A common endpoint of general anesthetics is behavioral unresponsiveness, which is commonly associated with loss of consciousness. However, subjects can become disconnected from the environment while still having conscious experiences, as demonstrated by sleep states associated with dreaming. Among anesthetics, ketamine is remarkable in that it induces profound unresponsiveness, but subjects often report "ketamine dreams" upon emergence from anesthesia. Here, we aimed at assessing consciousness during anesthesia with propofol, xenon, and ketamine, independent of behavioral responsiveness. To do so, in 18 healthy volunteers, we measured the complexity of the cortical response to transcranial magnetic stimulation (TMS)--an approach that has proven helpful in assessing objectively the level of consciousness irrespective of sensory processing and motor responses. In addition, upon emergence from anesthesia, we collected reports about conscious experiences during unresponsiveness. Both frontal and parietal TMS elicited a low-amplitude electroencephalographic (EEG) slow wave corresponding to a local pattern of cortical activation with low complexity during propofol anesthesia, a high-amplitude EEG slow wave corresponding to a global, stereotypical pattern of cortical activation with low complexity during xenon anesthesia, and a wakefulness-like, complex spatiotemporal activation pattern during ketamine anesthesia. Crucially, participants reported no conscious experience after emergence from propofol and xenon anesthesia, whereas after ketamine they reported long, vivid dreams unrelated to the external environment. These results are relevant because they suggest that brain complexity may be sensitive to the presence of disconnected consciousness in subjects who are considered unconscious based on behavioral responses.

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Cardiac surgery using cardiopulmonary bypass resulted in a profound intraoperative decrease of whole blood levels of antioxidant trace elements. Low selenium concentrations at end of surgery were an independent predictor for the postoperative development of multiorgan failure.

In cardiac surgery, postoperative low cardiac output has been shown to correlate with increased rates of organ failure and mortality. Catecholamines have been the standard therapy for many years, although they carry substantial risk for adverse cardiac and systemic effects, and have been reported to be associated with increased mortality. On the other hand, the calcium sensitiser and potassium channel opener levosimendan has been shown to improve cardiac function with no imbalance in oxygen consumption, and to have protective effects in other organs. Numerous clinical trials have indicated favourable cardiac and non-cardiac effects of preoperative and perioperative administration of levosimendan. A panel of 27 experts from 18 countries has now reviewed the literature on the use of levosimendan in on-pump and off-pump coronary artery bypass grafting and in heart valve surgery. This panel discussed the published evidence in these various settings, and agreed to vote on a set of questions related to the cardioprotective effects of levosimendan when administered preoperatively, with the purpose of reaching a consensus on which patients could benefit from the preoperative use of levosimendan and in which kind of procedures, and at which doses and timing should levosimendan be administered. Here, we present a systematic review of the literature to report on the completed and ongoing studies on levosimendan, including the newly commenced LEVO-CTS phase III study (NCT02025621), and on the consensus reached on the recommendations proposed for the use of preoperative levosimendan.

BackgroundThe α2-adrenoreceptor agonist dexmedetomidine is known to provide neuroprotection under ischemic conditions. In this study we investigated whether dexmedetomidine has a protective effect in an in vitro model for traumatic brain injury.MethodsOrganotypic hippocampal slice cultures were subjected to a focal mechanical trauma and then exposed to varying concentrations of dexmedetomidine. After 72 h cell injury was assessed using propidium iodide. In addition, the effects of delayed dexmedetomidine application, of hypothermia and canonical signalling pathway inhibitors were examined.ResultsDexmedetomidine showed a protective effect on traumatically injured hippocampal cells with a maximum effect at a dosage of 1 μM. This effect was partially reversed by the simultaneous administration of the ERK inhibitor PD98059.ConclusionIn this TBI model dexmedetomidine had a significant neuroprotective effect. Our results indicate that activation of ERK might be involved in mediating this effect.

Levosimendan is a positive inotrope with vasodilating properties (inodilator) indicated for decompensated heart failure (HF) patients with low cardiac output. Accumulated evidence supports several pleiotropic effects of levosimendan beyond inotropy, the heart and decompensated HF. Those effects are not readily explained by cardiac function enhancement and seem to be related to additional properties of the drug such as anti-inflammatory, anti-oxidative and anti-apoptotic ones. Mechanistic and proof-of-concept studies are still required to clarify the underlying mechanisms involved, while properly designed clinical trials are warranted to translate preclinical or early-phase clinical data into more robust clinical evidence. The present position paper, derived by a panel of 35 experts in the field of cardiology, cardiac anesthesiology, intensive care medicine, cardiac physiology, and cardiovascular pharmacology from 22 European countries, compiles the existing evidence on the pleiotropic effects of levosimendan, identifies potential novel areas of clinical application and defines the corresponding gaps in evidence and the required research efforts to address those gaps.

Eudra CT: 2014-001499-73; 31/7/2014.

Acute kidney injury (AKI) represents the most frequent complication after cardiac surgery. Macrophage migration inhibitory factor (MIF) is a stress-regulating cytokine that was shown to protect the heart from myocardial ischemia-reperfusion injury, but its role in the pathogenesis of AKI remains unknown. In an observational study, serum and urinary MIF was quantified in 60 patients scheduled for elective conventional cardiac surgery with the use of cardiopulmonary bypass. Cardiac surgery triggered an increase in MIF serum concentrations, and patients with high circulating MIF (>median) 12 hours after surgery had a significantly reduced risk of developing AKI (relative risk reduction, 72.7%; 95% confidence interval, 12 to 91.5%; = 0.03). Experimental AKI was induced in wild-type and mice by 30 min of ischemia followed by 6 or 24 hours of reperfusion, or by rhabdomyolysis. -deficient mice exhibited increased tubular cell injury, increased regulated cell death (necroptosis and ferroptosis), and enhanced oxidative stress. Therapeutic administration of recombinant MIF after ischemia-reperfusion in mice ameliorated AKI. In vitro treatment of tubular epithelial cells with recombinant MIF reduced cell death and oxidative stress as measured by glutathione and thiobarbituric acid reactive substances in the setting of hypoxia. Our data provide evidence of a renoprotective role of MIF in experimental ischemia-reperfusion injury by protecting renal tubular epithelial cells, consistent with our observation that high MIF in cardiac surgery patients is associated with a reduced incidence of AKI.