[Guideline 'Precautionary measures for contrast media containing iodine']. / Richtlijn 'Voorzorgsmaatregelen bij jodiumhoudende contrastmiddelen'.

Annually, 0.5-1 million injections of contrast media containing iodine are administered in the Netherlands. Almost all contrast media nowadays are low-osmolar and nonionic. Nevertheless, the development ofcontrast-induced nephropathy is still a relevant clinical problem. Through an initiative by the Radiological Society of the Netherlands and with aid of the Dutch Institute for Healthcare Improvement (CBO), a guideline was conceived for the intravascular use of iodine-containing contrast media, based on recent scientific literature. The guideline defines the risk factors for contrast-induced nephropathy. One of the major risk factors is an impaired renal function. It is important to measure the glomerular filtration rate (GFR) in patients with a possible impaired kidney function, preferably by using the 'Modification of diet in renal disease' (MDRD)-study formula. The key measures for avoidance of contrast nephropathy are: limiting the amount of contrast agent used and to assure good hydration, by infusion of sodium chloride 0.9% 12-16 ml/kg body weight, both prior to and after contrast infusion. If time is limited, intravenous administration of sodium bicarbonate is an option. The guideline recommends discontinuation of metformin use from the day of contrast injection, if the GFR < 60 ml/min/1.73 m2, and to restart metformin 2 days following contrast infusion providing the GFR has not significantly deteriorated. Only in the case of previous moderate or severe adverse reactions to contrast media, prophylaxis with corticosteroids and antihistamines is recommended. Iodine allergy or an atopic condition is not a contraindication for the use of iodine-containing contrast media, and no prophylaxis is required. No specific measures are indicated in case of hyperthyroidism, acute pancreatitis, or phaeochromocytoma. Injection of contrast media is not contraindicated in case of pregnancy or lactation.

Absorption kinetics and pharmacodynamics of two oral dosage forms of flecainide in patients with an episode of paroxysmal atrial fibrillation.

OBJECTIVES: The objectives were to study the absorption kinetics and pharmacodynamics of two oral formulations of flecainide in patients with atrial fibrillation (AF) and to assess the relationship between pharmacokinetic parameters and the efficacy in restoring sinus rhythm. METHODS: The data of 54 patients included in a randomised, open, parallel-group study were used. Patients received an oral solution containing 300 mg flecainide and 20 mg cisapride or three tablets each containing 100 mg flecainide. The pharmacokinetic profile of flecainide was fitted using a one-compartment model with lag-time and first-order absorption. RESULTS: The tablets gave a maximum concentration (C (max\ fit)) of 0.43+/-0.14 mg/l at 2.37+/-1.20 h. The oral solution resulted in a much faster peak concentration at 1.05+/-0.71 h (P<0.0001). The C (max\ fit) of the oral solution of 0.60+/-0.17 mg/l was higher (P=0.0002) than that of the tablets, and interindividual variabilities of C (max\ fit) were 28% and 33%, respectively. The absorption rate constant (ka) of the oral solution was twofold larger (P<0.0001). A higher ka (P=0.04) and a duration of AF less than 24 h (P=0.006) increased the probability of cardioversion. If atrial fibrillation lasted less than 24 h, only ka (P=0.016) was obtained as a significant variable in multivariate analysis. The linear models of QRS interval changes versus flecainide concentrations of both formulations had similar slopes with similar interindividual variabilities. CONCLUSIONS: The probability of cardioversion after an oral loading dose of flecainide in patients with AF is dependent on ka. Rapid loading of the effect compartment, i.e. the atria, appears to be critical to reach cardioversion. Higher flecainide serum concentrations and a more rapid absorption does not increase interindividual variability of pharmacokinetics and pharmacodynamics, which is important when safety is considered.

Surgical site infections in orthopedic surgery: the effect of mupirocin nasal ointment in a double-blind, randomized, placebo-controlled study.

The objective of this study was to determine whether use of mupirocin nasal ointment for perioperative eradication of Staphylococcus aureus nasal carriage is effective in preventing the development of surgical site infections (SSIs). A randomized, double-blind, placebo-controlled design was used. Either mupirocin or placebo nasal ointment was applied twice daily to 614 assessable patients from the day of admission to the hospital until the day of surgery. A total of 315 and 299 patients were randomized to receive mupirocin and placebo, respectively. Eradication of nasal carriage was significantly more effective in the mupirocin group (eradication rate, 83.5% versus 27.8%). In the mupirocin group, the rate of endogenous S. aureus infections was 5 times lower than in the placebo group (0.3% and 1.7%, respectively; relative risk, 0.19; 95% confidence interval, 0.02-1.62). Mupirocin nasal ointment did not reduce the SSI rate (by S. aureus) or the duration of hospital stay.

Ascorbic acid prevents cimetidine-induced decrease of serum hydrocortisone concentrations.

A blind, parallel, prospective, clinical study was conducted to investigate the effect of ascorbic acid on human serum hydrocortisone concentrations which were decreased by the administration of cimetidine. The study population included 16 male adults scheduled for major abdominal vascular surgery. The study was conducted in surgical patients under anaesthesia, in which steroidogenesis was inhibited by cimetidine. The results showed a reduction in serum hydrocortisone concentrations in patients receiving a placebo. In patients receiving ascorbic acid, there was a significant increase in serum hydrocortisone concentration. This reflects the normal serum hydrocortisone profile for this operation and anaesthetic technique. Cimetidine can bind to cytochrome P-450 covering the active haem group, the cytochrome proves to be of vital importance for hydroxylation reactions, involved in human steroidogenesis. Serum hydrocortisone concentrations will decrease when cytochrome P-450 becomes blocked. Intravenous administration of ascorbic acid was supposed to cause relief for this decrease. The reasons are undetermined yet. This investigation proved that ascorbic acid can prevent cimetidine-induced decrease of human serum hydrocortisone concentrations.