The relationship of bispectral index values to conscious state: an analysis of two volunteer cohort studies.

Background: The ability of current depth-of-anaesthesia monitors to differentiate subtle changes in the conscious state has not been well characterised. We examine the variability in bispectral index (BIS) scores associated with disconnected conscious and unconscious states as confirmed by a novel serial awakening paradigm.

Methods: Seventy adult participants, given propofol or dexmedetomidine, had a cumulative 1381 electroencephalographic (EEG) recordings across two centres.

Circulating oxylipin and bile acid profiles of dexmedetomidine, propofol, sevoflurane, and S-ketamine: a randomised controlled trial using tandem mass spectrometry.

Background: This exploratory study aimed to investigate whether dexmedetomidine, propofol, sevoflurane, and S-ketamine affect oxylipins and bile acids, which are functionally diverse molecules with possible connections to cellular bioenergetics, immune modulation, and organ protection.

Methods: In this randomised, open-label, controlled, parallel group, Phase IV clinical drug trial, healthy male subjects (=160) received equipotent doses (EC for verbal command) of dexmedetomidine (1.5 ng ml; =40), propofol (1.

Subjective experiences during dexmedetomidine- or propofol-induced unresponsiveness and non-rapid eye movement sleep in healthy male subjects.

Background: Anaesthetic-induced unresponsiveness and non-rapid eye movement (NREM) sleep share common neural pathways and neurophysiological features. We hypothesised that these states bear resemblance also at the experiential level.

Methods: We compared, in a within-subject design, the prevalence and content of experiences in reports obtained after anaesthetic-induced unresponsiveness and NREM sleep.

Response to Letter to the Editor.

It is crucial to consider the possible influence of anesthetic agents on esophageal function testing. Dexmedetomidine has been shown to affect primary peristalsis during esophageal manometry. In the two case reports presented by Toaz et al.

Decreased Thalamic Activity Is a Correlate for Disconnectedness during Anesthesia with Propofol, Dexmedetomidine and Sevoflurane But Not S-Ketamine.

Establishing the neural mechanisms responsible for the altered global states of consciousness during anesthesia and dissociating these from other drug-related effects remains a challenge in consciousness research. We investigated differences in brain activity between connectedness and disconnectedness by administering various anesthetics at concentrations designed to render 50% of the subjects unresponsive. One hundred and sixty healthy male subjects were randomized to receive either propofol (1.

Effects of dexmedetomidine on pharyngeal swallowing and esophageal motility-A double-blind randomized cross-over study in healthy volunteers.

Background: Sedative agents increase the risk of pulmonary aspiration, where an intact swallowing function is an important defense mechanism. Dexmedetomidine is an α -adrenoceptor agonist widely used during procedural sedation due to beneficial properties with minimal respiratory effects. The effects of dexmedetomidine on pharyngeal swallowing and esophageal motility are not known in detail.

On no man's land: Subjective experiences during unresponsive and responsive sedative states induced by four different anesthetic agents.

To understand how anesthetics with different molecular mechanisms affect consciousness, we explored subjective experiences recalled after responsive and unresponsive sedation induced with equisedative doses of dexmedetomidine, propofol, sevoflurane, and S-ketamine in healthy male participants (N = 140). The anesthetics were administered in experimental setting using target-controlled infusion or vapouriser for one hour. Interviews conducted after anesthetic administration revealed that 46.

Effects of dexmedetomidine, propofol, sevoflurane and S-ketamine on the human metabolome: A randomised trial using nuclear magnetic resonance spectroscopy.

Background: Pharmacometabolomics uses large-scale data capturing methods to uncover drug-induced shifts in the metabolic profile. The specific effects of anaesthetics on the human metabolome are largely unknown.

Objective: We aimed to discover whether exposure to routinely used anaesthetics have an acute effect on the human metabolic profile.

Effect of Inhaled Xenon on Cardiac Function in Comatose Survivors of Out-of-Hospital Cardiac Arrest-A Substudy of the Xenon in Combination With Hypothermia After Cardiac Arrest Trial.

Unlabelled: This explorative substudy aimed at determining the effect of inhaled xenon on left ventricular function by echocardiography in comatose survivors of out-of-hospital cardiac arrest.

Design: A randomized two-group single-blinded phase 2 clinical drug trial.

Setting: A multipurpose ICU in two university hospitals.

Seasonal Variation in the Brain μ-Opioid Receptor Availability.

Seasonal rhythms influence mood and sociability. The brain μ-opioid receptor (MOR) system modulates a multitude of seasonally varying socioemotional functions, but its seasonal variation remains elusive with no previously reported evidence. Here, we first conducted a cross-sectional study with previously acquired human [C]carfentanil PET imaging data (132 male and 72 female healthy subjects) to test whether there is seasonal variation in MOR availability.

Alpha band frontal connectivity is a state-specific electroencephalographic correlate of unresponsiveness during exposure to dexmedetomidine and propofol.

