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.

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.

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.

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.

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).

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.

Returning from oblivion: imaging the neural core of consciousness.

One of the greatest challenges of modern neuroscience is to discover the neural mechanisms of consciousness and to explain how they produce the conscious state. We sought the underlying neural substrate of human consciousness by manipulating the level of consciousness in volunteers with anesthetic agents and visualizing the resultant changes in brain activity using regional cerebral blood flow imaging with positron emission tomography. Study design and methodology were chosen to dissociate the state-related changes in consciousness from the effects of the anesthetic drugs.

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.

Delta entropy of heart rate variability along with deepening anesthesia.

Background: Conventional time and frequency domain measures of heart rate variability (HRV) are strongly influenced by anesthetic drugs, and are therefore not able to detect subtle changes in HRV, even during light anesthesia. Approximate entropy of R-R intervals is an HRV measure that has a tendency to decrease during anesthesia, but it is severely compromised by low-frequency variations of the signal. However, the negative effect of the low-frequency variations can be eliminated by differentiating the R-R interval tachogram before analysis.

The effects of xenon anesthesia on the relationship between cerebral glucose metabolism and blood flow in healthy subjects: a positron emission tomography study.

Background: General anesthetics can alter the relationship between regional cerebral glucose metabolism (rCMR(glc)) and blood flow (rCBF). In this positron emission tomography study, our aim was to assess both rCMR(glc) and rCBF in the same individuals during xenon anesthesia.

Methods: (18)F-labeled fluorodeoxyglucose and (15)O-labeled water were used to determine rCMR(glc) and rCBF, respectively, in five healthy male subjects at baseline (awake) and during 1 minimum alveolar anesthetic concentration of xenon.

Pharmacokinetics of intravenous dexmedetomidine in children under 11 yr of age.

Background: Information has been very limited on the pharmacokinetics of the selective alpha(2)-adrenoceptor agonist dexmedetomidine in children, particularly in children <2 yr of age.

Methods: Eight children aged between 28 days and 23 months and eight children aged between 2 and 11 yr undergoing either elective bronchoscopy or nuclear magnetic resonance imaging were included in the study. Dexmedetomidine 1 microg kg(-1) was infused i.

Xenon does not affect gamma-aminobutyric acid type A receptor binding in humans.

Background: The noble gas xenon acts as an anesthetic with favorable hemodynamic and neuroprotective properties. Based on animal and in vitro data, it is thought to exert its anesthetic effects by inhibiting glutamatergic signaling, but effects on gamma-aminobutyric acid type A (GABA(A)) receptors also have been reported. The mechanism of anesthetic action of xenon in the living human brain still remains to be determined.

Bispectral index, entropy, and quantitative electroencephalogram during single-agent xenon anesthesia.

Background: The aim was to evaluate the performance of anesthesia depth monitors, Bispectral Index (BIS) and Entropy, during single-agent xenon anesthesia in 17 healthy subjects.

Methods: After mask induction with xenon and intubation, anesthesia was continued with xenon only. BIS, State Entropy and Response Entropy, and electroencephalogram were monitored throughout induction, steady-state anesthesia, and emergence.

Effects of xenon anesthesia on cerebral blood flow in humans: a positron emission tomography study.

Background: Animal studies have demonstrated a strong neuroprotective property of xenon. Its usefulness in patients with cerebral pathology could be compromised by deleterious effects on regional cerebral blood flow (rCBF).

Methods: 15O-labeled water was used to determine rCBF in nine healthy male subjects at baseline and during 1 minimum alveolar concentration (MAC) of xenon (63%).

The effects of surgical levels of sevoflurane and propofol anaesthesia on heart rate variability.

Background And Objective: We compared heart rate dynamics during surgical levels of propofol and sevoflurane anaesthesia in a highly standardized setting.

Methods: We recorded electrocardiography from 24 anaesthetized healthy male subjects. In the first parallel part of the study, the subjects were anaesthetized either with sevoflurane (n = 8) or propofol (n = 8) targeted to match 1.

Increase in high frequency EEG activity explains the poor performance of EEG spectral entropy monitor during S-ketamine anesthesia.

Objective: To study the effects of S-ketamine on the EEG and to investigate whether spectral entropy of the EEG can be used to assess the depth of hypnosis during S-ketamine anesthesia.

