Effect of rivaroxaban on blood coagulation using the viscoelastic coagulation test ROTEM™.

This study investigated the influence of the oral direct inhibitor of factor Xa rivaroxaban on blood coagulation measured by rotation thrombelastometry ROTEM™. Blood was obtained from 11 healthy male volunteers before and 2.5 h after oral administration of 10 mg rivaroxaban. In addition to standard coagulation tests clot formation was measured by ROTEM™ analyzing extrinsic (Extem) and intrinsic thrombelastometry (Intem). Significant differences to the baseline values were found in the Extem clotting time (Extem-CT, 58 ± 9 s and 87 ± 17 s, p < 0.01), Intem-CT (194 ± 26 s and 239 ± 43 s; p = 0.02), prothrombin time (PT, 86 ± 9% and 67 ± 7%; p < 0.01) and activated partial thromboplastin time (aPTT, 28 ± 1 s and 35 ± 2 s; p < 0.01). There was a low correlation between Extem-CT and PT as well as between Intem-CT and aPTT before and after rivaroxaban intake. The receiver operating characteristic curve (ROC) analysis determined aPTT to be the most appropriate parameter for the prediction of rivaroxaban-induced anticoagulation, Intem-CT and Extem-CT proved to be moderate tests and PT had no significance in the prediction of rivaroxaban-induced anticoagulation. Of utmost clinical importance was the fact that rivaroxaban treated patients could still show normal ROTEM™ values. Thus, ROTEM™ cannot be a suitable test method to exclude inhibition of blood coagulation by rivaroxaban.

Scientific fraud in 20 falsified anesthesia papers : detection using financial auditing methods.

Data from natural sources show counter-intuitive distribution patterns for the leading digits to the left of the decimal point and the digit 1 is observed more frequently than all other numbers. This pattern, which was first described by Newcomb and later confirmed by Benford, is used in financial and tax auditing to detect fraud. Deviations from the pattern indicate possible falsifications. Anesthesiology journals are affected not only by ghostwriting and plagiarism but also by counterfeiting. In the present study 20 publications in anesthesiology known to be falsified by an author were investigated for irregularities with respect to Benford's law using the χ(2)-test and the Z-test. In the 20 retracted publications an average first-digit frequency of 243.1 (standard deviation SD ± 118.2, range: 30-592) and an average second-digit frequency of 132.3 (SD ± 72.2, range: 15-383) were found. The observed distribution of the first and second digits to the left of the decimal point differed significantly (p< 0.01) from the expected distribution described by Benford. Only the observed absolute frequencies for digits 3, 4 and 5 did not differ significantly from the expected values. In an analysis of each paper 17 out of 20 studies differed significantly from the expected value for the first digit and 18 out of 20 studies varied significantly from the expected value of the second digit. Only one paper did not vary significantly from expected values for the digits to the left of the decimal. For comparison, a meta-analysis using complex mathematical procedures was chosen as a control. The analysis showed a first-digit distribution consistent with the Benford distribution. Thus, the method used in the present study seems to be sensitive for detecting fraud. Additional statements of specificity cannot yet be made as this requires further analysis of data that is definitely not falsified. Future studies exploring conformity might help prevent falsified studies from being published.

Effects on coagulation of balanced (130/0.42) and non-balanced (130/0.4) hydroxyethyl starch or gelatin compared with balanced Ringer's solution: an in vitro study using two different viscoelastic coagulation tests ROTEMTM and SONOCLOTTM.

BACKGROUND: Hydroxyethyl starch (HES) solutions compromise blood coagulation. Low molecular weight, low-substituted HES products, and electrolyte-balanced solutions might reduce this effect. We compared the effects of in vitro haemodilution on blood coagulation with a balanced 6% HES 130/0.42 solution (HES(BAL)), a saline-based 6% HES 130/0.4 solution (HES(SAL)), a balanced lactated Ringer's solution (RL) and a saline-based 4% gelatin solution (GEL). METHODS: Blood was obtained from 10 healthy male volunteers and diluted with the test solutions by 33% and 66%. Quality of clot formation was measured using two viscoelastic coagulation tests: SONOCLOT and activated rotation thromboelastometry ROTEM. RESULTS: Of 16 parameters measured by the viscoelastic devices, we found three statistically significant differences compared with baseline for RL, but 11 for GEL, 10 for HES(SAL), and 11 for HES(BAL) in the 33% haemodilution group (P=0.01). Comparing the different solutions, we observed a significant difference between crystalloids and colloids but none between GEL and HES. In the 66% dilution group, effects on blood coagulation were increased when compared with the 33% dilution group. We found no differences in coagulation impairment between balanced and non-balanced HES products and no differences in the detection of impaired blood coagulation due to haemodilution between the two viscoelastic coagulation tests. CONCLUSIONS: Both ROTEM and SONOCLOT are sensitive tests for the detection of impaired blood coagulation due to haemodilution. There are fewer effects on blood coagulation using crystalloids compared with colloids. The effects of GEL and HES are similar. There is no difference between balanced HES 130/0.42 and non-balanced HES 130/0.4.

