Simvastatin-fluconazole causing rhabdomyolysis

OBJECTIVE: To report a case of rhabdomyolysis after concomitant use of simvastatin, a commonly used hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, and fluconazole, an azole antifungal agent. CASE SUMMARY: An 83-year-old white man with a history of congestive heart failure and hyperlipidemia presented to the hospital 1 week following the addition of fluconazole to a medication regimen that included simvastatin 40 mg once daily. The patient had severe muscle weakness and a markedly elevated serum creatine kinase activity, which resolved following discontinuation of simvastatin and fluconazole. DISCUSSION: Rhabdomyolysis is a recognized adverse effect of HMG-CoA reductase inhibitors (statins), commonly caused by their interaction with other drugs, such as azole antifungals, that inhibit the cytochrome P450 isoenzyme family. An objective causality assessment revealed that the adverse drug event was probable. Although drug interactions have been described for combinations of other HMG-CoA reductase inhibitors and azole antifungals, rhabdomyolysis likely caused by the interaction between simvastatin and fluconazole has not yet been reported. This case reinforces the importance of being vigilant for drug interactions, particularly in connection with commonly prescribed medications such as statins. CONCLUSIONS: Patients receiving statins who have cancer may receive azole antifungals and other drugs that inhibit CYP3A4 during treatment, predisposing them to toxicity. These patients should therefore be monitored closely for drug interactions.     

Choledochal cysts in children: evaluation with three-dimensional sonography

In this report, we describe the application of 3-dimensional (3D) sonography for diagnosing choledochal cysts in 3 girls who were 18 months, 2 years, and 11 years old. The 3D images that were obtained during the sonographic examination revealed that all 3 patients had a type I choledochal cyst and also demonstrated dilatation of the biliary tracts. The 3 patients then underwent surgical excision of their cysts, cholecystectomy, and hepaticojejunostomy. Besides its other clinical applications, 3D sonography promises to be a valuable adjunct to conventional 2-dimensional imaging for the evaluation of choledochal cysts in pediatric patients.     

Measurement of respiratory function: gas exchange and its clinical applications

Gas exchange is the main function of the lungs. Lungs have a large reserve for gas exchange. Oxygen and carbon dioxide diffuse along their partial pressure gradient across the alveolar–capillary membrane. Alveolar ventilation and pulmonary circulation are closely matched to provide efficient gas exchange in the lungs. Hypoxaemia often results from mismatch in ventilation–perfusion. Gas exchange can be impaired in various disease states. Measurement of the diffusing capacity for carbon monoxide (DLCO) provides estimation of the gas exchange function. A low DLCO indicates an impairment of oxygen transfer across the alveolar–capillary membrane. Based on the lung function tests one can assess the risks of perioperative pulmonary complications. Anaesthesia and surgery adversely affect pulmonary function, many of which adverse effects can be prevented.     

The effects of atorvastatin treatment on the fibrinolytic system in dyslipidemic patients

Statins have pleiotrophic effects related to the pathogenesis of atherosclerosis and thrombogenicity of the vessel wall beyond lipid lowering. The aim of the present study was to examine the effect of atorvastatin treatment on the fibrinolytic system in patients with dyslipidemia. The investigation was carried out on 41 dyslipidemic patients (21 males and 20 females) with a mean age of 53.8 years (range, 30-76). The patients were divided into subgroups according to their cholesterol and triglyceride levels as hypercholesterolemic (n = 26) and mixed-type hyperlipidemic (n = 15) and their risk factors for coronary heart disease including age, sex, hypertension, obesity, smoking, and family history. The patients were started on atorvastatin 10 mg/day, and evaluated within 6-12 weeks to assess the changes in fibrinolytic parameters including global fibrinolytic capacity, plasminogen activator inhibitor type-1 and tissue plasminogen activator, and lipids. After successful lipid-lowering therapy, global fibrinolytic capacity (P = 0.003) and tissue plasminogen activator levels (P = 0.04) were found to be increased and plasminogen activator inhibitor type-1 levels (P = 0.02) decreased in dyslipidemic patients. Global fibrinolytic capacity levels increased (P < 0.001) and plasminogen activator inhibitor type-1 levels decreased (P = 0.01) in patients with hypercholesterolemia (n = 26). However, no significant changes were observed in fibrinolytic parameters in patients with mixed-type hyperlipidemia (n = 15). When the patients were separately evaluated according to risk factors, significant beneficial effects on the fibrinolytic system were observed, especially in patients without obesity and hypertension as well as in older patients and males. These findings suggest that atorvastatin treatment has a beneficial effect on the fibrinolytic system in patients with hypercholesterolemia, but not in patients with mixed-type hyperlipidemia. Further studies are needed to show whether higher doses and longer periods of lipid lowering treatment have beneficial effects in patients with mixed type hyperlipidemia and some risk factors.     

The Effects of Two Different Anaesthesia Techniques on Bispectral Index Values and Awareness During Off-Pump Coronary Artery Bypass Grafting

Objective. The aim of this study was to evaluate Bispectral Index values and awareness during two different anaesthesia regimens (fentanyl-propofol and fentanyl-midazolam) in patients undergoing off-pump CABG surgery. Methods. Fifty patients were included in the study. Patients were premedicated with midazolam and were randomly divided into two groups. Anaesthesia was induced with fentanyl (7–15 μg/kg), with either propofol (2–2.5 mg/kg, Group I) or midazolam (0.1–0.3 mg/kg, Group II) and vecuronium (0.1 mg/kg). Anaesthesia was maintained with fentanyl (15 μg/kg/h) together with either propofol (6 mg/kg/h) or midazolam (0.1 mg/kg/h). Depth of anaesthesia was adjusted according to clinical signs and haemodynamic responses. The level of sedation was monitored with Bispectral index continuously, but these levels were not shown to the attending anaesthetist. Bispectral index values were recorded for nine phases. Twenty-four hours after the operation, the patients were interviewed to determine intraoperative awareness and recall. Results. In all patients, Bispectral index values were found to decrease after induction (in Group I, p = 0.005, in Group II, p = 0.008) with the mean values remaining below 60 for all phases. The differences between the groups were not statistically significant in inter-group comparison. No patients were noted to recall the sounds presented during the operation and the preoperative events. Conclusions. BIS monitoring with clinical signs may be used to assess the adequacy of both types of anaesthesia techniques as well as to detect awareness during off-pump CABG surgery.