Browsing by Author "Sinner, Barbara"

Objective: To investigate changes in intracellular Ca2+ -regulation and Ca2+-sensitivityof the contractile apparatus in murine skeletal muscle fibers during sepsis. Design and Setting. Animal study in a university-based research laboratory. Subjects: Isolated muscle fibers (M. extensor digitorum longus) of septic mice. Interventions: In one group, sepsis was induced in "black six" mice using cecal ligation and puncture (CLP). In a second group, laparotomy (SHAM), and in a third group, general anesthesia (GA) was performed. Saponin-skinned skeletal muscle fibers were examined 2, 3, 5, and 7 days after treatment, and caffeine-induced Ca2+-release from the sarcoplasmic reticulum (SR) as well as Ca2+-sensitivity of the contractile apparatus were assessed. Measurements and Results: In the CLP group, Ca2+-release significantly decreased over 5 days and increased again after 7 days. In the SHAM group, Ca2+-release decreased at days 2 and 3, whereas no changes were observed in the GA group. Ca (2+)- sensitivity significantly increased over 5 days in the CLP group and decreased again at day 7. In the SHAM group, Ca2+-sensitivity increased at days 2 and 3, and no changes were seen in the GA group. Conclusions: In murine skeletal muscle fibers, Ca2+-release from the SR decreases during sepsis, with effects being most pronounced 2-3 days after CLP. In parallel, Ca2+-sensitivity of the contractile apparatus is increased, and all changes are reversible. Thus, these effects might be involved in skeletal muscle dysfunction during sepsis as corresponding changes are less pronounced or absent in control groups.

Background and goal: Forced by the current economical situation, German hospitals have to reconsider their clinical productivity. When caregivers introduce new therapeutic concepts medical quality should either be improved without increasing costs or when reducing costs medical quality should be maintained. In the surgical field postoperative shivering reduces both patient comfort and medical quality. We therefore investigated the clinical pathway prevention of shivering with dolasetron in a prospective, randomized, placebo-controlled analysis of cost-effectiveness. Material and methods. After written informed consent we randomized 40 patients scheduled for lumbar disc hernia repair or head and neck surgery into two groups: patients of group D received dolasetron 1 mg/kg body weight during surgery whereas patients of group K received 100 ml saline as placebo. Primary endpoints were the incidence of shivering, the length of stay in the postanesthesia care unit and process-associated costs. Secondary endpoint was the influence on perioperative thermoregulation. Results. We observed postanesthetic shivering in 5 patients belonging to group D in comparison to 15 patients receiving the placebo (p < 0.05). The length of stay in the postanesthesia care unit was shorter in patients allocated to dolasetron (mean +/- SD; group D: 43 +/- 16 min, group K 62 +/- 18 min, p < 0.05). There was a significant saving in process-associated personnel costs (personnel costs in group D EUR 41.26 +/- 14, personnel costs in group K EUR 53.15 +/- 15) but in contrast the process-associated material costs were significantly increased (group D EUR 17.16 +/- 3, group K EUR 0.73 +/- 1, p < 0.05). Conclusions. The optimization of the clinical process and medical quality induced by a prophylaxis against shivering and postoperative nausea and vomiting compensates for the increased use of pharmaceutical resources in our setting.

Background: Spontaneous Ca2+-oscillations are a possible mechanism of Ca2+-mediated signal transduction in neurons. They develop by a periodical interplay of Ca2+, which enters the neuron from the extracellular medium and triggers Ca2+ release from the endoplasmic reticulum (ER). Ca2+-oscillations are terminated by reuptake into the ER or plasmalemmal extrusion. Spontaneous Ca2+-oscillations are glutamate dependent and appear to be responsible for neuronal plasticity and integration of information. Here, we examined the role of the gamma-aminobutyric acid (GABA,) receptor on spontaneous Ca2+-oscillations and studied the effects of the anaesthetics miclazolam, thiopental and the non-anesthetic barbituric acid on spontaneous Ca2+-oscillations. Methods: Hippocampal neuronal cell cultures of 19-day-old embryonic Wistar rats 17-18 days in culture were loaded with the Ca2+-sensitive dye Fura-2AM. Experiments were performed using dual wave-length excitation fluorescence microscopy and calibration constants were obtained from in situ calibration. Results: Spontaneous Ca2+-oscillations are influenced by the GABA(A) receptor. The intravenous anaesthetics midazolam and thiopental suppressed the amplitude and frequency reversibly in a dose-dependent manner with EC50 in clinically relevant concentrations. This effect was mediated via the GABA(A) receptor as it could be reversed by the GABA(A) receptor antagonist bicuculline. In contrast, the application of barbituric acid had no effects on the spontaneous Ca2+-oscillations. Conclusion: Spontaneous Ca2+-oscillations are influenced by the GABAA receptor. Spontaneous Ca2+-oscillations might represent an interesting model system to study anaesthetic mechanisms on neuronal information processing.

