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Microvascular permeability during experimental human endotoxemia
Critical Care volume 8, Article number: P66 (2004)
In patients with septic shock, increased microvascular permeability and subsequent formation of edema is frequently encountered and a major determinant of end organ damage. As a model to examine the pathophysiology of sepsis, endotoxin administration to humans has facilitated the research on inflammation, coagulation and cardiovascular effects. The present study was undertaken to test whether endotoxin administration to human volunteers can be used as a model to study the sepsis-induced increase in microvascular permeability.
In healthy, nonsmoking volunteers, microvascular permeability was assessed before and 5 hours after the administration of endotoxin (2 ng/kg body weight, n = 8) or placebo (n = 8), by (1) transcapillary escape rate of I125-albumin (TER-alb); (2) venous occlusion strain-gauge plethymography to determine the filtration capacity (Kf); and (3) bioelectrical impedance analysis (BIA) to determine extracellular water (ECW) and total body water (TBW). Administration of endotoxin resulted in the expected increase of pro-inflammatory cytokines (TNF-α from < 0.015 to 856 ± 158 pg/ml, P = 0.002), accompanied by fever (maximum temperature 38.7 ± 0.3°C, P < 0.0001), flu-like symptoms and cardiovascular changes (heart rate from 63 ± 3 bpm at baseline to 91 ± 3 bpm at t = 5 hours, P < 0.0001; mean arterial pressure from 96 ± 3 mmHg to 79 ± 4 mmHg, P < 0.0001; and forearm blood flow from 3.7 ± 0.8 ml/min/dl to 6.8 ± 1.1 ml/min/dl forearm volume). All changes were significantly different from the control group. In the endotoxin-treated subjects all microvascular permeability parameters remained unchanged: TER-alb from 7.2 ± 0.6% to 7.7 ± 0.9% (P = NS); Kf from 5.0 ± 0.4 to 4.2 ± 0.4 (P = NS); and ECW/TBW measured by BIA from 0.42 ± 0.01 to 0.40 ± 0.01 (P = NS). Also, no significant changes appeared in the microvascular permeability parameters in the control group.
Although endotoxin is frequently used as a model to study sepsis-associated effects, an endotoxin-induced increase in microvascular permeability in vivo could not be detected by three different methods. Endotoxin administration to human volunteers is not suitable as a model to study changes in microvascular permeability.
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van Eijk, L., Pickkers, P., Smits, P. et al. Microvascular permeability during experimental human endotoxemia. Crit Care 8, P66 (2004). https://doi.org/10.1186/cc2533
- Human Volunteer
- Total Body Water
- Venous Occlusion
- Bioelectrical Impedance Analysis
- Forearm Blood Flow