Markus Mieth

Implementation of Practice Guidelines for Antifungal Therapy in a Surgical Intensive Care Unit and Its Impact on Use and Costs

Background: Considering the complexity of diagnosis, high costs of therapy and high morbidity and mortality of systemic fungal infections, antifungal therapy of intensive care patients should follow clearly defined guidelines. We outline the impact of a standardised practice of antifungal treatment in an interdisciplinary surgical intensive care unit of a university hospital. Methods: Therapy was intended to be optimised by implementation of standardised practice guidelines supported by the clinical pharmacist. Costs for antifungal agents during a period of 18 months before and after implementation of the practice guidelines were compared, respectively. Results: The intervention was associated with a significant decrease in use of antifungal agents. Analysis of data revealed a reduction in costs by 50%. This could substantially be attributed to the implementation of the practice guidelines. Conclusion: The implementation of standardised practice guidelines for antifungal therapy in intensive care units decreased the use of selected antifungal agents and resulted in substantial reduction in expenditure on antifungal agents.

L-arginine and asymmetric dimethylarginine are early predictors for survival in septic patients with acute liver failure.

Dysfunctions of the L-arginine (L-arg)/nitric-oxide (NO) pathway are suspected to be important for the pathogenesis of multiple organ dysfunction syndrome (MODS) in septic shock. Therefore plasma concentrations of L-arg and asymmetric dimethylarginine (ADMA) were measured in 60 patients with septic shock, 30 surgical patients and 30 healthy volunteers using enzyme linked immunosorbent assay (ELISA) kits. Plasma samples from patients with septic shock were collected at sepsis onset, and 24 h, 4 d, 7 d, 14 d and 28 d later. Samples from surgical patients were collected prior to surgery, immediately after the end of the surgical procedure as well as 24 h later and from healthy volunteers once. In comparison to healthy volunteers and surgical patients, individuals with septic shock showed significantly increased levels of ADMA, as well as a decrease in the ratio of L-arg and ADMA at all timepoints. In septic patients with an acute liver failure (ALF), plasma levels of ADMA and L-arg were significantly increased in comparison to septic patients with an intact hepatic function. In summary it can be stated, that bioavailability of NO is reduced in septic shock. Moreover, measurements of ADMA and L-arg appear to be early predictors for survival in patients with sepsis-associated ALF.

Pretransplant model for end stage liver disease score predicts posttransplant incidence of fungal infections after liver transplantation.

Liver transplant recipients are at a significant risk for invasive fungal infections (IFI). This retrospective study evaluated the impact of the pretransplant model for end stage liver disease (MELD) on the incidence of posttransplant IFI in a single centre. From 2004 to 2008, 385 liver transplantations were included, from which 210 transplantations were conducted allocated by Child Turcotte Pugh and 175 were allocated by MELD score. Both groups differed regarding the age of transplant recipients (50.1 ± 10.7 vs. 52.5 ± 9.9, P = 0.036), pretransplant MELD score (16.43 ± 8.33 vs. 18.29 ± 9.05), rate of re‐transplantations, duration of surgery, demand in blood transfusions and rates of renal impairments. In the MELD era, higher incidences of IFI (pre‐MELD 11.9%, MELD 24.0%, P < 0.05) and Candida infections (9% vs. 18.9%, P < 0.05) were observed. There was no difference in the incidence of probable or possible aspergillosis. Mortality, length of stay in intensive care or hospital, and duration of mechanical ventilation did not differ between the pre‐MELD and MELD era. Regardless the date of transplantation, patients with fungi‐positive samples showed higher mortality rates than patients without. MELD score was analysed as independent predictors for posttransplant IFI. Higher MELD scores predispose to a more problematic postoperative course and are associated with an increase in fungal infections.

