Fluconazole dosing in continuous veno-venous haemofiltration (CVVHF): need for a high daily dose of 800 mg

To cover intermediate sensitive Candida glabrata in ICU patients,fluconazole plasma peak levels at least in the range of 16–32µg/ml appear necessary for treatment. Previous studiesdid not reach these fluconazole levels under continuous veno-venoushaemofiltration (CVVHF) with dosages of 200–600 mg fluconzoledaily. In the present study, nine patients simultaneously requiringCVVHF for treatment of acute oligoanuric renal failure and antimycotictherapy of Candida septicemia received fluconazole 800 mg/day.Fluconazole plasma levels were determined to evaluate whetherthis dosage is adequate to reach the advised fluconazole levels.Patients were dialysed on two consecutive days with an ultrafiltrationrate (UF) of 1000 ml/h or 2000 ml/h, respectively, in a randomizedorder. The predilution was 800 ml/h and 1800 ml/h, respectively.The treatment was tolerated without adverse effects. All patientsreached plasma fluconazole concentrations between 16 and 32µg/ml, remaining in this range for a minimum of 1 up to24 h with a mean of 9.6 h and a UF rate of 2000 ml/h, and 15.7h with a UF rate of 1000 ml/h. So far, there are no in vivodata on the fluconazole plasma concentrations required for effectivetreatment. However, our data demonstrate, that at least thefluconazole concentrations desirable on the basis of in vitrosusceptibility testing can be reached in critically ill patientson CVVHF in an ICU setting. However, in these patients, 800mg fluconazole/day are necessary to achieve fungicidal drugconcentrations.     

Update on the management of neuromuscular block: focus on sugammadex

Steroidal neuromuscular blocking agents (NMBAs), such as rocuronium, are widely used in clinical anesthesia and emergency medicine to facilitate endotracheal intubation and artificial ventilation and to allow surgical access to body cavities. Reversal of neuromuscular blockade is important for the acceleration of patient recovery and prevention of postoperative residual neuromuscular blockade and reduces the incidence of severe morbidity and mortality associated with anesthesia management. Sugammadex is the first selective relaxant binding agent (SRBA) and has been designed to reverse the steroidal neuromuscular blocking drug rocuronium. Encapsulation of the rocuronium molecule by sugammadex results in a rapid decrease in free rocuronium in the plasma and subsequently at the nicotinic receptor at the motor endplate. After encapsulation, rocuronium is not available to bind to the nicotinic receptor in the neuromuscular junction. This promotes the liberation of acetylcholine receptors, and muscle activity reappears. This new concept of reversal of neuromuscular block induced by rocuronium (or vecuronium) led to impressive results in animal and phase 1 and 2 studies. Sugammadex is currently in phase 3 clinical studies and may be commercially available by 2008.     

Chirurgisches Konzept und Ergebnisse bei nekrotisierender Fasziitis

BACKGROUND: Necrotizing fasciitis (NF) is still a source of high morbidity and mortality. These difficult cases are increasingly referred to burn centers due to special wound and critical care issues. Here we examine our institution's recent experience with a large series of NF. METHOD: We performed a retrospective chart review of 32 consecutive patients over a 10-year period with NF who required radical surgical debridement and surface reconstruction. RESULTS: Overall survival was 85%, with average length of stay of 74.0+/-7.5 days for survivors (S) and 68.8+/-6.3 days for nonsurvivors (NS) (P>0.05). Time until first operation was 5.2 days in S and 3.4 days in NS (P<0.05). Patient age averaged 51.1+/-11.2 years for S and 57.0+/-12.0 years for NS (P<0.05). Survivors averaged 1.6 relevant comorbidities and NS averaged 3.6 (P<0.05). Affected total body surface (TBS) per patient averaged 6.8+/-3.3% for S and 10.2+/-5.1% for NS (P<0.05). All NS had affection of the trunk, and none of the patients with exclusive affection of extremities died. CONCLUSIONS: There were frequent delays in diagnosis and referrals to our institution, and progress can be made in educating the medical community to identify these patients. Not only the affected TBS and location but also comorbidities, age, and immediate surgical treatment are important prognostic factors. Referral to a specialized facility such as a burn center is urgently recommended for optimal surgical intervention, wound care, and critical care management.     

