Effect of high-dose intravenous ascorbic acid on microcirculation and endothelial glycocalyx during sepsis and septic shock: a double-blind, randomized, placebo-controlled study.

Previous studies indicate supplemental vitamin C improves microcirculation and reduces glycocalyx shedding in septic animals. Our randomized, double-blind, placebo-controlled trial aimed to investigate whether a high dose of intravenous ascorbic acid (AA) might improve microcirculation and affect glycocalyx in septic patients. In our study, 23 septic patients were supplemented with a high dose (50 mg/kg every 6 h) of intravenous AA or placebo for 96 h. Sublingual microcirculation was examined using a handheld Cytocam-incident dark field (IDF) video microscope. A sidestream dark field video microscope (SDF), connected to the GlycoCheck software (GlycoCheck ICU®; Maastricht University Medical Center, Maastricht, the Netherlands), was employed to observe glycocalyx. We found a significantly higher proportion of perfused small vessels (PPV) 6 h after the beginning of the trial in the experimental group compared with placebo. As an indicator of glycocalyx thickness, the perfused boundary region was lower in capillaries of the 5-9 µm diameter in the AA group than placebo after the first dose of AA. Our data suggest that high-dose parenteral AA tends to improve microcirculation and glycocalyx in the early period of septic shock. The study was retrospectively registered in the clinicaltrials.gov database on 26/02/2021 (registration number NCT04773717).

Alterations of retinal vessels in patients with sepsis.

To compare the retinal vasculature of septic patients with age-matched healthy volunteers. This is a single-centre prospective observational study from January 2018 to May 2019 in a third-level ICU. We performed a single fundus imaging using a hand-held digital fundus camera in patients with sepsis or septic shock (n = 40) during the first 24 h after ICU admission and compared these data with age-matched healthy controls (n  =  20). Semi-automated image analysis was performed. The average retinal arteriolar and venular caliber were calculated and summarized as the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). Arteriole:venular ratio (AVR) was defined as the ratio of CRAE:CRVE. The vascular length density of segmented retinal vessels was = defined as the skeletonized vessel area/total area × 100%. Median CRAE of septic patients was significantly higher in comparison to healthy controls (165[149-187] vs. 146[142-158] µm, p = 0.002). However, median CRVE and AVR of septic patients did not differ with healthy controls (247[223-282] vs. 244[215-272], p = 0.396 and 0.64[0.58-0.74] vs. 0.61[0.55-0.68], p = 0.145) respectively. Patients with sepsis showed a significant decrease in retinal vascular length density compared with healthy subjects (p < 0.001). Retinal observation using a hand-held fundus imaging device showed signs of arteriolar vasodilation with decreased vascular density in septic patients in comparison to healthy controls.

Alterations of conjunctival glycocalyx and microcirculation in non-septic critically ill patients.

As of now the relationship between glycocalyx degradation and microcirculatory perfusion abnormalities in non-septic critical ill patients is unclear. In addition, conjunctival sidestream dark field-imaging for the purpose of glycocalyx thickness estimation has never been performed. We aimed to investigate whether changes in glycocalyx thickness in non-septic patients are associated with microcirculatory alterations in conjunctival and sublingual mucosa. In this single-centre prospective observational study, using techniques for direct in-vivo observation of the microcirculation, we performed a single measurement of microcirculatory perfusion parameters and visualized glycocalyx thickness in both ocular conjunctiva and sublingual mucosa in mixed cardio surgical (n = 18) and neurocritical patients (n = 27) and compared these data with age-matched healthy controls (n = 20). In addition we measured systemic syndecan-1 levels. In the sublingual and conjunctival region we observed a significant increase of the perfused boundary region (PBR) in both neuro-critical and cardiac surgical ICU patients, compared to controls. There was a significant increase of syndecan-1 in ICU patients comparing with controls and in cardiac patients comparing with neurological (120.0[71.0-189.6] vs. 18.0[7.2-40.7], p < 0.05). We detected a weak correlation between syndecan-1 and sublingual PBR but no correlations between global glycocalyx damage and conjuctival glycocalyx thickness. We found significantly lower perfused vessel density (PVD) of small vessels in sublingual mucosa in patients after cardiac surgery in comparison with healthy subjects. In neuro-critical, but not cardiac surgery patients conjunctival TVD and PVD of small vessels were found to be significantly lower in comparison with controls.

