Billing, A.; Winter, H.; Steines, W.; Gippner-Steppert, C.; Jochum, M. Author Information

Cytokine levels during infection and sepsis have been extensively studied in the past. In contrast to the excellent data on tumour necrosis factor alpha (TNF-alpha), interleukin 8 (IL-8), and polymorphonuclear (PMN) granulocyte elastase (PMN-E) concentrations in blood, little is known about cytokine and PMN-E levels in tissue or local fluids like abdominal exudate in secondary, purulent peritonitis of man. Therefore, the authors studied perioperative intra-abdominal levels of TNF-alpha, IL-8 and PMN-E in 21 patients with severe purulent peritonitis. The average pre-operative levels of TNF-alpha were 694 +/- 239 pg/ml in exudate and 26 +/- 6 pg/ml in plasma, for IL-8 100 +/- 34 ng/ml and 0.7 +/- 0.5 ng/ml, and for PMN-E 68 +/- 14 microg/ml and 0.7 +/- 0.1 microg/ml, respectively. Standard surgical procedures reduced the intra-abdominal concentrations of cytokines and PMN-E to as low as one tenth of the pre-operative levels. Postoperatively, TNF-alpha and IL-8 levels recovered rapidly and pre-operative levels of IL-8 were reached again after 1 h and for TNF-alpha after 8 h. PMN-E concentration remained below the initial baseline within 8 h of observation. TNF-alpha concentration, but not IL-8 or PMN-E, depended on the microbiological load of the abdominal exudate (< or > 10(3) cfu/ml). There were no significant differences in the intra-abdominal or plasma levels of cytokines or PMN-E between survivors and non-survivors at any observation time.

Fifty-one survivors of > 9 days of ICU treatment for abdominal sepsis were analysed for prognostic factors. Long term survival was achieved in 23 patients. Neither a single factor alone nor the constellation of organ failure allowed for correct prediction of outcome.

Fifty-one survivors of >9 days of ICU treatment for abdominal sepsis were analysed for prognostic factors. Long term survival was achieved in 23 patients. Neither a single factor alone nor the constellation of organ failure allowed for correct prediction of outcome.

Fifty-one survivors of >9 days of ICU treatment for abdominal sepsis were analysed for prognostic factors. Long term survival was achieved in 23 patients. Neither a single factor alone nor the constellation of organ failure allowed for correct prediction of outcome.

A major portion of the lysosomal proteinases responsible for intracellular degradation of phagocytized proteins are cysteine proteinases, the “acid” cathepsins B, H, L, and S (see [1] for review). As we have shown previously [2, 3], increased cysteine proteinase activity is found in blood plasma of polytraumatized and septic patients as well as in local inflammatory secretions such as bronchoalveolar lavage fluid and peritonitis exudate. Most of this activity is due to cathepsin B, which is relatively stable at neutral pH (half-life about 30 min at pH 7.4) and is protected in the form of reversible complexes with its endogenenous protein inhibitors (stefins, cystatins, and kininogens). Here we report some evidence for the role of cathepsin B as a marker of macrophage activation and of lysosomal cysteine proteinases as potential nonspecific mediators of inflammation.

Der Einfluß von Taurolin auf phagozytoserelevante physiologische Abwehrfunktionen und auf die Keimelimination bei der menschlichen Peritonitis wurde in einer kontrollierten Studie untersucht. Die Opsonierungsleistung von Serum, eine wesentliche Voraussetzung für die suffiziente Phagozytose, wurde durch Taurolinkonzentrationen bis zu 0,1% nicht wesentlich beeinträchtigt. Die intraabdominale Taurolinapplikation bewirkte im Vergleich zu einer Kontrollgruppe einen unveränderten Leukozyteneinstrom. Die Opsonierungsleistung im Peritonealexsudat der Therapiegruppe war, vermutlich als Folge eines spezifischen Opsoninverbrauchs, erniedrigt. Die Taurolingabe führte zu einer wesentlichen Keimreduktion. Die konkordant wirkenden physiologischen Abwehrfunktionen wurden nicht beeinträchtigt.

In order to define rational criteria for "planned relaparotomies" (PR) in the treatment of critical intra-abdominal infections we have analysed characteristics and the clinical course of 377 patients with diffuse peritonitis 152 of whom were treated by PR. More detailed prognostic aspects and data of the clinical course were prospectively investigated in 111 cases. Patient's age and an underlying malignoma revealed to be of prognostic significance in both univariate and multivariate analysis. The number of organs involved in septic organ failure during the treatment was a further indicator of risk. 40% of our patients, however, survived even an impairment of 5 organ-systems. The successful eradication of the source of peritonitis either with the 1st operation or only with consecutive operations resulted in a crucial difference of the mortality rate with 14% and 64% respectively. The failure to accomplish a definite operative resolution was accompanied by a mortality rate of 90%. The systematical application of PR facilitated control and completion of the eradication of the source of peritonitis. In one third of the patients treated by PR this technique led to early detection of relevant complications and adequate operative treatment. Patients in whom primarily a definitive eradication of the source of peritonitis had been accomplished did not benefit from PR. In patients with persisting or relapsing peritonitis, however, PR was accompanied by a 27% reduction of mortality.

