Sublingual Sidestream Dark Field Research Articles

End organ perfusion and pediatric microcirculation assessment.

Cardiovascular instability and reduced oxygenation are regular perioperative critical events associated with anesthesia requiring intervention in neonates and young infants. This review article addresses the current modalities of assessing this population's adequate end-organ perfusion in the perioperative period. Assuring adequate tissue oxygenation in critically ill infants is based on parameters that measure acceptable macrocirculatory hemodynamic parameters such as vital signs (mean arterial blood pressure, heart rate, urinary output) and chemical parameters (lactic acidosis, mixed venous oxygen saturation, base deficit). Microcirculation assessment represents a promising candidate for assessing and improving hemodynamic management strategies in perioperative and critically ill populations. Evaluation of the functional state of the microcirculation can parallel improvement in tissue perfusion, a term coined as "hemodynamic coherence". Less information is available to assess microcirculatory disturbances related to higher mortality risk in critically ill adults and pediatric patients with septic shock. Techniques for measuring microcirculation have substantially improved in the past decade and have evolved from methods that are limited in scope, such as velocity-based laser Doppler and near-infrared spectroscopy, to handheld vital microscopy (HVM), also referred to as videomicroscopy. Available technologies to assess microcirculation include sublingual incident dark field (IDF) and sublingual sidestream dark field (SDF) devices. This chapter addresses (1) the physiological basis of microcirculation and its relevance to the neonatal and pediatric populations, (2) the pathophysiology associated with altered microcirculation and endothelium, and (3) the current literature reviewing modalities to detect and quantify the presence of microcirculatory alterations.

Comparison of sublingual microcirculatory parameters measured by sidestream darkfield videomicroscopy in anesthetized pigs and adult humans.

This study aimed to compare sublingual microcirculatory parameters between anesthetized pigs and conscious adult humans using sidestream darkfield videomicroscopy. The overarching aim of the work was to validate the pig as an experimental model of changes in microcirculatory function following traumatic haemorrhagic shock and resuscitation. Fourteen large white pigs and 14 humans were recruited for the study. Sublingual sidestream darkfield videomicroscopy clips were captured in anesthetized pigs and conscious humans. Clips underwent manual analysis in Automated Vascular Analysis 3.2 software. The total vessel density (TVD), perfused vessel density (PVD), proportion of perfused vessels (PPVs) and microvascular flow index (MFI) were quantified. An independent samples t test was used for between species comparison of microcirculatory parameters. Conscious humans had a significantly lower TVD, PVD and MFI than anesthetized pigs. No significant difference in PPVs was observed between the species. Perfusion of the microcirculation is a critical determinant of tissue metabolic function and viability. Whilst it may not be surprising that some interspecies differences in the sublingual microcirculatory anatomy were identified between pig and human subjects, it is interesting to report the insignificant difference in PPVs. This direct microcirculatory measure represents a relative change which should hold translatable value across species. We therefore conclude the pig is a suitable model for microcirculatory research and may be a suitable species to investigate changes in microcirculatory perfusion following perturbations in cardiovascular homeostasis, for example during traumatic haemorrhagic shock and resuscitation.

Variability of microcirculatory measurements in healthy volunteers

Reliable assessment of the microcirculation is important to investigate microcirculatory properties in various disease states. The GlycoCheck system automatically analyzes sublingual sidestream dark field images to determine the perfused boundary region (PBR; a measure of glycocalyx thickness), red blood cell filling percentage, and microvascular vessel density. Although GlycoCheck has been used to study the microcirculation in patients, little is known about the reproducibility of measurements in healthy volunteers. We assessed intra- and interobserver agreement by having two experienced observers perform three consecutive microcirculation measurements with the GlycoCheck system in 49 healthy volunteers. Intraobserver agreement of single measurements were poor (intraclass correlation coefficients (ICCs) < 0.4) for PBR, red blood cell filling percentage and microvascular vessel density. ICCs increased to values > 0.6 (indicating good reproducibility) for all parameters when performing and averaging three consecutive measurements. No systematic differences were observed between observers for any parameter. Interobserver variability was fair for PBR (ICC = 0.53) and red blood cell filling percentage (ICC = 0.58) and poor for perfused vessel density (ICC = 0.20). In conclusion, GlycoCheck software can be used with acceptable reliability and reproducibility for microcirculation measurements on a population level when averaging three consecutive measurements. Repeated measurements are preferably performed by the same observer.

Microvascular rarefaction in patients with cerebrovascular events.

