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Various noninvasive microscopic camera technologies have been used to visualize the sublingual microcirculation in patients. We describe a comprehensive approach to bedside in vivo sublingual microcirculation video image capture and analysis techniques in the human clinical setting. We present a user perspective and guide suitable for clinical researchers and developers interested in the capture and analysis of sublingual microcirculatory flow videos. We review basic differences in the cameras, optics, light sources, operation, and digital image capture. We describe common techniques for image acquisition and discuss aspects of video data management, including data transfer, metadata, and database design and utilization to facilitate the image analysis pipeline. We outline image analysis techniques and reporting including video preprocessing and image quality evaluation. Finally, we propose a framework for future directions in the field of microcirculatory flow videomicroscopy acquisition and analysis. Although automated scoring systems have not been sufficiently robust for widespread clinical or research use to date, we discuss promising innovations that are driving new development.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1213-9) contains supplementary material, which is available to authorized users.

Clinical diagnosis of complex regional pain syndrome (CRPS) is a dichotomous (yes/no) categorization, a format necessary for clinical decision making. Such dichotomous diagnostic categories do not convey an individual's subtle gradations in the severity of the condition over time and have poor statistical power when used as an outcome measure in research. This prospective, international, multicenter study slightly modified and further evaluated the validity of the CRPS Severity Score (CSS), a continuous index of CRPS severity. Using a prospective design, medical evaluations were conducted in 156 patients with CRPS to compare changes over time in CSS scores between patients initiating a new treatment program and patients on stable treatment regimens. New vs stable categorizations were supported by greater changes in pain and function in the former. Results indicated that CSS values in the stable CRPS treatment group exhibited much less change over time relative to the new treatment group, with intraclass correlations nearly twice as large in the former. A calculated smallest real difference value revealed that a change in the CSS of ≥4.9 scale points would indicate real differences in CRPS symptomatology (with 95% confidence). Across groups, larger changes in CRPS features on the CSS over time were associated in the expected direction with greater changes in pain intensity, fatigue, social functioning, ability to engage in physical roles, and general well-being. The overall pattern of findings further supports the validity of the CSS as a measure of CRPS severity and suggests it may prove useful in clinical monitoring and outcomes research.

There have been some modest recent advancements in the research of Complex Regional Pain Syndrome, yet the amount and quality of the work in this complicated multifactorial disease remains low (with some notable exceptions; e.g., the recent work on the dorsal root ganglion stimulation). The semi-systematic (though in some cases narrative) approach to review is necessary so that we might treat our patients while waiting for “better research.” This semi-systematic review was conducted by experts in the field, (deliberately) some of whom are promising young researchers supplemented by the experience of “elder statesman” researchers, who all mention the system they have used to examine the literature. What we found is generally low- to medium-quality research with small numbers of subjects; however, there are some recent exceptions to this. The primary reason for this paucity of research is the fact that this is a rare disease, and it is very difficult to acquire a sufficient sample size for statistical significance using traditional statistical approaches. Several larger trials have failed, probably due to using the broad general diagnostic criteria (the “Budapest” criteria) in a multifactorial/multi-mechanism disease. Responsive subsets can often be identified in these larger trials, but not sufficient to achieve statistically significant results in the general diagnostic grouping. This being the case the authors have necessarily included data from less compelling protocols, including trials such as case series and even in some instances case reports/empirical information. In the humanitarian spirit of treating our often desperate patients with this rare syndrome, without great evidence, we must take what data we can find (as in this work) and tailor a treatment regime for each patient.

BackgroundWe sought to determine the effects of alternative resuscitation strategies on microcirculatory perfusion and examine any association between microcirculatory perfusion and mortality in sepsis.MethodsThis was a prospective, formally designed substudy of participants in the Protocolized Care in Early Septic Shock (ProCESS) trial. We recruited from six sites with the equipment and training to perform these study procedures. All subjects were adults with septic shock, and each was assigned to alternative resuscitation strategies. The two main analyses assessed (1) the impact of resuscitation strategies on microcirculatory perfusion parameters and (2) the association of microcirculatory perfusion with 60-day in-hospital mortality. We measured sublingual microcirculatory perfusion using sidestream dark field in vivo video microscopy at the completion of the 6-h ProCESS resuscitation protocol and then again at 24 and 72 h.ResultsWe enrolled 207 subjects (demographics were similar to the overall ProCESS cohort) and observed 40 (19.3%) deaths. There were no differences in average perfusion characteristics between treatment arms. Analyzing the relationship between microcirculatory perfusion and mortality, we found an association between vascular density parameters and mortality. Total vascular density (beta = 0.006, p < 0.003), perfused vascular density (beta = 0.005, p < 0.04), and De Backer score (beta = 0.009, p < 0.01) were higher overall in survivors in a generalized estimating equation model, and this association was significant at the 72-h time point (p < 0.05 for each parameter).ConclusionsMicrocirculatory perfusion did not differ between three early septic shock treatment arms. We found an association between microcirculatory perfusion parameters of vascular density at 72 h and mortality.Trial registrationClinicalTrials.gov, NCT00510835. Registered on August 2, 2007.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2240-5) contains supplementary material, which is available to authorized users.