In order to define rational criteria for "planned relaparotomies" (PR) in the treatment of critical intra-abdominal infections we have analysed characteristics and the clinical course of 377 patients with diffuse peritonitis 152 of whom were treated by PR. More detailed prognostic aspects and data of the clinical course were prospectively investigated in 111 cases. Patient's age and an underlying malignoma revealed to be of prognostic significance in both univariate and multivariate analysis. The number of organs involved in septic organ failure during the treatment was a further indicator of risk. 40% of our patients, however, survived even an impairment of 5 organ-systems. The successful eradication of the source of peritonitis either with the 1st operation or only with consecutive operations resulted in a crucial difference of the mortality rate with 14% and 64% respectively. The failure to accomplish a definite operative resolution was accompanied by a mortality rate of 90%. The systematical application of PR facilitated control and completion of the eradication of the source of peritonitis. In one third of the patients treated by PR this technique led to early detection of relevant complications and adequate operative treatment. Patients in whom primarily a definitive eradication of the source of peritonitis had been accomplished did not benefit from PR. In patients with persisting or relapsing peritonitis, however, PR was accompanied by a 27% reduction of mortality.

Um Kriterien für einen sinnvollen Einsatz der Etappenlavagebehandlung (EL) zu erstellen, wurde das Krankheitsbild und der Therapieverlauf von 377 Patienten mit diffuser Peritonitis untersucht, von denen 152 mittels EL behandelt wurden. Prognostische Aspekte und Einzelheiten des Therapieverlaufs wurden bei 111 Fällen prospektiv erfaßt und analysiert. Die vorliegenden Daten vermitteln Hinweise auf Risikogruppen bei der Peritonitisbehandlung. Das Patientenalter und das Vorliegen eines Malignoms erwiesen sich in einer univariaten und multivariaten Analyse als prognoserelevant. Auch die Anzahl der während des Behandlungsverlaufs auftretenden septischen Organfunktionsstörungen war prognosebestimmend. Selbst eine passagere Funktionsstörung in allen 5 untersuchten Organsystemen wurde von 40% der Patienten überlebt. Die Sanierung der Peritonitisquelle bei der Erstoperation bzw. erst im weiteren Verlauf war gefolgt von einer Letalität von 14 bzw. 64%. War eine definitive operative Sanierung nicht möglich, so betrug die Letalität 90%. Die gezielte Anwendung der El erlaubte eine Kontrolle und Fortführung der Herdsanierung. Bei 1/3 der mit EL behandelten Patienten wurden durch die programmierte Relaparotomie operationsbedürftige Komplikationen frühzeitig erkannt und versorgt. Patienten, deren Peritonitisquelle primär saniert wurden konnte, profitierten nicht von der EL-Behandlung. Bei den Patienten mit rezidivierender oder persistierender Peritonitis war der Einsatz der EL dagegen von einer Verminderung der Letalität um 27% begleitet.

The influence of taurolin on phagocytosis-related defense functions and on the elimination of bacteria has been investigated in a controlled study. Particle opsonisation, a prerequisite for sufficient phagocytosis, was undisturbed in presence of up to 0.1 % taurolin. Intraabdominal taurolin application did not diminish the leukocyte influx into the abdominal cavity. Opsonic capacity of peritoneal exudate was low in the taurolin group. These exudates contained more severe bacterial contamination, suggesting that this deficit was due to enhanced specific consumption of opsonins. Taurolin treatment resulted in a marked reduction of bacterial growth. Thus the substance provides antiseptic capacities without afflicting the physiological defense systems.

The contribution of the kininogens and cystatin C to the functional inhibitory capacity for cysteine proteinases of blood plasma and inflammatory secretions was estimated from ex vivo experiments. 98.5% of the inhibitory capacity of blood plasma for cathepsin L (4-5 microM) is provided by the kininogens ensuring a complete control of this enzyme even at a lowered kininogen concentration. Control of cathepsin B activity by the kininogens is incomplete and depends critically on the active concentration of cystatin C (70 nM in normal plasma), which is reduced in blood plasma of polytraumatized and septic patients and very low in epithelial lining fluid of the shock lung.

This study represents our experience with severe blunt gastrointestinal injury in 29 polytrauma and 3 solitary trauma patients. The primary diagnosis was missed in intestinal perforation (4x) and mesenteric disrupture (1x). In 2 other patients contusion of the gastrointestinal wall led to postprimary perforation. The average mortality was 21.8%; only 2 patients died from abdominal sepsis. Blunt gastrointestinal trauma differs from penetrating injury as far as the diagnostic and therapeutic aspects are concerned. In some cases, explorative laparotomy alone leads to early diagnosis. For sufficient management, the blunt contusion/compression aspects must be taken into account.