Capillary density rarefaction and endothelial dysfunction contribute to chronic hypoperfusion and cerebral small vessel disease. Previous animal experiments revealed spatiotemporal microvascular remodeling directing post-stroke brain reorganization. We hypothesized that microcirculatory changes during acute cerebrovascular events could be reflected systemically and visualized sublingually. In a prospective observational trial in vivo sublingual sidestream darkfield videomicroscopy was performed in twenty-one patients with either acute stroke (n=13 ischemic, n=1 ischemic with hemorrhagic transformation and n=2 hemorrhagic stroke) or transitory ischemic attacks (n=5) within 24h after hospital admission and compared to an age- and sex-matched control group. Repetitive measurements were performed on the third day and after one week. Functional and perfused total capillary density was rarefied in the overall patient group (3060 vs 3717μm/mm2, p=0.001 and 5263 vs 6550μm/mm2, p=0.002, respectively) and in patients with ischemic strokes (2897 vs. 3717μm/mm2, p<0.001 and 5263 vs. 6550μm/mm2, p=0.006, respectively) when compared to healthy controls. The perfused boundary region (PBR), which was measured as an inverse indicator of glycocalyx thickness, was markedly related to red blood cell (RBC) filling percentage (regarded as an estimate of microvessel perfusion) in the overall patient group (r=-0.843, p<0.001), in patients with ischemic strokes (r=-0.82, p=0.001) as well as in healthy volunteers (r=-0.845, p<0.001). In addition, there were significant associations between platelet count or platelet aggregation values (as measured by whole blood impedance aggregometry) and microvascular parameters in the overall patient collective, as well as in patients with ischemic strokes. In conclusion, cerebrovascular events are associated with altered systemic microvascular perfusion.

Effects of therapeutic plasma exchange on the endothelial glycocalyx in septic shock

BackgroundDisruption of the endothelial glycocalyx (eGC) is observed in septic patients and its injury is associated with multiple-organ failure and inferior outcomes. Besides this biomarker function, increased blood concentrations of shedded eGC constituents might play a mechanistic role in septic organ failure. We hypothesized that therapeutic plasma exchange (TPE) using fresh frozen plasma might influence eGC-related pathology by removing injurious mediators of eGC breakdown while at the time replacing eGC protective factors.MethodsWe enrolled 20 norepinephrine-dependent (NE > 0.4 μg/kg/min) patients with early septic shock (onset < 12 h). Sublingual assessment of the eGC via sublingual sidestream darkfield (SDF) imaging was performed. Plasma eGC degradation products, such as heparan sulfate (HS) and the eGC-regulating enzymes, heparanase (Hpa)-1 and Hpa-2, were obtained before and after TPE. A 3D microfluidic flow assay was performed to examine the effect of TPE on eGC ex vivo. Results were compared to healthy controls.ResultsSDF demonstrated a decrease in eGC thickness in septic patients compared to healthy individuals (p = 0.001). Circulating HS levels were increased more than sixfold compared to controls and decreased significantly following TPE [controls: 16.9 (8–18.6) vs. septic patients before TPE: 105.8 (30.8–143.4) μg/ml, p < 0.001; vs. after TPE: 70.7 (36.9–109.5) μg/ml, p < 0.001]. The Hpa-2 /Hpa-1 ratio was reduced in septic patients before TPE but normalized after TPE [controls: 13.6 (6.2–21.2) vs. septic patients at inclusion: 2.9 (2.1–5.7), p = 0.001; vs. septic patients after TPE: 13.2 (11.2–31.8), p < 0.001]. Ex vivo stimulation of endothelial cells with serum from a septic patient induced eGC damage that could be attenuated with serum from the same patient following TPE.ConclusionsSeptic shock results in profound degradation of the eGC and an acquired deficiency of the protective regulator Hpa-2. TPE removed potentially injurious eGC degradation products and partially attenuated Hpa-2 deficiency.Trial registration clinicaltrials.gov NCT04231994, retrospectively registered 18 January 2020

Abstract MP61: Evidence of Impaired Microvascular Function a Decade After Delivery in Women With Placental Malperfusion Lesions