[Statistical process control as a monitoring tool for the evaluation of reorganisation measures. Investigation in an intensive care unit]. / ''Statistische Prozesskontrolle'' als Monitoring-Tool zur Evaluierung von Reorganisationsmassnahmen. Untersuchung auf einer Intensivstation.

INTRODUCTION: The German health care system is currently in a constant state of flux owing to enhanced competition and to the increasing focus on economic aspects. Medical services, especially treatment processes, are being reorganised in an attempt to adapt them to the new economic challenges. Ideally, radical reorganisation and streamlining of medical therapy processes should be accompanied by controlling and quality management systems. The purpose of this is to monitor the intensity of any economic and any patient-related (side)-effects. Business management techniques are needed that allow online and long-term performance reviews of reorganisation measures once initiated. METHODS: In industry, the method applied for this purpose is statistical process control (SPC). The present study demonstrates for the first time that use of this monitoring tool can be extended to the medical sector. In an intensive care unit (ICU) the following process parameters were monitored: duration of sedation, time to persisting spontaneous breathing, length of stay in ICU, length of stay in hospital, patient mortality in ICU and in the next 30 days after admission to the ICU. Group 1 was made up of 87 patients examined before and group 2, 93 patients after process optimisation. The main feature of the reorganisation was application of a new analgo-sedation technique and of the weaning concept. RESULTS: In group 2 duration of sedation, time to spontaneous breathing and length of stay on the ICU were significantly shorter than in group 1. The length of stay in hospital, patient mortality in the ICU and 30 days after the initiation of intensive care did not differ significantly between the two groups. CONCLUSION: Economic and patient-related key figures can be evaluated with SPC. It allows online assessment both before and during process optimisation, and especially in the long term afterprocess optimisation.

[Respiratory failure due to delta-9-tetrahydrocannabinol in a tetraplegic patient]. / Respiratorische Insuffizienz durch Delta-9-Tetrahydrocannabinol bei tetraplegischem Patienten.

We report on a patient with an incomplete tetraplegia below C2 who suffered from a post-traumatic abdominal spasticity, spasticity of the legs, and bladder contractions of high intensity. Breathing was possible during the day using accessory respiratory musculature. All standard therapeutic regimes against spasticity failed. Treatment was started with delta-9-tetrahydrocannabinol administered orally in a dosage of 2 x 2.5 mg/day. The spasticity of the legs and the bladder improved with the treatment. After 3 days, the patient complained about dyspnea and shortness of breath. Treatment with delta-9-tetrahydrocannabinol was discontinued after 5 days but the patient needed ventilatory support for 1 week. After 1 week, spontaneous breathing was possible again. The reasons for respiratory failure in endangered patients during treatment with delta-9-tetrahydrocannabinol could be effects such as sedation, combined treatment with baclofen, muscle weakness, or central nervous effects in the medulla oblongata.

Improving time-sensitive processes in the intensive care unit: the example of 'door-to-needle time' in acute myocardial infarction.

OBJECTIVE: To assess and reduce delays in coronary thrombolysis in patients with acute myocardial infarction. DESIGN: Prospective, descriptive study using statistical process control. SETTING: Interdisciplinary intensive care unit of a 300-bed community hospital. SUBJECTS: Thirty-seven consecutive patients with acute myocardial infarction who were receiving thrombolytic therapy. INTERVENTIONS: To perform an interdisciplinary formal process analysis aimed at detecting delay-causing factors, review of existing house rules, generation and implementation of new practice guidelines. MAIN OUTCOME MEASURES: Comparison of 'door-to-needle times' of patients admitted before, during and after formal process analysis and implementation of new guidelines. RESULTS: Mean 'door-to-needle time' fell significantly from 57 minutes (+/-25.4) in 16 patients studied before, to 32 minutes (+/-9.0) in 16 patients studied after the formal process analysis and the implementation of new guidelines (P < 0.002). An even more pronounced but transient decrease to 24 minutes (+/-3.8) was observed in five patients studied during the phase of formal process analysis (P < 0.004). Delay-causing factors were identified in the areas 'communication', 'people' and 'methods/rules/guidelines'. Equipment failure was never responsible for delays. CONCLUSIONS: Formal process analysis, followed by implementation of revised guidelines resulted in a significant reduction of 'door-to-needle time'. An initial dramatic but transient reduction of 'door-to-needle time' was considered observational and must not be mistaken as the definite new level of performance. We conclude that formal process analysis techniques are suited to improve processes in the intensive care unit.