Mildly elevated lactate levels are associated with microcirculatory flow abnormalities and increased mortality: a microSOAP post hoc analysis.

BACKGROUND: Mildly elevated lactate levels (i.e., 1-2 mmol/L) are increasingly recognized as a prognostic finding in critically ill patients. One of several possible underlying mechanisms, microcirculatory dysfunction, can be assessed at the bedside using sublingual direct in vivo microscopy. We aimed to evaluate the association between relative hyperlactatemia, microcirculatory flow, and outcome. METHODS: This study was a predefined subanalysis of a multicenter international point prevalence study on microcirculatory flow abnormalities, the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Microcirculatory flow abnormalities were assessed with sidestream dark-field imaging. Abnormal microcirculatory flow was defined as a microvascular flow index (MFI) < 2.6. MFI is a semiquantitative score ranging from 0 (no flow) to 3 (continuous flow). Associations between microcirculatory flow abnormalities, single-spot lactate measurements, and outcome were analyzed. RESULTS: In 338 of 501 patients, lactate levels were available. For this substudy, all 257 patients with lactate levels ≤ 2 mmol/L (median [IQR] 1.04 [0.80-1.40] mmol/L) were included. Crude ICU mortality increased with each lactate quartile. In a multivariable analysis, a lactate level > 1.5 mmol/L was independently associated with a MFI < 2.6 (OR 2.5, 95% CI 1.1-5.7, P = 0.027). CONCLUSIONS: In a heterogeneous ICU population, a single-spot mildly elevated lactate level (even within the reference range) was independently associated with increased mortality and microvascular flow abnormalities. In vivo microscopy of the microcirculation may be helpful in discriminating between flow- and non-flow-related causes of mildly elevated lactate levels. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01179243 . Registered on August 3, 2010.

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

BACKGROUND: Hemodialysis (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. METHODS: The 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. RESULTS: Baseline 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 (r s = 0.52, p = 0.006). CONCLUSION: During 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.

Conjunctival microcirculatory blood flow is altered but not abolished in brain dead patients: a prospective observational study.

BACKGROUND: The conjunctival microcirculation has potential as a window to cerebral perfusion due to related blood supply, close anatomical proximity and easy accessibility for microcirculatory imaging technique, such as sidestream dark field (SDF) imaging. Our study aims to evaluate conjunctival and sublingual microcirculation in brain dead patients and to compare it with healthy volunteers in two diametrically opposed conditions: full stop versus normal arterial blood supply to the brain. METHODS: In a prospective observational study we analyzed conjunctival and sublingual microcirculation using SDF imaging in brain dead patients after reaching systemic hemodynamic targets to optimize perfusion of donor organs, and in healthy volunteers. All brain death diagnoses were confirmed by cerebral angiography. Microcirculatory images were obtained and analyzed using standardized published recommendations. Study registered at ClinicalTrials.gov, number NCT02483273. RESULTS: Eleven brain dead patients and eleven apparently healthy controls were enrolled in the study. Microvascular flow index (MFI) of small vessels was significantly lower in brain dead patients in comparison to healthy controls in ocular conjunctiva (2.7 [2.4-2.9] vs. 3.0 [2.9-3.0], p = 0.01) and in sublingual mucosa (2.8 [2.6-2.9] vs. 3.0 [2.9-3.0], p = 0.02). Total vessel density (TVD) and perfused vessel density (PVD) of small vessels were significantly lower in brain dead patients in comparison to healthy controls in ocular conjunctiva (10.2 [6.6-14.8] vs. 18.0 [18.0-25.4] mm/mm(2), p = 0.001 and 5.0 [3.5-7.3] vs. 10.9 [10.9-13.5] 1/mm, p = 0.001), but not in sublingual mucosa. CONCLUSION: In comparison to healthy controls brain dead patients had a significant reduction in conjunctival microvascular blood flow and density. However, the presence of conjunctival flow in case general cerebral flow is completely absent makes it impossible to use the conjunctival microcirculation as a substitute for brain flow, and further research should focus on the link between the ocular microcirculation, intracranial pressure and alternative ocular circulation.