Introduction: Maternal vascular malperfusion (MVM) lesions in the placenta are characterized by incomplete vascular remodeling and vessel features similar to atherosclerosis. MVM lesions indicate a maladaptive maternal vascular response to pregnancy, are often detected in hypertensive disorders of pregnancy (HDP), and may provide a pathologic link to future cardiovascular disease. The endothelial glycocalyx is a glycoprotein-rich layer that is critical for microvascular health and damage may have an important role in the pathophysiology of microcardiovascular disease risk. Hypothesis: We hypothesized that women with malperfusion lesions of the placenta are more likely to evidence microvascular glycocalyx derangement a decade after delivery compared to women without these lesions and that this effect would be most pronounced among women with a history of HDP. Methods: A total of 412 women with placental pathology (N=129 with MVM lesions, N=283 without MVM lesions) were evaluated at 8-10 years postpartum. Placental specimens were reviewed by a blinded perinatal pathologist . HDP (including preeclampsia and gestational hypertension) were abstracted from the medical record. Glycocalyx barrier function was assessed using sublingual sidestream dark field imaging, with reduction defined as deeper penetration of red blood cells (RBCs) into the glycocalyx of the sublingual microcirculation (5-25μm diameter). We compared the median diameter (size) of microvessels, penetration of RBCs into the glycocalyx (perfused boundary region, PBR) and microvascular density (total length of perfused microvessels/mm 2 surface area) in women with and without MVM lesions. Results: Women with placental MVM lesions had smaller-sized sublingual vessels (median 8.59 μM [IQR 8.12, 9.19] vs. 9.01 μM [IQR 8.37, 9.64]; p&lt;0.001), and a lower density of vessels compared to women without lesions. Glycocalyx perfused boundary region was unexpectedly lower in women with MVM lesions (median 2.20 μM [IQR 2.06, 2.43] vs. 2.32 μM [IQR 2.15, 2.50]; p=0.003) in 10-19 μM vessels. Women with HDP and MVM lesions appear to be the most impacted, with the smallest size vessels (median 8.47 [IQR 8.09-9.13]) and the lowest glycocalyx PBR across all vessel sizes. Women with MVM lesions without a HDP similarly had evidence of microvascular glycocalyx derangement whereas women with HDP without placental lesions had a glycocalyx profile similar to women without MVM or a history of HDP. Conclusions: A decade after delivery, women with a history of placental malperfusion lesions had alterations in microvascular perfusion. Women with MVM lesions and a history of HDP appear to be the most severely impacted, which may reflect an underlying maladaptive vascular phenotype detected in the placenta at the time of pregnancy that might provide pathologic insight into future maternal microvascular health.

New insights into antiphospholipid-related endothelial dysfunction by assessment of vascular glycocalyx layer: results from a preliminary cross-sectional study.

Antiphospholipid syndrome (APS) is associated with greater atherothrombotic risk and endothelial dysfunction, suggesting that endothelial glycocalyx is impaired in this disease. The aim was to investigate the endothelial glycocalyx and the relationship between glycocalyx markers, endothelial dysfunction parameters and atherosclerotic markers in APS. A total of 15 primary arterial APS patients and healthy controls were included in the study. Glycocalyx was assessed in both groups by sublingual sidestream dark field imaging and syndecan-1 plasma level. Endothelial function was evaluated by brachial artery flow-mediated dilatation (FMD) and early atherosclerosis by carotid intima media thickness (IMT). Thrombotic profile was also performed by measuring the plasma level of the tissue factor (TF). APS patients had significantly increased syndecan-1 plasma level 38.6 ± 5.0 pg/ml vs. 19.1 ± 3.5 pg/ml; p < 0.01 and a reduced glycocalyx thickness 0.26 ± 0.03 µm vs. 0.75 ± 0.07 µm; p < 0.01 compared with control. FMD was impaired in APS patients compared with control, 5.68% ± 0.42 vs. 8.29 ± 0.30, p < 0.01, respectively. IMT was significantly increased in APS patients compared with control, 0.52 ± 0.13 mm vs. 0.40 ± 0.06 mm, p < 0.01, respectively. Soluble TF, thiobarbituric acid-reactive substances levels were increased in the sera from APS patients compared with control. This preliminary study supports, for the first time, that in APS patients endothelial glycocalyx is impaired, which could lead to thrombosis, endothelial dysfunction and early atherosclerosis.

Variability of Microcirculatory Measurements in Critically Ill Patients.

Monitoring the microcirculation may be helpful in guiding resuscitation in patients with circulatory shock. Sublingual side-stream dark field imaging cameras allow for noninvasive, bedside evaluation of the microcirculation, although their use in clinical practice has not yet been validated. The GlycoCheck system automatically analyzes images to determine glycocalyx thickness, red blood cell filling percentage, and vessel density. Although GlycoCheck has been used to study microcirculation in critically ill patients, little is known about the reproducibility of measurements in this population. A total of 60 critically ill patients were studied. Three consecutive microcirculation measurements were performed with the GlycoCheck system in 40 of these patients by one of two experienced observers. Twenty patients were assessed by both observers. Intra- and interobserver variability were assessed using intraclass correlation coefficients (ICCs). ICCs of single measurements were poor for glycocalyx thickness and good for filling percentage and vessel density. Reproducibility could be substantially increased for all parameters when three consecutive measurements were performed and averaged. GlycoCheck can be used to study microcirculation. However, to obtain reliable results three consecutive measurements should be performed and averaged. The variation of the measurements currently hampers the clinical application in individual patients.

