with controls, the visual snow syndrome group had significantly reduced alpha-gamma phase-amplitude coupling, p < 0.05, indicating a potential excitation-inhibition imbalance in visual snow syndrome, as well as a potential disruption to top-down 'noise-cancellation' mechanisms. Overall, these results suggest that rhythmical brain activity in the primary visual cortex is both hyperexcitable and disorganized in visual snow syndrome, consistent with this being a condition of thalamocortical dysrhythmia.

Project description:BackgroundAccidental Accidental awareness during general anesthesia (AAGA) occurs in 1-2% of high-risk practice patients and is a cause of severe psychological trauma, termed post-traumatic stress disorder (PTSD). However, no monitoring techniques can accurately predict or detect AAGA. Since the first reflex for a patient during AAGA is to move, a passive brain-computer interface (BCI) based on the detection of an intention of movement would be conceivable to alert the anesthetist. However, the way in which propofol (i.e., an anesthetic commonly used for the general anesthesia induction) affects motor brain activity within the electroencephalographic (EEG) signal has been poorly investigated and is not clearly understood. For this reason, a detailed study of the motor activity behavior with a step-wise increasing dose of propofol is required and would provide a proof of concept for such an innovative BCI. The main goal of this study is to highlight the occurrence of movement attempt patterns, mainly changes in oscillations called event-related desynchronization (ERD) and event-related synchronization (ERS), in the EEG signal over the motor cortex, in healthy subjects, without and under propofol sedation, during four different motor tasks.MethodsMOTANA is an interventional, prospective, exploratory, physiological, monocentric, and randomized study conducted in healthy volunteers under light anesthesia, involving EEG measurements before and after target-controlled infusion of propofol at three different effect-site concentrations (0 μg.ml -1, 0.5 μg.ml -1, and 1.0 μg.ml -1). In this exploratory study, 30 healthy volunteers will perform 50 trials for the four motor tasks (real movement, motor imagery, motor imagery with median nerve stimulation, and median nerve stimulation alone) in a randomized sequence. In each conditions and for each trial, we will observe changes in terms of ERD and ERS according to the three propofol concentrations. Pre- and post-injection comparisons of propofol will be performed by paired series tests.DiscussionMOTANA is an exploratory study aimed at designing an innovative BCI based on EEG-motor brain activity that would detect an attempt to move by a patient under anesthesia. This would be of interest in the prevention of AAGA.Trial registrationAgence Nationale de Sécurité du Médicament (EUDRACT 2017-004198-1), NCT03362775. Registered on 29 August 2018. https://clinicaltrials.gov/ct2/show/NCT03362775?term=03362775&rank=1.

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A comparison of GABA-ergic (propofol) and non-GABA-ergic (dexmedetomidine) sedation on visual and motor cortical oscillations, using magnetoencephalography.

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