International study on microcirculatory shock occurrence in acutely ill patients.

OBJECTIVES: 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. DESIGN: Multicenter observational point prevalence study. SETTING: The Microcirculatory Shock Occurrence in Acutely ill Patients study was conducted in 36 ICUs worldwide. PATIENTS: A heterogeneous ICU population consisting of 501 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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.

Effects of whole body heat stress on sublingual microcirculation in healthy humans.

PURPOSE: To assess the effect of whole body heat stress on sublingual microcirculation. METHODS: Fourteen apparently healthy subjects participated in the study. Passive body heating was performed by immersing the subjects up to the waist in a water bath at 44 °C continuously until a rectally obtained core temperature of 39.5 °C was reached. Systemic hemodynamic parameters and sublingual microcirculation were evaluated and recorded before heating, immediately after heating, and 1 h after heating. RESULTS: The subjects showed very high physiological stress and significantly increased noradrenaline and prolactin concentrations in the blood. Whole body heating resulted in significantly increased oxygen uptake, heart rate, and cardiac output. One hour after heating, heart rate remained increased, but cardiac output almost returned to baseline. Mean arterial pressure significantly decreased after heating and remained decreased for at least 1 h. There was no significant difference in the microvascular flow index and proportion of perfused vessels of small vessels at the end of heating and 1 h after heating, in comparison with baseline variables. However, functional capillary density and total vessel density of small vessels significantly increased at the end of heating (10.8 ± 2.4 vs. 11.7 ± 2.0 1/mm and 19.5 ± 3.5 vs. 22.2 ± 3.3 mm/mm(2), p < 0.05, respectively) and remained increased 1 h after heating. CONCLUSION: Whole body heat stress increases sublingual functional capillary density, oxygen consumption, and cardiac output.

Microcirculatory effects of L-arginine during acute anaerobic exercise in healthy men: A pilot study.

BACKGROUND/OBJECTIVE: We hypothesized that L-arginine supplementation increases sublingual capillary perfusion during acute anaerobic exercise. METHODS: In a double-blind randomized study, 20 healthy men were randomly assigned to an L-arginine group or a placebo group. Both groups performed a standard 60-second duration BOSCO jumping test. Before the exercise, immediately after, and 30 minutes after exercise, systemic hemodynamic parameters were recorded. Sublingual evaluation of microcirculation using sidestream dark field (SDF) videomicroscopy was also carried out. RESULTS: There were no differences in mean arterial blood pressure and cardiac output between the placebo and L-arginine groups immediately after exercise and at 30 minutes after exercise. Both groups had no changes in the microvascular flow index and proportion of perfused vessels of small vessels over the testing period. We observed significantly higher functional capillary density [14.1 (12.5 - 16.0) vs. 11.7 (10.9 - 12.9) 1/mm, p = 0.021] and total vessel density of small vessels [27.8 (24.4 - 29.2) vs. 23.0 (21.6 - 24.2) mm/mm2, p = 0.041] in the L-arginine group compared with the placebo group immediately after exercise, but after 30 minutes these differences had disappeared. CONCLUSION: Our findings show that supplementation with L-arginine may cause additional effects on the acute anaerobic exercise-induced transient increase in capillary density in the sublingual mucosa of untrained men.

Microcirculatory, mitochondrial, and histological changes following cerebral ischemia in swine.

BACKGROUND: Ischemic brain injury due to stroke and/or cardiac arrest is a major health issue in modern society requiring urgent development of new effective therapies. The aim of this study was to evaluate mitochondrial, microcirculatory, and histological changes in a swine model of global cerebral ischemia. RESULTS: In our model, significant microcirculatory changes, but only negligible histological cell alterations, were observed 3 h after bilateral carotid occlusion, and were more pronounced if the vascular occlusion was combined with systemic hypotension. Analysis of mitochondrial function showed that LEAK respiration (measured in the presence of pyruvate + malate but without ADP) was not affected in any model of global cerebral ischemia in pigs. The OXPHOS capacity with pyruvate + malate as substrates decreased compared with the control levels after bilateral carotid artery occlusion, and bilateral carotid artery occlusion + hypotension by 20% and 79%, respectively, resulting in decreases in the respiratory control index of 14% and 73%, respectively. OXPHOS capacity with succinate as a substrate remained constant after unilateral carotid artery occlusion or bilateral carotid artery occlusion, but decreased by 53% after bilateral carotid artery occlusion and hypotension compared with controls (p < 0.05, n = 3-6). Addition of exogenous cytochrome c to mitochondria isolated from ischemia brains had no effect on respiration in all models used in this study. CONCLUSIONS: We found a decrease in microcirculation and mitochondrial oxidative phosphorylation activity, but insignificant neuronal death, after 3 h ischemia in all our pig models of global cerebral ischemia. Dysfunction of the mitochondrial oxidative phosphorylation system, particularly damage to complex I of the respiratory chain, may be the primary target of the ischemic insult, and occurs before signs of neuronal death can be detected.

