Reply: We would like to thank Dr Dahlqvist and colleagues for their interest and insightful commentaries regarding our review. As stated in the article, our purpose with the article was to summarize the parameters most commonly used in clinical practice to guide volemic resuscitation in the scenarios of severe sepsis/septic shock. We agree with the authors that there may be important limitations concerning macrocirculatory variables as end points of fluid resuscitation during sepsis and that perfusional parameters must be taken considerably into account. However, every parameter used to guide resuscitation in critical illness, whether hemodynamic or perfusional, is subject to criticisms. As the authors appropriately acknowledged, the correlation between most macrocirculatory parameters and tissue perfusion is weak. In addition, the precise relationship between global hemodynamics and microcirculatory blood flow remains incompletely understood. For instance, some studies demonstrated that increasing MAP from 65 to 85 mmHg does not significantly affect microcirculatory blood flow or tissue perfusion (1, 2). Although normalization of macrocirculatory hemodynamic variables is often insufficient to guarantee microcirculatory optimization of septic patients, one must remember that MAP is a key feature of the cardiovascular system and that the occurrence of hypotension of less than 60 mmHg during the course of sepsis is independently associated with mortality (3). We believe, therefore, that the initial approach should be optimization of macrohemodynamic variables, but the therapy obviously should not be limited to these parameters. Besides the variables described in the review, clearly several other hemodynamic and perfusional parameters may be used to guide fluid resuscitation during sepsis. We agree that the markers of skin perfusion are among these end points. Markers such as capillary refill time and gradient temperatures have been described as indicators of inadequate tissue perfusion in circulatory shock (4) and after initial resuscitation (5). Nevertheless, to our knowledge, no prospective randomized large study has been reported that evaluated these variables as end points for fluid resuscitation in early stages of severe sepsis/septic shock. Skin perfusion parameters may be subject to biases such as room temperature and derangements in thermoregulatory response (like in anesthetized patients) and even distributive shock may intervene in skin temperature and capillary refill time (4). Vincent et al. (6) described that a cardiac index less than 1.8 L/min−1 m−2 was associated with a decrease in toe ambient temperature gradient of 5°C and that the increase in this gradient precedes the augmentation in skin oxygen partial pressure during recovery. A similar correlation, however, was not found in septic shock patients (6). Recently, new devices such as capillary microscopy, laser Doppler flowmetry, and sidestream dark field were incorporated to research in intensive care. These techniques allowed the evaluation of microcirculation in "real time" and demonstrated that even when macrohemodynamic variables and global parameters of perfusion are "normalized," regional microcirculation dysfunction could persist and lead to irreversible tissue damage. However, microcirculatory imaging is still investigational in humans and has not been incorporated into routine practice. In addition, important issues related to the limitations of these technologies in "real life" are the limited number of human microcirculatory studies; the visualization only of body surface microcirculation, which might not reflect vital organs microcirculatory dysfunction; the complex interpretation of microcirculatory imaging data; and the difficulty in depicting a parallel to the clinical sepsis stages (7). An intact microcirculatory network is a critical intermediary between the cardiovascular system and tissue oxygenation. Once microcirculation serves as the bridge between macrocirculation and tissue oxygenation, by tracking the response of variables related to tissue perfusion such as acid-base parameters, lactate, and venous oxygen saturation, we are indirectly evaluating the effectiveness of tissue perfusion (8). In our opinion, until now the best evidence-based therapeutic approach for hemodynamic optimization in sepsis is based on the adjustment of circulatory support and the evaluation of global tissue perfusion. We hope that briefly new important studies focused on therapeutic interventions concerning microcirculation may allow a significant improvement in the management of septic patients based on the interplay between macrocirculatory parameters, global perfusion markers, and direct microcirculatory optimization. Fernando José da Silva Ramos Luciano Cesar Pontes Azevedo Research and Education Institute Hospital Sírio-Libanê São Paulo, Brazil