The intricate relationship between capillary refill time and systemic hemodynamics in septic shock.

The emergence and validation of capillary refill time (CRT) as a resuscitation target together with its rapid kinetics of response to increases in systemic blood flow makes it the ideal variable to assess clinical reperfusion and the status of macro-to-microcirculatory coupling in septic shock. Moreover, previous studies have shown that resuscitation can be safely stopped after CRT normalization, thus decreasing the risk of over-resuscitation. From a physiological point of view, CRT is a complex variable integrating microvascular flow and reactivity. Additionally, it may be understood as a dynamic test that evaluates the preservation or disruption of normal responses of the microcirculation to maintain blood flow after transient ischemic challenges. The relationship between systemic hemodynamics and CRT is complex. Indeed, single time-point asssessments of CRT are not able to predict absolute cardiac output values and this is logical since they belong to different phsyiological categories. An abnormal CRT may be explained by insufficient macrohemodynamic resuscitation but also by several derangements at the microvascular level that may preclude CRT normalization, thus signaling a state of macro-to-microcirculatory uncoupling. CRT response to an acute fluid or mean arterial pressure challenge, may not only reveal the adequacy of systemic blood flow but also contribute to tailor interventions to personalize septic shock resuscitation. The lack of CRT response to these challenges discloses a more complex pathophysiological condition that is associated with higher mortality. Further research efforts should be focused on better understanding the factors associated with CRT non-response as a first step to develop a more phsyiologically-based resuscitation, that could eventually improve outcomes.