Resuscitation aims at normalizing systemic hemodynamic variables, such as stroke volume or blood pressure, with the expectation that a parallel improvement will occur in the perfusion and oxygenation of the microcirculation feeding the tissue beds of the organ systems. Homeostatic coupling between the systemic circulation and the microcirculation is essential for such an expectation to be met; in addition to the primary disease, resuscitation fluids and medications themselves can adversely affect this regulation. We have termed the required coupling between the macro- and microcirculation essential for successful resuscitation based on the correction of systemic hemodynamic variables as “hemodynamic coherence” [
37]. Loss of hemodynamic coherence can occur if the factors affecting the microcirculation are not corrected by the resuscitation procedure focused on correction of the macrocirculation by resuscitation following shock. Such factors affecting the microcirculation can include immunological and/or factors affecting endothelial, leucocyte, and red blood cell function. In this context, its manifestation should be regarded as a dynamic process depending on the interactions between disease, therapy, and time. Whether the correction of systemic hemodynamic variables achieves adequate microcirculatory and tissue perfusion is often unknown and may manifest at the bedside as the patient being unresponsive. Such a situation prompts the clinician to administer even more fluids and medications, potentially causing harm. Assessment of the presence or absence of hemodynamic coherence requires the simultaneous measurement of the response of the macro- and the microcirculation. The microcirculation can be effectively visualized in the sublingual area using hand-held vital microscopy (e.g., [
38]), which allows the parallel improvement in the microcirculation to resuscitation efforts based on the response of systemic parameters to be verified [
39]. Identification of the presence or absence of hemodynamic coherence and the response of the microcirculation to therapy forms the third pillar of personalized physiological medicine because it assesses the physiological coupling between the various compartments in the hierarchy of the circulation to achieve uniform resuscitation. Loss of hemodynamic coherence at the level of the microcirculation can be divided into four types (Fig.
1). Type 1 loss of hemodynamic coherence is characteristic of states of sepsis, in which inflammatory mediators and oxidative and nitrosative stress factors cause endothelial and erythrocyte injury resulting in obstruction of the capillaries. This causes a heterogeneous microcirculatory flow and functional shunting in parts of the microcirculation, resulting in reduced oxygen extraction capacity characteristic of sepsis [
40]. Type 2 loss of hemodynamic coherence occurs when an excessive volume of fluids is given in an attempt to correct systemic variables, such as stroke volume and blood pressure. While systemic variables may be normalized, hemodilution causes reduced viscosity and dilution of the blood, both of which cause a reduction in capillary filling. This increases the diffusion distances between oxygen-carrying erythrocytes and tissue cells, thereby reducing the oxygen delivery capacity of the microcirculation and its oxygen extraction capacity [
39]. Type 3 loss of hemodynamic coherence is the condition where high levels of vasopressors intended to improve blood pressures can paradoxically cause constriction of microcirculatory blood flow [
41]. Similarly, microcirculatory impediment of flow can occur when high venous pressures are targeted, resulting in microcirculatory flow restriction due to tamponade [
42]. Type 4 loss of hemodynamic coherence occurs as a result of edema (e.g., in burns [
43] and in malaria [
44]) in which leaky vessels also cause increased diffusion distances and a reduction in oxygen extraction.