© 2002 American Thoracic Society
The Microcirculation UnveiledDepartment of Anesthesiology Academic Medical Center University of Amsterdam Amsterdam, The Netherlands Sepsis is a disorder of the microcirculation. It could in fact be argued that the microcirculation is the first organ to fail in the progression of sepsis to multiorgan failure syndrome. The inflammatory cells and mediators evoked by sepsis cause havoc in the microcirculation with vascular dysregulation, loss of barrier function (capillary leak syndrome), endothelial cell-impaired function, as well as a host of blood-associated disturbances such as increased clotting, red blood cell rigidity, and leukocyte activation (1). The upshot of this catastrophe is a complete collapse of microcirculatory function, which together with inflammatory mediators ultimately leads to cell death. The translation of results from animal studies of sepsis to the clinic has been disappointing. This has resulted from the inadequacy of animal models that mimic the clinical situation but even more because clinical techniques are not capable of directly observing the course of events at the microscopic level. Experimental studies have shown that a great number of cellular functions become deranged during experimental sepsis. Moreover, there is still no adequate clinical resolution to the paradox in the treatment of sepsis where oxygen delivery achieved through a high cardiac output and low vascular resistance is apparently adequate, whereas a deficit in oxygen extraction is evident alongside clear signs of regional dysoxia. The question is which one of the host of pathophysiologic mechanisms holds the key to successful management of clinical sepsis. In this issue of the AJRCCM, De Backer and colleagues (pp. 98–104) show that the events occurring at the microcirculatory level may provide the key to these questions (2). By their observation of the dramatic derangements in the microcirculation during sepsis and especially their demonstration of the reversibility of these derangements, they have introduced the microcirculation to the clinical arena of sepsis. In their innovative and well-performed study, De Backer and colleagues applied a new optical technique called orthogonal polarization spectral imaging to visualize directly the microcirculation in patients being treated for sepsis (2). Originally introduced by Slaaf and colleagues, this technique uses green polarized light to observe the microcirculation in vivo (3). Incorporated into a hand-held type of microscope, orthogonal polarization spectral imaging was clinically introduced by us and applied to identify microcirculatory pathologies during surgery (4, 5). De Backer and coworkers used orthogonal polarization spectral imaging to investigate the properties of sublingual microcirculation of septic patients in great detail. What gives their study an extra dimension is the opportunity for the reader to see the moving images of microcirculation in the online data supplement for the article (available online at http://ajrccm.atsjournals.org/cgi/content/full/166/1/98/DC1 ), a first for the AJRCCM that will undoubtedly set a trend for the future. Observation of these images gives a lasting impression of the dynamic and heterogeneous nature of microcirculatory flow and conveys its sensitivity to sepsis. Through these observations, De Backer and colleagues have provided new insights into the pathophysiology of clinical sepsis. First, microcirculatory perfusion was reduced by approximately half, despite overall correction of systemic hemodynamic variables and parameters of oxygen delivery. The severity of this microcirculatory depression was correlated to outcome as well as to blood lactate levels and Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation II scores, but not to any of the other clinical variables being monitored. Their findings that depressed microcirculatory flow occurred more severely in the smallest vessels, leaving the larger vessels more or less unaffected, provide direct support for the idea that shunting of the microcirculation is a prominent feature of sepsis (6). These results also provide an explanation as to why systemic hemodynamic variables are a poor reflection of the hemodynamic properties of the microcirculation. The surprising and completely novel finding by De Backer and colleagues, however, is the observation that endothelial responsiveness to vasodilatory stimuli such as acetylcholine seems to be preserved despite severe sepsis (2). This was demonstrated by topical application of acetylcholine sublingually and observing the reaction of the microcirculation using orthogonal polarization spectral imaging. Endothelial responsiveness to acetylcholine was preserved which, by causing vasodilation, was able to correct and restore microcirculatory flow back to normal values and patterns. In a similar recent study using orthogonal polarization spectral imaging in septic patients, we found that systemic administration of nitroglycerin restored and corrected microcirculatory flow that had previously been depressed (7). De Backer and coworkers had earlier predicted that such a mechanisms may account for the improved oxygen extraction seen in septic patients when given the potent vasodilator prostacyclin (8). Whether resuscitating the sublingual microcirculation is an important treatment target is too early to tell. Important questions need to be answered. How do the various resuscitation strategies affect the microcirculation? How representative is sublingual microcirculation of microcirculatory beds in other more vital organs? Do the observed derangements in microcirculatory flow lead to tissue hypoxia? In this context, the introduction of sublingual tonometry by Weil and colleagues (9) and the demonstration by Marik (10) that sublingual capnography is correlated with gastric tonometry in septic patients suggest that sublingual monitoring may be a tool of the future. The most important question that needs to be answered however is this: Does resuscitating sublingual microcirculation result in better patient outcome? If the answer turns out to be yes, correction of sublingual microcirculation may provide a new resuscitation end point (11). On the other hand, it is clear that the microcirculation is an essential compartment whose function is a prerequisite for tissue survival. From the study of De Backer and coworkers (2), it is evident that correction of global hemodynamic variables is insufficient to guarantee adequate microcirculatory perfusion and oxygen transport. In the early days, the toe was considered a sensitive indicator for the depth of shock (12), and later came gastric tonometry as the canary of multiorgan failure syndrome (13). Has microcirculation become the new canary for early detection of this syndrome? Who can tell? One thing, however, is for certain. With their study, De Backer and colleagues have firmly and squarely introduced microcirculation into the clinical arena in the treatment of sepsis. They are to be congratulated on this fine study. REFERENCES
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