Oesophageal Doppler guided goal-directed haemodynamic therapy in thoracic surgery - a single centre randomized parallel-arm trial.

BACKGROUND: Postoperative pulmonary and renal complications are frequent in patients undergoing lung surgery. Hyper- and hypovolaemia may contribute to these complications. We hypothesized that goal-directed haemodynamic management based on oesophageal Doppler monitoring would reduce postoperative pulmonary complications in a randomized clinical parallel-arm trial. METHODS: One hundred patients scheduled for thoracic surgery were randomly assigned to either standard haemodynamic management (control group) or goal-directed therapy (GDT group) guided by an oesophageal Doppler monitoring-based algorithm. The primary endpoint was postoperative pulmonary complications, including spirometry. Secondary endpoints included haemodynamic variables, renal, cardiac, and neurological complications, and length of hospital stay. The investigator assessing outcomes was blinded to group assignment. RESULTS: Forty-eight subjects of each group were analysed. Compared to the control group, fewer subjects in the GDT group developed postoperative pulmonary complications (6 vs. 15 patients; P = 0.047), while spirometry did not differ between groups. Compared to the control group, patients of the GDT group showed higher cardiac index (2.9 vs. 2.1 [l min - 1 m - 2 ]; P < 0.001) and stroke volume index (43 vs. 34 [ml m 2 ]; P < 0.001) during surgery. Renal, cardiac and neurological complications did not differ between groups. Length of hospital stay was shorter in the GDT compared to the control group (9 vs. 11 days; P = 0.005). CONCLUSIONS: Compared to standard haemodynamic management, oesophageal Doppler monitor-guided GDT was associated with fewer postoperative pulmonary complications and a shorter hospital stay. CLINICAL TRIAL REGISTRATION.: The study was registered in the German Clinical Trials Register (DRKS 00006961). https://drks-neu.uniklinik-freiburg.de/drks_web/.

Increasing positive end-expiratory pressure (re-)improves intraoperative respiratory mechanics and lung ventilation after prone positioning.

BACKGROUND: Turning a patient prone, changes the respiratory mechanics and potentially the level of positive end-expiratory pressure (PEEP) that is necessary to prevent alveolar collapse. In this prospective clinical study we examined the impact of PEEP on the intratidal respiratory mechanics and regional lung aeration in the prone position. We hypothesized that a higher PEEP is required to maintain compliance and regional ventilation in the prone position. METHODS: After ethical approval, 45 patients with healthy lungs undergoing lumbar spine surgery were examined in the supine position at PEEP 6 cm H2O and in the prone position at PEEP (6, 9 and 12 cm H2O). Dynamic compliance (CRS) and intratidal compliance-volume curves were determined and regional ventilation was measured using electrical impedance tomography. The compliance-volume curves were classified to indicate intratidal derecruitment, overdistension, or neither. RESULTS: CRS did not differ between postures and PEEP levels (P>0.28). At a PEEP of 6 cm H2O a compliance-volume profile indicating neither derecruitment nor overdistension was observed in 38 supine, but only in 20 prone positioned patients (P<0.001). The latter increased to 33 and 37 (both P<0.001) when increasing PEEP to 9 and 12 cm H2O, respectively. Increasing PEEP from 6 to 9 cm H2O in the prone position increased peripheral ventilation significantly. CONCLUSIONS: Respiratory system mechanics change substantially between supine and prone posture, which is not demonstrated in routine measurements. The intratidal compliance analysis suggests that in most patients a PEEP above commonly used settings is necessary to avoid alveolar collapse in the prone position. CLINICAL TRIAL REGISTRATION: DRKS 00005692.

A Model-Based Product Evaluation Protocol for Comparison of Safety-Engineered Protection Mechanisms of Winged Blood Collection Needles.

OBJECTIVE: To evaluate differences in product characteristics and user preferences of safety-engineered protection mechanisms of winged blood collection needles. DESIGN: Randomized model-based simulation study. SETTING: University medical center. PARTICIPANTS: A total of 33 third-year medical students. METHODS: Venipuncture was performed using winged blood collection needles with 4 different safety mechanisms: (a) Venofix Safety, (b) BD Vacutainer Push Button, (c) Safety-Multifly, and (d) Surshield Surflo. Each needle type was used in 3 consecutive tries: there was an uninstructed first handling, then instructions were given according to the operating manual; subsequently, a first trial and second trial were conducted. Study end points included successful activation, activation time, single-handed activation, correct activation, possible risk of needlestick injury, possibility of deactivation, and preferred safety mechanism. RESULTS: The overall successful activation rate during the second trial was equal for all 4 devices (94%-100%). Median activation time was (a) 7 s, (b) 2 s, (c) 9 s, and (d) 7 s. Single-handed activation during the second trial was (a) 18%, (b) 82%, (c) 15%, and (d) 45%. Correct activation during the second trial was (a) 3%, (b) 64%, (c) 15%, and (d) 39%. Possible risk of needlestick injury during the second trial was highest with (d). Possibility of deactivation was (a) 0%, (b) 12%, (c) 9%, and (d) 18%. Individual preferences for each system were (a) 11, (b) 17, (c) 5, and (d) 0. The main reason for preference was the comprehensive safety mechanism. CONCLUSION: Significant differences exist between safety mechanisms of winged blood collection needles.

