Ketamiini ja kallonsisäinen paine : todellinen ongelma vai paljon melua tyhjästä

Ketamiinin käyttö ensihoidossa on lisääntynyt, sillä se ei lamaa hengitystä eikä verenkiertoa. Ketamiini saattaa kuitenkin nostaa kallonsisäistä painetta. Onko ketamiini turvallinen lääke ensihoidossa aivotapahtumapotilaita hoidettaessa? Kannattaako teho-osastolla aivotapahtumapotilaita lääkitä ketamiinilla?</p

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). We attempted to arouse participants during constant dosing (return of responsiveness [ROR]), and the target concentration was then increased 50% to achieve presumed loss of consciousness. We collected 64-channel EEG data and prefrontal-frontal and anterior-posterior functional connectivity in the alpha band (8-14 Hz) was measured using coherence and weighted phase lag index (wPLI). Directed connectivity was measured with directed phase lag index (dPLI).Results: Prefrontal-frontal EEG-based connectivity discriminated the states at the different drug concentrations. At ROR, prefrontal-frontal connectivity reversed to the level observed before LOR, indicating that connectivity changes were related to unresponsiveness rather than drug concentration. Unresponsiveness was associated with emergence of frontal-to-prefrontal dominance (dPLI: -0.13 to -0.40) in contrast to baseline (dPLI: 0.01-0.02). Coherence, wPLI, and dPLI had similar capability to discriminate the states that differed in terms of responsiveness and drug concentration. In contrast, anterior-posterior connectivity in the alpha band did not differentiate LOR and ROR.Conclusions: Local prefrontal-frontal EEG-based connectivity reflects unresponsiveness induced by propofol or dexmedetomidine, suggesting its utility in monitoring the anaesthetised state with these agents.Clinical trial registration:NCT01889004</div

Foundations of human consciousness: Imaging the twilight zone

What happens in the brain when conscious awareness of the surrounding world fades? We manipulated consciousness in two experiments in a group of healthy males and measured brain activity with positron emission tomography. Measurements were made during wakefulness, escalating and constant levels of two anesthetic agents (Experiment 1, n=39) and during sleep-deprived wakefulness and Non-Rapid Eye Movement sleep (Experiment 2, n=37). In Experiment 1, the subjects were randomized to receive either propofol or dexmedetomidine until unresponsiveness. In both experiments, forced awakenings were applied to achieve rapid recovery from an unresponsive to a responsive state, followed by immediate and detailed interviews of subjective experiences during the preceding unresponsive condition. Unresponsiveness rarely denoted unconsciousness, as the majority of the subjects had internally generated experiences. Unresponsive anesthetic states and verified sleep stages, where a subsequent report of mental content included no signs of awareness of the surrounding world, indicated a disconnected state. Functional brain imaging comparing responsive and connected vs. unresponsive and disconnected states of consciousness during constant anesthetic exposure revealed that activity of the thalamus, cingulate cortices and angular gyri are fundamental for human consciousness. These brain structures were affected independent from the pharmacologic agent, drug concentration and direction of change in the state of consciousness. Analogous findings were obtained when consciousness was regulated by physiological sleep. State-specific findings were distinct and separable from the overall effects of the interventions, which included widespread depression of brain activity across cortical areas. These findings identify a central core brain network critical for human consciousness.</p

Directional connectivity between frontal and posterior brain regions is altered with increasing concentrations of propofol.

Recent 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. rPDC was applied here in order to investigate propofol induced changes in causal connectivity between four states of consciousness: awake (AWA), deep sedation (SED), loss (LOC) and return of consciousness (ROC) by gathering full 10/20 system human EEG data in ten healthy male subjects. The target-controlled drug infusion was started at low rate with subsequent gradual stepwise increases at 10 min intervals in order to carefully approach LOC (defined as loss of motor responsiveness to a verbal stimulus). The direction of the causal EEG-network connections clearly changed from AWA to SED and LOC. Propofol induced a decrease (p = 0.002-0.004) in occipital-to-frontal rPDC of 8-16 Hz EEG activity and an increase (p = 0.001-0.040) in frontal-to-occipital rPDC of 10-20 Hz activity on both sides of the brain during SED and LOC. In addition, frontal-to-parietal rPDC within 1-12 Hz increased in the left hemisphere at LOC compared to AWA (p = 0.003). However, no significant changes were detected between the SED and the LOC states. The observed decrease in back-to-front EEG connectivity appears compatible with impaired information flow from the posterior sensory and association cortices to the executive prefrontal areas, possibly related to decreased ability to perceive the surrounding world during sedation. The observed increase in the opposite (front-to-back) connectivity suggests a propofol concentration dependent association and is not directly related to the level of consciousness per se

Time-courses of plasma IL-6 and HMGB-1 reflect initial severity of clinical presentation but do not predict poor neurologic outcome following subarachnoid hemorrhage

