Prämedikationsqualität und Patientenzufriedenheit nach Prämedikation mit Midazolam, Clonidin oder Placebo: Randomisierte Doppelblindstudie mit altersangepasster Dosierung

Zusammenfassung: Hintergrund: Die Prämedikation hat u.a. zum Ziel, Angstgefühle und innere Unruhe vor einem chirurgischen Eingriff zu lindern und gleichzeitig möglichst wenig unerwünschte Wirkungen zu verursachen. Es gibt bisher keine Untersuchungen, die die Wirkungen und Nebenwirkungen von Clonidin (Catapresan®), Midazolam (Dormicum®) und Placebo in altersabhängig unterschiedlicher Dosierung verglichen und deren Akzeptanz beim Patienten untersucht haben. Patienten und Methoden: In dieser randomisierten, placebokontrollierten Studie wurden 139 erwachsene Patienten untersucht und 60min vor der Narkoseeinleitung mit Clonidin, Midazolam oder Placebo prämediziert. Angst, Sedierungstiefe und Nebenwirkungen wurden an 6 aufeinanderfolgenden Zeitpunkten erfasst. Ergebnisse: Midazolam zeigte eine stärkere anxiolytische und sedative Wirkung als Clonidin. Die Prämedikation mit Midazolam verminderte die Sauerstoffsättigung. Es gab keine klinisch relevanten Veränderungen in der Hämodynamik in allen Gruppen. Midazolam und Clonidin verminderten das Risiko für "postoperative nausea and vomiting" (PONV). Midazolam zeigte die geringsten Nebenwirkungen. Placebo wurde von den Patienten weitaus am schlechtesten beurteilt, im Gegensatz zu Clonidin und Midazolam, das am besten beurteilt wurde. Schlussfolgerung: Die sedierende und anxiolytische Wirkung von Midazolam ist stärker als diejenige von Clonidin. Midazolam wurde von den Patienten besser angenommen als Clonidin, Clonidin siginfikant besser als Placebo. Die meisten Patienten würden Midazolam wieder wähle

Impact of preoperative right-ventricular function and platelet transfusion on outcome after lung transplantation

Objective: Lung transplantation has become an established treatment option for end-stage pulmonary diseases. However, outcome depends on preoperative condition and co-morbidity. Furthermore, perioperative blood-product use is known to be associated with worse outcome even in transplant surgery. We investigated the impact of poor preoperative right-ventricular function and blood-product use on outcome after lung transplantation. Methods: The medical records of 169 lung-transplant recipients from 1996 to 2006 were examined. Duration of hospital stay, hours on mechanical ventilation, duration of stay in the intensive care unit, perioperative complications, death during hospital stay, and long-term survival were recorded. These outcome parameters were analyzed regarding coherence with right-ventricular function and the perioperative administration of crystalloids, colloids, allogeneic red blood cells, fresh frozen plasma, and platelets. Results: Patients with poor preoperative right-ventricular function had a significant increase in postoperative hours on ventilation (p=0.005), intensive care stay (p=0.003), and in-hospital death (p=0.012). The hours on ventilation increased also with high intra-operative fluid administration (p=0.026). Blood-product use was associated with prolonged mechanical ventilation and intensive care stay. After multivariate analysis, transfusion of platelets (p=0.022) was an independent prognostic factor for in-hospital death. Hours of mechanical ventilation was the only independent prognostic factor for long-term mortality (p=0.014). Conclusions: Perioperative transfusion of platelets is an independent prognostic factor for perioperative mortality. Furthermore, the study indicated that poor preoperative right-ventricular function might worsen perioperatively after lung transplantation. Therefore, pre-transplant treatment of pulmonary hypertension to protract right-ventricular failure and a restrictive use of allogeneic blood products may be options to improve outcom

Normal gas exchange after 30-h ischemia and treatment with phosphodiesterase inhibitor PDI747

