Recruiting the microcirculation in septic shock

© The Author(s) 2019, corrected publication 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Mortality of critically ill patients is driven by severity of the insult, comorbidities, appropriate treatment, and organ failure. The pathophysiological mechanisms leading to organ failure during sepsis remain poorly understood. The direct toxicity of pro-inflammatory mediators and/or bacterial components and/or circulating particles released from damaged cells has been suggested to contribute to organ dysfunction. Alterations of microcirculatory perfusion were associated with organ failure severity and mortality in septic shock patients. Tissue perfusion is likely to play a role in the development of organ dysfunction either due to systemic or regional alterations. Interestingly, organ dysfunction may persist despite apparent restoration of systemic macrohemodynamic variables [1]. Optimal macrohemodynamic targets to perfuse and recruit the microvessels may vary, however, between patients and between vascular beds [2]. Altogether, these associations suggest that intra-organ blood flow defects might be (at least partially) causal in the development of organ failure and targeting the microcirculation might promote organ recovery and better outcome. The question of which therapeutics may be implemented based on peripheral perfusion or microcirculation assessment is central. While animal studies have shown a beneficial impact of treatment targeting the microcirculation on organ blood flow and damage recovery, clinical data are scarcer [3]. Therapeutic intervention can help improving organ perfusion in selected patients. Fluid loading was shown to improve microcirculatory blood flow when applied early on during the course of sepsis [4] or in the operating room [5]. Dobutamine improved microvascular perfusion in some patients but not in others [6]. In post-cardiopulmonary bypass shock, increasing the perfusion pressure (PP) by increasing the mean arterial pressure (MAP) from 60 to 75 mmHg using norepinephrine could increase renal blood flow and glomerular filtration rate. Variability in the best PP for optimizing renal blood flow, however, further underlined the variability in response to treatments. Some patients did improve their renal hemodynamic while other deteriorated while further increasing MAP from 75 to 90 mmHg [7]. Others showed that increasing the MAP above 65 mmHg did not improve microperfusion or even could worsen it in some patients [8–10]. A vasopressor challenge in patients with multiple organ failure remaining hypoperfused despite fluids (i.e. oliguria, increased capillary refilling time, mottling, cold extremities) can work out the best perfusion pressure to recruit microvessels. Monitoring the perfusion response to an increase of PP is, however, warranted to avoid overtreatment in unresponsive patients. Transfusion of red blood cells can increase the microcirculatory flow and the proportion of perfused vessels after an haemorrhagic shock [11] or in some but not all septic patients with anaemia [12]. In any case, a wide variability exists between patients regarding the impact of fluids and vasopressors to recruit the microcirculation. The benefit of improving cardiac output and increasing MAP on the microcirculation appear prominent when these parameters and the capillary perfusion are altered at baseline before the therapeutic challenge. Yet imaging monitoring tools (i.e. side-dark field imaging) have revealed that microcirculatory disorders may persist despite the apparent normalization of macrohemodynamic variables. Among the mechanisms implicated in the impairment of microcirculatory blood flow (i.e. intravascular thrombosis, endothelial dysfunction, increased extravascular tissue pressure), altered balance between levels of vasoconstrictive and vasodilating substances may be sensitive Open Access