Changes in sublingual microvascular flow during experimental human endotoxemia

Introduction

We examined sublingual microvascular changes in experimental human endotoxemia. Changes in microcirculation and mitochondrial dysfunction appear to be key mechanisms in sepsis, since they can lead to regional mismatch of oxygen supply and demand. Lipopolysaccharide (LPS) can be used to induce endo-toxemia as a model of sepsis, but the effects on microcirculatory perfusion have not been tested before, particularly after tolerance induction during repeated challenges of LPS.

Methods

Six healthy volunteers received an intravenous injection of 2 ng/kg Escherichia coli LPS to induce endotoxemia on five consecutive days. Microvascular perfusion was sublingually measured using sidestream darkfield imaging just before, and 2 and 4 hours after LPS injection on day 1. All measurements were repeated on day 5 of LPS administration. Sublingual capillary flow was estimated using a semiquantative microvascular flow index (MFI) in small (10–25 μm), medium (25–50 μm) and large-sized (50–100 μm) microvessels (no flow, 0; intermittent flow, 1; sluggish flow, 2; and continuous flow, 3). Changes were evaluated with the paired Wilcoxon test and sign test. P < 0.05 was judged to indicate a significant difference. Values are expressed as the median (P25–P75).

Results

Two hours after the induction of endotoxemia (n = 6), sublingual flow in small (2 (1.7–2.3)), medium-sized (1.5 (1.2–1.9)), and large microvessels (2.5 (1.2–2.7)) did not differ from baseline values (2.3 (1.5–2.8), 2.3 (1.4–2.5), and 2.3 (1.3–2.5), respectively, all P = not significant). Microvascular flow did not change in the subsequent 2 hours. In addition, no difference in microvascular flow could be demonstrated between timepoints on day 1 and day 5 of intermittent endotoxemia.

Conclusion

In this small pilot study in experimental human endotoxemia, no significant effect of LPS administration on microcirculatory perfusion could be observed, nor any sign of tolerance. Further studies should reveal whether microvascular impairment does not occur in early human experimental endotoxemia, or that sidestream darkfield imaging is not useful in this specific setting.