Flow-controlled expiration: a novel ventilation mode to attenuate experimental porcine lung injury.

BACKGROUND: Whereas the effects of various inspiratory ventilatory modifications in lung injury have extensively been studied, those of expiratory ventilatory modifications are less well known. We hypothesized that the newly developed flow-controlled expiration (FLEX) mode provides a means of attenuating experimental lung injury. METHODS: Experimental acute respiratory distress syndrome was induced by i.v. injection of oleic acid in 15 anaesthetized and mechanically ventilated pigs. After established lung injury ([Formula: see text]ratio <27 kPa), animals were randomized to either a control group receiving volume-controlled ventilation (VCV) or a treatment group receiving VCV with additional FLEX (VCV+FLEX). At predefined times, lung mechanics and oxygenation were assessed. At the end of the experiment, the pigs were killed, and bronchoalveolar fluid and lung biopsies were taken. Expression of inflammatory cytokines was analysed in lung tissue and bronchoalveolar fluid. Lung injury score was determined on the basis of stained tissue samples. RESULTS: Compared with the control group (VCV; n=8), the VCV+FLEX group (n=7) demonstrated greater dynamic lung compliance and required less PEEP at comparable [Formula: see text] (both P<0.05), had lower regional lung wet-to-dry ratios and lung injury scores (both P<0.001), and showed less thickening of alveolar walls (an indicator of interstitial oedema) and de novo migration of macrophages into lung tissue (both P<0.001). CONCLUSIONS: The newly developed FLEX mode is able to attenuate experimental lung injury. FLEX could provide a novel means of lung-protective ventilation.

Determination of respiratory system mechanics during inspiration and expiration by FLow-controlled EXpiration (FLEX): a pilot study in anesthetized pigs.

BACKGROUND: Differences between inspiratory and expiratory lung mechanics result in the hysteresis of the pressure volume-loop. While hysteresis area is a global parameter describing the difference between inspiration and expiration in mechanics under quasi-static conditions, a detailed analysis of this difference under the dynamic conditions of mechanical ventilation is feasible once inspiratory and expiratory compliance (Cin/Cex) are determined separately. This requires uncoupling of expiratory flow rate and volume (V). METHODS: Five piglets were mechanically ventilated at positive end-expiratory pressure (PEEP) levels ranging from 0 to 15 cmH2O. Expiratory flow rate was linearized by a computer-controlled resistor (flow-controlled expiration). The volume-dependent Cin(V) and Cex(V) profiles were calculated from the tracheal pressure volume-loops. RESULTS: The intratidal curve-progression of Cex(V) was altogether higher with a steeper slope compared to Cin(V). With increasing positive end-expiratory pressure (PEEP) dynamic hysteresis area decreased and Cex(V) tended to run more parallel to Cin(V). CONCLUSION: The relation between inspiratory and expiratory compliance profiles is associated with the hysteresis area and behaves PEEP dependent. Analysing the Cin-Cex-relation might therefore potentially offer a new approach to titrate PEEP and tidal volume.

[Management of anaphylaxis : part 2: treatment and emergency equipment]. / Management der Anaphylaxie : Teil 2: Therapie und Notfallausrüstung.

Anaphylaxis is an extreme form of allergic reaction that can be life-threatening. Early treatment of circulatory and pulmonary disturbances is decisive for prognosis. Initial management of anaphylaxis comprises, where possible, interrupting allergen exposure; ensuring a stable airway; summoning emergency services; placing the patient in a safe position, obtaining venous access and monitoring vital signs. Adrenaline, histamine-antagonists and glucocorticoids have proven effective, as has administration of oxygen and volume substitutes. Many anaphylaxis patients are unable to successfully avoid the elicitor and the feasibility of self-treatment is limited if the patient is inadequately informed. An educational program for adult patients and parents of children with a high risk of anaphylaxis has been developed by the German Working Group for Anaphylaxis Training and Education (AGATE). This program aims to help prevent anaphylactic attacks, foster optimal first-line treatment and offer psychological and social support for anaphylaxis patients. Preliminary results confirm the efficacy of the AGATE approach. This article presents an overview of the stage-wise management of anaphylaxis in accordance with the S2 position paper of the German allergological societies and international guidelines.