Background: Coherent alpha electroencephalogram (EEG) rhythms in the frontal cortex have been correlated with the hypnotic effects of propofol and dexmedetomidine, but less is known about frontal connectivity as a state-specific correlate of unresponsiveness as compared with long-range connectivity. We aimed to distinguish dose- and state-dependent effects of dexmedetomidine and propofol on EEG connectivity.

Methods: Forty-seven healthy males received either dexmedetomidine (n=23) or propofol (n=24) as target-controlled infusion with stepwise increments until loss of responsiveness (LOR).

Interindividual variability and lateralization of μ-opioid receptors in the human brain.

Alterations in the brain's μ-opioid receptor (MOR) system have been associated with several neuropsychiatric disorders. Central MOR availability also varies considerably in healthy individuals. Multiple epidemiological factors have been proposed to influence the MOR system, but due to small sample sizes the magnitude of their influence remains inconclusive.

The influence of dexmedetomidine and propofol on circulating cytokine levels in healthy subjects.

Background: Surgery and diseases modify inflammatory responses and the immune system. Anesthetic agents also have effects on the human immune system but the responses they induce may be altered or masked by the surgical procedures or underlying illnesses. The aim of this study was to assess how single-drug dexmedetomidine and propofol anesthesia without any surgical intervention alter acute immunological biomarkers in healthy subjects.

Single-subject analysis of N400 event-related potential component with five different methods.

There are several different approaches to analyze event-related potentials (ERPs) at single-subject level, and the aim of the current study is to provide information for choosing a method based on its ability to detect ERP effects and factors influencing the results. We used data from 79 healthy participants with EEG referenced to mastoid average and investigated the detection rate of auditory N400 effect in single-subject analysis using five methods: visual inspection of participant-wise averaged ERPs, analysis of variance (ANOVA) for amplitude averages in a time window, cluster-based non-parametric testing, a novel Bayesian approach and Studentized continuous wavelet transform (t-CWT). Visual inspection by three independent raters yielded N400 effect detection in 85% of the participants in at least one paradigm (active responding or passive listening), whereas ANOVA identified the effect in 68%, the cluster-method in 59%, the Bayesian method in 89%, and different versions of t-CWT in 22-59% of the participants.

Alterations in heart rate variability in patients with peripheral arterial disease requiring surgical revascularization have limited association with postoperative major adverse cardiovascular and cerebrovascular events.

Objective: Obstructive sleep apnea (OSA) is common in peripheral arterial disease (PAD) and associates with high mortality after surgery. Since abnormal heart rate variability (HRV) is predictive of postoperative complications, we investigated the relations of HRV with PAD, OSA and major adverse cardiovascular and cerebrovascular events (MACCE).

Materials And Methods: Seventy-five patients (67±9 years) scheduled for sub-inguinal revascularization and 15 controls (63±6 years) underwent polysomnography and HRV analyses.

Comparative effects of dexmedetomidine, propofol, sevoflurane, and S-ketamine on regional cerebral glucose metabolism in humans: a positron emission tomography study.

Introduction: The highly selective α-agonist dexmedetomidine has become a popular sedative for neurointensive care patients. However, earlier studies have raised concern that dexmedetomidine might reduce cerebral blood flow without a concomitant decrease in metabolism. Here, we compared the effects of dexmedetomidine on the regional cerebral metabolic rate of glucose (CMR) with three commonly used anaesthetic drugs at equi-sedative doses.

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.

Dreaming and awareness during dexmedetomidine- and propofol-induced unresponsiveness.

Background: Experiences during anaesthetic-induced unresponsiveness have previously been investigated by interviews after recovery. To explore whether experiences occur during drug administration, we interviewed participants during target-controlled infusion (TCI) of dexmedetomidine or propofol and after recovery.

Methods: Healthy participants received dexmedetomidine (n=23) or propofol (n=24) in stepwise increments until loss of responsiveness (LOR1).

Using Positron Emission Tomography in Revealing the Mystery of General Anesthesia: Study Design Challenges and Opportunities.

Functional neuroimaging with positron emission tomography (PET) is one of the cornerstones for studying the central nervous system effects of general anesthetics and anesthesia mechanisms. General anesthesia offers a unique and safe way to directly manipulate consciousness, and can thus be used as a powerful research tool to study the neurobiology of human consciousness. In this chapter, we will address the possibilities of PET imaging in revealing the mysteries of general anesthesia and anesthetic induced unconsciousness and summarize some of the recent advancements in the field.

Differentiating Drug-related and State-related Effects of Dexmedetomidine and Propofol on the Electroencephalogram.

Background: Differentiating drug-related changes and state-related changes on the electroencephalogram during anesthetic-induced unconsciousness has remained a challenge. To distinguish these, we designed a rigorous experimental protocol with two drugs known to have distinct molecular mechanisms of action. We hypothesized that drug- and state-related changes can be separated.