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.
View Article and Find Full Text PDFBackground: The choice of what patient outcomes are included in clinical quality registries is crucial for comparable and relevant data collection. Ideally, a uniform outcome framework could be used to classify the outcomes included in registries, steer the development of outcome measurement, and ultimately enable better patient care through benchmarking and registry research. The aim of this study was to compare clinical quality registry outcomes against the COMET taxonomy to assess its suitability in the registry context.
View Article and Find Full Text PDFTo 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.
View Article and Find Full Text PDFBackground: Synovial fluid bacterial culture is the cornerstone of confirmation or exclusion of periprosthetic joint infection (PJI). The aim of this study was to assess synovial fluid and serum biomarker patterns of patients with total joint arthroplasty (TJA), and the association of these patterns with PJI.
Methods: Synovial fluid and serum samples were collected from 35 patients who were admitted to the Arthroplasty Unit of the Department of Orthopaedics and Traumatology at Turku University Hospital.
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).
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.
View Article and Find Full Text PDFBackground: 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.
View Article and Find Full Text PDFRecent studies using electroencephalography (EEG) suggest that alteration of coherent activity between the anterior and posterior brain regions might be used as a neurophysiologic correlate of anesthetic-induced unconsciousness. One way to assess causal relationships between brain regions is given by renormalized partial directed coherence (rPDC). Importantly, directional connectivity is evaluated in the frequency domain by taking into account the whole multichannel EEG, as opposed to time domain or two channel approaches.
View Article and Find Full Text PDFOne 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.
View Article and Find Full Text PDFNoradrenergic neurons of the locus coeruleus project throughout the cerebral cortex and multiple subcortical structures. Alterations in the locus coeruleus firing are associated with vigilance states and with fear and anxiety disorders. Brain ionotropic type A receptors for gamma-aminobutyric acid (GABA) serve as targets for anxiolytic and sedative drugs, and play an essential regulatory role in the locus coeruleus.
View Article and Find Full Text PDFBackground: 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.
Purpose: [(11)C]Carfentanil has been widely used in positron emission tomography (PET) studies for measuring micro-opioid receptor binding in humans, but the reproducibility of the binding parameter estimates is unknown.
Materials And Methods: Eight healthy volunteers were scanned twice during the same day with [(11)C]carfentanil PET, and binding to receptors was assessed with both reference tissue and arterial plasma input-based models using region of interest (ROI) and voxel-based quantification.
Results: The two-tissue compartmental model distribution volume (V(T)) was highly reproducible as indicated by low variability (VAR < 6%) and high intraclass correlation coefficients (ICC > 0.
[(11)C]Flumazenil is widely used in positron emission tomography (PET) studies to measure GABA(A) receptors in vivo in humans. Although several different methods have been applied for the quantification of [(11)C]flumazenil binding, the reproducibility of these methods has not been previously examined. The reproducibility of a single bolus [(11)C]flumazenil measurements was studied by scanning eight healthy volunteers twice during the same day.
View Article and Find Full Text PDFBackground: 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.
View Article and Find Full Text PDFBackground: 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.
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%).
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.