Sepsis is associated with numerous hemodynamic complications, including alterations in microvascular permeability. A study by Christ, et al. (Intensive Care Med 1998; 24:18–27) demonstrated enhanced capillary filtration coefficient (Kf) in patients with septic shock. Sepsis is associated with neutrophil activation and increased levels of plasma nitrites/nitrates (NOx). We hypothesized that nitric oxide (NO) and activated neutrophils have a causal role in the permeability alterations in sepsis and thus anticipated significant correlations between Kf and one marker of neutrophil activation (alpha 4 integrin) and nitric oxide activity (as measured by neutrophil iNOS activity and plasma NOx concentration).
Kf was measured with venous occlusion plethysmography; neutrophil alpha-4 integrin expression by flow cytometry; neutrophil iNOS activity by a functional assay and plasma NOx concentration by chemiluminescence.
Kf in septic patients was 6.10+/- 0.54 x 10–3 ml/min/100ml/mmHg, whereas in healthy volunteers Kf was 4.03 +/- 0.49 x 10–3 ml/min/10ml/mmHg (p = 0.006). Septic patients had enhanced neutrophil alpha-4 integrin expression but there was no correlation with filtration coefficient. Plasma NOx levels were elevated in septic patients but did not correlate with Kf. There was no correlation between neutrophil iNOS activity and filtration coefficient. Kf was elevated in septic patients with peripheral edema; septic patients without edema did not demonstrate increased Kf.CONCLUSIONS: These preliminary data are consistent with the notion that systemic increases in vascular permeability in sepsis are independent of neutrophil alpha-4 integrin expression and enhanced nitric oxide synthesis. The presence of clinically detectable edema in septic patients is associated with enhanced microvascular permeability to water.
K. Mahadevan, None.