Hyperthermic therapy procedures for supplementing radiotherapy of malignant intraocular tumors

Since more than a century ago, temperatures above 40 degrees C have been known to be effective in cancer treatment. Since that time numerous studies have documented that hyperthermia alone causes tumor regression and that the therapeutic effect depends on the amount and duration of heat delivered to a malignant tumor. However, after it was shown that heat combined with irradiation or chemotherapy potentiates the effect of hyperthermia, both thermoradiotherapy and thermochemotherapy were applied in experimental and clinical studies in several medical specialties. In ophthalmic oncology both retinoblastoma and uveal melanoma are treated by irradiation combined with local hyperthermia. In the present paper the use of ultrasound and microwave energy as locally applicable heat sources in intraocular malignancies is described and their suitability discussed. As is the case with malignant skin tumors and malignant tumors of the gastrointestinal and urogenital systems, malignant ocular tumors are accessible to externally applied heat and can thus be treated well by ultrasound and microwave hyperthermia. On the basis of experimental and clinical results gained with both ultrasound and microwave energy the advantages and drawbacks of these two technical modalities in intraocular tumor therapy are pointed out.     

Echographic findings in metastization in an extraocular muscle

Clinical, echographic, radiological (CT, NMR), and histopathological findings in a 57-year-old male patient who presented with proptosis of the left eye and diplopia caused by a histologically proven metastasis of a clinically silent small-cell carcinoma of the lung. Echographic problems of the differential diagnosis of orbital metastases are discussed.     

Incompatibility of contrast agents with intravascular medications. Work in progress

In vitro and in vivo precipitation of iodinated contrast agents when ioxaglate and papaverine are given together has been reported. To verify these reports and to investigate other medications not previously tested, the authors analyzed mixtures of contrast agents and medications in vitro with a light spectrophotometer and observed them for visible precipitates for up to 120 minutes. Previously reported incompatibilities between ionic or low-osmolality contrast media and medications were verified, and several new incompatibilities were discovered. No incompatibilities were found when the drugs tested were mixed with the new nonionic contrast media.     

Der unbekannte akute kindliche Schiefhals 3 F?lle von Grisel-Syndrom 3 F?lle von Grisel-Syndrom

Das nach Grisel benannte Syndrom ist offenbar eine nicht so seltene Komplikation, wie gemeinhin angenommen. Der Verlauf dreier F?lle, das Literaturstudium und pathophysiologisch-biomechanische überlegungen lassen an eine hohe Dunkelziffer denken. Leitsymptom scheint ein ausgedehntes ?dem im Bereich der oberen Halswirbels?ule zu sein. Das ?dem kann verschiedene Ursachen haben. Flie?ende überg?nge zwischen banalen Entzündungsvorg?ngen im Bereich der Weichteile der oberen Halswirbels?ule bis hin zu Subluxationen von Atlas und/oder Axis suggerieren, dass die frühzeitige konservative Therapie zur Vermeidung chirurgischer Interventionen essentiell ist. Es drohen ernste, irreversible Deformit?ten des wachsenden Skeletts und neurologische Komplikationen. Vor manualmedizinischen Behandlungsversuchen wird auch anhand eines Beispiels gewarnt.     

Cellular kinetics of prednimustine versus chlorambucil plus prednisolone in vitro

Summary Intracellular concentrations of prednimustine (PM), chlorambucil (CLB), phenylacetic acid mustard (PAAM) and prednisolone (P) were measured in different experimental tumor cell lines that had been incubated with either PM or CLB+P. For intracellular analytical determination, we modified a high-pressure liquid chromatographic method for the detection of these substances in plasma. Intact PM could be detected in the intracellular compartment of the incubated tumor cells. PM-incubated cells from PM-injected rats exhibited a higher intracellular concentration-time integral (PAAM) and longer concentration-time profiles for drugs with alkylating capacity than did cells exposed to the CLB+P mixture or to CLB. PAAM was not detectable after incubation of cells with PM, whereas in CLB-incubated cells the AUC of PAAM exceeded that of the parent drug CLB. Our in vitro results therefore favour the concept of a facilitated intracellular uptake and an increased antiproliferative effect for PM versus CLB and CLB+P.Dedicated to Prof. Dr. H. J. Dengler on the occasion of his 65th birthday. This study was supported by the Ministry of Science and Research of Nordrhein-Westfalen