These responses are very rare and are likely due to the cardioinhibitory Bezold-Jarisch reflex. A thorough screening regarding a history of vagal sensitivity and liberal oral or intravenous fluid administration prior to and during the endotoxin challenge may decrease the risk of these events.

No abstract

Introduction Septic shock is associated with increased microvascular permeability. As a model for study of the pathophysiology of sepsis, endotoxin administration to humans has facilitated research into inflammation, coagulation and cardiovascular effects. The present study was undertaken to determine whether endotoxin administration to human volunteers can be used as a model to study the sepsisassociated increase in microvascular permeability.Methods In an open intervention study conducted in a university medical centre, 16 healthy volunteers were evaluated in the research unit of the intensive care unit. Eight were administered endotoxin intravenously (2 ng/kg Escherichia coli O113) and eight served as control individuals. Microvascular permeability was assessed before and 5 hours after the administration of endotoxin (n = 8) or placebo (n = 8) by three different methods: transcapillary escape rate of I 125 -albumin; venous occlusion straingauge plethysmography to determine the filtration capacity; and bioelectrical impedance analysis to determine the extracellular and total body water. Results Administration of endotoxin resulted in the expected increases in proinflammatory cytokines, temperature, flu-like symptoms and cardiovascular changes. All changes were significantly different from those in the control group. In the endotoxin group all microvascular permeability parameters remained unchanged from baseline: transcapillary escape rate of I 125 -albumin changed from 7.2 ± 0.6 to 7.7 ± 0.9%/hour; filtration capacity changed from 5.0 ± 0.3 to 4.2 ± 0.4 ml/min per 100 ml mmHg × 10 -3 ; and extracellular/total body water changed from 0.42 ± 0.01 to 0.40 ± 0.01 l/l (all differences not significant). Conclusion Although experimental human endotoxaemia is frequently used as a model to study sepsisassociated pathophysiology, an endotoxin-induced increase in microvascular permeability in vivo could not be detected using three different methods. Endotoxin administration to human volunteers is not suitable as a model in which to study changes in microvascular permeability.

No abstract

No abstract