Bench-to-bedside review: Mechanisms of critical illness – classifying microcirculatory flow abnormalities in distributive shock

Bottom Line: In this paper, we classify the different types of heterogeneous flow patterns of microcirculatory abnormalities found during different types of distributive shock.Analysis of these patterns gave a five class classification system to define the types of microcirculatory abnormalities found in different types of distributive shock and indicated that distributive shock occurs in many other clinical conditions than just sepsis and septic shock.Functionally, however, they all cause a distributive defect resulting in microcirculatory shunting and regional dysoxia.
Affiliation: Department of Physiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Abstract: Over 30 years ago Weil and Shubin proposed a re-classification of shock states and identified hypovolemic, cardiogenic, obstructive and distributive shock. The first three categories have in common that they are associated with a fall in cardiac output. Distributive shock, such as occurs during sepsis and septic shock, however, is associated with an abnormal distribution of microvascular (sublingual microcirculation,clinical microcirculation,Tongue microcirculation,lingua microcirculation) blood flow and metabolic distress in the presence of normal or even supranormal levels of cardiac output. This Bench-to-bedside review looks at the recent insights that have been gained into the nature of distributive shock. Its pathophysiology can best be described as a microcirculatory and mitochondrial distress syndrome, where time and therapy form an integral part of the definition. The clinical introduction of new microcirculatory imaging techniques, such as orthogonal polarization spectral and side-stream dark-field imaging, have allowed direct observation of the microcirculation(sublingual microcirculation,clinical microcirculation,Tongue microcirculation,lingua microcirculation) at the bedside. Images of the sublingual microcirculation during septic shock and resuscitation have revealed that the distributive defect of blood flow occurs at the capillary level. In this paper, we classify the different types of heterogeneous flow patterns of microcirculatory(sublingual microcirculation,clinical microcirculation,Tongue microcirculation,lingua microcirculation) abnormalities found during different types of distributive shock. Analysis of these patterns gave a five class classification system to define the types of microcirculatory abnormalities found in different types of distributive shock and indicated that distributive shock occurs in many other clinical conditions than just sepsis and septic shock. It is likely that different mechanisms defined by pathology and treatment underlie these abnormalities observed in the different classes. Functionally, however, they all cause a distributive defect resulting in microcirculatory shunting and regional dysoxia. It is hoped that this classification system will help in the identification of mechanisms underlying these abnormalities and indicate optimal therapies for resuscitating septic and other types of distributive shock.
Figure 3: Examples of sidestream dark-field images of sublingual microcirculation(clinical microcirculation,Tongue microcirculation,lingua microcirculation) from septic patients with distributive shock. (a) Image taken from a resuscitated septic patient with a class I type of microcirculatory abnormality, complete stasis in the capillaries. (b) An example of a patient with class IV abnormalities with some capillaries showing stasis and others showing high flow. (c) Image of a healthy volunteer with microcirculatory flow in all vessels.

