Sugammadex and neostigmine dose-finding study for reversal of residual neuromuscular block at a train-of-four ratio of 0.2 (SUNDRO20)†,.

BACKGROUND: The aim of this dose-finding study was to evaluate the dose-response relationship of sugammadex and neostigmine to reverse a commonly observed level of incomplete recovery from rocuronium-induced neuromuscular block, that is, a train-of-four ratio (TOFR) ≥0.2. METHODS: Ninety-nine anaesthetized patients received rocuronium 0.6 mg kg(-1) i.v. for tracheal intubation and, if necessary, incremental doses of 0.1-0.2 mg kg(-1). Neuromuscular monitoring was performed by calibrated electromyography. Once the TOFR recovered to 0.2, patients were randomized to receive sugammadex (0.25, 0.5, 0.75, 1.0, or 1.25 mg kg(-1) i.v.), neostigmine (10, 25, 40, 55, or 70 µg kg(-1) i.v.), or saline (n=9 per group). Primary and secondary end points were the doses necessary to restore neuromuscular function to a TOFR≥0.9 with an upper limit of 5 and 10 min for 95% of patients, respectively. RESULTS: Neostigmine was not able to fulfil the end points. Based on the best-fitting model, the sugammadex dose estimation for recovery to a TOFR≥0.9 for 95% of patients within 5 and 10 min was 0.49 and 0.26 mg kg(-1), respectively. CONCLUSION: A residual neuromuscular block of a TOFR of 0.2 cannot be reversed reliably with neostigmine within 10 min. In the conditions studied, substantially lower doses of sugammadex than the approved dose of 2.0 mg kg(-1) may be sufficient to reverse residual rocuronium-induced neuromuscular block at a recovery of TOFR≥0.2. CLINICAL TRIAL REGISTRATION: NCT01006720.

Impingement-free range of movement, acetabular component cover and early clinical results comparing 'femur-first' navigation and 'conventional' minimally invasive total hip arthroplasty: a randomised controlled trial.

We report the kinematic and early clinical results of a patient- and observer-blinded randomised controlled trial in which CT scans were used to compare potential impingement-free range of movement (ROM) and acetabular component cover between patients treated with either the navigated 'femur-first' total hip arthroplasty (THA) method (n = 66; male/female 29/37, mean age 62.5 years; 50 to 74) or conventional THA (n = 69; male/female 35/34, mean age 62.9 years; 50 to 75). The Hip Osteoarthritis Outcome Score, the Harris hip score, the Euro-Qol-5D and the Mancuso THA patient expectations score were assessed at six weeks, six months and one year after surgery. A total of 48 of the patients (84%) in the navigated 'femur-first' group and 43 (65%) in the conventional group reached all the desirable potential ROM boundaries without prosthetic impingement for activities of daily living (ADL) in flexion, extension, abduction, adduction and rotation (p = 0.016). Acetabular component cover and surface contact with the host bone were > 87% in both groups. There was a significant difference between the navigated and the conventional groups' Harris hip scores six weeks after surgery (p = 0.010). There were no significant differences with respect to any clinical outcome at six months and one year of follow-up. The navigated 'femur-first' technique improves the potential ROM for ADL without prosthetic impingement, although there was no observed clinical difference between the two treatment groups.

[Lymphadenectomy for malignancies of the upper gastrointestinal tract]. / Lymphadenektomie bei Malignomen des oberen Gastrointestinaltraktes.

Studies from specialized and high volume centers revealed an improved overall survival for patients subjected to extended lymphadenectomy. The drawbacks of radical lymph node dissection seem to be represented in higher rates of morbidity and mortality and thus are correlated to the surgical expertise of the respective institution. Especially patients in the early stages of metastatic lymph node spread benefit from extended and more radical lymphadenectomy. In a retrospective analysis of this institution's own patients, a pN0 category pT stage and the amount of retrieved lymph nodes have been found to be independent prognostic factors. In patients with up to six positive nodes (pN1) pT stage, the number of retrieved nodes, the number of positive nodes and R stage are correlated to survival prognosis. If more than six nodes are invaded only the amount of metastatic nodes and R stage are relevant prognostic factors. It will be of upmost interest to compare these data with analyses from regional and national cancer registers for gastric and esophageal cancer. As so far no reliable procedure for preoperative determination of lymphatic spread exists, the recommendations by the respective research organizations will have to be adopted until further notice, which is D2 lymphadenectomy for locally advanced gastric cancer and 2-field lymphadenectomy for patients with advanced esophageal cancer.Due to higher complication rates for patients subjected to radical lymphadenectomy, it is recommended that these procedures be performed in specialized high volume centers with corresponding surgical experience.

