Background: Patients who are going thorugh mechanical ventilation in the intensive care unit (ICU) often receive a high fraction of inspired oxygen (Fio2 ) and have a high arterial oxygen tension. The conservative use of oxygen may reduce oxygen exposure, diminish lung and systemic oxidative injury, and thereby increase the number of ventilator-free days (days alive and free from mechanical ventilation). Methods: We randomly assigned 1000 adult patients who were anticipated to require mechanical ventilation beyond the day after recruitment in the ICU to receive conservative or usual oxygen therapy. In the two groups, the default lower limit for oxygen saturation as measured by pulse oximetry (Spo2 ) was 90%. In the conservativeoxygen group, the upper limit of the Spo2 alarm was set to sound when the level reached 97%, and the Fio2 was decreased to 0.21 if the Spo2 was above the acceptable lower limit. In the usual-oxygen group, there were no specific measures limiting the Fio2 or the Spo2 . The primary outcome was the number of ventilatorfree days from randomization until day 28. Results: The number of ventilator-free days did not differ significantly between the conservative-oxygen group and the usualoxygen group, with a median duration of 21.3 days (interquartile range, 0 to 26.3) and 22.1 days (interquartile range, 0 to 26.2), respectively, for an absolute difference of −0.3 days (95% confidence interval [CI], −2.1 to 1.6; P=0.80). The conservativeoxygen group spent more time in the ICU with an Fio2 of 0.21 than the usual-oxygen group, with a median duration of 29 hours (interquartile range, 5 to 78) and 1 hour (interquartile range, 0 to 17), respectively (absolute difference, 28 hours; 95% CI, 22 to 34); the conservative-oxygen group spent less time with an Spo2 exceeding 96%, with a duration of 27 hours (interquartile range, 11 to 63.5) and 49 hours (interquartile range, 22 to 112), respectively (absolute difference, 22 hours; 95% CI, 14 to 30). At 180 days, mortality was 35.7% in the conservative-oxygen group and 34.5% in the usual-oxygen group, for an unadjusted odds ratio of 1.05 (95% CI, 0.81 to 1.37). Conclusions: In adults undergoing mechanical ventilation in the ICU, the use of conservative oxygen therapy, as compared with usual oxygen therapy, did not significantly affect the number of ventilator-free days.

Results with two different measurement technologies differed significantly for plasma sodium and chloride concentrations. These differences significantly affected the calculated AG and SID values and might lead clinicians to different assessments of acid-base and electrolyte status.

Summary: Purpose:We describe a sheep model of penicillininduced seizure activity using electroencephalography (EEG) and functional MRI (fMRI).Methods: Ten adult sheep were used. Spikes and seizures were generated by instillation of 8,000-10,000 IU of penicillin into the right prefrontal cortex via a specially designed port. Bilateral intracranial EEG was acquired by using carbon fiber electrodes. Animals had behavioral characterization of their seizures and were then anesthetized for fMRI studies. Functional MRI was performed at 1.5 and 3 Tesla by measuring blood oxygen level-dependent (BOLD) weighted signal intensity at different times during the evolution of seizures.Results: Behavioral seizures were associated with electrographic seizures. Intracranial EEG obtained in the MR scanner was of high quality. Focal spiking and seizures were seen in all animals and developed 11.3 ± 11.2 s and 17.3 ± 12.1 min after penicillin administration, respectively. An average of 13 ± 4.8 seizures were seen per animal, each lasting 27.3 ± 12.3 s. Functional MR images with little parenchymal artefact were obtained. Regional BOLD signal-intensity changes were observed during seizures at the seizure focus and ipsilateral amygdala.Conclusions: We have developed an animal model of partial epilepsy in which seizures can be reliably elicited with concurrent fMRI and intracranial EEG. During unilateral electrographic seizures, focal BOLD signal changes occurred at the seizure focus and ipsilateral amygdala, suggesting the presence of a cortico-subcortical loop. This observation illustrates the potential of the model for understanding seizure generation, spread, and possibly the consequences of repeated seizures on the brain. Key Words: EEG-Epilepsy-Functional MRIMagnetic resonance-Seizure models-Sheep.Seizures are associated with electrical discharges measured on the electroencephalogram (EEG) together with increased blood flow and oxygenation at the site of the epileptic focus (1-3). Functional magnetic resonance imaging (fMRI) shows increased signal intensity in areas of high blood flow due to a decrease in deoxyhemoglobin concentration, as detected by blood oxygen leveldependent (BOLD) contrast techniques (4). Sequential images can be rapidly obtained, giving fMRI the unique ability to provide good temporal and excellent spatial information. The response predictably follows neuronal activation, typically beginning after 3 s and peaking after ∼6 s (5-8). During seizures, however, the temporal relation between blood-flow changes, electrical discharges, and behavioral seizures is not understood. Indeed, BOLD signals may even precede the onset of electrographic seizures (9,10).Some attempts have been made to study seizures in humans with fMRI, but these reports are few and anecdotal, and none correlates EEG with the BOLD response (10,11). As seizures are not predictable and difficult to study in the MR system, imaging of interictal activity by EEG spike-triggered fMRI techniques has been developed (12-16). None of these studies, however...