Generating a learning curve for pediatric caudal epidural blocks: an empirical evaluation of technical skills in novice and experienced anesthetists.

BACKGROUND AND OBJECTIVES: Learning curves for anesthesia procedures in adult patients have been determined, but no data are available on procedures in pediatric anesthesia. The aim of this study was to assess the number of caudal blocks needed to guarantee a high success rate in performing caudal epidural analgesia in children. METHODS: At a teaching hospital, the technical skills of 7 residents in anesthesiology who performed caudal blocks were evaluated during 4 months using a standardized self-evaluation questionnaire. At the start of the study period, the residents had no prior experience in pediatric anesthesia or in performing caudal epidural blocks. All residents entered the pediatric rotation after a minimum of 1 year of training in adult general and regional anesthesia. The blocks were rated using a binary score. For comparison, the success rates of 8 experienced staff anesthesiologists were collected during the same period using the same self-evaluation questionnaire. Statistical analyses were performed by generating individual and institutional learning curves using the pooled data. The learning curves were calculated with the aid of a least-square fit model and 95% confidence intervals were estimated by a Monte Carlo procedure with a bootstrap technique. RESULTS: The success rate of residents was 80% after 32 procedures (95% confidence interval of 0.59 to 1.00). The pooled success rate of the staff anesthesiologists was 0.73 (mean) with a standard deviation of 0.45, which was not statistically different from the success rate of the residents. CONCLUSION: High success rates in performing caudal anesthesia in pediatric patients can be acquired after a limited number of cases. Success rates of residents learning this procedure are comparable to the results of staff anesthesiologists.

In vitro effects of different medium molecular hydroxyethyl starch solutions and lactated Ringer's solution on coagulation using SONOCLOT.

UNLABELLED: Hydroxyethyl starch (HES) solutions are widely used to replace intravascular volume. HES solutions differ from each other with regard to molecular weight and mode of hydroxyl substitution (degree of hydroxylation, C2:C6 hydroxyethyl ratio, concentration), factors which may have varying effects on coagulation. We studied, in vitro, three different HES preparations (molecular weight/degree of hydroxylation/concentration/C2:C6 ratio of substitution 70.000/0. 5/6%/3.2; Pharmacia & Upjohn Co., Erlangen, Germany; 130.000/0. 4/6%/11.2 and 200.000/0.5/6%/4.6; Fresenius Co., Bad Homburg, Germany) and, for comparison, lactated Ringer's solution (RL) at 33% and 66% dilution with whole blood. The influence of hemodilution was measured by using routine laboratory variables and SONOCLOT (Sonoclot II Coagulation and Platelet Function Analyzer, Sienco Co.) analysis, using a viscoelastic test, on the cellular as well as on the plasmatic hemostatic system. For statistical analysis of quantitative data, we used nonparametric analysis of variance and adequate post hoc tests. Qualitative data were analyzed by using the nonparametric Kruskal-Wallis test. A P value below 0.05 was considered significant. In contrast to the control group with RL, the liquid phase of coagulation (activated clotting time) was slightly affected by the 33% diluted HES solutions. HES 70.000, 130. 000, and 200.000 interfered significantly with the early stage of coagulation as expressed by the clot rate (gel/fibrin formation). Clot maturation and speed of maturation (time to peak) were strongly affected by HES 70.000 at all grades of dilution. HES 130.000 showed a faster clot formation process compared with the other HES solutions. HES 130.000 diluted 33% showed a better clot retraction as compared with the other HES solutions. In conclusion, in vitro hemodilution comparing different medium molecular weight HES solutions reveals that HES 130.000 seems preferable regarding some aspects of clot formation and retraction. RL affected clot formation only minimally, except for the early activation of clotting, which was measured by a shortened activated clotting time. IMPLICATIONS: We investigated the effect of different hydroxyethyl starch (HES) solutions (70.000, 130.000, 200.000) on coagulation. Regarding clot formation and retraction, HES 130.000 had some advantages over the other tested HES solutions. Lactated Ringer's solution affected coagulation only minimally, except for the early stage of clot formation.

The effects of in vitro hemodilution with gelatin, hydroxyethyl starch, and lactated Ringer's solution on markers of coagulation: an analysis using SONOCLOT.