High-salt intake affects sublingual microcirculation and is linked to body weight change in healthy volunteers: a randomized cross-over trial.

The pathophysiology of salt-sensitive hypertension remains uncertain, but may involve microvascular alterations. High-salt intake decreases microvascular density in hypertensive patients, but due to lack of studies in normotensive patients the causal pathway remains unclear. We studied whether high-salt intake decreases sublingual microvascular density in normotensive individuals and assessed the influence of body weight on changes in microvascular density. In an open label randomized cross-over trial 18 healthy men were included to study the effect of a 2-week high-salt (>12 g/day) and low-salt (<3 g/day) diet on microvascular (diameter <20 μm) density with sublingual sidestream darkfield imaging. We used sublingual nitroglycerin (NTG) to recruit microvessels. There was no significant difference in microvascular density between diets (0.96 ± 3.88 mm/mm; P = 0.31, following NTG; and -0.03 ± 1.64 mm/mm; P = 0.95, without NTG). Increased salt intake was correlated with a decrease in microvascular density following NTG (r = -0.47; P = 0.047), but not without NTG (r = 0.06; P = 0.800). The decrease in microvascular density following high-salt intake was significantly larger for those with a large change in body weight as compared with those with a small changer in body weight (-0.79 ± 1.35 and 0.84 ± 1.56 mm/mm respectively, P = 0.031). We demonstrate in healthy volunteers that higher salt intake is correlated with decreased sublingual microvascular density following administration of NTG and; larger changes in body weight following high-salt intake coincide with a larger decrease in microvascular density. Changes in microvascular density occurred without blood pressure effects, indicating that high-salt load as such contributes to microvascular changes, and may precede hypertension development.

3379 Associations between Diabetes Mellitus and Sublingual Microvascular Disease: A Prospective Cross-Sectional Study

OBJECTIVES/SPECIFIC AIMS: Diabetes mellitus (DM) is a risk factor for the development of microvascular complications. We sought to determine the association between diabetes mellitus status and microvascular circulatory disease, as measured in the sublingual capillary bed. METHODS/STUDY POPULATION: We prospectively recruited adults with cardiovascular (CV) risk factors or established CV disease, with and without DM, who were referred for invasive coronary angiography at an urban tertiary care medical center. All participants underwent non-invasive sublingual sidestream darkfield microscopy. The primary outcome was the perfused boundary region (PBR), a measure reflecting the extent to which red blood cells (RBC) penetrate the sublingual glycocalyx in vessels between 5 and 25 µm in width. RESULTS/ANTICIPATED RESULTS: 57 participants were enrolled. The mean age was 66.1 ± 11.1 years and a majority of participants (66%) were men. DM was present in 18 (31.6%) participants. Sublingual PBR measurements were not different between participants with and without DM overall (1.93µm vs. 1.96µm, p=0.63) or in vessels with high flow (1.48µm vs. 1.59µm, p=0.08). No differences in capillary RBC filling (72.9% vs 73.0%, p=0.95) or perfused microvascular density (3112 vs. 3236 µm/mm2, p=0.32) by DM status were observed. DISCUSSION/SIGNIFICANCE OF IMPACT: In a population of adults with CV risk factors or disease, DM was not associated with impaired sublingual microvascular glycocalyx. Additional investigation into diabetes-induced microvascular impairment is warranted.

Postoperative microcirculatory perfusion and endothelial glycocalyx shedding following cardiac surgery with cardiopulmonary bypass.