BACKGROUND: Cardiac toxicity significantly correlates with the lipophilicity of local anesthetics (LAs). Recently, the infusion of lipid emulsions has been shown to be a promising approach to treat LA-induced cardiac arrest. As the postulated mechanism of action, the so-called "lipid sink" effect may depend on the lipophilicity of LAs. In this study, we investigated whether lipid effects differ with regard to the administered LAs. METHODS: In the isolated rat heart, cardiac arrest was induced by administration of equipotent doses of bupivacaine, ropivacaine, and mepivacaine, respectively, followed by cardiac perfusion with or without lipid emulsion (0.25 mL . kg(-1) . min(-1)). Subsequently, the times from the start of perfusion to return of first heart activity and to recovery of heart rate and rate-pressure product (to 90% of baseline values) were assessed. RESULTS: In all groups, lipid infusion had no effects on the time to the return of any cardiac activity. However, recovery times of heart rate and rate-pressure product (to 90% of baseline values) were significantly shorter with the administration of lipids in bupivacaine-induced cardiac toxicity, but not in ropivacaine- or mepivacaine-induced cardiac toxicity. CONCLUSIONS: These data show that the effects of lipid infusion on LA-induced cardiac arrest are strongly dependent on the administered LAs itself. We conclude that lipophilicity of LAs has a marked impact on the efficacy of lipid infusions to treat cardiac arrest induced by these drugs. (Anesth Analg 2009;109:1323-6)

Intramuscular injections of local anaesthetic agents regularly result in reversible muscle damage, with a dose-dependent extent of the lesions. All local anaesthetic agents that have been examined are myotoxic, whereby procaine produces the least and bupivacaine the most severe muscle injury. The histological pattern and the time course of skeletal muscle injury appear relatively uniform: hypercontracted myofibrils become evident directly after injection, followed by lytic degeneration of striated muscle sarcoplasmic reticulum myocyte edema and necrosis. Intriguingly, in most cases myoblasts, basal laminae and connective tissue elements remain intact which subsequently ensures complete muscular regeneration. Subcellular pathomechanisms of local anaesthetic myotoxicity are still not understood in detail. Increased intracellular Ca2+ levels are suggested to be the most important element in myocyte injury, since denervation, inhibition of sarcolemmal Na+ channels and direct toxic effects on myofibrils have been excluded as sites of action. Although experimental myotoxic effects are impressively intense and reproducible, only few case reports of myotoxic complications in patients after local anaesthetic administration have been published. In particular, the occurrence of clinically relevant myopathy and myonecrosis has been described after continuous peripheral blockades, infiltration of wound margins, trigger point injections, peribulbar and retrobulbar blocks.

Background. In medicine, the use of standard operating procedures (SOPs) is often evaluated using questionnaires (QUES). However, QUES can have limitations with regard to method, thus leading to errors. Simulation (SIM) offers another opportunity for evaluation. We hypothesized that medical errors in the evaluation of SOPs using QUES could be detected by SIM, and that SIM is better qualified to demonstrate applied medicine. Methods. We investigated the use of SOPs in anaesthesia, rapid sequence induction (RSI), by means of a QUES (n=42) or SIM (n=42) among 84 anaesthesiologists. Seven measures for preventing aspiration during induction of anaesthesia were examined and evaluated according to a predetermined points system. Results. The average number of times that precautionary measures to prevent aspiration were mentioned in the QUES [4.8 (0.9)] or performed during SIM [5.0 (1.1)] did not differ between the two groups. Pre-oxygenation was the most frequently described or performed measure (95% vs 93%). However, other measures, such as avoidance of positive pressure ventilation (45% vs 85%), differed significantly between the two groups. Conclusions. QUES and SIM are powerful instruments for evaluating the implementation of SOPs such as RSI. SIM demonstrates automated behaviours and thus more clearly represents behaviours used in clinical practice than is possible to demonstrate using QUES. Using a combination of these two instruments, method errors resulting from the individual instruments can be reduced.