[Quality assurance concepts in intensive care medicine]. / Qualitätssicherungskonzepte in der Intensivmedizin.

Intensive care medicine (ICM) is characterized by a high degree of complexity and requires intense communication and collaboration on interdisciplinary and multiprofessional levels. In order to achieve good quality of care in this environment and to prevent errors, a proactive quality and error management as well as a structured quality assurance system are essential. Since the early 1990s, German intensive care societies have developed concepts for quality management and assurance in ICM. In 2006, intensive care networks were founded in different states to support the implementation of evidence-based knowledge into clinical routine and to improve medical outcome, efficacy, and efficiency in ICM. Current instruments and concepts of quality assurance in German ICM include core intensive care data from the data registry DIVI REVERSI, quality indicators, peer review in intensive care, IQM peer review, and various certification processes. The first version of German ICM quality indicators was published in 2010 by an interdisciplinary and interprofessional expert commission. Key figures, indicators, and national benchmarks are intended to describe the quality of structures, processes, and outcomes in intensive care. Many of the quality assurance tools have proved to be useful in clinical practice, but nationwide implementation still can be improved.

Feasibility and influence of hTEE monitoring on postoperative management in cardiac surgery patients.

Monoplane hemodynamic TEE (hTEE) monitoring (ImaCor(®) ClariTEE(®)) might be a useful alternative to continuously evaluate cardiovascular function and we aimed to investigate the feasibility and influence of hTEE monitoring on postoperative management in cardiac surgery patients. After IRB approval we reviewed the electronic data of cardiac surgery patients admitted to our intensive care between 01/01/2012 and 30/06/2013 in a case-controlled matched-pairs design. Patients were eligible for the study when they presented a sustained hemodynamic instability postoperatively with the clinical need of an extended hemodynamic monitoring: (a) hTEE (hTEE group, n = 18), or (b) transpulmonary thermodilution (control group, n = 18). hTEE was performed by ICU residents after receiving an approximately 6-h hTEE training session. For hTEE guided hemodynamic optimization an institutional algorithm was used. The hTEE probe was blindly inserted at the first attempt in all patients and image quality was at least judged to be adequate. The frequency of hemodynamic examinations was higher (ten complete hTEE examinations every 2.6 h) in contrast to the control group (one examination every 8 h). hTEE findings, including five unexpected right heart failure and one pericardial tamponade, led to a change of current therapy in 89% of patients. The cumulative dose of epinephrine was significantly reduced (p = 0.034) and levosimendan administration was significantly increased (p = 0.047) in the hTEE group. hTEE was non-inferior to the control group in guiding norepinephrine treatment (p = 0.038). hTEE monitoring performed by ICU residents was feasible and beneficially influenced the postoperative management of cardiac surgery patients.

Breed-specific hematologic reference intervals in healthy adult Dogues de Bordeaux.

BACKGROUND: There is an increasing interest for breed-specific reference intervals in veterinary medicine. In a previous study, breed-specific biochemical reference intervals (RIs) have been established for Dogues de Bordeaux (DDBs). This breed is predisposed to familial juvenile glomerulonephropathy and hypothyroidism, and would benefit from hematologic RI. OBJECTIVE: The purpose was de novo establishment of breed-specific hematologic RIs for the DDB in accordance with the International Federation of Clinical Chemistry and Clinical and Laboratory Standards Institute guidelines. METHODS: One hundred and twenty DDBs from France and Belgium were recruited. CBCs were determined with the Sysmex XT-2000iV analyzer within 12 hours of blood collection. RIs were determined using the nonparametric method. Effects of sex, age, and face mask color were studied. RESULTS: RIs were determined in 58 healthy dogs. DDBs had higher RIs for HGB, HCT, MCV, MCHC, and mean platelet volume, and lower RIs for reticulocytes counts, platelets by impedance (PLT-I) and optical count (PLT-O), and plateletcrit when compared with generic canine RIs. Age significantly affected RIs for HGB, HCT, MCHC, WBC, neutrophil, lymphocyte, and monocyte counts. CONCLUSION: The generic canine RIs established in the same laboratory with analogous preanalytical and analytical variations did not differ significantly from breed-specific RIs, and thus have no significant impact on clinical decision making; however, breed-specific RIs are advised for some RBC and all platelet-related variables to avoid erroneous suspicion of polycythemia and thrombocytopenia when using general canine RIs for evaluation of DDB.

[Quality management in intensive care medicine]. / Qualitätsmanagement in der Intensivmedizin.