WITHDRAWN: Rationale and Design of a Randomised Controlled Trial Comparing Stent-Protected Angioplasty with Bypass Surgery for Intermittent Claudication: The ABC Study.

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Effect of perioperative administration of a drug regimen on the primary function of human renal allografts.

Delayed graft function (DGF) has one of the greatest effects on short- and long-term outcomes of cadaveric renal allografts. Ischemia reperfusion injury in the context of cold ischemia time and acute calcineurin inhibitor (CNI) nephrotoxicity is a major factor predisposing to DGF. A drug regimen consisting of prostaglandin E(1) (PGE(1)) furosemide and dopamine has been used to reduce DGF after kidney transplantation. Prostaglandin E(1) has multiple anti-ischemic and tissue-protective abilities, furosemide improves diuresis, and dopamine augments renal blood flow and urinary volume. To evaluate a potential positive effect of this drug regimen on the primary function of cadaveric renal allografts, we performed a retrospective single-center study that compared 100 patients who received this regimen with a control group. The results showed no significant improvement in renal function. In contrast, plasma levels of creatinine and urea were increased in the drug regimen group. Thus, the effectiveness of PGE(1) in combination with high-dose furosemide and dopamine in diminishing DGF was not demonstrated in this trial.

[MCI-plus: mild cognitive impairment with rapid progression. Part II: Biomarkers and research methods]. / MCI-plus: leichte kognitive Beeinträchtigung mit rascher Progredienz. Teil II: Biomarker und Untersuchungsmethoden.

Long-term studies will be pivotal in order to examine the efficacy of preventive and early therapeutic interventions during the preclinical phase of dementia. Biomarkers will be of importance due to the large sample sizes and the necessary logistic efforts, high drop-out rates and slow clinical progression. The validity of functional and even structural imaging methods is currently investigated with early and promising results; it is presently unclear whether conventional csf-markers of Alzheimer's disease (beta-amyloid and tau-proteins) are sufficiently sensitive to monitor the effects of early interventions. It also remains doubtful whether modifications of these methods will ever be useful and available for practical purposes.

Muscle relaxant use for tracheal intubation in pediatric anaesthesia: a survey of clinical practice in Germany.

OBJECTIVES: Aim of this Germany-wide study was to evaluate the use and application customs of neuromuscular blocking drugs (NMBDs) for tracheal intubation in children of age 5 years or younger. MATERIAL AND METHODS: In the year 2005, a total of 3260 questionnaires were sent out to all heads of anesthesia departments at all types of hospitals as well as ambulatory anesthesia centers in Germany. The fields covered by the questionnaire were regarding institutional size, amount of general anesthesia and specifically pediatric cases, number of intubations and NMBDs used, frequency of use of the individual relaxants and techniques utilized when administering muscle relaxants. RESULTS: Of the sent-out questionnaires 66.9% could be analyzed: 82% of hospitals use 1-3 muscle relaxants in children; 91% of the ambulatory anesthesia centers use a repertoire of 1-2 neuromuscular blockers for pediatric cases. However, general anesthesia with tracheal intubation in children is often induced without using any NMBD at all. Mivacurium is the predominantly used NMBD for pediatric intubation in Germany. In contrast, the use of succinylcholine is far less in ambulatory anesthesia centers than in hospitals. Despite controversial discussion, precurarization, priming, and timing are still utilized in German anesthesia practice. CONCLUSION: In Germany, mivacurium, with its favorable pharmacologic profile for short cases, is the predominantly used NMBD for pediatric tracheal intubation. Despite the known adverse effects of intubation without muscle relaxation, this technique is also wide-spread, especially among German anesthetists in ambulatory anesthesia centers. Surveys like these are important to determine a status quo of use and application customs of NMBDs in pediatric anesthesia and provide a basis for numerous other studies.

[MCI-plus: mild cognitive impairment with rapid progression. Part I: prevention and therapy]. / MCI-plus: leichte kognitive Beeinträchtigung mit rascher Progredienz. Teil I: Prävention und Therapie.

Mild Cognitive Impairment (MCI) is a prevalent problem in the elderly and many patients show predictors of rapid cognitive decline ("MCI-plus"). MCI-plus represents a syndrome with growing importance in an ageing society, which will increasingly affect primary medicine and most other clinical specialties. We will have to face the dilemma of fast progress in the field of neurodiagnostics with innovative therapeutic strategies lagging behind. Psychological and medical co-morbidity in MCI-plus will therefore offer important opportunities to delay and to avoid the manifestation of dementia. We will review and discuss current training and treatment options including symptomatic and causal interventions.

