E. Klar

The efficacy of N-acetylcysteine as a hepatoprotective agent in liver transplantation

Abstract One of the most common complications after liver transplantation is primary graft dysfunction which results from severe deterioration of the microcirculation. The data obtained from our experimental studies indicate that N‐acetylcysteine (NAC) is able to reduce the severity of ischemia/reperfusion injury and improves postoperative graft function after liver transplantation in rats. The aim of this pilot study was to evaluate the efficacy of NAC as a hepatoprotective agent under clinical conditions. A group of 30 liver transplanted patients were treated with NAC, and 30 patients (control group) were treated with a 5 % solution of glucose only. In the NAC group we observed a distinct reduction in ischemia/reperfusion injury and improved liver function with less elevated peak transaminases, better macrocirculation, improved liver synthesis function and a lower incidence of primary nonfunction compared with the control group. We conclude that NAC is a very promising substance for reducing graft dysfunction in clinical liver transplantation.

In vivo microscopy reveals that complement inhibition by C1-esterase inhibitor reduces ischemia/reperfusion injury in the liver

Abstract Complement plays a decisive role in postischemic tissue injury, a process responsible for severe damage after organ ischemia. Several pathophysiologic mechanisms initiated upon reperfusion are mediated by complement inducing micro‐circulatory disturbances. Here, we demonstrate the effects of complement inhibition using C1‐esterase inhibitor (C1‐INH) on microcirculation after liver ischemia by invivo microscopy (IVM). In rats, the left liver lobe was clamped for 70 min. C1‐INH was given 1 min prior to reperfusion. Controls received Ringers solution. IVM was performed 30‐100 min after reperfusion. Non‐perfused acini decreased and sinusoidal perfusion increased substantially after treatment. Leukocyte adherence to sinusoidal and venular endothelium was markedly reduced by C1‐INH. Transaminases were significantly decreased by C1‐INH. Our data obtained by IVM suggest that complement activation is an early key event of ischemia/reperfusion injury. These observations demonstrate for the first time that reperfusion related microcirculatory disorders can be minimized by C1‐INH. This compound should be evaluated in clinical application.

Neue pathophysiologische Kenntnisse der akuten Pankreatitis

Abstract. Induction of acute pancreatitis follows a uniform mechanism independent of the different etiologic factors such as gallstones, alcohol, ischemia, hyperlipidemia, hypercalcemia, hereditary and others. Each cause seems to affect primarily the acinar cell, resulting in premature intracellular activation of trypsinogen and other digestive enzymes. Activated enzymes and oxygen free radicals injure the acinar cell and cause a release of cytokines and vasoactive mediators, attract inflammatory cells and activate the vascular endothelium as well as the expression of adhesion molecules. The disturbance of the pancreatic microcirculation induces a progression from edematous to necrotizing pancreatitis independent of the early intracellular events, including protease activation. Specific therapy must be directed towards microperfusion failure as a secondary pathogenetic step, since the initial enzyme activation and cytokine release is irreversible by the time of clinical presentation. In experimental designs comparable to the clinical situation the following therapeutic principles have proven beneficial: increase of blood fluidity by dextran, inhibition of leukocyte-endothelium interaction by ICAM-1 antibodies, and blockade of local vasoconstriction by endothelin-receptor antagonists.Zusammenfassung. Die Induktion der akuten Pankreatitis folgt einem vergleichbaren Reaktionsablauf unabhängig vom jeweiligen ätiologischen Faktor. Eine frühzeitige intracelluläre Aktivierung von Trypsinogen und im Gefolge auch der übrigen digestiven Enzyme führt zusammen mit der Bildung von Sauerstoffradikalen zum Acinuszellschaden. Die konsekutiv freigesetzten vasoaktiven Mediatoren und proinflammatorischen Cytokine wirken chemotaktisch auf Leukocyten und führen zur Aktivierung von vasculärem Endothel und vermehrter Expression von Adhäsionsmolekülen. Die Folge ist eine gestörte Mikroperfusion des Pankreas mit Verstärkung von Extravasation von Leukocyten und Entzündungsinfiltrat. Die Mikrozirkulationsstörung des Pankreas bewirkt als zentraler pathogenetischer Schritt die Progression von der milden zur nekrotisierenden Pankreatitis und führt so die Erkrankung unabhängig von der primären Ätiologie fort. Spezifische therapeutische Ansätze müssen gegen die Mikrozirkulationsstörung als sekundären pathogenetischen Schritt der akuten Pankreatitis gerichtet sein, da die initiale Proteasenaktivierung und Cytokinfreisetzung zum Zeitpunkt der klinischen Präsentation bereits irreversibel abgelaufen ist. In der klinischen Situation vergleichbaren experimentellen Studien haben sich folgende Ansätze besonders bewährt: Steigerung der Blutfluidität mittels Dextran, Hemmung der Leukocyten-Endothel-Interaktion durch monoklonale Antikörper gegen ICAM-1 und Aufhebung lokaler Vasokonstriktion durch Endothelin-Rezeptor Antagonisten.