SummaryWe investigated microcirculatory perfusion disturbances following cardiopulmonary bypass in the early postoperative period and whether the course of these disturbances mirrored restoration of endothelial glycocalyx integrity. We performed sublingual sidestream dark field imaging of the microcirculation during the first three postoperative days in patients who had undergone on‐pump coronary artery bypass graft surgery. We calculated the perfused vessel density, proportion of perfused vessels and perfused boundary region. Plasma was obtained to measure heparan sulphate and syndecan‐1 levels as glycocalyx shedding markers. We recruited 17 patients; the mean (SD) duration of non‐pulsatile cardiopulmonary bypass was 103 (18) min, following which 491 (29) ml autologous blood was transfused through cell salvage. Cardiopulmonary bypass immediately decreased both microcirculatory perfused vessel density; 11 (3) vs. 16 (4) mm.mm−2, p = 0.052 and the proportion of perfused vessels; 92 (5) vs. 69 (9) %, p < 0.0001. The proportion of perfused vessels did not increase after transfusion of autologous salvaged blood following cardiopulmonary bypass; 72 (7) %, p = 0.19 or during the first three postoperative days; 71 (5) %, p < 0.0001. The perfused boundary region increased after cardiopulmonary bypass; 2.2 (0.3) vs. 1.9 (0.3) μm, p = 0.037 and during the first three postoperative days; 2.4 (0.3) vs. 1.9 (0.3) μm, p = 0.003. Increased plasma heparan sulphate levels were inversely associated with the proportion of perfused vessels during cardiopulmonary bypass; R = −0.49, p = 0.02. Plasma syndecan‐1 levels were inversely associated with the proportion of perfused vessels during the entire study period; R = −0.51, p < 0.0001. Our study shows that cardiopulmonary bypass‐induced acute microcirculatory perfusion disturbances persist in the first three postoperative days, and are associated with prolonged endothelial glycocalyx shedding. This suggests prolonged impairment and delayed recovery of both microcirculatory perfusion and function after on‐pump cardiac surgery.

Oral Nitrate Increases Microvascular Reactivity and the Number of Visible Perfused Microvessels in Healthy Volunteers

Nitric oxide (NO) plays an important role in controlling microcirculatory function, but the effects of exogenous administration of nitrate (NO₃^-) on the microcirculation have not been well studied. We evaluated whether NO₃^- could influence the microvascular response to hypoxia in 17 healthy volunteers. We used a vascular occlusion test (VOT) to assess the response of near-infrared spectroscopy-derived indexes to hypoxic stress before and 2 h 15 min after oral administration of 800 mg potassium nitrate. We also monitored changes in the sublingual microcirculation using side-stream dark-field (SDF) video microscopy. The descending (7.3 [6.8-8.1] to 8.2 [7.9-9.8] %/min, p = 0.01) and ascending (201 [180-233] to 240 [197-285] %/min, p = 0.01) thenar oxygen saturation (StO₂) slopes were significantly greater during VOT after nitrate administration than before. Sublingual SDF measurements showed increases in the total number of visible perfused vessels (i.e., from 14.1 [13.2-15.5] to 16.3 [15.4-16.7] vessels/mm, p < 0.01) and in the number of visible perfused small vessels (i.e., from 12.2 [11.5-13.7] to 14.2 [13.5-15.3] vessels/mm, p < 0.01) after nitrate administration but no changes in the microvascular flow index or in the proportion of visible perfused vessels, which were already maximal at baseline. Oral administration of nitrate therefore significantly influenced the response to a hypoxic challenge, increasing the number of visible perfused vessels and thus possibly limiting the O₂ diffusion distance.

Effects of short-term hyperoxia on erythropoietin levels and microcirculation in critically Ill patients: a prospective observational pilot study

BackgroundThe normobaric oxygen paradox states that a short exposure to normobaric hyperoxia followed by rapid return to normoxia creates a condition of ‘relative hypoxia’ which stimulates erythropoietin (EPO) production. Alterations in glutathione and reactive oxygen species (ROS) may be involved in this process. We tested the effects of short-term hyperoxia on EPO levels and the microcirculation in critically ill patients.MethodsIn this prospective, observational study, 20 hemodynamically stable, mechanically ventilated patients with inspired oxygen concentration (FiO2) ≤0.5 and PaO2/FiO2 ≥ 200 mmHg underwent a 2-hour exposure to hyperoxia (FiO2 1.0). A further 20 patients acted as controls. Serum EPO was measured at baseline, 24 h and 48 h. Serum glutathione (antioxidant) and ROS levels were assessed at baseline (t0), after 2 h of hyperoxia (t1) and 2 h after returning to their baseline FiO2 (t2). The microvascular response to hyperoxia was assessed using sublingual sidestream dark field videomicroscopy and thenar near-infrared spectroscopy with a vascular occlusion test.ResultsEPO increased within 48 h in patients exposed to hyperoxia from 16.1 [7.4–20.2] to 22.9 [14.1–37.2] IU/L (p = 0.022). Serum ROS transiently increased at t1, and glutathione increased at t2. Early reductions in microvascular density and perfusion were seen during hyperoxia (perfused small vessel density: 85% [95% confidence interval 79–90] of baseline). The response after 2 h of hyperoxia exposure was heterogeneous. Microvascular perfusion/density normalized upon returning to baseline FiO2.ConclusionsA two-hour exposure to hyperoxia in critically ill patients was associated with a slight increase in EPO levels within 48 h. Adequately controlled studies are needed to confirm the effect of short-term hyperoxia on erythropoiesis.Trial registrationClinicalTrials.gov (www.clinicaltrials.gov), NCT02481843, registered 15th June 2015, retrospectively registered