Experimental Study of Cardiorespiratory and Stress Factors in Esophageal Surgery Using Robot-Assisted Thoracoscopic or Open Thoracic Approach

BACKGROUND Our aim was to compare cardiovascular and stress response to robotic technology during thoracoscopic mobilization and anastomosis of the esophagus vs the conventional open approach. DESIGN Randomized experimental study. SETTING Department of Experimental Surgery, University of Heidelberg. SUBJECTS Twelve pigs randomized to undergo robotic or conventional surgery (6 animals each). INTERVENTIONS Fundus rotation gastroplasty followed by esophageal mobilization and intrathoracic anastomosis by conventional or robotic surgery. MAIN OUTCOME MEASURES Mean arterial pressure, central venous pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac output, pulmonary vascular resistance, partial oxygen pressure, alveolar-arterial difference in partial pressure of oxygen, and arteriovenous oxygen content difference measured preoperatively, during esophageal manipulation, and 30 minutes after operation. Operative stress was assessed by plasma levels of cortisol and substance P. RESULTS Hemodynamic measures showed higher intraoperative central venous pressure and pulmonary vascular resistance in the open surgery group, whereas cardiac output was significantly decreased compared with the robotic group. Blood gas values showed significant deterioration during esophageal manipulation with open surgery in contrast to the robotic group. Substance P and cortisol levels were significantly higher with the open approach. CONCLUSIONS The robot-assisted approach is associated with improved intraoperative cardiopulmonary function and seems to be a less stressful technique.

Chirurgische Leistungsdokumentation – Hilft viel wirklich viel? Vergleich der Auswirkung von maximaler und geringer Dokumentationstiefe klinischer Patientendaten auf das theoretische Ertragsvolumen einer chirurgischen Klinik nach Einführung des DRG-basierten Entgeltsystems

ZusammenfassungEinleitung. Die bevorstehende Einführung eines DRG-basierten Abrechnungssystems in Deutschland soll der Forderung nach höherer Transparenz und Wirtschaftlichkeit im stationären Versorgungssektor Rechnung tragen. Eine maximale Dokumentationsqualität unter Erfassung aller potenziell relevanten Diagnosen erscheint als optimaler Lösungsweg zur Erzielung maximaler Erträge. Ziel der vorliegenden Studie war, die Abrechungsrelevanz unterschiedlicher Dokumentationstiefen klinischer Patientendaten zu ermitteln und abzuschätzen, wie evtl. zu treffende Qualitätssteigerungen personell zu realisieren sind. Methodik. In einer prospektiven Querschnittserhebung wurden klinische Daten von 402 Patienten erhoben und die theoretischen Ertragsvolumina einer Minimal-, und Maximaldokumentation unter Verwendung des Australian-Refined DRG-Systems verglichen. Hierfür wurden verschiedene Dokumentationsqualitäten definiert. Zur Detektierung von Bereichen besonderer Relevanz wurden die betrachteten Fälle 23 Behandlungsgruppen zugeordnet. Ergebnisse. In 267 Fällen bestimmte nur eine Hauptdiagnose den Ertrag, in 137 Fällen (34%) wurde der Ertrag maßgeblich durch die Dokumentation weiterer Diagnosen erhöht. Die Hälfte dieses theoretischen dokumentationsbedingten Ertragsgewinnes konnte nur durch den Einsatz eines zusätzlichen, von der Patientenbehandlung unabhängigen ärztlichen Dokumentars erzielt werden. Dabei scheint es eine Effizienzobergrenze zu geben, da höchste Gewinne keine maximale Anzahl an dokumentierten Diagnosen erfordern. Besonders bei gravierenden Pathologien und komplexen Operationen erbrachte die maximale Dokumentation Ertragsgewinne. Schlussfolgerungen. Eine hohe Dokumentationstiefe hat einen bedeutenden Einfluss auf das Ertragsvolumen ärztlicher Leistung im Hinblick auf eine leistungsgerechte Vergütung in Zeiten der DRGs. Die Höhe der theoretischen Ertragsgewinne einer Maximaldokumentation unterstreicht die Notwendigkeit einer maximalen Dokumentationsqualität. Diese maximale Dokumentationsqualität und Effizienz scheint nicht durch alleinige Dokumentationsarbeit des behandelnden Stationsarztes in der klinischen Routine erreichbar.AbstractIntroduction. The forthcoming introduction of a DRG-based account system in Germany aims at higher transparency and economic efficiency, particularly in the sector of in-patient health care. The availability of documentation of the highest quality, taking into account all potentially relevant diagnoses, appears to be the best method for achieving maximum revenue in individual surgical units. The aim of the study was to determine the relevance of various degrees of documentation depth on calculated DRG-based revenue. Furthermore, we evaluated whether improvements in the quality of documentation can be realized in current hospital organization. Methods. In a prospective study, clinical data from 402 in-patients were collected and revenues were calculated based on the Australian-Refined DRG system. Various qualities of documentation were defined. In order to find the medical sectors most sensitive to “under-documentation”, homogenous cases were classified into 23 treating groups, according to diagnosis. Results. In 267 cases, maximum revenue was determined only by one main diagnosis, while better results could be achieved in 137 cases (34%) by extended documentation quality. Half of this gain could only be achieved by an independent medical documentation specialist. An upper limit of documentation intensity (number ofdiagnoses) could be defined. Maximum gain did not require maximum number ofdiagnoses. Conclusions. Documentation depth has an important influence on the calculated revenue of surgical therapy based on AR-DRG system. The quality and depth of the documentation is not, in itself, sufficient. In order to be really effective, it requires the highest degree of professionalism from hospital staff.