Treatment of critical ill patients in the intensive care unit is tantamount to well-designed risk or quality management. Several tools of quality management and quality assurance have been developed in intensive care medicine. In addition to external quality assurance by benchmarking with regard to the intensive care medicine, peer review procedures have been established for external quality assurance in recent years. In the process of peer review of an intensive care unit (ICU), external physicians and nurses visit the ICU, evaluate on-site proceedings, and discuss with the managing team of the ICU possibilities for optimization. Furthermore, internal quality management in the ICU is possible based on the 10 quality indicators of the German Interdisciplinary Society for Intensive Care Medicine (DIVI, "Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin"). Thereby every ICU has numerous possibilities to improve their quality management system.

Hematologic reference intervals in Cynomolgus (Macaca fascicularis) monkeys.

BACKGROUND: Reference intervals are important aids for interpreting clinical pathology laboratory data especially in Cynomolgus monkey (Macaca fascicularis), the non-human primate species most widely used in biomedical research. The purpose of this study was to establish hematologic reference intervals for Cynomolgus according to the International Federation of Clinical Chemistry and Clinical and Laboratory Standards Institute guidelines using the databank at a primatology center. METHODS: Blood specimens from 272 healthy Cynomolgus imported from Mauritius, the Philippines and Vietnam, were analyzed. Reference intervals were established by nonparametric method. Effects of sex, age, body weight, and breeding origin were investigated. RESULTS: Hemoglobin, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration decreased slightly and mean corpuscular volume increased slightly with age. Lower red blood cell concentration, hemoglobin, and hematocrit were observed in monkeys from the Philippines. CONCLUSIONS: These hematology reference intervals, established according to international recommendations, can be used in settings using similar animals and analyzers.

Breed-specific biochemical reference intervals for the adult Dogue de Bordeaux.

BACKGROUND: Breed-specific reference intervals are of increasing interest in veterinary medicine. The health monitoring of the Dogue de Bordeaux, a breed predisposed to familial juvenile glomerulonephropathy and hypothyroidism, would benefit from specific reference intervals. OBJECTIVE: The purpose of this study was to establish breed-specific biochemical reference intervals for the Dogue de Bordeaux in accordance with the International Federation of Clinical Chemistry and Clinical and Laboratory Standards Institute guidelines. METHODS: One hundred and twenty Dogues de Bordeaux from France and Belgium were recruited. Complete urinalysis and chemistry panels, venous blood gas variables, total thyroxin and thyroid stimulating hormone, and fibrinogen and antithrombin were measured for each dog. Reference intervals were determined using the non-parametric method. Confounding variables such as sex, age and color of facial mask were analyzed. RESULTS: Due to pre-defined criteria for exclusion, 62 healthy dogs were finally selected for the reference intervals determination. Using the instrument manufacturer's generic canine RI for most analytes did not have a significant impact on potential clinical decisions, except for total proteins, ALT, AST, total cholesterol, lipase and total thyroxin, for which possible clinically relevant differences were noted. CONCLUSION: Specific reference intervals for biochemical analytes in the Dogue de Bordeaux were determined under controlled pre-analytical and analytical conditions, and according to international recommendations. The use of these breed-specific reference intervals is recommended when using the specified analytic instruments, especially for the 6 analytes for which the reference intervals differed considerably from those provided by manufacturers.

Confidence intervals of reference limits in small reference sample groups.

BACKGROUND: Reference intervals are the most common tool used to interpret results of laboratory tests. However, in veterinary clinical pathology, the number of available reference individuals is often small. OBJECTIVES: The purpose of this study was to investigate the effects of small reference sample groups on the imprecision of the reference limits. METHODS: Gaussian and log-Gaussian distributions of 10 ≤ n ≤ 750 values were analyzed. Reference limits and 90% confidence interval of limits (90% CI) were calculated. Imprecision of limits was estimated by the ratio of the width of the 90% CI: width of the reference interval (WCI/WRI). RESULTS: For Gaussian distributions, the WCI/WRI ratio cannot be expected to be lower than 0.2 when n < 55. In log-Gaussian distributions, the ratio greatly increases for the upper limit with skewness toward high values, whereas it moderately decreases for the lower limit. CONCLUSION: Independent of the size of the reference sample group, it is very important to report the CIs of the reference limits, which can be very large for small reference sample groups. When the sample size is very small (n < 20), calculations maybe misleading and it is better to instead report all values.

[Quality management in intensive care medicine]. / Qualitätsmanagement in der Intensivmedizin.

