Critical care : the official journal of the Critical Care Forum
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Comparative Study
Anti-L-selectin antibody therapy does not worsen the postseptic course in a baboon model.
Anti-adhesion molecule therapy prevents leukocytes from extravasating. During exaggerated inflammation, this effect is wanted; however, during infection, blocking diapedesis may be detrimental. In this study, therefore, the potential risks of anti-L-selectin antibody therapy were evaluated in a primate model of sepsis. ⋯ Anti-L-selectin therapy did not adversely affect survival, promote organ dysfunction or result in major side effects in the baboon sepsis model. Additionally, as anti-L-selectin therapy improved the bacterial clearance rate, it appears that this therapy is not detrimental during sepsis. This is in contrast to previous studies using the baboon model, in which antibody therapy used to block CD18 increased mortality.
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Human sepsis is an intrinsically complex disease. Populations of patients enrolled into clinical trials of novel sepsis therapies are notoriously heterogeneous with respect to the inciting cause of their disease, the co-morbid conditions that define its course, and the acute severity of their initial presentation. This heterogeneity is reflected in strikingly variable mortality risks across studies, and probably, though less clearly-established, in variable response rates to a given intervention. ⋯ On the other hand, if we view severity as a crude surrogate for a particular pathologic state, we would shift our focus to better defining those populations most likely to benefit from intervention, including patients who may not have met criteria for entry in the original PROWESS trial--those with disseminated intravascular coagulation or acute organ dysfunction from causes other than sepsis. Staging systems that stratify heterogeneous patient populations by risk and by potential to benefit from intervention have proven to be essential to the development of multimodal adjuvant treatment for cancer. They will be no less important in the optimal management of sepsis.
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Hemodynamic monitoring is a central component of intensive care. Patterns of hemodynamic variables often suggest cardiogenic, hypovolemic, obstructive, or distributive (septic) etiologies to cardiovascular insufficiency, thus defining the specific treatments required. Monitoring increases in invasiveness, as required, as the risk for cardiovascular instability-induced morbidity increases because of the need to define more accurately the diagnosis and monitor the response to therapy. ⋯ Newer methods for assessing preload responsiveness include monitoring changes in central venous pressure during spontaneous inspiration, and variations in arterial pulse pressure, systolic pressure, and aortic flow variation in response to vena caval collapse during positive pressure ventilation or passive leg raising. Defining preload responsiveness using these functional measures, coupled to treatment protocols, can improve outcome from critical illness. Potentially, as these and newer, less invasive hemodynamic measures are validated, they could be incorporated into such protocolized care in a cost-effective manner.