UNLABELLED: Blood-saving strategies have recently been established to avoid allogeneic transfusion during surgery or after trauma. This includes an expanding use of crystalloids and colloids. These solutions interfere with coagulation systems, but quantitative measurements are still lacking. The SONOCLOT (Sienco Company, Morrison, CO) analysis (SCT), a viscoelastic test, measures clot formation and includes information on the cellular, as well as the plasmatic coagulation, system. To quantify hemodilutional effects on in vitro coagulation, we studied gelatin (G), hydroxyethyl starch 6% (HES; molecular weight 450,000), and lactated Ringer's solution (RL) in 33% and 66% dilutions measuring routines laboratory and SCT variables. Hemodilution with RL tended to increase in vitro coagulability. Among the tested colloids, G had the least impact on markers of coagulation. G33% did not differ significantly from the undiluted control group. HES had the largest impact on markers of coagulation compared with G and RL. In conclusion, SCT provides a fast and easy to perform bedside test to quantify in vitro hemodilution. IMPLICATIONS: The effects of progressive hemodilution on coagulation are difficult to measure. SONOCLOT analyses provide an easy to perform test with fast information on cellular and plasmatic coagulation properties. Among colloids, hydroxyethyl starch has the largest impact on markers of coagulation compared with gelatin or lactated Ringer's solution.

Transurethral resection syndrome: effect of the introduction into clinical practice of a new method for monitoring fluid absorption.

STUDY OBJECTIVE: To determine the effects of introduction of a new monitoring system for fluid absorption during transurethral resection of the prostate (TURP) using an irrigating solution containing 0.5% alcohol. STUDY DESIGN: Prospective clinical investigation, with implementation of statistical process control. SETTING: Inpatients for TURP at a major non-university teaching hospital. PATIENTS: 312 male ASA physical status I, II, III, and IV patients scheduled for TURP. INTERVENTIONS: Intraoperative breath alcohol levels were measured for detection of fluid absorption. MEASUREMENTS AND MAIN RESULTS: Calculation of the amount of fluid absorbed using measured breath alcohol values. Process variability (i.e., numbers of patients with significant fluid absorption) was defined by statistical process control tools. No trend change of prevalence of fluid absorption was noted until 150 procedures had been completed. Reduction of prevalence of significant fluid absorption was noted and no patients were treated postoperatively in the intensive care unit. No relevant side effects were seen in patients with significant fluid absorption. No mortality and no severe clinical morbidity was seen after the introduction of the new monitoring. CONCLUSION: Using an irrigating fluid marked with 0.5% ethanol resulted in a decreased prevalence of fluid absorption over time.

The prevalence of latex sensitivity among anesthesiology staff.

Reports dealing with allergic reactions to latex among health care professionals are increasing steadily. This study is the first epidemiological investigation of latex allergy among anesthesia staff. We tested 101 persons of the staff of the Institute of Anesthesiology, Kantonsspital, Lucerne, Switzerland, using a standardized questionnaire, prick test (latex extract), scratch test (latex glove), and immunoglobin E (IgE) analysis. Sixteen of 101 persons (15.8%) had a positive skin test. Two of them had a positive radioallergosorbent test (RAST) Class II, and one person was Class I. Risk factors were a history of atopy (P < 0.001) and positive skin tests on atopy screening (P = 0.016). IgE levels were increased in the latex-sensitive group. Three of the 11 sensitized persons (total sensitized persons 16) who performed spirometry had significantly reduced expiratory peak flow values during working hours. It is concluded that anesthesiology staff is at high risk of allergic sensitization to latex. The most important risk indicator was an atopy. Skin tests are more sensitive than blood tests (i.e., specific antibodies, IgE).

Are fractures of the base of the skull influenced by the mass of the protective helmet? A retrospective study in fatally injured motorcyclists.

STUDY HYPOTHESIS: Information on the influence of the mass of the helmet on the pattern of head injuries suffered by motorcyclists involved in collisions is scarce. This study was undertaken to verify a possible connection between the weight of the helmet worn and the occurrence of a ring fracture of the base of the skull surrounding the foramen magnum. DESIGN: One hundred twenty-two fatally injured motorcyclists were studied retrospectively. In all cases, an autopsy had been performed. Data, including the autopsy report, were obtained from official police files. All helmets were studied in a technical laboratory. Statistical tests were performed using ANOVA, Fisher's exact test, Student's t test, and the chi 2 test. A p < 0.05 was considered significant. RESULTS: The overall incidence of this type of injury was 9.2%. There was a positive correlation between the incidence of complete or partial circular fractures of the base of the skull and the weight of the involved helmet. There was a significant increase (p = 0.012) in the incidence of this type of fracture when the helmet weighed more than 1,500 grams. An increase in the dynamic active mass caused by the combination of head and helmet leads to a supramaximal stress load during a collision, resulting in such injuries. CONCLUSIONS: In accidents with axial load shift, helmets weighing more than 1,500 grams increase the risk of a basal skull fracture. Therefore high-weight helmets should be avoided.