AimTo compare the pharmacokinetics/pharmacodynamics, antibiotic resistance and clinical efficacy of continuous (CA) vs. intermittent administration (IA) of cefotaxime in patients with obstructive pulmonary disease and respiratory infections. MethodsA randomized controlled prospective nonblinded study was per formed in 93 consecutive hospitalized patients requiring antibiotics for acute exacerbations of chronic obstructive pulmonary disease. Forty-seven patients received 2 g of cefotaxime intravenously over 24 h plus a loading dose of 1 g, and 46 patients were given the drug intermittently (1 g three times daily). ResultsSimilar pathogens were identified in both groups, being mostly Haemophilus influenzae (51%), Streptococcus pneumoniae (21%) and Moraxella catharralis (18%). Mean minimal inhibitory concentration (MIC) values were also similar before and after treatment in both groups. Clinical cure was achieved in 37/40 (93%) (CA) vs. 40/43 (93%) (IA) of patients ( P = 0.93). In microbiologically evaluable patients, criteria such as 70% of treatment time with antibiotic concentrations ≥ MIC (CA 100% vs. IA 60% of patients) and/or ≥ 5 × MIC (CA 100% vs. IA 55% of patients) were significantly better following continuous administration ( P < 0.01). Samples with suboptimal antibiotic concentrations were found in 0% of CA vs. 65% of IA patients ( P < 0.01). ConclusionsAlthough clinical cure rates were comparable, continuous cefota xime administration led to significantly greater proportions of concentrations > MIC and > 5 × MIC compared with intermittent dosing. Continuous administration of cefota xime at a lower dose [2 g (CA) vs. 3 g (CI)] is equally effective pharmacodynamically and microbiologically, may be more cost-effective and offers at least the same clinical efficacy. Based on these observations, we recommend continuous administration of cefotaxime as the preferred mode of administration. Continuous vs. intermittent cefotaxime infusion in COPDBr J Clin Pharmacol 63 :1 101

SummaryAcute Physiology and Chronic Health Evaluation (APACHE) II scoring is widely used as an index of illness severity, for outcome prediction, in research protocols and to assess intensive care unit performance and quality of care. Despite its widespread use, little is known about the reliability and validity of APACHE II scores generated in everyday clinical practice. We retrospectively re-assessed APACHE II scores from the charts of 186 randomly selected patients admitted to our medical and surgical intensive care units. These`new' scores were compared with the original scores calculated by the attending physician. We found that most scores calculated retrospectively were lower than the original scores; 51% of our patients would have received a lower score, 26% a higher score and only 23% would have remained unchanged. Overall, the original scores changed by an average of 6.4 points. We identified various sources of error and concluded that wide variability exists in APACHE II scoring in everyday clinical practice, with the score being generally overestimated. Accurate use of the APACHE II scoring system requires adherence to strict guidelines and regular training of medical staff using the system. [4] are used widely in most intensive care units (ICUs). They are used not only as an index of illness severity and outcome prediction, but also to assess clinical performance and quality of care [5, 6]. The APACHE II score is the most frequently used scoring system and has become an important tool in efforts to improve effective use of intensive care [7±11]. In addition, it is often used in research protocols to ascertain that different treatment groups are comparable.Despite its widespread use in ICUs, little is known about the reliability and validity of the APACHE II scoring system in everyday medical practice. We reported that there was wide interobserver variation in the application of the APACHE II score when a group of doctors (residents and intensivists) assessed the same patient [12]. Chen et al.[13] studied interobserver variability and variability in data collection in a number of community and teaching hospitals; they reported that revised mortality predictions were similar to the original [13]. However, their study did not discuss in detail the specific sources of error and problems in APACHE II scoring.This study was designed to: (i) assess the accuracy of APACHE II scoring in a medical and surgical ICU; (ii) assess the influence of the method of data collection, manual or via a patient data management system (PDMS), on accuracy and overall variability in scoring; (iii) specifically identify and discuss sources of error and q 2001 Blackwell Science Ltd 47 confusion; and (iv) provide suggestions on how to decrease variability. MethodsThe charts of 64 patients admitted to the medical ICU and 122 patients admitted to the surgical ICU over a 6-month period were randomly selected. APACHE II scores are assessed routinely in all patients admitted to the ICU within 2 days of admission. In the medical ICU...

The effects of fenoldopam (FD), a selective dopamine -1 (DA1) agonist in doses from 0.05 to 0.50 μg/ kg/min and of the aselective dopamine antagonist metoclopramide (MCP) on blood pressure (BP), sodium excretion and renal hemodynamics were investigated in 10 healthy volunteers. During FD infusion the diastolic BP fell 9 mm Hg with a rise in heart rate. During combined infusion of FD and MCP no changes in BP occurred. Effective renal plasma flow rose for all doses of FD with a maximal increase of 36% and was not influenced by MCP infusion. Glomerular filtration rate remained unchanged. FD induced an increase in sodium and calcium excretion compared to placebo study, which was abolished by MCP. A marked rise of plasma renin activity during FD infusion was noted, blunted by MCP. MCP induced a marked increase of aldosterone, sustained, but blunted, during subsequent FD infusion, suggesting a DA1-mediated influence on aldosterone secretion. During infusion of FD alone, an increased urinary dopamine excretion was observed. We conclude that FD induces: (1) systemic and renal vasodilation and (2) natriuresis by direct stimulation of DA1 receptors in the proximal tubule, which is (partially) counteracted by a rise of plasma renin activity and subsequently of aldosterone.

Hyperthermic isolated limb perfusion with recombinant TNF-alpha leads to high systemic concentrations of TNF-alpha, probably due to leakage of recombinant TNF-alpha from the perfusion circuit, mainly through collateral blood flow. A sepsis-like syndrome is seen in all patients. Despite high concentrations of systemic TNF-alpha, this sepsis syndrome is short-lived and recovery is rapid and complete in most patients.