Erstes kontinuierliches Nerven-Monitoring in der Schilddrüsenchirurgie

Abstract. A new „all in one“ sensing device was developed for continuous transtracheal intraoperative monitoring and in situ detection of the recurrent laryngeal nerve (RLN) during thyroid surgery. Patients and methods: The new system is based on a double-balloon endotracheal tube with integrated atraumatic stimulating and tracing electrodes. The recurrent laryngeal nerve is stimulated transtracheally and compound action potentials are recorded from the laryngeal muscles. Fifty-five patients were introduced into a phase-one clinical trial. Thirty-five patients with primary thyroid operations, 20 patients with reoperations, 10 of whom had neck dissections. All patients were evaluated laryngoscopically and phoniatrically by an ENT specialist before and after surgery. Results: Compound muscle action potentials were recorded continuously during the whole operation and responded sensitively to tension and pressure to the nerve. There were no accidental permanent RLN palsies. Conclusion: The new system offers five advantages: (1) it is atraumatic; (2) it is easy to use; (3) it can monitor continuously with an audio feedback to the surgeon; (4) it works outside the operation field; and (5) it is highly sensitive, even indicating reversible irritation to the nerve.Zusammenfassung. Ein neuartiges „all in one“ Monitoringsystem für den N. laryngeus recurrens (NLR) erlaubt sowohl eine kontinuierliche, atraumatische Überwachung des NLR als auch eine in situ Detektion des Nerven. Patienten und Methode: Das System basiert auf einem Doppelballontubus mit integrierten Oberflächenelektroden zur transtrachealen Stimulation und Ableitung des Erfolgsorgans. Fakultativ kann über eine elektrische Stimulationsnadel der NLR im OP-Feld identifiziert werden. Die Signalverarbeitungs-Software stellt eine Neuentwicklung unserer Arbeitsgruppe dar und führt eine Echtzeit-Signalanalyse mit akustischer Rückkoppelung durch. 55 Patienten wurden in die klinische Zulassungsstudie eingebracht, 35 Primäreingriffe, 20 Sekundäreingriffe, davon 10 Halsausräumungen. Ergebnisse: Die Plazierung des EMG-Tubus ist mit der Routineintubation abgeschlossen und erfordert keinen zusätzlichen Zeitbedarf. Das System ist außerhalb des OP Feldes lokalisiert und beeinträchtigt daher nicht den OP Ablauf. Die akustische Rückkoppelung wurde von allen 8 Operateuren als hilfreich und nicht störend beurteilt. Die phoniatrische und HNO-ärztliche Analyse erbrachte keine permanenten Beeinträchtigungen. Schlußfolgerung: Das neue kontinuierliche Monitoringsystem ermöglicht erstmals eine atraumatische nebenwirkungsfreie Dauerüberwachung des NLR. Es ist einfach anzuwenden, arbeitet außerhalb des OP-Gebiets und ist so sensitiv, daß auch reversible Irritationen erkannt werden können.

