Concentrations of Cefuroxime in Brain Tissue of Neurointensive Care Patients.

Effective concentrations of antibiotics in brain tissue are essential for antimicrobial therapy of brain infections. However, data concerning cerebral penetration properties of antibiotics for treatment or prophylaxis of central nervous system infections are rare. Six patients suffering subarachnoid hemorrhage and requiring cerebral microdialysis for neurochemical monitoring were included in this study. Free interstitial concentrations of cefuroxime after intravenous application of 1,500 mg were measured by microdialysis in brain tissue, as well as in plasma at steady-state (n = 6) or after single-dose administration (n = 1). At steady state, free area under the concentration-time curve from 0 to 24 h (AUC0-24) values of 389.0 ± 210.3 mg/liter·h and 131.4 ± 72.8 mg/liter·h were achieved for plasma and brain, respectively, resulting in a brain tissue penetration ratio (AUC0-24 brain/AUC0-24 free plasma) of 0.33 ± 0.1. Plasma and brain tissue concentrations at individual time points correlated well (R = 0.59, P = 0.001). At steady-state time over MIC (t>MIC) values of >40% of dosing interval were achieved up to an MIC of 16 mg/liter for plasma and 4 mg/liter for brain tissue. Although MIC90 values could not be achieved in brain tissue for relevant bacteria, current dosing strategies of cefuroxime might be sufficient to treat pathogens with MIC values up to 4 mg/liter. The activity of cefuroxime in brain tissue might be overestimated when relying exclusively on plasma levels. Although currently insufficient data after single dose administration exist, lower brain-plasma ratios observed after the first dose might warrant a loading dose for treatment and perioperative prophylaxis.

Cerebral and Peripheral Metabolism to Predict Successful Reperfusion After Cardiac Arrest in Rats: A Microdialysis Study.

BACKGROUND: In clinical practice, monitoring of the efficacy of resuscitation can be challenging. The prediction of cerebral and overall outcome in particular is an unmet medical need. Microdialysis is a minimally invasive technique for the continuous determination of metabolic parameters in vivo. Using this technique, we set out to establish a model allowing for concomitant determination of cerebral and peripheral metabolism in a cardiac arrest setting in rodents. METHODS: Microdialysis settings were optimized in vitro and then used in male Sprague-Dawley rats. Probes were implanted into the CA1 region of the right hippocampus and the right femoral vein. With a time interval of 8 min, glucose, lactate, pyruvate, and glutamate levels were determined during baseline conditions, untreated ventricular fibrillation cardiac arrest, cardiopulmonary resuscitation (CPR), reperfusion, and death. RESULTS: In 16 rodents, restoration of spontaneous circulation was achieved in seven animals. Characteristic metabolic changes were evident during cardiac arrest and reperfusion with both probes. Ischemic patterns in peripheral compartments were delayed and more variable compared to the changes in cerebral metabolism highlighting the importance of cerebral metabolic monitoring. Microdialysis allowed distinguishing between survivors and non-survivors 8 min after termination of CPR. Cerebral glutamate showed a trend toward higher levels in non-survivors during CPR. CONCLUSIONS: We established a new rodent model for research in hypoxic ischemic encephalopathy. This setting allows to investigate the impact of resuscitation methods on cerebral and peripheral metabolism simultaneously. The present model may be used to evaluate different resuscitation strategies in order to optimize brain survival in future studies.

Applicability of NeuroTrend as a bedside monitor in the neuro ICU.

OBJECTIVE: To assess whether ICU caregivers can correctly read and interpret continuous EEG (cEEG) data displayed with the computer algorithm NeuroTrend (NT) with the main attention on seizure detection and determination of sedation depth. METHODS: 120 screenshots of NT (480h of cEEG) were rated by 18 briefly trained nurses and biomedical analysts. Multirater agreements (MRA) as well as interrater agreements (IRA) compared to an expert opinion (EXO) were calculated for items such as pattern type, pattern location, interruption of recording, seizure suspicion, consistency of frequency, seizure tendency and level of sedation. RESULTS: MRA as well as IRA were almost perfect (80-100%) for interruption of recording, spike-and-waves, rhythmic delta activity and burst suppression. A substantial agreement (60-80%) was found for electrographic seizure patterns, periodic discharges and seizure suspicion. Except for pattern localization (70.83-92.26%), items requiring a precondition and especially those who needed interpretation like consistency of frequency (47.47-79.15%) or level of sedation (41.10%) showed lower agreements. CONCLUSIONS: The present study demonstrates that NT might be a useful bedside monitor in cases of subclinical seizures. Determination of correct sedation depth by ICU caregivers requires a more detailed training. SIGNIFICANCE: Computer algorithms may reduce the workload of cEEG analysis in ICU patients.

Effect of primary bile acids on bile lipid secretion from perfused dog liver.

An isolated canine liver perfusion technique featuring a second dog as the pump oxygenator was used to compare biliary lipid secretion during randomized, steady-state perfusions at two different rates of cholyl taurine or chenodeoxycholyl taurine infusions. The hepatic extraction of the trihydroxy-conjugated bile acid was considerably greater than that of the dihydroxy conjugate, possibly explained by ultrafiltration experiments which indicated that cholyl taurine was less protein bound than chenodeoxycholyl taurine. Both bile acids induced phospholipid and cholesterol secretion that was linearly proportional to bile acid secretion. However, each mole of secreted chenodeoxycholyl taurine induced a greater relative secretion of phospholipid and cholesterol than did that of cholyl taurine. Thus in the canine liver, the two primary bile acids are extracted at different rates and induce biliary secretion of different relative lipid composition.