[Management of anaphylaxis. Part 1: Causes and pathophysiology]. / Management der Anaphylaxie. Teil 1: Ursachen und Pathophysiologie.

Anaphylactic reactions reveal the maximal grade of allergic reactions and are potentially life-threatening. The most common agents involved in anaphylactic reactions are drugs, food, Hymenoptera, aeroallergens, Latex, and physical stress. Anaphylactic reactions are induced by the liberation of various mediators. Symptoms are determined by the kind, quantity, and relation of these mediators and by the individual predisposition of the patient. In general, symptoms occur at the skin, the lungs, the cardiovascular system and the gastrointestinal tract. Early treatment of circulatory and pulmonary disturbances is decisive for the prognosis of the patient. Adequate therapy has to be given immediately according to the severity of symptoms in a step-wise approach. In the specific drug-therapy, a few substances have proved to be reliable, e.g. adrenalin, histamine antagonists, glucocorticosteroids, oxygen and volume substitutes. This article provides an overview of prevalence, symptoms and therapeutic options for managing anaphylaxis.

Protective effects of inhaled carbon monoxide in pig lungs during cardiopulmonary bypass are mediated via an induction of the heat shock response.

BACKGROUND: Cardiopulmonary bypass (CPB) may cause acute lung injury leading to increased morbidity and mortality after cardiac surgery. Preconditioning by inhaled carbon monoxide reduces pulmonary inflammation during CPB. We hypothesized that inhaled carbon monoxide mediates its anti-inflammatory and cytoprotective effects during CPB via induction of pulmonary heat shock proteins (Hsps). METHODS: Pigs were randomized either to a control group, to standard CPB, to carbon monoxide+CPB, or to quercetin (a flavonoid and unspecific inhibitor of the heat shock response)+control, to quercetin+CPB, and to quercetin+carbon monoxide+CPB. In the carbon monoxide groups, lungs were ventilated with 250 ppm carbon monoxide in addition to standard ventilation before CPB. At various time points, lung biopsies were obtained and pulmonary Hsp and cytokine concentrations determined. RESULTS: Haemodynamic parameters were largely unaffected by CPB, carbon monoxide inhalation, or administration of quercetin. Compared with standard CPB, carbon monoxide inhalation significantly increased the pulmonary expression of the Hsps 70 [27 (SD 3) vs 69 (10) ng ml(-1) at 120 min post-CPB, P<0.05] and 90 [0.3 (0.03) vs 0.52 (0.05) after 120 min CPB, P<0.05], induced the DNA binding of heat shock factor-1, reduced interleukin-6 protein expression [936 (75) vs 320 (138) at 120 min post-CPB, P<0.001], and decreased CPB-associated lung injury (assessed by lung biopsy). These carbon monoxide-mediated effects were inhibited by quercetin. CONCLUSIONS: As quercetin, a Hsp inhibitor, reversed carbon monoxide-mediated pulmonary effects, we conclude that the anti-inflammatory and protective effects of preconditioning by inhaled carbon monoxide during CPB in pigs are mediated by an activation of the heat shock response.

[Teaching emergency medicine at the University Medical Center Freiburg: establishment of an integrative concept]. / Lehrveranstaltung Notfallmedizin am Universitätsklinikum Freiburg : Etablierung eines integrativen Gesamtkonzeptes.

Efforts to improve the quality of undergraduate medical education are commonly hampered by limited human and financial resources. This deficiency may be offset by the development of well structured and innovative teaching concepts, which optimize available assets. The newly conceived modular course "Emergency Medicine" at the University Medical Center Freiburg was conducted for the first time in the winter semester 2006/2007. The core of the course is a 3-day practical training period. It provides the possibility to teach a maximum number of medical students with only four lecturers using patient simulators, interactive case scenarios (simulation software MicroSim), and case scenarios with standardized patients. Evaluation of the course revealed standardized patients to be the best of all teaching methods with an overall average grade of 1.1 (patient simulators 1.2, computer simulation 1.4). Of the students, 88% stated that the practical training encouraged their interest in the speciality emergency medicine. The excellent student evaluation results show that the new course "Emergency Medicine" for medical students constitutes a successful balance between the constraint of resource limitation and the goal of excellent medical education.

The genetics of osteoarthritis in STR/ort mice.