Ultrafiltration rate is an important determinant of microcirculatory alterations during chronic renal replacement therapy

BackgroundHemodialysis (HD) with ultrafiltration (UF) in chronic renal replacement therapy is associated with hemodynamic instability, morbidity and mortality. Sublingual Sidestream Dark Field (SDF) imaging during HD revealed reductions in microcirculatory blood flow (MFI). This study aims to determine underlying mechanisms.MethodsThe study was performed in the Medical Centre Leeuwarden and the Lithuanian University of Health Sciences. Patients underwent 4-h HD session with linear UF. Nine patients were subject to combinations of HD and UF: 4 h of HD followed by 1 h isolated UF and 4 h HD with blood-volume-monitoring based UF. Primary endpoint: difference in MFI before and after intervention. During all sessions monitoring included blood pressure, heartrate and SDF-imaging. Trial registration number: NCT01396980.ResultsBaseline characteristics were not different between the two centres as within the HD/UF modalities. MFI was not different before and after HD with UF. Total UF did not differ between modalities. Median MFI decreased significantly during isolated UF [2.8 (2.5–2.9) to 2.5 (2.2–2.8), p = 0.03]. Baseline MFI of each UF session was correlated with MFI after the intervention (rs = 0.52, p = 0.006).ConclusionDuring HD with UF or isolated HD we observed no changes in MFI. This indicates that non-flow mediated mechanisms are of unimportance. During isolated UF we observed a reduction in MFI in conjunction with a negative intravascular fluid balance. The correlation between MFI before and after intervention suggests that volume status at baseline is a factor in microvascular alterations. In conclusion we observed a significant decrease of sublingual MFI, related to UF rate during chronic renal replacement therapy.

Testing a conceptual model on early opening of the microcirculation in severe sepsis and septic shock: a randomised controlled pilot study.

Organ failure in severe sepsis and septic shock may be caused by microcirculatory failure. The objective of this study is to test a conceptual model of microcirculatory failure by using a resuscitation strategy targeting early opening of the constricted microcirculation with active vasodilatation. A randomised controlled pilot study. Single-centre mixed medical and surgical tertiary ICU. Ninety severe sepsis and septic shock patients randomised to early opening microcirculation resuscitation group or standard resuscitation group. Standard resuscitation group: fluids, noradrenaline, dobutamine and hydrocortisone were given to achieve a mean arterial pressure (MAP) of more than 60 mmHg, cardiac index more than 2.5 l min m and ScvO2 more than 70%. Microcirculation resuscitation group: nitroglycerin, enoximone, dopamine and dexamethasone targeting a microvascular flow index (MFI), measured by sublingual side-stream dark field imaging, more than 2.5. A decrease in organ failure score (SOFA) on day four of ICU treatment. Data from 37 microcirculation resuscitation and 28 standard resuscitation patients were analysed. In the microcirculation resuscitation group, MFI of more than 2.5 was achieved after a mean ± SD of 7.0 ± 4.6 h. The microcirculation resuscitation group received more fluids, and noradrenaline was equally prescribed in both groups. Per protocol, the decrease in SOFA score at day 4 was not different between groups (P = 0.64). There was a significant reduction in SOFA score in both groups compared with admission (1.2 and 1.6 in microcirculation resuscitation and standard resuscitation groups, respectively; P = 0.028 and P = 0.045). Early opening of the microcirculation in patients with severe sepsis and septic shock using nitroglycerin, enoximone, dopamine and corticosteroids did not result in a faster reduction in organ failure than standard resuscitation. Clinicaltrials.gov identifier NCT00484133.