[Application of neuromuscular monitoring in Germany]. / Einsatz des neuromuskulären Monitorings in Deutschland.

The aim of the present study was to evaluate application customs of neuromuscular monitoring in hospitals and private practice. Of the 3,260 questionnaires sent out, 2,182 could be analyzed. Of these 54% were from anaesthetists in private practice, 41% from heads of hospital anaesthesia departments and 5% from heads of level 1 hospital anaesthesia departments. In 12.1% of the hospital departments and 66.7% of private practices, no neuromuscular monitoring was available at all. In both hospital departments and private practices, clinical signs were the most often applied criteria for timing of reinjection of myorelaxants as well as for evaluation of neuromuscular recovery.

Blood interleukin 12 as preoperative predictor of fatal postoperative sepsis after neoadjuvant radiochemotherapy.

INTRODUCTION: The value of preoperative whole-blood interleukin (IL) 12 levels in predicting death from postoperative sepsis was evaluated, in patients stratified by underlying malignancy, neoadjuvant tumour treatment and surgical procedure. METHODS: Blood samples were collected from 1444 patients before major surgery. Whole blood was incubated with Escherichia coli lipopolysaccharide (LPS) and IL-12 production in supernatants was assessed by enzyme-linked immunosorbent assay. The prognostic impact of ability to synthesize IL-12 before surgery was investigated in patient subgroups with respect to sepsis-related mortality using multivariate binary logistic regression analysis. RESULTS: IL-12 synthesizing capability in patients who survived sepsis was significantly higher than that in patients who developed fatal sepsis (P = 0.006). In multivariate analysis only IL-12 was associated with a lethal outcome from postoperative sepsis (P = 0.006). The prognostic impact of IL-12 was evident in patients with underlying malignancy (P = 0.011) and in those who had undergone neoadjuvant tumour treatment (P = 0.008). When patients were analysed according to the type of neoadjuvant therapy, preoperative ability to synthesize IL-12 had a significant prognostic impact in patients who had neoadjuvant radiochemotherapy (P = 0.026), but not in those who had neoadjuvant chemotherapy. CONCLUSION: IL-12 production after stimulation of whole blood with LPS appears to be useful for the preoperative assessment of risk of sepsis-related death after operation in patients who have undergone neoadjuvant radiochemotherapy.

[Muscle relaxants in Germany 2005: a comparison of application customs in hospitals and private practices]. / Muskelrelaxanzien in Deutschland 2005: Ein Vergleich zwischen den Anwendungsgewohnheiten in Krankenhäusern und Praxen.

Aim of this study was to evaluate application customs of muscles relaxants in hospitals compared to their use in private practice. Of the 3,260 questionnaires sent-out, 66.9% could be analyzed. Of these 54% were from anesthetists in private practice, 41% from heads of hospital anesthesia departments and 5% from heads of level one hospital anesthesia departments. The first difference between private practices and hospitals was the number of available muscle relaxants: 87% of private practices use 1-3 relaxants, whereas 79% of hospitals use 3-5. Another apparent difference was the relationship between general anesthesia and the number of intubations: 60% of private practices have over 80% of general anesthesia cases, but only 50% of these patients are intubated. On the contrary, two thirds of the hospitals have 50-80% general anesthesia cases and 60-70% of patients are intubated. The main wish for an ideal muscle relaxant was independent of private practice or hospital, short onset time, followed by fast recovery. In accordance 74% of anesthetists in hospitals and 72% of anesthetists in private practice voiced the wish for a non-depolarizing succinylcholine substitute. The results of this nationwide survey suggest that time pressure in combination with an increased specialization of anesthetists in private practice are the main factors for availability and use of muscle relaxants in routine anesthesia.

Silica, silicosis and lung-cancer: results from a cohort study in the stone and quarry industry.

