Abstract
BackgroundThe use of in vivo videomicroscopy at the bedside has demonstrated microcirculatory flow disturbances in sepsis. The ability of in vivo videomicroscopy to detect changes in the prevalence of rolling and adhered leukocytes that occur in sepsis is not well-described in humans. We sought to (1) develop methodology for accessing and quantifying sublingual leukocyte rolling and adherence with sidestream dark field (SDF) imaging; (2) compare the number of rolling and adhered leukocytes between patients with septic shock and non-infected controls; and (3) compare the number of rolling and adhered leukocytes between survivors and non-survivors of septic shock.MethodsWe included adult (age > 18 years) patients in the emergency department presenting with septic shock prospectively enrolled in the ProCESS trial. We recruited comparison non-infected patients as emergency department controls. Using a SDF videomicroscope, we obtained image sequences from the sublingual mucosa, quantifying rolling and adhered leukocytes per 1 mm × 1 mm visual field in a standardized 3-s clip. We report data as median and interquartile range and depicted as box plots. We compared groups using the Mann-Whitney U test, considering a p value < 0.05 significant.ResultsWe included a total of 64 patients with septic shock and 32 non-infected controls. The median number of adhered leukocytes per field in the sepsis group was 1.0 (IQR 0–3.5) compared to 0 (0–0) in the non-infected group (p < 0.001). The median number of rolling leukocytes was 26 (10.3–42) in the sepsis group and 9.8 (4.8–17.3) in the non-infected group (p < 0.001) per field. Among the patients with sepsis (n = 64), there was an increased number of adhered leukocytes in non-survivors compared to survivors (3.0 (1–5.5) vs. 1.0 (0–3.0)) (p < 0.05); however, there was no difference in rolling leukocytes (35 (20–48) vs. 26 (10–41)) (p = 0.31).ConclusionsOur results demonstrated a higher number of rolling and adhered leukocytes in patients with septic shock when compared to non-infected controls, and an increased number of adhered leukocytes in non-survivors.Trial registrationClinicalTrials.gov, NCT00793442; Registered on 19 November 2008PG0GM076659 (US NIH Grant/Contract). First submitted 18 July 2007. First posted 2 August 2007.
Highlights
The use of in vivo videomicroscopy at the bedside has demonstrated microcirculatory flow disturbances in sepsis
We included 64 patients from the emergency department (ED) presenting with septic shock, who were enrolled in the prospective clinical Protocolized Care for Early Septic Shock (ProCESS) trial, and 32 non-infected control ED patients (Table 1)
Leukocyte rolling and adhesion in sepsis versus control There was an increase in the median number of adhered leukocytes per field in the sepsis group 1.0 (IQR 0–3.5) compared to 0 (0–0) in the non-infected group (p < 0.001) (Fig. 2)
Summary
The use of in vivo videomicroscopy at the bedside has demonstrated microcirculatory flow disturbances in sepsis. The ability of in vivo videomicroscopy to detect changes in the prevalence of rolling and adhered leukocytes that occur in sepsis is not well-described in humans. Many have observed leukocyte-endothelial cell interactions and microcirculatory flow disturbances in sepsis [3, 4], primarily using intravital microscopy in different animal models. Others using the same tool have observed increased numbers of rolling and adhered leukocytes on the endothelial surface of different organs during experimental sepsis [3, 5]. Recent advances in imaging techniques such as sidestream dark field (SDF) imaging have enabled direct in vivo bedside visualization of the human sublingual microcirculation. Microcirculatory disturbances may occur in the presence of normalized macrocirculation (and macrocirculatory disturbances may occur with intact microcirculation), and microcirculatory changes are independently prognostic of adverse outcomes [8, 9]
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