Microvascular and endothelial function for risk prediction in dengue: an observational study

BackgroundDengue infection can result in a wide spectrum of disease. The defining feature of severe disease is increased capillary permeability, which can lead to hypovolaemic shock. Microvascular and endothelial dysfunction might underlie hypovolaemic shock, but they have not been assessed clinically. We aimed to investigate the use of microvascular assessment as a prognostic method in dengue. MethodsThis is an ongoing prospective observational study that aims to recruit 300 participants: children over the age of 3 years and adults presenting to two outpatient departments in Vietnam with fever of less than 72 h duration and suspected dengue, and patients admitted to hospital with warning signs or severe disease. Participants are being clinically assessed daily for 6 days, and 2 weeks later. Microvascular imaging using sublingual sidestream darkfield imaging (SDF) and endothelial function testing using peripheral artery tonometry are being performed at enrolment, defervescence, and follow-up FindingsTo date, 167 patients have been recruited (92 outpatient arm, 75 inpatient arm, median age 27 years [IQR 21–33], 78 male [47%]). Dengue has been confirmed in 67 individuals in the outpatient arm, of whom 29 (43%) developed warning signs, three (4%) developed severe disease, and 35 had uncomplicated dengue; the other 25 outpatients (27%) were diagnosed as other febrile illness. At enrolment, the reactive hyperaemic index, a marker of endothelial function, was lowest in the patients who went on to develop severe dengue (median 1·54, IQR 1·36–1·77) followed by those who developed warning signs (1·78, 1·43–2·36) and then uncomplicated dengue (2·18, 1·65–2·24). Initial SDF results showed a lower proportion of perfused vessels and mean flow index during the febrile phase of dengue compared with follow-up, and were worst in the severe group at defervescence. InterpretationThis study of vascular function at serial timepoints in dengue is, to our knowledge, the first and most comprehensive. Our preliminary results suggest that microvascular and endothelial dysfunction are associated with severity of dengue, and occur before the appearance of severe clinical manifestations. These techniques might be useful in risk prediction in dengue. A limitation is that a formal sample size could not be calculated because no previous microvascular data in dengue exist. FundingWellcome Trust.

International study on microcirculatory shock occurrence in acutely ill patients.

Microcirculatory alterations are associated with adverse outcome in subsets of critically ill patients. The prevalence and significance of microcirculatory alterations in the general ICU population are unknown. We studied the prevalence of microcirculatory alterations in a heterogeneous ICU population and its predictive value in an integrative model of macro- and microcirculatory variables. Multicenter observational point prevalence study. The Microcirculatory Shock Occurrence in Acutely ill Patients study was conducted in 36 ICUs worldwide. A heterogeneous ICU population consisting of 501 patients. None. Demographic, hemodynamic, and laboratory data were collected in all ICU patients who were 18 years old or older. Sublingual Sidestream Dark Field imaging was performed to determine the prevalence of an abnormal capillary microvascular flow index (< 2.6) and its additional value in predicting hospital mortality. In 501 patients with a median Acute Physiology and Chronic Health Evaluation II score of 15 (10-21), a Sequential Organ Failure Assessment score of 5 (2-8), and a hospital mortality of 28.4%, 17% exhibited an abnormal capillary microvascular flow index. Tachycardia (heart rate > 90 beats/min) (odds ratio, 2.71; 95% CI, 1.67-4.39; p < 0.001), mean arterial pressure (odds ratio, 0.979; 95% CI, 0.963-0.996; p = 0.013), vasopressor use (odds ratio, 1.84; 95% CI, 1.11-3.07; p = 0.019), and lactate level more than 1.5 mEq/L (odds ratio, 2.15; 95% CI, 1.28-3.62; p = 0.004) were independent risk factors for hospital mortality, but not abnormal microvascular flow index. In reference to microvascular flow index, a significant interaction was observed with tachycardia. In patients with tachycardia, the presence of an abnormal microvascular flow index was an independent, additive predictor for in-hospital mortality (odds ratio, 3.24; 95% CI, 1.30-8.06; p = 0.011). This was not true for nontachycardic patients nor for the total group of patients. In a heterogeneous ICU population, an abnormal microvascular flow index was present in 17% of patients. This was not associated with mortality. However, in patients with tachycardia, an abnormal microvascular flow index was independently associated with an increased risk of hospital death.

PO-0338 Evaluation Of Sublingual Microcirculation In Critically Ill Children Using Sidestream Dark Field Microscopy: Correlation With Other Routinely Used Variables