Objective: Patients with aneurysmal subarachnoid hemorrhage (aSAH) experience high mortality and morbidity. Neuroinflammation causes brain damage expansion after aSAH. Due to the complexity of the inflammatory response multiple biomarkers are needed to evaluate its' progression. We studied inflammatory process after aSAH by measuring two inflammatory biomarkers, interleukin-6 (IL-6) and high-mobility group box 1 (HMGB1) at simultaneous time-points after aSAH. Methods: In this prospective population-based study, IL-6 and HMGB1 were measured in aSAH patients (n = 47) for up to five days. Plasma concentrations of IL-6 and HMGB1 were measured at 0, 12 and 24 h after hospital admission, and thereafter daily for up to five days or until the patient was transferred from the intensive care unit (ICU). The patients' neurological outcomes were evaluated with the modified Rankin Scale at six months after aSAH. Results: A high IL-6 level during the first day after aSAH was associated with a severe initial clinical presentation (p = 0.002) and infection during follow-up (p = 0.031). The HMGB1 level did not associate with these parameters. There was no correlation between IL-6 and HMGB1 levels at any time point during the follow-up. The concentrations of IL-6 and HMGB1 were not associated with neurological outcome. Conclusions: High initial IL-6 values seem to reflect the intensity of the inflammatory response but not the brain damage per se. An early inflammatory response might even be beneficial since although elevated IL-6 levels were observed in patients with a more severe initial clinical presentation, they were not associated with neurological outcome. The lack of correlation between IL-6 and HMGB1 questions the role of macrophages in the process of the secretion of these inflammatory markers after aSAH, instead pointing to the activation of alternative pro-inflammatory pathways

Ketamiini ja kallonsisäinen paine : todellinen ongelma vai paljon melua tyhjästä

Teema : Aivo

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. Methods: Thirty-five healthy, young male subjects were anesthetized using increasing concentrations of dexmedetomidine (n = 18) or propofol (n = 17) until loss of responsiveness (LOR) was detected. The treatment allocation was randomized. Multi-parametric immunoassays for the detection of 48 cytokines, chemokines and growth factors were used. Concentrations were determined at baseline and at the highest drug concentration for each subject. Results: The changes in the concentration of eotaxin (decrease after dexmedetomidine) and platelet-derived growth factor (PDGF, increase after propofol) were statistically significantly different between the groups. Significant changes were detected within both groups; the concentrations of monocyte chemotactic protein 1, chemokine ligand 27 and macrophage migration inhibitory factor were lower in both groups after the drug administration. Dexmedetomidine decreased the concentration of eotaxin, interleukin-18, interleukin-2Ra, stem cell factor, stem cell growth factor and vascular endothelial growth factor, and propofol decreased significantly the levels of hepatocyte growth factor, IFN-.-induced protein 10 and monokine induced by IFN-gamma, and increased the levels of interleukin-17, interleukin-5, interleukin-7 and PDGF. Conclusions: Dexmedetomidine seemed to have an immunosuppressive effect on the immune system whereas propofol seemed to induce mixed pro- and anti-inflammatory effects on the immune system. The choice of anesthetic agent could be relevant when treating patients with compromised immunological defense mechanisms. Trial registration: Before subject enrollment, the study was registered in the European Clinical Trials database (EudraCT number 2013-001496-21, The Neural Mechanisms of Anesthesia and Human Consciousness) and in ClinicalTrials.gov (Principal Investigator: Harry Scheinin, number NCT01889004, The Neural Mechanisms of Anesthesia and Human Consciousness, Part 2, on the 23rd of June 2013)

Individual and mean rPDC values at different stages of the study.

<p>Individual fronto-occipital (F3–O1, F4–O2) 10–20 Hz and occipito-frontal (O1–F3, O2–F4) 8–16 Hz rPDC values during stepwise increased propofol infusion during the awake (AWA) state, sedation (SED), loss of consciousness (LOC) and return of consciousness (ROC). Individual and mean rPDC values are presented with thin and thick lines, respectively.</p

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

Background herent 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. thods rty-seven healthy males received either dexmedetomidine (n=23) or propofol (n=24) as target-controlled infusion with stepwise increments until loss of responsiveness (LOR). We attempted to arouse participants during constant dosing (return of responsiveness [ROR]), and the target concentration was then increased 50% to achieve presumed loss of consciousness. We collected 64-channel EEG data and prefrontalâ\u80\u93frontal and anteriorâ\u80\u93posterior functional connectivity in the alpha band (8â\u80\u9314 Hz) was measured using coherence and weighted phase lag index (wPLI). Directed connectivity was measured with directed phase lag index (dPLI). sults efrontalâ\u80\u93frontal EEG-based connectivity discriminated the states at the different drug concentrations. At ROR, prefrontalâ\u80\u93frontal connectivity reversed to the level observed before LOR, indicating that connectivity changes were related to unresponsiveness rather than drug concentration. Unresponsiveness was associated with emergence of frontal-to-prefrontal dominance (dPLI: â\u80\u930.13 to â\u80\u930.40) in contrast to baseline (dPLI: 0.01â\u80\u930.02). Coherence, wPLI, and dPLI had similar capability to discriminate the states that differed in terms of responsiveness and drug concentration. In contrast, anteriorâ\u80\u93posterior connectivity in the alpha band did not differentiate LOR and ROR. nclusions cal prefrontalâ\u80\u93frontal EEG-based connectivity reflects unresponsiveness induced by propofol or dexmedetomidine, suggesting its utility in monitoring the anaesthetised state with these agents. inical trial registrationCC BY-NC-ND. 4.0</p