Treatment of critical ill patients in the intensive care unit is tantamount to well-designed risk or quality management. Several tools of quality management and quality assurance have been developed in intensive care medicine. In addition to extern quality assurance by benchmarking with regard to the intensive care medicine, peer review procedures have been established for external quality assurance in recent years. In the process of peer review of an intensive care unit (ICU), external physicians and nurses visit the ICU, evaluate on-site proceedings, and discuss with the managing team of the ICU possibilities for optimization. Furthermore, internal quality management in the ICU is possible based on the 10 quality indicators of the German Interdisciplinary Society for Intensive Care Medicine (DIVI, "Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin"). Thereby every ICU has numerous possibilities to improve their quality management system.

[Quality management in intensive care medicine. Indispensable for daily routine]. / Qualitätsmanagement in der Intensivmedizin : Unverzichtbar in der täglichen Routine.

In areas requiring maximum safety like intensive care units or operating room departments, modern quality management and risk management are essential. Treatment of critically ill patients is associated with high risk and, therefore, demands risk management and quality management. External quality assessment in intensive care medicine has been developed based on a core data set and quality indicators. A peer review procedure has been established. In addition, regional networks of intensive care physicians result in improved local networking. In intensive care medicine, this innovative modular system of quality management and risk management is pursued more consequently than in any other specialty.

An electronic tool for visual feedback to monitor the adherence to quality indicators in intensive care medicine.

Evidence-based medicine is often inadequately implemented in intensive care units (ICU); the aim of this study was to improve its implementation via a technical feedback system, using key performance indicators (KPI). The study evaluated 205 patients treated in a cardiac surgical ICU over a 6-month period (3 months before and 3 months after implementation of the feedback system). KPI adherence rates for sedation, delirium and pain monitoring, and completion of a weaning protocol before and after the implementation of the feedback system, were compared. Adherence rates for pain and delirium monitoring, and implementation of the weaning protocol, were significantly increased by the intervention. Adherence to KPIs for sedation, which were high at baseline, could not be further improved. Daily display of KPI implementation had a positive effect on adherence to standard operating procedures. Adherence to guidelines may be improved by using this feedback system as part of the clinical routine.

Estimation of reference intervals from small samples: an example using canine plasma creatinine.

BACKGROUND: According to international recommendations, reference intervals should be determined from at least 120 reference individuals, which often are impossible to achieve in veterinary clinical pathology, especially for wild animals. When only a small number of reference subjects is available, the possible bias cannot be known and the normality of the distribution cannot be evaluated. A comparison of reference intervals estimated by different methods could be helpful. OBJECTIVE: The purpose of this study was to compare reference limits determined from a large set of canine plasma creatinine reference values, and large subsets of this data, with estimates obtained from small samples selected randomly. METHODS: Twenty sets each of 120 and 27 samples were randomly selected from a set of 1439 plasma creatinine results obtained from healthy dogs in another study. Reference intervals for the whole sample and for the large samples were determined by a nonparametric method. The estimated reference limits for the small samples were minimum and maximum, mean +/- 2 SD of native and Box-Cox-transformed values, 2.5th and 97.5th percentiles by a robust method on native and Box-Cox-transformed values, and estimates from diagrams of cumulative distribution functions. RESULTS: The whole sample had a heavily skewed distribution, which approached Gaussian after Box-Cox transformation. The reference limits estimated from small samples were highly variable. The closest estimates to the 1439-result reference interval for 27-result subsamples were obtained by both parametric and robust methods after Box-Cox transformation but were grossly erroneous in some cases. CONCLUSION: For small samples, it is recommended that all values be reported graphically in a dot plot or histogram and that estimates of the reference limits be compared using different methods.

A new approach for the determination of reference intervals from hospital-based data.

BACKGROUND: Reference limits are some of the most widely used tools in the medical decision process. Their determination is long, difficult, and expensive, mainly because of the need to select sufficient numbers of reference individuals according to well-defined criteria. Data from hospitalized patients are, in contrast, numerous and easily available. Even if all the information required for a direct reference interval computation is usually not available, these data contain information that can be exploited to derive at least rough reference intervals. METHODS: In this article, we propose a method for the indirect estimation of reference intervals. It relies on a statistical method which has become a gold-standard in other sciences to separate components of mixtures. It relies on some distributional assumptions that can be checked graphically. For the determination of reference intervals, this new method is intended to separate the healthy and diseased distributions of the measured analyte. We assessed its performance by using simulated data drawn from known distributions and two previously published datasets (from human and veterinary clinical chemistry). RESULTS AND DISCUSSION: The comparison of results obtained by the new method with the theoretical data of the simulation and determination of the reference interval for the datasets was good, thus supporting the application of this method for a rough estimation of reference intervals when the recommended procedure cannot be used.