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Background: High cut-off (HCO) membranes may increase β₂-microglobulin (β2M) removal compared to standard high-flux membranes.Methods:Eight stable haemodialysis patients were enrolled in a prospective, randomized, double-blind, cross-over study and treated with HCO and high-flux membranes for 2 weeks each, between a 1-week washout period. Primary end point was serum β2M removal. Secondary end points included serum albumin concentrations, albumin and small solute clearances. Results: HCO membranes achieved significantly lower median post-dialysis β2M concentration (10.8 vs. 14.2 mg/l; p = 0.003) and greater β2M reduction ratio (62.3 vs. 51.0%; p < 0.002). Serum albumin decreased with HCO membranes (from 36 to 29.5 g/l; p = 0.018) but increased to 33.5 g/l after the washout period. Albumin clearance was significantly greater with HCO membranes (2.2 vs. 0.06 ml/min; p = 0.004). Urea reduction ratio was significantly lower with HCO membranes (64.8 vs. 71.5%; p < 0.001). Conclusion: β2M removal was superior with HCO membranes. Reduction in serum albumin and lower small solute clearance require further investigations.

Purpose:The optimal ventilatory settings in patients after cardiac arrest and their association with outcome remain unclear. The aim of this study was to describe the ventilatory settings applied in the first 72 h of mechanical ventilation in patients after out-of-hospital cardiac arrest and their association with 6-month outcomes.Methods: Preplanned sub-analysis of the Target Temperature Management-2 trial. Clinical outcomes were mortality and functional status (assessed by the Modified Rankin Scale) 6 months after randomization.Results: A total of 1848 patients were included (mean age 64 [Standard Deviation, SD = 14] years). At 6 months, 950 (51%) patients were alive and 898 (49%) were dead. Median tidal volume (V T ) was 7 (Interquartile range, IQR = 6.2-8.5) mL per Predicted Body Weight (PBW), positive end expiratory pressure (PEEP) was 7 (IQR = 5-9) cmH 2 0, plateau pressure was 20 cmH 2 0 (IQR = 17-23), driving pressure was 12 cmH 2 0 (IQR = 10-15), mechanical power 16.2 J/min (IQR = 12.1-21.8), ventilatory ratio was 1.27 (IQR = 1.04-1.6), and respiratory rate was 17 breaths/minute (IQR = 14-20). Median partial pressure of oxygen was 87 mmHg (IQR = 75-105), and partial pressure of carbon dioxide was

Background and objectives It is unknown whether cytokine adsorption to the membrane during continuous renal replacement therapy is affected by the technique. Such knowledge might affect the choice of technique in vivo. Accordingly, we conducted an ex vivo study to test whether continuous veno-venous hemofiltration (CVVH) or continuous veno-venous hemodialysis (CVVHD) affect cytokine adsorption differently. Setting Laboratory attached to the Intensive Care Unit of a tertiary hospital Design Six healthy human volunteers donated blood, which was incubated with endotoxin. Control blood was left at room temperature, and treatment blood was recirculated for eight hours through closed circuits using polyacrylonitrile membranes (AN69). The effect of CVVH and CVVHD on cytokine removal from the circuits was compared. Measurements The concentrations of interleukins (IL)-1ß, 6, 8, 10 and TNF were measured in the control samples, pre-and post-filter and in the effluent at baseline and hourly thereafter. The clearances by adsorption, and filtration were calculated. Results Control cytokine concentrations remained the same or increased slightly. Adsorption was the major mechanism of removal for all cytokines with the exception of IL-1ß, but the effect was short-lived. Peak adsorption generally occurred at baseline before the start of CVVH and CVVHD, with clearances ranging from 43.7ml/min (for IL-8) to 7.6ml/min (for IL-10). The time-weighted average total clearances during CVVH were 23.3, 4.3, 3.8, –2.0, and 15ml/min for IL-8, IL-1ß, TNF, IL-6, and IL-10 respectively. The corresponding clearances during CVVHD were 19.0, 10.7, 2.7, 2.4, and 0.3ml/min. IL-10 clearances were greater during CVVH than CVVHD (p=0.03). Non adsorptive CVVH clearance of IL-1ß was greater than CVVHD clearance, but this advantage was outweighed by an increased tendency of the membrane to release IL-1ß into the circuit during HF. Conclusions The technique of solute removal had only a minor effect on the magnitude of cytokine adsorption, and neither technique had the advantage for all the measured cytokines.