Mark Wefers Bettink

Chapter 2 28 hypoxia might need more complex monitoring than lactate and central venous oxygen concentration to effectively monitor its development and reaction to therapy during sepsis (56). If an infection produces enough inflammatory molecules to produce a SIRS reaction, the first vital signs of a serious infection include tachycardia and hypotension resulting in shock. Macrohemodynamic collapse is prevented by aggressive fluid resuscitation and circulatory support via noradrenaline. However, monitoring the effect of collapse and resuscitation on microcirculatory or mitochondrial function is not part of the standard of care. The return of microcirculation during the resuscitation of a patient with sepsis improves survival (57). In animal models a clear link is also found between a SIRS reaction and mitochondrial dysfunction,(44,45,58,59) and early mitochondrial dysfunction in sepsis limits the chance of patient survival.(51) Mitochondrial dysfunction in sepsis is not a new concept, as early as in 2002 a direct link between mitochondrial function, organ dysfunction and mortality was described (3). Aggressive and early fluid resuscitation is one of the pillars of sepsis treatment, with a modest improvement of mortality (60). Mortality is mostly dependent on the amount of organ dysfunction and responsiveness on early treatment goals (60,61). Preserving vital parameters and microcirculatory perfusion during resuscitation only seems to lead to a modest improvement of mortality. Since mitochondrial dysfunction is linked to an increase in mortality, this results in a complex interaction. On one side, the microcirculation is influenced by the mitochondria of the parenchymal cells and on the other side it is affected by the macrocirculation (4). The important question then is whether the (apparent) loss of hemodynamic coherence between the macrocirculation and microcirculation should be treated aggressively by hemodynamic measures or that, alternatively, apparent microcirculatory dysfunction should be seen as an epiphenomenon caused by cellular and mitochondrial issues (dysfunction or adaptation). In the latter case, additional attempts to “optimize” macrohemodynamic parameters and microcirculatory perfusion might prove counterproductive. The answer probably varies in different patients and might even change in single patients over the course of the disease and due to given treatments.