BACKGROUND: Workers compensated for silicosis outside the mining industry are at an increased risk of developing lung cancer. In the meta-analyses no data from Germany are involved. Furthermore, exposure data are necessary if a threshold value is to be assessed in order to reduce the risk for silicosis and also for lung cancer. METHOD: A cohort study among workers compensated for silicosis between 1988 and 2000 from the stone and quarry industry in Germany has been initiated. The cohort was followed up until the end of 2001. From all workers a detailed description of their jobs was assessed. RESULTS: Four hundred and forty workers were enrolled in the study. During the follow-up 144 workers died, compared with 74.35 expected cases based on the mortality rates of the general population from Germany, leading to a standard mortality ratio (SMR) of 1.94 (95% CI 1.63-2.28). Lung cancer was the cause of death in 16 cases (SMR 2.40; 95% CI 1.37-3.90). All workers had a peak exposure above 0.15 mg/m3, the current threshold value. The cumulative exposure was above 2 mg/m3.years and the average exposure was 0.10 mg/m3 or larger. No association between the exposure and the risk of developing lung cancer could be observed. CONCLUSIONS: Workers from the stone and quarry industry compensated for silicosis are at an increased risk of developing lung cancer. In order to reduce that risk, the exposure has to be lowered, with a peak exposure below 0.15 mg/m3 and an average exposure below 0.10 mg/m3.

[Telemedicine stroke department network. Introduction of a telemedicine pilot project for integrated stroke management in South Bavaria and analysis of its efficiency]. / Telemedizinisch vernetzte Schlaganfallstationen. Vorstellung des telemedizinischen Pilotprojekts zur integrierten Schlaganfallversorgung in Südostbayern und seiner Effizienzanalyse.

More than 100 stroke units have been established in Germany. In rural areas, however, acute stroke care needs to be improved. In order to advance clinical stroke therapy, two specialized stroke centers founded a telemedicine network (TEMPiS) among 12 community hospitals in eastern Bavaria. Each network hospital established specialized stroke wards where qualified teams manage acute stroke patients. Twenty-four hours daily, physicians in local hospitals are able to contact the stroke centers via videoconferencing including transmission of digital DICOM data. To study the efficacy of this network, a controlled trial will be performed. Five TEMPiS-network hospitals will be matched with five other hospitals equal in size, catchment area, and diagnostic techniques. For about 1 year, all consecutive stroke cases in the matched study hospitals will be prospectively recorded in a database. Neurological deficits will be quantified on the National Institute of Health Stroke Scale within 24 h after stroke onset. Mortality and institutional care as a combined primary endpoint will be assessed after 3 and 12 months. Furthermore, functional outcome according to the modified Rankin scale, Barthel score, and quality of life will be assessed using a standard telephone interview. Data acquisition started in July 2003, and final results are expected in 2005.

[Application of muscle relaxants for rapid-sequence induction of anaesthesia]. / Die Anwendung von Muskelrelaxanzien zur Blitzintubation in Deutschland.

The present study evaluates the use of muscle relaxants for rapid-sequence induction (RSI) and different application techniques (pre-curarisation, priming, timing) as a part of a nationwide survey in Germany. In 86.8% of anaesthesia departments succinylcholine is used for RSI and an average of 56.5% of respondents used only succinylcholine for RSI. Of all non-depolarising muscle relaxants rocuronium is the most frequently used alternative. Of the anaesthesia departments 2.6% use rocuronium regularly in patients with increased risk for aspiration of stomach contents; level one centres significantly more than others, 12.9% answered that pre-curarisation techniques were never used, whereas 45.6% use non-depolarising neuromuscular blocking drugs before giving succinylcholine in 80-100% of cases. Priming is not used by 64.4% of respondents, as opposed to 9.8% who utilise this technique regularly. The statements regarding timing are 71.1% and 5.4%, respectively. Alcuronium is used for RSI in departments in which the financial aspect is the primary decision criteria. Despite ist known side-effects and the on-going discussion over the past years, succinylcholine is still the most frequently used muscle relaxants for RSI. Priming is often declined by anaesthetists in Germany, most probably due to the absence of clear advantages and the possibility of severe complications. It is the opinion of the authors that timing but also drugs with a slow onset (e.g., alcuronium and Pancuronium) are obsolete in the context of RSI.

[The use of neuromuscular monitoring in Germany]. / Einsatz des neuromuskulären Monitorings in Deutschland.

AIM: As there are no reliable epidemiological data for the use of muscle relaxants in Germany,we conducted a mailing study. The aim of the study was to compare the use of muscle relaxants between German anaesthesia departments. In the present part of the presentation we focused on neuromuscular monitoring (NMM) and management of residual paralysis. METHODS: A total number of 2,996 questionnaires were sent to all registered anaesthesiological facilities in Germany and the return was 68.6% (2054 questionnaires). RESULTS: In 574 of the returned questionnaires (28%) the regular use of NMM was confirmed. Intraoperative monitoring of neuromuscular block and assessment of neuromuscular recovery were the most frequent applications of NMM, i.e. 25% and 18% of returned questionnaires, respectively. Clinical signs, however, are still the most popular way to estimate the degree of neuromuscular blockade. Moreover, routine reversal at the end of surgery with a neostigmin/atropine mixture was not practiced in 75% of the anaesthesia departments. CONCLUSIONS: This survey revealed that NMM is still very rarely used in daily clinical practice. Especially the seldom use of NMM to assess residual paralysis has to be improved.