A multicentric retrospective study of serum/plasma urea and creatinine concentrations in dogs using univariate and multivariate decision rules to evaluate diagnostic efficiency.

BACKGROUND: Urea and creatinine are the most frequently used indirect markers in plasma and serum of glomerular filtration rate in dogs. Both have been shown to lack sensitivity but their diagnostic efficiency for the diagnosis of kidney disease has been minimally investigated. OBJECTIVE: The purpose of this retrospective study was to investigate the influence of possible factors of variation on both analytes and to determine whether specific decision rules should be drawn up for subpopulations of dogs. METHODS: The results of urea and creatinine measurements, breed, sex, age, and health status (healthy, renal disease, or nonrenal disease) of 3822 dogs were collected from the archives of 5 veterinary clinics. Data were analyzed with univariate and multivariate decision rules with and without adjustment. RESULTS: There were significant effects and interactions of almost all of the sources of variation. Slight improvements in diagnostic efficiency were obtained by adjusting the decision rules to these sources of variations. Univariate decision rules gave approximately the same diagnostic efficiency for urea and creatinine concentrations, with sensitivity and specificity in the range of 70% and 90%, respectively, using the upper limit of the reference interval as the threshold value. Multivariate decision rules provided only minor improvements in diagnostic efficiency. CONCLUSION: Simultaneous measurement of both urea and creatinine is of limited diagnostic value over the analysis of a single variable. Creatinine is the preferred analyte as it is affected by fewer extrarenal factors of variation.

Comparison of measurements of canine plasma glucose, creatinine, urea, total proteins, alanine aminotransferase, and alkaline phosphatase obtained with the APOLOWAKO and Vitros 250 analyzers.

The APOLOWAKO is an entirely automatic benchtop biochemistry analyzer that uses stabilized liquid reagents. It was tested for canine blood and plasma glucose, creatinine, urea, total proteins, alanine aminotransferase, and alkaline phosphatase. The APOLOWAKO gave very similar results for whole blood and the corresponding plasma (n=32). Within-laboratory imprecision was below 2.2% and 5.8% for substrates and enzymes, respectively. Comparison of results with whole blood by APOLOWAKO and with the corresponding plasma by Vitros 250 (n=139) showed very good correlations. Passing-Bablok's regression slopes ranged from 0.83 to 1.12 and intercepts were close to zero, except for ALP where the results obtained by APOLOWAKO were approximately 1.5 times higher than by Vitros. The APOLOWAKO system can be a reliable instrument in veterinary practices where larger systems are not available but it should be further validated and reference intervals should be determined.

Establishment of the European College of Veterinary Clinical Pathology (ECVCP) and the current status of veterinary clinical pathology in Europe.

After 5 years of development, the European College of Veterinary Clinical Pathology (ECVCP) was formally recognized and approved on July 4, 2007 by the European Board of Veterinary Specialisation (EBVS), the European regulatory body that oversees specialization in veterinary medicine and which has approved 23 colleges. The objectives, committees, basis for membership, constitution, bylaws, information brochure and certifying examination of the ECVCP have remained unchanged during this time except as directed by EBVS. The ECVCP declared full functionality based on the following criteria: 1) a critical mass of 65 members: 15 original diplomates approved by the EBVS to establish the ECVCP, 37 de facto diplomates, 7 diplomates certified by examination, and 5 elected honorary members; 2) the development and certification of training programs, laboratories, and qualified supervisors for residents; currently there are 18 resident training programs in Europe; 3) administration of 3 annual board-certifying examinations thus far, with an overall pass rate of 70%; 4) European consensus criteria for assessing the continuing education of specialists every 5 years; 5) organization of 8 annual scientific congresses and a joint journal (with the American Society for Veterinary Clinical Pathology) for communication of scientific research and information; the College also maintains a website, a joint listserv, and a newsletter; 6) collaboration in training and continuing education with relevant colleges in medicine and pathology; 7) development and strict adherence to a constitution and bylaws compliant with the EBVS; and 8) demonstration of compelling rationale, supporting data, and the support of members and other colleges for independence as a specialty college. Formal EBVS recognition of ECVCP as the regulatory body for the science and practice of veterinary clinical pathology in Europe will facilitate growth and development of the discipline and compliance of academic, commercial diagnostic, and industry laboratories in veterinary clinical pathology. Future needs are in developing sponsorship for resident positions, increasing employment opportunities, increasing compliance with laboratory, training, and continuing education standards, and advancing relevant science and technology.

