Sevofluran: Metabolismus und Toxizität

The new inhalational anesthetic sevoflurane is biotransformed by approximately 5%. Serum fluoride concentrations resulting from transformation mainly depend on rate of hepatic defluorination, total amount of anesthetic given and the solubility of the volatile anesthetic, as expressed by its blood gas partition coefficient. Enflurane is metabolized by 5–11%. However subsequent peak fluoride levels are lower than after sevoflurane which is a consequence of its lower rate of hepatic defluorination. To date numerous studies have examined the nephrotoxic potential of the sevoflurane degradation product fluoride. However, fluoride-related toxicity was not observed, neither in clinical or in animal studies, nor after prolonged administration or in patients with preexisting renal disease. New insights into intrarenal metabolisation of volatile anesthetics may well explain absence of nephrotoxicity after sevoflurane. The threshold of fluoride nephrotoxicity of 50 μmol/l, which has been empirically found after methoxyflurane, and which is still listed in many medical textbooks, can not be assumed a marker of nephrotoxicity after isoflurane, enflurane or sevoflurane. Therefore also, the elevated serum fluoride concentrations, as regularly obtained after anesthesia with sevoflurane are devoid of clinical significance. In addition, exposure to sevoflurane or its metabolites is not associated with hepatic toxicity.     

Oleic acid induced pancreatitis in pigs

An experimental model of edematous pancreatitis in pigs was established and measurement of pancreatic macro- and microcirculatory parameters and determinations of pancreatic enzymes (lipase, phospholipase A) and vasoactive mediators (prostanoids, kallikrein, kininogen) were performed. During general anesthesia the pancreas was isolated in situ. Pancreatic microcirculatory parameters were measured using videofluorescence microscopy after iv administration of FITC-Dextran. In hourly collected samples lipase and phospholipase A activities were determined enzymatically, concentrations of kallikrein, kininogen, and selected prostanoids were measured by radioimmunoassay. Two experimental groups were studied: (1) control (n = 9); (2) edematous pancreatitis induced by injection of oleic acid into the pancreatic artery (free fatty acid, ffa; n = 10). The animals were followed up for 6 hr. Systemic hemodynamic parameters remained constant in both groups. In the pancreatitis group pancreatic blood flow and O2-consumption decreased significantly (-55 and -49%), while pancreatic vascular resistance increased significantly (+50%). During baseline conditions 41% of all capillaries were perfused. In the pancreatitis group there were both areas with persistent stasis as well as areas with continuous perfusion. However, in the latter areas the portion of perfused capillaries decreased significantly to 27%. In the control group the portion of perfused capillaries remained constant. Liberation of lipase and phospholipase A especially into lymph and ascites fluid was measured during pancreatitis. Furthermore, considerable releases of kallikrein into lymph (+50%) and ascites (+800%) and a marked consumption of kininogen in lymph (+90%) and in ascites fluid (+80%) were measured. Activation of the arachidonic acid cascade and a significant release of prostacyclin and thromboxane A2 into pancreatic venous blood and lymph was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Effect of parental age on fertilization and pregnancy characteristics in couples treated by intracytoplasmic sperm injection

The purpose of this study was to investigate any influence of maternal and/or paternal age on gamete characteristics and pregnancy outcomes in intracytoplasmic sperm injection (ICSI) cycles. In all, 821 consecutive ICSI cases were analysed retrospectively. While a significant linear decline in semen volume was detected, no significant differences in the concentration, motility or morphology of the spermatozoa were found with paternal ageing. A significant decline in the number of oocytes retrieved and the number of mature oocytes obtained was found with advancing maternal age. An increase in the occurrence of digyny was noted with parental ageing, while no difference in single or bipronuclear fertilization was found. Older women had a decreased incidence of single pronucleus formation and an increase in digyny, but no significant difference in the percentage of oocytes that underwent two-pronuclear fertilization was detected with regard to maternal ageing. Pregnancy outcomes were not influenced by the age of the male partner, while a strong negative correlation was found with maternal ageing. To better analyse male partner ageing as a factor affecting pregnancy outcome, we analysed a subgroup of patients with a female partner aged <35 years who underwent ICSI. No paternal influence on ICSI pregnancy outcome was found in this subgroup of patients. We conclude that the influence on pregnancy outcome after ICSI is related mostly to maternal and not paternal age.