Objective: Phosphodiesterases (PDEs) negatively regulate the concentrations of cAMP and/or cGMP, which act as downstream second messengers to the prostaglandins. PDE type-4 (PDE4) is selective for cAMP and is found in high concentrations in endothelial, epithelial, and different blood cells. The aim of this study was to evaluate if PDI747, a novel selective inhibitor of PDE4, can restore pretransplant cAMP levels and thereby posttransplant organ function after prolonged cold ischemia. Methods: Left lung transplantation was performed in pigs (25-31 kg). Donor lungs were flushed with low potassium dextran glucose (LPDG) solution only (control, n=5)or, in addition with 1 μmol of PDI747 (PDI747, n=5) and stored for 30 h at 1 °C. PDI747 animals further received a bolus of PDI747 (0.3 mg/kg) 15 min prior to reperfusion and a continuous infusion (0.3 mg/kg per hour) during the 5 h after reperfusion. After occlusion of the right pulmonary arteries and the right main bronchus, hemodynamic and gas exchange parameters and extravascular lung water (EVLW) levels of the transplanted lung were assessed. Results: Two control animals died of severe lung edema leading to heart failure (control, n=3). One animal in the treatment group was excluded due to a patent ductus arteriosus (PDI747, n=4). Gas exchange at the end of the experiment was restored to normal levels in the PDI747 group (Pa, o2 47.6±11.2 kPa, Pa,co2 6.4±1.8 kPa) but not in the control group (Pa, o2 7.7±2.9 kPa, Pa, co2 11.9±3.0 kPa, PPao2<0.0001, PPa, co2=0.06). Extravascular lung water (EVLW) was normal in the PDI747 group (8.5±1.1 ml/kg) and clearly elevated in the control group (16.2±5.6 ml/kg, P=0.007). Airway pressure in the PDI747 group was significantly lower than in the control group (7.8±0.5 cm H2O vs. 11.3±0.6 cm H2O, respectively, P<0.0001). The free radical mediated tissue injury measured by lipid peroxidation (TBARS) was significantly reduced (P=0.001) in the PDI747 group. Conclusions: With the inhibition of PDE4 with PDI747 we achieved normal gas exchange, no posttransplant lung edema, normal airway pressures, and a reduced free radical injury after 30 h of cold ischemi

Survival and graft function in a large animal lung transplant model after 30 h preservation and substitution of the nitric oxide pathway

Objective: Substitution of the nitric oxide- (NO-) pathway improves early graft function following lung transplantation. We previously demonstrated that 8-Br-cGMP (second messenger of NO) to the flush solution and tetrahydrobiopterin (BH4, coenzyme of NO synthase) given as additive during reperfusion improve post-transplant graft function. In the present study, the combined treatment with 8-Br-cGMP and BH4 was evaluated. Methods: Unilateral left lung transplantation was performed in weight matched outbred pigs (24-31kg). In group I, grafts were preserved for 30h (n=5). 8-Br-cGMP (1mg/kg) was added to the flush solution (Perfadex™, 1.5l, 1°C) and BH4 (10mg/kg/h) was given to the recipient for 5h after reperfusion. In group II, lungs were transplanted after a preservation time of 30h (n=3) and prostaglandin E1 (250g) was given into the pulmonary artery (PA) prior to flush. In all recipients 1h after reperfusion the contralateral right PA and bronchus were ligated to assess graft function only. Survival time after reperfusion, extravascular lung water index (EVLWI), hemodynamic variables, and gas exchange (PaO2) were assessed during a 12h observation period. Results: All recipients in group I survived the 12h assessment, whereas none of the group II animals survived more than 4h after reperfusion with a rapid increase of EVLWI up to 24.8±6.7ml/kg. In contrast, in group I EVLWI reached up to 8.9±1.5ml/kg and returned to nearly normal levels at 12h (6.1±0.8ml/kg). In two animals of group I the gas exchange deteriorated slightly. The other three animals showed normal arterial oxygenation over the entire observation time. Conclusion: Our data indicate that the combined substitution of the NO pathway during preservation and reperfusion reduces ischemia/reperfusion injury substantially and that this treatment even allows lung transplantation after 30h preservation in this mode

Effect of rofecoxib on platelet aggregation and blood loss in gynaecological and breast surgery compared with diclofenac