Barrier function of the gut and multiple organ dysfunction after cardiac surgery.

We studied the influence of sequential involvement of the gastrointestinal (GI) tract on the development of multiple organ dysfunction (MOD) after cardiopulmonary bypass (CPB). One hundred and forty-six patients undergoing elective cardiac surgery were included in this prospective observational study. Standardized oral inert-sugar tests (sucrose, lactulose, mannitol, sucralose) were performed before and after CPB in different patients. Enzyme-linked immunosorbent assay of plasma levels of endotoxin core antibodies (EndoCAb) were performed peri-operatively. The functional mucosal surface was calculated from the amount of mannitol absorbed from the GI tract. Lower urine concentrations of absorbed mannitol were observed pre-operatively in patients developing MOD. In binary logistic regression this was an independent parameter. Decreased plasma concentrations of EndoCAb after surgery were seen in every patient, but were more significant in patients developing MOD. A reduced pre-operative functional mucosal surface may predict the early occurrence of MOD after surgery.

[Analysis of personnel costs after reorganization of intensive care using calculated diagnosis-related groups comparative data. An investigation at the Charité Berlin]. / Analyse der Personalkosten nach Reorganisation der Intensivmedizin mithilfe kalkulierter DRG-Vergleichsdaten. Eine Untersuchung an der Charité, Berlin.

BACKGROUND: In an extensive project intensive care units (ICUs) of the Charité University Hospital were reorganized. The aim of this investigation was to determine if staff costs after this reorganization are financed by modular profits of diagnosis-related groups (DRGs). METHODS: Staff costs of all non-pediatric intensive care units, including ICUs, intermediate care units and post-anaesthesia care units (PACUs) in the Charité University Hospital were compared with the modular profits of all DRGs of patients older than 14 years in 2005. These DRGs were converted into the German refined DRG (GDRG) system 4.0 from 2006 with calculations based on actual income for medical doctors and nurses in 2006. Due to changed wage agreements for the incomes of physicians in 2006 there was an increase of costs. For the other professional groups an increase in income is expected, which cannot be estimated at present. RESULTS: The calculation revealed that staff costs of the ICUs at the Charité University Hospital based on a current German mean base rate of 2,836 EUR were 4.2% above the modular profits of the DRGs. As a result of a structural reorganization of the ICUs, the costs of staff could be adapted to the modular profits. Under the conditions of the actual reduced base rate of Berlin of 2,955 EUR the costs and profits were nearly equal. As the financial impact of the reorganization of the ICUs will take full effect in the coming years, it can be anticipated that with an expected base rate of 2,949 EUR in 2010 the intensive care medicine of a University hospital in Germany can become profitable. DISCUSSION: The spectrum of intensive care medicine at the Charité University Hospital covers the maximum range of operative and non-operative medicine. After an extensive reorganization of the ICUs under the aspect of staff costs, intensive care medicine can become profitable under the 4.0 G-DRG system. With consequent reorganization the cost efficiency of staff can be optimized, particularly in the setting of high-end intensive care medicine.

Simultaneous and minimally invasive assessment of muscle tolerance and bioavailability of different volumes of an intramuscular formulation in the same animals.

Evaluation of skeletal muscle tolerance during development of new drug formulations for i.m. use is most often based on terminal methods performed in the target species after slaughtering. The objective of this study was to evaluate the effect of muscle damage on the pharmacokinetic parameters of the drug delivered into the muscle using an alternative, noninvasive method. Phenylbutazone (PBZ) was used as the test article. Six ewes received increasing volumes of a 20% PBZ i.m. formulation, according to a cross-over design, and an i.v. bolus of the same formulation. Serial blood samples were taken, and a pharmacokinetic analysis of the plasma activity of creatine kinase and plasma PBZ concentrations was carried out. The amount of muscle damage after i.m. administration of 2, 4, or 8 mL of PBZ, calculated from the area under the curve of plasma creatine kinase across time was 36, 76, and 178 g for a 70-kg ewe. The corresponding absolute bioavailability of PBZ was 100 +/- 32%, 96 +/- 19%, and 100 +/- 17%, and the maximal PBZ concentrations were 42 +/- 3.4, 74 +/- 8.8, and 119 +/- 18.2 microg/mL. The plasma clearance of PBZ (i.v.) was 4.2 +/- 0.94 mL.kg(-1).h(-1). In conclusion, the absolute bioavailability of PBZ after i.m. administration was not altered by the increased volume of formulation administered despite the overall increase in the extent of muscle damage.