First clinical realization of continuous monitoring of liver microcirculation after transplantation by thermodiffusion

Abstract  To date, no method is available for the continuous long‐term monitoring of liver microcirculation in patients. Experimentally, thermodiffusion has been validated in the quantification of hepatic per‐fusion. In an attempt to investigate the practicability of thermodiffusion technology in patients after liver transplantation thermodiffusion probes were inserted into the graft in seven patients during liver transplantation. Continous monitoring started intraoperatively and was performed until day 7, when the probes were extracted transcutane‐ously. No probe‐related complications (i. e., hemorrhage, infection) were observed. In four patients with normal graft function, liver perfu‐sion recovered within 12 h from the intraoperative reduction to a range between 85 and 93 ml/100 g per min. In contrast, primary graft failure (n= 1) was characterized by a constant decrease of hepatic perfusion (< 50 ml/100 g per min). In prolonged reperfusion injury (n= 1), a second peak of transaminases was paralled by an impairment of liver microcirculation. In one patient, rejection on day 7 was preceded by a drop in hepatic perfusion 48 h earlier. Thus, thermodiffusion is a safe and reliable method for the continuous quantification of liver micro‐circulation after transplantation in patients. Measurements are reproducible for at least 7 days. Changes in hepatic perfusion during postoperative complications can be detected. The characteristics of micro‐circulatory disorders will have to be defined in a larger number of patients.

Ischemic preconditioning improves liver microcirculation after ischemia/reperfusion.

THE ISCHEMIA/REPERFUSION injury plays an important role in liver transplantation and surgery. Oxidative stress after reperfusion results in activation and adherence of leucocytes and platelets. Consequently, alterations in microcirculation develop that lead to impairment of hepatic function. In 22% of the cases extensive reperfusion injury causes severe deterioration of microcirculation leading to primary dysfunction or primary graft failure. A more detailed understanding of pathophysiological mechanisms resulting into treatment possibilities is therefore essential. Ideal treatment makes use of intrinsic protective mechanisms and is offered before damage takes place. Ischemic preconditioning takes that into account. Ischemic preconditioning describes the phenomenon that a brief ischemia and reperfusion, the so-called preclamping, increases the ischemic tolerance of a following ischemic period. It was first described for the heart in 1986 by Murry and since then has been extensively examined. Studies concerning other organs such as muscle and kidney followed. The first study about preclamping in the liver was performed in 1993 by Lloris-Carsi et al. He and others studied different preclamping and reperfusion times, focusing on laboratory liver function tests, energy content of the tissue, histological analyses of cellular integrity, and survival after sublethal stress. The underlying effect of ischemic preconditioning has been of special interest ever since. Some substances such as heat shock protein, adenosine, and nitric oxide (NO) seem to be involved, the exact mechanism has not yet been identified. Thus far, analyses of liver microcirculation after ischemic preconditioning have not been performed. Microcirculatory disturbances can directly be related to organ function and, therefore, to the extent of ischemia/reperfusion injury, respectively, to the benefit of an applied treatment. Therefore, it was the goal of this study to evaluate the effect of ischemic preconditioning on the hepatic microcirculation after warm ischemia/reperfusion by intravital microscopy in rats.

Aktuelle Therapie bei Verletzungen des hepatobiliopankreatischen Kompartments

Summary. The management of hepatic trauma should be, if possible, non-operative and is initially determined by hemodynamic stability, absence of coagulopathy and limited need for blood transfusions. In hemodynamically unstable patients specific attempts to controll intraparenchymal hemorrhage and resection are contraindicated. Perihepatic packing is the therapy of choice. If the hemorrhage cannot be controlled, parenchymal resection or hepatectomy with subsequent transplantation must be performed. Biliary leakage is the cause of chronic complications. The current management of intraparenchymal lesions consists of longterm drainage or stenting as combined radiological and endoscopical techniques. Pancreatic ruptures without ductal injury are treated non-operatively or by external drainage. Ductal lesions with persistent fistulas are handled depending on localization either by distal resection, pancreaticojejunostomy of the injured segment, or partial pancreaticoduodenectomy if massive disruption of the pancreatic head, duodenum or bile duct are present.Zusammenfassung. Die Therapie von Lebertraumata ist wenn irgend möglich konservativ und orientiert sich initial an Kreislaufstabilität, Fehlen einer Gerinnungsstörung und Transfusionsbedarf. Die operative Versorgung sollte dem Zweistufenprinzip folgen mit primärer Blutstillung oder Kompression und definitiver Versorgung unter stabilen Bedingungen. Beim kreislaufinstabilen Patienten sind gezielte Versuche intraparenchymatöser Blutstillung kontraindiziert. Gelingt eine Kontrolle der Blutung trotz Kompression nicht, muß reseziert oder sogar hepatektomiert werden mit anschließender Transplantation. Gallelecks sind Ursache chronischer Komplikationen. Die aktuelle Therapie intraparenchymatöser Läsionen besteht in einer Langzeitdrainage bzw. Schienung in der Kombination radiologischer und endoskopischer Techniken. Pankreasrupturen ohne Gangbeteiligung werden konservativ oder durch alleinige Drainage behandelt. Gangrupturen mit persistierender Fistel werden lokalisationsabhängig therapiert durch Linksresektion mit Übernähung, Pancreatico-Jejunostomie des verletzten Segmentes oder bei schwerer Laceration von Pankreaskopf, Duodenum und Gallengang partieller Pancreaticoduodenotomie.

