Microcirculation-guided resuscitation in sepsis: the next frontier?

Abstract

Microcirculatory dysfunction plays a key role in the pathogenesis of tissue dysoxia and organ failure in sepsis. Sublingual videomicroscopy techniques enable the real-time non-invasive assessment of microvascular blood flow. Alterations in sublingual microvascular perfusion were detected during sepsis and are associated with poor outcome. More importantly, sublingual videomicroscopy allowed to explore the effects of commonly applied resuscitative treatments in septic shock, such as fluids, vasopressors and inotropes, and showed that the optimization of macro-hemodynamic parameters may not be accompanied by an improvement in microvascular perfusion. This loss of "hemodynamic coherence," i.e., the concordance between the response of the macrocirculation and the microcirculation, advocates for the integration of microvascular monitoring in the management of septic patients. Nonetheless, important barriers remain for a widespread use of sublingual videomicroscopy in the clinical practice. In this review, we discuss the actual limitations of this technique and future developments that may allow an easier and faster evaluation of the microcirculation at the bedside, and propose a role for sublingual microvascular monitoring in guiding and titrating resuscitative therapies in sepsis.

Keywords: glycocalyx; microcirculation; sepsis; septic shock; sublingual videomicroscopy; tissue perfusion.

Figure 1

Integration of sublingual microcirculatory monitoring with a complete hemodynamic and physiological patient evaluation, including signs of tissue hypoperfusion (i.e., increased capillary refilling time, increased central-to-toe temperature difference, mottling skin) and the standard hemodynamic monitoring. CO, cardiac output, SV, stroke volume, GEDV, global end-diastolic volume, EVLW, extra-vascular lung water, CVP, central venous pressure, PAOP, pulmonary arterial occlusion pressure, ABG, arterial blood gasses, ABP, arterial blood pressure, PPV, pulse pressure variation, HR, heart rate.

Figure 2

Proposed algorithm for the hemodynamic optimization of the septic patient, in which sublingual microvascular monitoring accompanies the standard hemodynamic monitoring and helps in guiding therapy and titrating fluid, vasopressor and inotrope dose. In presence of signs of tissue hypoperfusion, we should first ask if there is a condition of hypovolemia. Both macro- and micro-hemodynamic fluid responsiveness should be tested: if there is no sign of macro-hemodynamic fluid responsiveness, then fluids are not indicated. If there are signs of fluid responsiveness, a fluid bolus is indicated and both the macro-hemodynamic and the microcirculatory response should be assessed. Fluid infusion should be continued until there is an improvement in both macro-hemodynamics and the microcirculation (fluid titration). If macro-hemodynamics improves but the microcirculation does not (i.e., loss of hemodynamic coherence), this may be an indication to stop fluid infusion. Secondly, we should ask if there is significant vasodilation and the need for vasopressors. If MAP is too low and the microcirculation is altered, add a vasopressor. The vasopressor dose could be titrated until there is an improvement in microvascular perfusion following an increase in MAP (considering the patient’s baseline AP as a target). If a vasopressor-induced increase in MAP is not followed by an improved microvascular perfusion, this may be an indication to stop increasing the vasopressor dose. Thirdly, we should ask if there is cardiac dysfunction. If cardiac contractility is reduced, consider adding an inotrope. The inotrope dose could be titrated until there is an improvement in microvascular perfusion following an increase in the cardiac output. If the increase in cardiac output is not associated with an improvement in microvascular perfusion, this may be an indication to stop increasing the inotrope dose. If after optimizing volume status, vascular tone and cardiac contractility the microcirculation is still significantly altered, consider a possible derangement in the endothelial glycocalyx. The possible role of adjunctive therapies and other microcirculatory-targeted therapies should be evaluated in future studies. CRF capillary refilling time, MACRO macro-hemodynamic parameters, MICRO microcirculation, MAP mean arterial pressure, ECHO echocardiography, Hb hemoglobin, RBCs red blood cells, EVLW extravascular lung water, PAOP pulmonary arterial occlusion pressure, CVP central venous pressure, ↑ improvement, ↓ worsening, = stable.