[The use of muscle relaxants for routine induction of anesthesia in Germany]. / Anwendung von Muskelrelaxanzien zur Routineeinleitung in Deutschland.

The aim of this study was to evaluate the use of muscle relaxants during induction of anesthesia in patients without risk of aspiration of stomach contents. Of the 2,996 questionnaires sent out, 2,054 (68.6%) could be analysed and the results show that succinylcholine is used regularly in 13.6% of anesthesia departments. The next most commonly used muscle relaxants are atracurium, vecuronium and mivacurium, followed by cis-atracrium, rocuronium and pancuronium. Alcuronium is the least frequently used muscle relaxant. During induction of an elective anesthesia procedure, a priming technique is used by 19% of anesthesiologists, 22% utilize precurarization, and a timing technique is performed in 7.1%. The use of muscle relaxants for on-going relaxation follows the same pattern as for induction of neuromuscular blockade and succinylcholine is used in 1.4% if further relaxation is needed. The desire for specific qualities of muscle relaxants is correlated with higher use of the specific substance: short onset time for rocuronium, good controllability with mivacurium, no side-effects with cisatracurium and economical aspects with alcuronium. Of the participants 76.6% voiced the desire for a non-depolarizing replacement for succinylcholine.Private practices use mivacurium more often than hospitals, level one hospitals use rocuronium and cisatracurium more often. This survey could not show a definite standard of use in terms of muscle relaxants for an elective case.Precurarization, priming and timing are used frequently in patients not at risk of aspiration. This should be reduced by on-going teaching.

[Application of muscle relaxants in Germany. A survey of German anaesthesia departments]. / Anwendung von Muskelrelaxanzien in Deutschland. Eine Umfrage an Deutschen Anästhesieeinrichtungen.

AIM: The aim of this study was to evaluate the use and application of muscle relaxants and neuromuscular monitoring in Germany. METHODS: A total of 2,996 questionnaires were sent out to the heads of German anaesthesia departments and private anaesthesia practices. The questions covered frequency of muscle relaxants used,how they were used, and neuromuscular monitoring. Influences on the way muscle relaxants were used could be derived from the desire for specific properties of a muscle relaxant, the desire for different monitoring conditions and from the size of the institution. We correlated these features with application practice using logistic regression analyses. RESULTS: Of the 2,996 questionnaires 2,058 could be analysed (68.6%). Amongst those were 102 level one hospitals (5%) and 903 private practices (44%). The replies from 350 (17%) departments were based on surveyed data, 1,613 (78.5%) were based on estimations. The desire for certain properties of muscle relaxants correlated with the use in practice, as were the desire for a non-depolarizing replacement for succinylcholine, the size of the department and the frequency of use of neuromuscular monitoring. Over 50% of all German anaesthesia departments limited the use of muscle relaxants to three. The use of laryngeal masks reduced the use of muscle relaxants. CONCLUSIONS: The survey regarding use of muscle relaxants in Germany could for the first time give an overview on the use of anaesthesia-specific substances in Germany. From the different frequencies of use and use modalities,conclusions could be drawn towards a standard of application for the year 2000. Changes in this standard would raise the need for further trend surveys. The methods of statistical analysis and survey evaluation can be used as a base for further surveys.

Estimation of the general threshold limit values for dust.

In 1997 the German MAK Commission set new general threshold limit values for dust. The procedure has recently been assessed (McLaughlin et al. 2001). One of the points raised was the use of inappropriate statistical methods. We want to address this point to a greater extent by discussing several alternatives implied by the already established threshold models, and we present results from a new approach that has been refined in the meantime: the use of the additive isotonic model. The underlined assumption of monotonicity regarding the dose-response relationship has been extensively investigated. One very flexible model, based on smoothing splines, shows in some of the samples a decline in the risk over a certain range of the exposure compared to the risk at baseline. Another approach with fractional polynomials and segmented regression lines shows that this result can be explained by chance. These methods show an increasing risk with increasing exposure. Additionally, permutation tests are used to prove the trend within the isotonic framework. The results from the additive isotonic model confirm previous assessments of the general threshold limit value.