Organ Dysfunction Syndrome Research Articles

Anti-thrombin III in the management of hematopoietic stem-cell transplantation-associated toxicity.

To describe the evidence assessing the use of anti-thrombin III (AT-III) in the management of toxicity associated with hematopoietic stem-cell transplantation (HSCT)-conditioning regimens. Clinical literature was accessed through conference proceedings, EMBASE, the Cochrane database, and MEDLINE (1966-December 2003). Case reports, small case series, case-control and cohort studies, and randomized controlled trials of AT-III in HSCT were evaluated. Publications examining AT-III use in the non-HSCT setting were also explored. Key search terms included AT-III, transplantation, and veno-occlusive disease (VOD). Severe VOD and ensuing multiple organ dysfunction is associated with high mortality in HSCT. A low AT-III level has been shown to correlate with the development of organ dysfunction. Phase II trials, case series, and one small, randomized, placebo-controlled study suggest a benefit when AT-III therapy is instituted early in the course of VOD/multiple organ dysfunction syndrome. In all of these reports, AT-III use was devoid of adverse events. Although further studies are needed to ascertain the optimal target level, method, and duration of administration, AT-III is still a viable alternative for the treatment of severe VOD and ensuing multiple organ dysfunction.

Pharmakologische Modulation der Splanchnikusdurchblutung beim kritisch Kranken – sinnvoller Therapieansatz oder Spielerei?

Acute strategies for the treatment of critically ill patients include the concept of a pharmacologically induced increase of splanchnic perfusion. This concept is based on the hypothesis that gut dysfunction plays an important role in the pathophysiology of systemic inflammatory response and organ dysfunction syndrome, since there is evidence that gut mucosal acidosis may promote bacterial translocation and poor clinical outcome. The pharmacologic support of gut perfusion in critically ill patients has been tested in numerous studies, using vasoactive agents like dopamine, dopexamine, dobutamine, epinephrine and norepinephrine or by application of non-adrenergic substances like prostacyclin, nitric oxide, N-acetylcysteine or pentoxifylline. In summary, dopamine and dopexamine seem to have a minimal effect on mucosal integrity and splanchnic blood flow, while dobutamine consistently showed beneficial effects on intramucosal pH and gut perfusion. Prostacyclin demonstrated promising results, while other non-adrenergic agents had no effect on splanchnic perfusion. The experimental and clinical examination of the pathophysiologic role of the gut and the support of the perfusion as a therapeutic strategy implicate some methodical problems (assessment and reliability of monitoring methods, experimental animal models and investigations in humans, definition of shock syndromes, heterogeneity of data base). Furthermore, in future studies it remains to be shown that correcting the abnormal physiologic state will confer clinical benefit.

Endothelial cell injury, as quantified by the soluble thrombomodulin level, predicts sepsis/multiple organ dysfunction syndrome after blunt trauma.

Article: Presented At The 57Th Annual Meeting Of The American Association For The Surgery Of Trauma And The Japanese Association For Acute Medicine, September 24-27, 1997, Waikoloa, Hawaii

Trauma-induced alterations in macrophage function

Background: The juxtaposition of immune suppression and a hyperactive inflammatory response after injury represents a paradox in immune function. The aim of this study was to evaluate the delayed macrophage hypersecretion of inflammatory mediators in relation to functional macrophage defects. Methods: BALB/c mice were randomized to control or trauma (femur fracture plus 40% blood volume hemorrhage) groups. One and 7 days after injury, splenic macrophages were isolated and assayed for antigen presentation and the production of inflammatory mediators tumor necrosis factor-α (TNF-α), interleukin (IL)-6, prostaglandin E 2, H 20 2, and nitric oxide. Results: One day after injury, there were significantly diminished macrophage antigen presentation and decreased mean production of TNF-α, IL-6, and H 20 2. In contrast, 7 days after injury, splenic macrophages produced significantly increased mean amounts of TNF-α, IL-6, prostaglandin E 2, H 20 2, and nitric oxide, with a persistent functional defect in antigen presentation. Conclusions: This phasic response to trauma suggests a persistent state of macrophage dysregulation that may help explain the paradox of immune suppression, manifested by functional defects predisposing patients to increased infections, in the setting of inflammatory mediator hypersecretion, predisposing patients to the systemic inflammatory response syndrome/multiple organ dysfunction syndrome. (Surgery 1998;123:96-101.)