Background. Non‐selective cyclooxygenase (COX) inhibitors or non‐steroidal anti‐ inflammatory drugs (NSAIDs) are frequently omitted for perioperative pain relief because of potential side‐effects. COX‐2‐selective inhibitors may have a more favourable side‐effect profile. This study tested the hypothesis that the COX‐2‐selective inhibitor rofecoxib has less influence on platelet function than the NSAID diclofenac in gynaecological surgery. In addition, analgesic efficacy and side‐effects of the two drugs were compared. Methods. In this single‐centre, prospective, double‐blind, active controlled study, women undergoing vaginal hysterectomy (n=25) or breast surgery (n=25) under general anaesthesia received preoperatively 50 mg of rofecoxib p.o. followed 8 and 16 h later by two doses of placebo or three doses of diclofenac 50 mg p.o. at the same time points. We assessed arachidonic acid‐stimulated platelet aggregation before and 4 h after the first dose of study medication, estimated intraoperative blood loss, and haemoglobin loss until the first morning after surgery. Analgesic efficacy, use of rescue analgesics, and side‐effects were also recorded. Results. In the rofecoxib group, stimulated platelet aggregation was disturbed less (P=0.02), and estimated intraoperative blood loss (P=0.01) and the decrease in haemoglobin were lower (P=0.01). At similar pain ratings, the use of anti‐emetic drugs was less in the rofecoxib group (P=0.03). Conclusion. Besides having a smaller effect on platelet aggregation, one oral dose of rofecoxib 50 mg given before surgery provided postoperative analgesia similar to that given by three doses of diclofenac 50 mg and was associated with less use of anti‐emetics and less surgical blood loss in gynaecological surgery compared with diclofenac. Br J Anaesth 2004; 92: 523-3

Bottom-up feedback to improve clinical teaching: validation of the Swiss System for Evaluation of Teaching Qualities (SwissSETQ).

AIMS OF THE STUDY Clinical teaching is essential in preparing trainees for independent practice. To improve teaching quality, clinical teachers should be provided with meaningful and reliable feedback from trainees (bottom-up feedback) based on up-to-date educational concepts. For this purpose, we designed a web-based instrument, "Swiss System for Evaluation of Teaching Qualities" (SwissSETQ), building on a well-established tool (SETQsmart) and expanding it with current graduate medical education concepts. This study aimed to validate the new instrument in the field of anaesthesiology training. METHODS Based on SETQsmart, we developed an online instrument (primarily including 34 items) with generic items to be used in all clinical disciplines. We integrated the recent educational frameworks of CanMEDS 2015 (Canadian Medical Educational Directives for Specialists), and of entrustable professional activities (EPAs). Newly included themes were "Interprofessionalism", "Patient centredness", "Patient safety", "Continuous professional development', and "Entrustment decisions". We ensured content validity by iterative discussion rounds between medical education specialists and clinical supervisors. Two think-aloud rounds with residents investigated the response process. Subsequently, the instrument was pilot-tested in the anaesthesia departments of four major teaching hospitals in Switzerland, involving 220 trainees and 120 faculty. We assessed the instrument's internal structure (to determine the factorial composition) using exploratory factor analysis, internal statistical consistency (by Cronbach's alpha as an estimate of reliability, regarding alpha >0.7 as acceptable, >0.8 as good, >0.9 as excellent), and inter-rater reliability (using generalisability theory in order to assess the minimum number of ratings necessary for a valid feedback to one single supervisor). RESULTS Based on 185 complete ratings for 101 faculty, exploratory factor analysis revealed four factors explaining 72.3% of the variance (individual instruction 33.8%, evaluation of trainee performance 20.9%, teaching professionalism 12.8%; entrustment decisions 4.7%). Cronbach's alpha for the total score was 0.964. After factor analysis, we removed one item to arrive at 33 items for the final instrument. Generalisability studies yielded a minimum of five to six individual ratings to provide reliable feedback to one supervisor. DISCUSSION The SwissSETQ possesses high content validity and an "excellent" internal structure for integrating up-to-date graduate medical education concepts. Thereby, the tool allows reliable bottom-up feedback by trainees to support clinical teachers in improving their teaching. Transfer to disciplines other than anaesthesiology needs to be further explored