<h3>Background and aims</h3> Microcirculation is usually evaluated by indirect means in critically ill children. The aim of this study is to evaluate if there is correlation between microcirculation parameters using sidestream dark field (SDF) microscopy and macrohaemodynamic parameters, perfusion parameters and the need for some treatments used in critically ill children. <h3>Methods</h3> Microcirculation measurements were performed using sublingual SDF microscopy in 18 children between 0.3 and 211.8 months. Microvascular flow index (MFI), Perfused vessel density (PVD), proportion of perfused vessels (PPV%) and heterogeneity index (HI) were determined. Clinical (heart rate, blood pressure, core and skin temperature), laboratory (blood gases, haemoglobin and lactate concentration) and treatment (vasoactive drug dose) variables were recorded simultaneously. <h3>Results</h3> 21 measurements were analysed. MFI showed negative correlation with central venous pressure (r=-0.506 p = 0.023), venous pH (r=-0.719 p = 0.001), haemoglobin (r=-0.439 p = 0.045), arterial lactate (r=-0.553 p = 0.011) and adrenaline dose (r=-0.659 p &lt; 0.001), and positive correlation with central venous O2 saturation (r = 0.565 p = 0.012) and systolic arterial pressure (SAP) (r = 0.534 p = 0.022). PPV% showed positive correlation with SAP (r = 0.604 p = 0.006) and core temperature (r = 0.491 p = 0.024) and negative correlation with adrenaline dose (r=-0.585 p = 0.025). HI showed negative correlation with SAP (r=-0.526 p = 0.005) and positive correlation with haemoglobin (r = 0.594 p = 0.005), venous lactate (r = 0.535 p = 0.032) and core temperature (r = 0.491 p = 0.024). PVD showed positive correlation with arterial O2 saturation (r = 0.453 p = 0.045). <h3>Conclusions</h3> Microcirculation parameters showed moderate correlation with other macrohaemodynamic and perfusion parameters as well as with the need for some treatments. SDF microscopy may enable evaluation of microcirculation in critically ill children.

Microcirculatory Perfusion Is Preserved During Off-Pump but Not On-Pump Cardiac Surgery

This study investigated the perioperative course of microcirculatory perfusion in off-pump compared with on-pump surgery. Additionally, the impact of changes in systemic hemodynamics, hematocrit, and body temperature was studied. Prospective, nonrandomized, observational study. Tertiary university hospital. Patients undergoing coronary artery bypass grafting with (n = 13) or without (n = 13) use of cardiopulmonary bypass. Microcirculatory measurements were obtained at 5 time points ranging from induction of anesthesia to ICU admission. Microcirculatory recordings were performed with sublingual sidestream dark field imaging. Despite a comparable reduction in intraoperative blood pressure between groups, the perfused vessel density decreased more than 20% after onset of extracorporeal circulation but remained stable in the off-pump group. The reduction in microvascular perfusion in the on-pump group was further paralleled by decreased hematocrit and temperature. Although postbypass hematocrit levels and body temperature were restored to similar levels as in the off-pump group, the median microvascular flow index remained reduced after bypass (2.4 [2.3-2.7]) compared with baseline (2.8 [2.7-2.9]; p = 0.021). Microcirculatory perfusion remained unaltered throughout off-pump surgery. In contrast, microvascular perfusion declined after initiation of cardiopulmonary bypass and did not recover in the early postoperative phase.

Sublingual microcirculation in patients with intra-abdominal hypertension: A pilot study in 15 critically ill patients

PurposeThe purpose of the study is to clarify whether increased intra-abdominal pressure (IAP) is associated with sublingual microcirculatory alterations in intensive care patients. MethodsFifteen adult, mechanically ventilated patients were included if their IAP was at least 12 mm Hg for at least 12 hours within the first 3 days after admission to the intensive care unit. Sublingual sidestream dark field (SDF) images were recorded twice a day for 7 days. ResultsMedian (interquartile range) IAP at inclusion was 14.5 (12.5-16.0) mm Hg. The total vascular density of small vessels at the sublingual area was 13.1 (10.6-14.3) per square millimeter at baseline; the proportion of perfused vessels, 78.9% (69.6%-86.2%); and perfused vessels density, 12.4 (10.8-13.8) per square millimeter. The calculated indices suggested relatively good blood flow in the capillaries, with a De Backer score of 9.0 (8.3-10.2) and a microvascular blood flow of 3.0 (2.9-3.0). Blood flow heterogeneity index was 0.3 (0.1-0.5) at study entry. Despite that IAP, vasopressors dose, and arterial lactate decreased significantly over time, no significant changes were observed in sublingual microvascular density or blood flow. Weak correlations of microvascular blood flow (positive) and heterogeneity index (negative) were detected with both mean arterial pressure and abdominal perfusion pressure. ConclusionsNeither grade I or II intra-abdominal hypertension (IAP from 12 to 18 mm Hg) is associated with significant changes of sublingual microcirculation in intensive care patients. Correlation analysis indicates better microvascular blood flow at higher mean arterial pressure and abdominal perfusion pressure levels.