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.

Reduction of hepatic reperfusion injury by antithrombin III and aprotinin.

Abstract Disturbance in hepatic microcirculation and leucocyte‐endothelium interaction after warm ischaemia represents one of the leading mechanisms for postoperative organ dysfunction. Recent studies have shown that pretreatment with antithrombin III (AT III) and aprotinin reduces the leucocyte‐endothelium interaction in ischaemic small intestine and during extracorporal circulation in cardiac surgery. Standardized warm hepatic ischaemia and intravital fluorescence videomicroscopy was performed in an experimental study with rats. Animals were pretreated with AT III or aprotinin. Analysis of intravital videomicroscopy showed that the hepatic microcirculation after warm hepatic ischaemia in rats was significantly enhanced by AT III and aprotinin, most likely by reducing the leucocyte‐endothelium interaction. We concluded that drug application before the Pringle manoeuvre might reduce the reperfusion damage after liver resection.

Characterization of hepatic parenchymous perfusion heterogeneity and regional flow kinetics after porcine liver transplantation

BACKGROUND In clinical practice, a heterogeneous hepatic tissue microperfusion (MC) is often observed after liver resection or transplantation (LTx). Nevertheless this hepatic perfusion phenomenon has never been really quantified with respect to its anatomic distribution and time course in detail. The aim of the study was to characterize liver perfusion heterogeneity and local flow kinetics both in the physiological situation and after standardized ischemia and reperfusion using an established model of porcine LTx. METHODS Regional distribution of hepatic MC in healthy native porcine livers (control group; n = 8) was analyzed in comparison with data derived 60 min, 24 h, and 72 h after porcine LTx (transplantation group; n = 8 each subgroup; cold ischemia time: 5.7 +/- 1.2 h). MC was measured with implanted thermal diffusion electrodes (TD). Flow in hepatic artery and portal vein was continuously detected by ultrasonic probes. For standardization of measurement localizations, porcine liver lobes were divided anatomically into three horizontal layers (cranial, medial, caudal), defining 12 distinct hepatic measurement regions. RESULTS In the control group, a homogenous liver MC with a mean flow of 81.6 +/- 13.9 ml/100 g/min was detected in all regions. After LTx, a marked MC heterogeneity was noted 60 min after reperfusion. MC rehomogenization was first documented within horizontal liver planes 24 h later. Comparison of MC between planes showed persisting heterogeneity with a significant intralober drop of mean MC in the cranio-caudal direction. Complete MC rehomogenization (both between horizontal and vertical liver planes) was detected 72 h after reperfusion. Still, an overall reduction of mean liver perfusion by about 15% was existent. CONCLUSIONS A homogenous tissue perfusion was observed in healthy porcine livers. In contrast, marked heterogeneity of hepatic MC was detected after LTx. Heterogeneity presents as a very dynamic and temporary phenomenon. Early horizontal flow rehomogenization and reconstitution of normal blood flow, particularly primarily in the cranial liver layers, appear to be characteristic features during early flow reconstitution after postischemic reperfusion. Due to heterogeneity and time-dependent flow dynamics, measurement of MC volumes at single hepatic regions may not always allow a valid characterization of liver perfusion quality during the first 24 h after postischemic reperfusion.