Effectiveness of rehabilitation intervention in persons with Friedreich ataxia

IntroductionThe relevance of rehabilitation in progressive neurological disorders, such as Friedreich’s Ataxia (FRDA), has yet to be convincingly proven. FRDA is characterized by ataxia, loss of gait, scoliosis, cardiomyopathy, dysarthria and dysphagia, with reduced life expectancy. The disease onset is usually in adolescence, leading to progressive disability. Omaveloxolone has been recently approved as the first pharmacological treatment for FRDA in adults and adolescents aged 16 years and older. Regarding non-pharmacological therapies, neurorehabilitation is a valuable aid in addressing the symptoms and in maintaining the residual functioning. We performed a prospective observational cohort study to evaluate the efficacy of inpatient rehabilitation (IR) for people with FRDA.MethodsA total of 42 individuals (29 adults and 13 children) with FRDA were recruited. There were 27 ambulant and 15 non-ambulant participants. The patients underwent IR of 3 and 4 weeks in children and adults, respectively. The IR treatment was designed to be applied within a multidisciplinary setting, so FRDA patients underwent, in addition to physiotherapy, also occupational therapy, practical manual activities and psychological support aiming to enhance transferable skills useful in the activities of daily living. The primary outcome was the Scale for the Assessment and Rating of Ataxia (SARA). Other measures were: Friedreich Ataxia Rating Scale (FARS) and Nine Hole Peg Test (NHPT). Furthermore, we used the 6 Minute Walk Test (6MWT), the Timed Up and Go (TUG) and the Berg Balance Scale (BBS) only on ambulant subjects. Outcomes were evaluated at baseline and at the end of the treatment.ResultsWe report that the IR significantly improves motor performance and ataxia symptoms in patients with FRDA. Our study shows significant functional improvement in all the outcome measures used, except for NHPT bilaterally. FARS and SARA scores post-IR are significatively reduced when compared (p &lt; 0.001).DiscussionWe demonstrate that IR programs in FRDA can provide a meaningful clinical improvement in terms of outcome measures. These findings could be useful when approaching progressive neurological disorders

Factors influencing preoperative stress response in coronary artery bypass graft patients

BACKGROUND: In many studies investigating measures to attenuate the hemodynamic and humoral stress response during induction of anaesthesia, primary attention was paid to the period of endotracheal intubation since it has been shown that even short-lasting sympathetic cardiovascular stimulation may have detrimental effects on patients with coronary artery disease. The aim of this analysis was, however, to identify the influencing factors on high catecholamine levels before induction of anaesthesia. METHODS: Various potential risk factors that could impact the humoral stress response before induction of anaesthesia were recorded in 84 males undergoing coronary aortic bypass surgery, and were entered into a stepwise linear regression analysis. The plasma level of norepinephrine measured immediately after radial artery canulation was chosen as a surrogate marker for the humoral stress response, and it was used as the dependent variable in the regression model. Accordingly, the mean arterial blood pressure, heart rate and the calculated pressure-rate product were taken as parameters of the hemodynamic situation. RESULTS: Stepwise regression analysis revealed that the oral administration of low-dose clonidine (mean dose 1.75 μg·kg(-1)) on the morning of surgery was the only significant predictor (p = 0.004) of the high variation in preoperative norepinephrine plasma levels. This intervention decreased norepinephrine levels by more than 40% compared to no clonidine administration, from 1.26 to 0.75 nmol·l(-1). There was no evidence for dose-responsiveness of clonidine. All other potential predictors were removed from the model as insignificant (p > 0.05). The use of beta-blocker, ace-inhibitors, ejection fraction, and body mass index were significant determinants for the hemodynamic situation (heart rate, mean arterial pressure, pressure rate product) of the patient during the pre-induction period. CONCLUSION: The oral administration of clonidine is the only significant predictor for the observed variation of norepinephrine levels during the preoperative period. Lack of significant dose responsiveness suggests that even a low dose of the drug can attenuate the preoperative stress response and thus is recommended in cardiovascular high risk patients