Aim We hypothesized that microcirculatory dysfunction, similar to that seen in sepsis, occurs in post-cardiac arrest patients and that better microcirculatory flow will be associated with improved outcome. We also assessed the association between microcirculatory dysfunction and inflammatory markers in the post-cardiac arrest state. Methods We prospectively evaluated the sublingual microcirculation in post-cardiac arrest patients, severe sepsis/septic shock patients, and healthy control patients using Sidestream Darkfield Microscopy. Microcirculatory flow was assessed using the Microcirculation flow index (MFI) at 6 and 24 hours in the cardiac arrest patients, and within 6 hours of Emergency Department admission in the sepsis and control patients. Results We evaluated 30 post-cardiac arrest patients, 16 severe sepsis/septic shock patients, and 9 healthy control patients. Sublingual microcirculatory blood flow was significantly impaired in post-cardiac arrest patients at 6 hours (MFI 2.6 [IQR: 2 - 2.9]) and 24 hours (2.7 [IQR: 2.3 - 2.9]) compared to controls (3.0 [IQR: 2.9 - 3.0]; p < 0.01 and 0.02, respectively). After adjustment for initial APACHE II score, post-cardiac arrest patients had significantly lower MFI at 6-hours compared to sepsis patients (p < 0.03). In the post-cardiac arrest group, patients with good neurologic outcome had better microcirculatory blood flow as compared to patients with poor neurologic outcome (2.9 [IQR: 2.4 – 3.0] vs. 2.6 [IQR: 1.9 – 2.8]; p < 0.03). There was a trend toward higher median MFI at 24 hours in survivors vs. non-survivors (2.8 [IQR: 2.4 – 3.0] vs. 2.6 [IQR: 2.1-2.8] respectively; p < 0.09). We found a negative correlation between MFI-6 and vascular endothelial growth factor (VEGF) (r= −0.49, P= 0.038). However, after Bonferroni adjustment for multiple comparisons, this correlation was statistically non-significant. Conclusion Microcirculatory dysfunction occurs early in post-cardiac arrest patients. Better microcirculatory function at 24 hours may be associated with good neurologic outcome.

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Objective Although storage alters red blood cells, several recent, randomized trials found no differences in clinical outcomes between patients transfused with red blood cells stored for shorter vs. longer periods of time. The objective of this study was to see if storage impairs the in vivo ability of erythrocytes to traverse the microcirculation and deliver oxygen at the tissue level. Methods A subset of subjects from a clinical trial of cardiac surgery patients randomized to receive transfusions of red blood cells stored ≤10d or ≥21d were assessed for thenar eminence and cerebral tissue hemoglobin oxygen saturation (StO2) using near-infrared spectroscopy, and sub-lingual microvascular blood flow using side-stream darkfield videomicroscopy. Results Among 55 subjects, there was little change in the primary endpoint (thenar eminence StO2 from before to after transfusion of one unit) and the change was similar in the two groups: +1.7%(95%CI:−0.3,3.8) for shorter-storage and +0.8%(95%CI:−1.1,2.9) for longer-storage (p=0.61). Similarly, no significant differences were observed for cerebral StO2 or sublingual microvascular blood flow. These parameters were also not different from preoperatively to one day postoperatively, reflecting the absence of a cumulative effect of all red blood cell units transfused during this period. Conclusions There were no differences in thenar eminence or cerebral StO2, or sublingual microcirculatory blood flow, in cardiac surgery patients transfused with red blood cells stored ≤10d or ≥21d. These results are consistent with the clinical outcomes in the parent study, which also did not differ, indicating that storage may not impair oxygen delivery by red blood cells in this setting.