Impaired vascular reactivity in sepsis – a systematic review with meta-analysis

INTRODUCTION: Vascular dysfunction due to reduced nitric oxide bioavailability plays an important role in the pathogenesis of sepsis. This meta-analysis examines evidence from published literature to evaluate whether in the adult population the presence/severity of sepsis is associated with impaired vasoreactivity. MATERIAL AND METHODS: We performed a search of the Medline, Scopus, and EMBASE databases to identify observational studies using measurement of reactive hyperaemia in adult patients with sepsis. After data extraction using predefined protocol, qualitative synthesis of findings was performed regarding consistency of findings between methods, evidence of association between vascular reactivity and severity of sepsis, multiple organ failure, and death. A meta-analyses of standardised mean differences in vasoreactivity between groups was performed, in which data were available for relevant outcomes. RESULTS: Eighteen studies using four methods to measure vascular reactivity from a total of 466 were included in the analysis. The pooled standardised mean difference estimate showed that septic patients had less reactive hyperaemia than controls (–2.59, 95% CI: –3.46 to –1.72; p < 0.00001), and peak hyperaemic blood flow was lower in patients with sepsis than in the control group (SMD = –1.42, 95% CI: –2.14 to –0.70; p = 0.0001). The combined SMD between non survivors and survivors was –0.36 (95% CI: –0.67 to –0.06; p = 0.02) for reactive hyperaemia and –0.70 (95% CI: –1.13 to –0.27; p = 0.001) for peak hyperaemic blood flow. CONCLUSIONS: Septic patients have attenuated vascular reactivity when compared to healthy volunteers. There are insufficient data indicating that these changes can identify patients at risk of worsening organ failure or death.