Clinical manifestations of disordered microcirculatory perfusion in severe sepsis

Abstract

Microcirculatory dysfunction plays a pivotal role in the development of the clinical manifestations of severe sepsis. Prior to the advent of new imaging technologies, clinicians had been limited in their ability to assess the microcirculation at the bedside. Clinical evidence of microcirculatory perfusion has historically been limited to physical examination findings or surrogates that could be derived from global parameters of oxygen transport. This review explores: (1) the clinical manifestations of severe sepsis that can be linked to microcirculatory dysfunction; (2) the relationship between conventional hemodynamic parameters and microcirculatory blood flow indices; (3) the incorporation of microcirculatory function into the definition of 'shock' in the sepsis syndrome; (4) the role of the microcirculation in oxygen transport; and (5) the potential impact of novel sepsis therapies on microcirculatory flow. Although the study of the microcirculation has long been the domain of basic science, newly developed imaging technologies, such as orthogonal polarization spectral imaging, have now given us the ability to directly visualize and analyze microcirculatory blood flow at the bedside, and see the microcirculatory response to therapeutic interventions. Disordered microcirculatory flow can now be associated with systemic inflammation, acute organ dysfunction, and increased mortality. Using new technologies to directly image microcirculatory blood flow will help define the role of microcirculatory dysfunction in oxygen transport and circulatory support in severe sepsis.

Figures

Figure 1

The role of the microcirculation in goal-directed circulatory support. The upstream endpoints of resuscitation are hemodynamic and oxygen-derived variables that can be modulated by circulatory support interventions. The downstream variables are markers of tissue perfusion and effectiveness of resuscitation. The microcirculation is the critical intermediary that delivers blood flow from the cardiovascular system to the tissues. BPM, beats per minute; CVP, central venous pressure; DO2, oxygen delivery; HR, heart rate; MAP, mean arterial pressure; PCWP, pulmonary capillary wedge pressure; pHi, gastric intramucosal pH; PslCO2, sublingual pCO2; SBP, systolic blood pressure; SV, stroke volume; SvO2, mixed venous oxygen saturation; SVR, systemic vascular resistance.

Figure 2

The Krogh conceptual model of oxygen diffusion from the capillaries. (a) The area of tissue that is supplied by an individual capillary is represented by a cylinder. The diffusion distance for oxygen in the tissues is shown (d). (b) If perfused capillaries drop out because of the microcirculatory alterations of severe sepsis, and the perfused vessel density decreases, the diffusion distance for oxygen increases (d2). This illustrates how perfused vessel density plays a critical role in oxygen transport.

Figure 3

A conceptual model of capillary flow and oxygen diffusion. A cylinder represents the area of tissue surrounding an individual capillary. A markedly low value for the (global) mixed venous oxygen saturation (SvO2) reflects markedly deoxygenated blood in the pooled post-capillary venules. Regardless of how well oxygenated the blood may be on the arteriolar side of the capillary (A), a very low SvO2 indicates that tissues near the venous end of the capillary (V) are supplied by deoxygenated blood ('lethal corner'). This conceptual model explains how a low SvO2 is associated with tissue dysoxia.

Figure 4

The microcirculatory shunting model of sepsis. Severe flow impairment (denoted by X) in weak microcirculatory units causes a shunting of blood to open microcirculatory units. Elevation of serum lactate concentration (from the microcirculatory units with impaired flow) may be simultaneously observed along with venous hyperoxia from the shunted units. Adapted with permission [22].