Methods: The effects of sub-anesthetic (159 (21); mean (SD) ng/ml) and anesthetic (1,959 (442) ng/ml) serum concentrations of S-ketamine on state entropy (SE), response entropy (RE) and classical EEG spectral power variables (recorded using the Entropy Module, GE Healthcare, Helsinki, Finland) were studied in 8 healthy males. These EEG data were compared with EEG recordings from 6 matching subjects anesthetized with propofol.

Subanesthetic ketamine does not affect 11C-flumazenil binding in humans.

Positron emission tomography (PET) studies suggest that propofol and inhaled anesthetics increase (11)C-flumazenil binding in the living human brain, thus supporting the involvement of gamma-aminobutyric acid type A (GABA(A)) receptors in the mechanism of action of these drugs. Ketamine produces its anesthetic effects primarily by N-methyl-d-aspartate receptor antagonism, but it may also have GABA(A) receptor agonistic properties. By using PET, we studied the cerebral (11)C-flumazenil binding in 10 healthy subjects before and during a subanesthetic racemic ketamine infusion reaching a serum concentration of 350 +/- 42 ng/mL.

Correlation of EEG spectral entropy with regional cerebral blood flow during sevoflurane and propofol anaesthesia.

ENTROPY index monitoring, based on spectral entropy of the electroencephalogram, is a promising new method to measure the depth of anaesthesia. We examined the association between spectral entropy and regional cerebral blood flow in healthy subjects anaesthetised with 2%, 3% and 4% end-expiratory concentrations of sevoflurane and 7.6, 12.

S-ketamine anesthesia increases cerebral blood flow in excess of the metabolic needs in humans.

Background: Animal studies have demonstrated neuroprotective properties of S-ketamine, but its effects on cerebral blood flow (CBF), metabolic rate of oxygen (CMRO2), and glucose metabolic rate (GMR) have not been comprehensively studied in humans.

Methods: Positron emission tomography was used to quantify CBF and CMRO2 in eight healthy male volunteers awake and during S-ketamine infusion targeted to subanesthetic (150 ng/ml) and anesthetic (1,500-2,000 ng/ml) concentrations. In addition, subjects' GMRs were assessed awake and during anesthesia.

Sevoflurane and propofol increase 11C-flumazenil binding to gamma-aminobutyric acidA receptors in humans.

Based on in vitro studies and animal data, most anesthetics are supposed to act via gamma-aminobutyric acid type A (GABA(A)) receptors. However, this fundamental characteristic has not been extensively investigated in humans. We studied (11)C-flumazenil binding to GABA(A) receptors during sevoflurane and propofol anesthesia in the living human brain using positron emission tomography (PET).

Ventilator add-on for delivering PET tracer gases.

Objectives: The increasing use of PET for assessing cerebral blood flow, oxygen metabolism, and blood volume in critically ill patients has created a need for reliable technical solutions for delivering (15)O-tracer gases to mechanically ventilated subjects. Our objective was to create such a solution.

Methods: We designed a ventilator add-on unit that enables complex functional brain studies using labeled oxygen and carbon monoxide gases as tracers.

Effects of subanesthetic ketamine on regional cerebral glucose metabolism in humans.

Background: The authors have recently shown with positron emission tomography that subanesthetic doses of racemic ketamine increase cerebral blood flow but do not affect oxygen consumption significantly. In this study, the authors wanted to assess the effects of racemic ketamine on regional glucose metabolic rate (rGMR) in similar conditions to establish whether ketamine truly induces disturbed coupling between cerebral blood flow and metabolism.

Methods: 18F-labeled fluorodeoxyglucose was used as a positron emission tomography tracer to quantify rGMR on 12 brain regions of interest of nine healthy male volunteers at baseline and during a 300-ng/ml ketamine target concentration level.

Sevoflurane is epileptogenic in healthy subjects at surgical levels of anesthesia.

Objective: To investigate EEG effects of three escalating concentrations of sevoflurane and propofol in single-agent anesthesia on healthy subjects.

Methods: Four-channel EEG was continuously recorded at 1, 1.5, and 2 minimum alveolar concentration (MAC)/effective plasma concentration 50 (EC50) levels of either sevoflurane or propofol anesthesia in 16 men, 8 subjects in each group.