Cost distribution of orthotopic liver transplantation: single-center analysis under DRG-based reimbursement.

Costs of orthotopic liver transplantation (OLT) are influenced by multiple factors. Surgeons must be interested in determining the probability of meeting the projected cost averages. Costs of procedures, labor, drugs and pharmaceuticals, materials, and overhead costs of infrastructure were calculated during the primary stay in 38 consecutive patients undergoing OLT at a single center. Endpoint of cost aggregation was discharge from acute care. Costs per patient were grouped to plot the cost density distribution function. Mean cost of OLT was &U20AC;49,000. Costs showed a large variation, ranging from &U20AC;18,000 to &U20AC;189,000 per case. Most patients were grouped in the G-DRG-A01C split (n=31), which characterizes the least resource consumptive split. Costs of OLT were not normally distributed. There was a left-skewed beta-distribution of costs. Labor-related costs were responsible for the largest cost fraction (mean 42.9%), whereas drugs and medication accounted for 24.9% on average. Most patients could be transplanted within cost groups below &U20AC;50,000. The marked cost heterogeneity after OLT suggests that primarily medical comorbidities are of relevance for extraordinary resource consumption. A minimum number of transplants should be performed in single institutions to improve chances to financially counterbalance higher costs of individual cases under DRG-based reimbursement. Small programs have to bear increased risks of financial distortion. The asymmetry of cost distribution after OLT should be taken into account in future reimbursement regulations.

Viral Infections in Septic Shock (VISS-Trial)-Crosslinks Between Inflammation and Immunosuppression

BACKGROUND Recent investigations provided evidence that herpes simplex virus (HSV-1) and cytomegalovirus (CMV) are reactivated in critically ill individuals. However, at this time, it remains unclear whether these viral infections are of real pathogenetic relevance or represent innocent bystanders. MATERIALS AND METHODS In total, 60 patients with septic shock were enrolled. Blood samples and tracheal secretion were collected at the time of sepsis diagnosis (T0) as well as 7 d (T1), 14 d (T2), 21 d (T3), and 28 d (T4) later. The following virologic diagnostics were performed: (1) Viral load of herpes simplex virus type1 (HSV-1) and cytomegalovirus (CMV) in blood samples as well as tracheal secretion using polymerase chain reaction (PCR). (2) Detection of CMV-antigen (pp65) in blood samples using immunofluorescence microscopy. Furthermore plasma levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were evaluated using ELISA-kits. RESULTS Thirty-one patients (51.7%) were found to be positive for HSV-1, whereas in 16 patients (26.7%) CMV could be identified. Patients with a positive PCR for HSV-1 and/or CMV showed a significantly prolonged length of hospital stay and absolute time of respirator-dependant ventilation. Furthermore, survival curves of patients with a high HSV-1-load (>10E8) in tracheal secretion in comparison with those with a lower HSV-1-load (<10E8) revealed a significantly impaired survival. CONCLUSIONS Viral superinfections with HSV-1 or CMV can frequently be observed in patients with septic shock, especially in those with increased disease severity and a prolonged need for respirator-dependant ventilation. In patients with a viral superinfection morbidity is increased, whereas differences in mortality seem to be dosage-dependant.