OBJECTIVE: The complex genetics of osteoarthritis (OA) are still poorly defined. To circumvent the problems of genetic and environmental diversity hampering the analysis in humans, we investigated quantitative trait loci (QTL) associated with murine OA in the STR/ort strain which spontaneously develops osteoarthritic changes of the knee joints, overweight and elevated serum cartilage oligomeric matrix protein (COMP) levels. METHODS: Two hundred and seventy six male F2 intercross (STR/ortxC57BL/6) animals were genotyped using 96 microsatellite markers and phenotyped by analyzing weight, serum COMP levels and osteoarthritic changes of the knee joints. Quantitative trait analyses were performed using the R/qtl software. RESULTS: Elevated weight, serum COMP levels and osteoarthritic changes of the knee joints in the F2 generation compared to C57BL/6 parental animals confirm Mendelian inheritance. Quantitative trait analyses revealed three weight-, one serum COMP- and one OA-locus. CONCLUSIONS: The weight-QTL coincide with previously described genes and QTL involved in fatty acid metabolism and offer a plausible explanation for the observed phenotype in STR/ort mice. The exact match of the COMP-QTL and the COMP gene itself suggests a regulatory polymorphism to account for elevated serum levels in STR/ort mice and questions the robustness of serum COMP as a prognostic marker in human knee OA. The newly identified QTL associated with degenerative changes of the knee joints support the concept of OA resulting from a defective chondrocyte metabolism and/or altered apoptosis rate. However, we also discuss the unlikelihood of one QTL being responsible for OA in STR/ort mice and the inherent limitations of microsatellite analyses for complex genetic diseases.

Smoking habits in patients diagnosed with ANCA associated small vessel vasculitis.

OBJECTIVES: To study the prevalence of smoking at onset of symptoms in patients with small vessel vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA). METHODS: A retrospective study, in 197 patients with ANCA associated vasculitis, of the history of cigarette smoking at onset of symptoms. Prevalence of smoking in patients with ANCA associated vasculitis was compared with age-specific values for the general population in Germany. RESULTS: 27 (14%) patients were smokers at the time of first disease manifestation (p < 0.001, compared with the entire population); 54 (27%) had smoked previously with 1-110 pack-years (median 18) but had stopped > or = 2 years before onset of vasculitis; 116 (59%) patients were lifelong non-smokers. At onset of symptoms, active smokers were younger (median age 42 years) than patients with vasculitis (median 54 years, p < 0.01, Mann-Whitney U test) with a lower percentage of women (15%, p < 0.005, Fisher's exact test) than in the entire group (47%). Smokers, non-smokers, or ex-smokers did not differ in organ manifestation, mortality, and development of end stage renal disease and relapse rate. CONCLUSIONS: The proportion of active smokers in the group of patients with ANCA associated vasculitis is significantly lower than in the entire population. Cigarette smoking may be associated with a reduced risk of ANCA associated vasculitis.

Necrotizing small-vessel vasculitis confined to the uterine cervix.

OBJECTIVES: To report our experience with five cases of apparently isolated small-vessel vasculitis of the uterine cervix. METHODS: Case study of five patients with necrotizing vasculitis discovered incidentally in surgical specimens of the female genital tract, and a review of the pertinent literature on this subject. RESULTS: All patients lacked clinical and serological features of the well-delineated vasculitic syndromes. Comprehensive workup failed to yield any evidence of an underlying disorder. All patients were managed expectantly and did not develop systemic vasculitis during follow-up ranging from 6 months to 5 years. CONCLUSIONS: Isolated vasculitis of the female genital tract can be encountered as an innocuous finding in otherwise healthy individuals. The cause and pathogenesis of this disorder remain obscure. Rheumatologists should be familiar with this rare and vexing form of vasculitis and with its benign prognosis.

Turkish pepper (extra hot).

A 38 year old female office worker was admitted with a newly discovered blood pressure of 250/110 mm Hg. Evaluation for secondary forms of hypertension was negative and treatment was begun. Sodium excretion was markedly reduced, plasma aldosterone was normal, and plasma renin activity was low. Therefore, presence of an aldosterone-like activity was suspected. Eventually, the patient confessed to abusing "Turkish Pepper", a brand of Scandinavian liquorice candies and "Fisherman's Friend", another brand of liquorice candies, concurrently. After eliminating liquorice from her diet, the hypertension disappeared thus allowing her antihypertensive treatment to be stopped.

Hypercalcemia due to talc granulomatosis.

Pulmonary disease due to talc, a group of hydrous magnesium silicates, is almost exclusively encountered after occupational exposure. One form of this rare disorder is talc granulomatosis. In varying degrees, hypercalcemia is typical of granulomatous disease but has not yet been reported in talcosis. We report the case of a former mold maker who presented with hypercalcemia. Laboratory findings indicated extra-renal 1-alpha-hydroxylation of 25-hydroxyvitamin D. Pulmonary infiltrates prompted a lung biopsy that disclosed talc granulomatosis. We suggest that talc granulomatosis should be added to the list of granulomatous disorders capable of causing hypercalcemia due to increased extra-renal 1-alpha-hydroxylation of 25-hydroxyvitamin D.