Mentions: At the microcirculatory(sublingual microcirculation,clinical microcirculation,Tongue microcirculation,lingua microcirculation) level, all classes of abnormalities seen during distributive shock show normal to hyperdynamic venular flow [8,9]. It is at the capillary level that the distributive defect is seen, with heterogeneous perfused capillaries resulting in the shunting of areas of the microcirculation. Although the classes of capillary abnormalities we identified may be caused by different mechanisms, they all have in common a distributive defect caused by functional shunting of capillaries in the presence of normal or hyperdynamic venular flow. This is also why we did not make a distinction between stagnant and stopped flow, as both of these result in functional shunting. Since microcirculatory(sublingual microcirculation,clinical microcirculation,Tongue microcirculation,lingua microcirculation) abnormalities are mainly characterized by a heterogeneous pattern of flow, we summarized the abnormalities per class in two main types of capillary flow patterns. This is shown in cartoon form in Figure 2 as two capillaries below each other, each with different flow patterns. Venules are depicted as a single large curved vessel over the capillaries (Fig. 2). In this way, we identified five classes of sublingual capillary flow abnormalities (Fig. 2). A Class I abnormality is defined by all capillaries being stagnant in the presence of normal or sluggish venular flow (Fig. 3). It is a condition that can be found in pressure resuscitated septic patients where pressors have been used excessively to normalize blood pressure [8,9]. Class II microcirculatory flow abnormalities are defined by empty capillaries next to capillaries with flowing red blood cells. This decrease of capillary density makes the diffusion distance between red blood cells in the remaining capillaries and the tissue cells larger, leading to regional hypoxia [6]. The red blood cells in the remaining capillaries show a high microcirculatory(sublingual microcirculation,clinical microcirculation,Tongue microcirculation,lingua microcirculation) hemoglobin saturation, indicating poor oxygen off-loading associated with the reduction in capillary exchange surface area [41]. Class II abnormalities were most frequently found during use of extracorporeal circuits in coronary artery bypass grafting (CABG) surgery and extracorporeal membrane oxygenation (ECMO). Class III abnormalities are described by capillaries with stagnant blood cells next to capillaries with normal flow. These abnormalities were most frequently observed in sickle cell patients and critically ill malaria patients, but also in septic patients. In critically ill malaria patients, who are often in a coma, strikingly normal hemodynamics are seen in the presence of high lactate levels. This feature, together with class III microcirculatory abnormalities, also identifies this condition as distributive shock. Class IV abnormalities show hyperdynamic flow patterns in some capillaries next to capillaries with stagnant cells (Fig. 3). Venules in such cases frequently also show a hyperdynamic flow profile. This condition is seen in resuscitated hyperdynamic septic patients. Class V abnormalities describe the condition where hyperdynamic flow is seen at all levels of the microcirculation(sublingual microcirculation,clinical microcirculation,Tongue microcirculation,lingua microcirculation). Blood cells usually travel so fast that individual cells can not be distinguished from each other. Metabolic distress seen under such conditions could be the result of cells moving too fast to off-load their oxygen, or, that they may originate from other organs or compartments being shunted [28]. Interestingly, the class V types of abnormality are also observed in extreme exercise. The pathogenic nature of class V abnormalities in septic patients remains to be determined. In Table 1, the diseases observed so far are listed next to the different classes of microcirculatory abnormalities seen in Figure 2. They are by no means complete and it is hoped that this list will continue to expand as more insight is obtained into the nature of distributive alterations. Scoring systems developed to quantify such images should greatly aid this process [42]. Examples of OPS/SDF(sublingual microcirculation,clinical microcirculation,Tongue microcirculation,lingua microcirculation) movies of each class of abnormality can be viewed on our web site [43].
http://openi.nlm.nih.gov/

SUBLINGUAL MICROCIRCULATION OF PREGNANT AND NON-PREGNANT WOMEN
Abstract Number: S-27
Abstract Type: Original Research
Allana Munro MD1 ; Ronald B George MD FRCPC2; Islam Saleh Abdo MD3; Christian Lehmann MD PhD4
Dalhousie University1 ; Dalhousie University2; Dalhousie University3; Dalhousie University4

Introduction: Microcirculation, the small vessels in the vasculature, embedded within organs, is responsible for the distribution of blood within tissues, regulation of blood pressure, delivery of oxygen and other nutrients. Sidestream Dark Field (SDF) imaging(sublingual microcirculation,clinical microcirculation,Tongue microcirculation,lingua microcirculation) is a stroboscopic imaging modality, allowing assessment of microcirculation. Blood flow is quantified using Microvascular Flow Index (MFI), perfused vessel density (PVD), and the proportion of perfused vessels (PPV). The objectives were to compare the sublingual microcirculation of pregnant subjects to that of comparable non-pregnant volunteers. Methodology: The primary outcome is the difference between the MFI of pregnant versus non-pregnant subjects. Inclusion criteria include ASA I-II participants in two groups; Pregnant – non-labouring women with singleton pregnancies, at term gestation, Non-Pregnant – healthy female volunteers, matched to pregnant participants for age ± 1 year. Participants were excluded with hypertensive and other cardiovascular disease, obesity, diabetes, or caffeine intake within 2 hours. The SDF (sublingual microcirculation,clinical microcirculation,Tongue microcirculation,lingua microcirculation)device was be applied to the sublingual mucosal surface obtaining steady images of at least 20 seconds duration. Each participant was be asked to provide 20 second measurements in five visual fields. Data Analysis: Video clips were analysed blindly and at random to prevent coupling between images. The mean MFI values for each individual was analyzed using paired t-test. Apriori power calculation was performed for the difference between two independent means; effect size 1.125, alpha 0.05, power 0.8. Fourteen subjects per group results in 82% power. To address our assumptions and potential drop-outs we will increase the group size by 20%. Results: Thirty-seven participants were recruited (19 pregnant, 18 non-pregnant), a single pregnant participant was withdrawn because of technical issues. Morphometric(sublingual microcirculation,clinical microcirculation,Tongue microcirculation,lingua microcirculation) characteristics are listed in table 1. The PVD and PPV were not significantly different, while the MFI was significantly higher in the pregnant group. Conclusion: The microvascular flow index of pregnant women is higher than a comparable non-pregnant group, which appears to correlate the physiological changes of pregnant women. Future projects of this novel imaging technique should focus on determining the time course of these changes and the impact of disease process, i.e. preeclampsia and gestational diabetes on the microvascular and ultimately on the maternal-fetal unit.

http://soap.org/display_2012_abstract.php?id=S-27

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