Does Borderline Kidney Allograft Rejection Always Require Treatment

Background. Borderline rejection (Bord-R) is a frequent diagnosis in renal transplantation, and there is increasing evidence that regulatory T lymphocytes are involved in its pathogenesis. Current histopathologic practice does not differentiate between graft-protecting and -damaging T lymphocytes, and patients with Bord-R routinely receive rejection treatment. We analyzed Treg-associated forkhead box P3 (Foxp3) gene expression in Bord-R and more severe forms of acute rejection episodes (ARE). Methods. Foxp3 transcripts were measured in 520 serial peripheral blood samples from 177 kidney graft recipients obtained during the first 20 days posttransplantation. Results. The highest Foxp3 transcripts were observed in patients with Bord-R or without rejection and the lowest in patients with ARE. Patients with Bord-R on posttransplant days 5 to 7 showed an increased Foxp3 transcript level of 156%, which increased to 302% by posttransplant days 14 to 16. In contrast, patients with ARE demonstrated significantly lower Foxp3 gene expression than that observed in Bord-R, nonrejectors, or acute tubular necrosis patients (P=0.001, P<0.001, and P=0.005, respectively, on days 11–13). Acute tubular necrosis patients demonstrated intermediately high Foxp3 gene expression. Conclusions. Our data indicate that increased Treg activity in peripheral blood is a frequent feature of Bord-R. This finding questions the appropriateness of rejection treatment in all patients with the histopathologic diagnosis “Bord-R”.

Cell death biomarkers as early predictors for hepatic dysfunction in patients after orthotopic liver transplantation.

Background Valid prognostic factors for early identification of a complicated course after orthotopic liver transplantation from deceased donors are rare. The aim of this study was to investigate the prognostic value of different cell death biomarkers and inflammatory markers in patients after orthotopic liver transplantation from deceased donors. Methods In total, 100 patients were evaluated for short-term complications within 10 days after orthotopic liver transplantation from deceased donors. Blood samples were collected before surgery, immediately after the end of the surgical procedure, and 1 day and 3, 5, and 7 days later. Plasma levels of total keratin 18, keratin 18 fragments, interleukin 6, tumor necrosis factor &agr;, and soluble intercellular adhesion molecule 1 were measured. Results Total keratin 18 was demonstrated to be favorable in its prognostic value for early identification of a complicated course in comparison to routine markers of liver impairment (e.g., aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase). In contrast, inflammation markers (e.g., interleukin 6, tumor necrosis factor &agr; and soluble intercellular adhesion molecule 1) were unsuitable for predicting early complications after liver transplantation from deceased donors. Conclusions For early identification of patients at high risk for complications, the implementation of total keratin 18 measurements in routine diagnostics after orthotopic liver transplantation from deceased donors should be taken into consideration.

Early post-transplant neopterin associated with one year survival and bacteremia in liver transplant recipients

Bacterial infections are the most common complications, and the major cause of mortality after liver transplantation (Tx). Neopterin, a marker of immune activation, is produced in monocyte/macrophages in response to inflammation. The aim of our study was to investigate whether early post-operation serum levels of neopterin were associated with post-transplant bacteremia and mortality in liver transplant recipients. We studied 162 of 262 liver Tx patients between January 2008 and February 2011 of whom pre- and early post-Tx sera samples were available. Pre- and early post-operative risk factors of infection and mortality were evaluated in 45 bacteremic patients and 117 non-bacteremic patients. During one-year follow-up, 28 of 262 patients died because of graft failure, septicemia and other diseases. Post-Tx serum neopterin on day 10 (p<0.001) were significantly higher in bacteriemic patients than in patients without bacteremia. Logistic regression analyses showed that day 10 post-Tx neopterin serum level ⩾40 nmol/l has a predictive value (OR=6.86: p<0.001) for bacteremia and mortality (OR=3.47: p=0.021). Our results suggest that early post-Tx neopterin serum levels are very sensitive predictive markers of one-year post-Tx bacteremia and mortality in liver Tx recipients.