Micro and Macro Circulation in Sepsis

There are few reliable prognostic indicators in early sepsis to predict disease progression, in part because the pathophysiologic mechanism of vascular dysregulation remains incompletely understood. The global Coronavirus Disease 2019 (COVID-19) pandemic has increased the number of patients with sepsis, straining hospital systems and illustrating the need for research into prognostic and therapeutic strategies. An important area of research is the role of the eGC, a thin vascular lining composed of proteoglycans, glycosaminoglycan side-chains, and plasma proteins that play a central role in microvascular homeostasis, the function of which is compromised in sepsis. Another growing field of inquiry is the phenomenon of HI, a condition in which MiH remain dysfunctional despite normalization of conventionally targeted MaH measures such as mean arterial pressure (MAP), leading to poor end-organ perfusion. It has been hypothesized that HI due to persistently deranged MiH and reduced end-organ perfusion result in an ongoing state of "microvascular shock", leading to worsening end-organ damage despite apparent normalization of conventionally targeted parameters. Importantly, HI has been shown to predict poor patient outcomes, with abnormal MiH predicting patient mortality despite normalization of MAP after administration of vasoactive medications. MiH measures have also been shown to differ significantly between septic patients and healthy controls. In one study of a large sepsis cohort, MiH parameters were predictive of adverse outcomes, while MaH parameters were not, suggesting that MiH measurements, and HI in particular may be more sensitive than conventional measures for predicting outcomes in sepsis. One hypothesis is that HI in sepsis is mediated by degradation of the eGC, with subsequent loss of microvascular homeostasis, though the role of the eGC as a vascular barrier remains controversial. One question that remains is whether or not microvascular changes can predict patient outcomes in patients judged to be adequately fluid resuscitated, as measured by MAP or Starling Stroke Volume/Non-invasive cardiac monitor (NICOM) testing.