Microcirculation in distress: A new resuscitation end point?*

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Abstract
Sepsis is a disease of the microcirculation. The orchestra of pathogenic mechanisms unleashed during sepsis targets almost every aspect of the function of the microcirculation, leading to distress of the tissue cells and ultimately to organ dysfunction. Cellular properties of immune cells, red blood cells, and endothelial cells, as well as the functional properties of subcellular structures such as membranes and mitochondria, change dramatically under the influence of hypoxia and inflammation occurring during sepsis. This pathology adversely affects vascular autoregulatory mechanisms and alters rheologic properties of blood (1, 2), thereby causing pathologic heterogeneous flow distribution of blood (3). This results in weak microcirculatory units becoming shunted and hypoxic, causing mismatch between oxygen need and oxygen supply of the cells by the microcirculation (4). Mitochondrial dysfunction has been demonstrated in septic patients (5) and is thought to contribute to disturbances in cellular oxygen utilization seen in sepsis (6). An intact functioning microcirculation, however, is an essential prerequisite for efficient oxygen delivery to the tissues cells. That is why correction of microcirculatory function is attributed to the beneficial effects of resuscitation procedures (7). It is thereby conceivable that the microcirculation itself may provide the needed (micro)hemodynamic end point for resuscitation from septic shock. This microcirculatory view of the sequel of events in the pathogenesis of sepsis has until now largely been supported by experimental and indirect measurements in clinical investigations. The role of the microcirculation in the treatment of septic shock has been more a theoretical aim than a practical component of resuscitation of patients: that is, until now. In the current issue of Critical Care Medicine Dr. Sakr and colleagues (8) present a study in which they examined the behavior of sublingual microcirculation of septic shock patients during the time course of their treatment and related these to the changes seen in global hemodynamic and oxygenation variables and to outcome. The authors applied the orthogonal polarization spectral imaging technique to directly observe the flowing blood cells in the microcirculatory network of the sublingual microcirculation. Most important for their study, this technique allowed observation and evaluation of the blood flow in the smallest vessels of the microcirculation, the capillaries. Dr. Sakr and colleagues (8) investigated the sensitivity and specificity of the perfusion of these capillaries to predict outcome. They asked the important question: Is a persistent deficit in microcirculatory perfusion associated with poor outcome? If the answer would be yes, it would identify the microcirculation and the preservation of its function as a key component in the pathogenesis of sepsis and multiple-organ failure. It could further allow identification of patients who might benefit from resuscitation interventions aimed at recruitment of the microcirculation. In previous sublingual orthogonal polarization spectral imaging studies in septic patients, De Backer et al. (9) as well as ourselves (10) observed that impairment of perfusion of sublingual capillaries but not of the larger microvessels characterized the microcirculation in septic shock patients, indicating the presence of shunting pathways in sepsis (4). De Backer demonstrated the importance of this impairment of capillary perfusion in sepsis by showing that it was related to poor outcome (9). In this study, however, sublingual microcirculatory measurements were only made early in the disease. To identify the central role of microcirculation in the pathogenesis of sepsis leading to multiple-organ failure, the authors would need to follow the progress of microcirculatory alterations in time, day by day. In the present study, Dr. Sakr and coworkers did just that.