Early association between respiratory mechanics and radiological changes in mechanically ventilated critically ill patients with COVID-19.

The chest X-ray (CXR) Brixia scoring system was developed exclusively for COVID-19 severity assessment. However, no association between the score and respiratory mechanics during mechanical ventilation has been examined. Our aim was to evaluate the association between the CXR Brixia score and respiratory mechanics on the first day of mechanical ventilation in critically ill COVID-19 patients. A total of 77 COVID-19 patients who underwent mechanical ventilation and CXR in the ICU setting were retrospectively included. The CXR Brixia scoring system was applied, and respiratory mechanics data were recorded on the first day of invasive mechanical ventilation. Median Simplified Acute Physiologic Score II (SAPSII) and Sequential Organ Failure Assessment (SOFA) scores were 40 (31-54) and 6 (4-8), respectively. The median Brixia score was 14 (11-16). The correlation between the Brixia score and static compliance or driving pressure was significant, at r = -0.38, p < 0.001 and r = 0.33, p = 0.003, respectively. Using multivariable linear regression, the model with the B zone was significantly better associated with static compliance (F = 11.5, R2 = 0.14, p = 0.001) and driving pressure (F = 11.3, R2 = 0.13, p = 0.001). In logistic regression analysis, the Brixia score (OR 1.24; 95% CI 1.07, 1.45; p = 0.005), B zone (OR 2.60; 95% CI 1.30, 5.20; p = 0.007), C zone (OR 2.50; 95% CI 1.23, 5.11; p = 0.012), A zone (OR 2.01; 95% CI 1.16, 3.44; p = 0.012), and D zone (OR 1.84; 95% CI 1.07, 3.17; p = 0.027) significantly predicted a driving pressure > 14 cmH2O. There is a relationship between changes in Brixia-scored chest X-ray images and compliance and driving pressure on the first day of invasive mechanical ventilation. We identified some CXR areas using the Brixia score, and evaluation of the Brixia score may provide additional information for predicting respiratory mechanics.

Differences in Hemodynamic Response to Passive Leg Raising Tests during the Day in Healthy Individuals: The Question of Normovolemia.

BACKGROUND: The passive leg-raising (PLR) test was developed to predict fluid responsiveness and reduce fluid overload. However, the hemodynamic response of healthy individuals to the PLR test and how it changes during the day, between the morning and evening, after individuals have consumed food and fluids, has not been profoundly explored. This study aimed to compare the systemic hemodynamic changes in healthy individuals between morning and evening PLR tests. METHODS: In this study, the PLR test was performed twice a day. The first PLR test was performed between 08h00 and 09h00 in the morning, while the second PLR test was performed between 20h00 and 21h00 in the evening. Hemodynamic parameters were measured using an impedance cardiography monitor, and a cutoff value of a 10% increase in stroke volume (SV) during the PLR test was used to differentiate between preload responders and non-responders. RESULTS: We included 50 healthy volunteers in this study. When comparing the morning and evening PLR test results, we found no PLR-induced differences in heart rate (-3 [-8-2] vs. -2 [-8-4] beats/min, p = 0.870), SV (11 [5-22] vs. 12 [4-20] mL, p = 0.853) or cardiac output (0.7 [0.2-1.3] vs. 0.8 [0.1-1.4] L/min, p = 0.639). We also observed no differences in the proportion of preload responders during the PLR test between the morning and evening (64% vs. 66%, p = 0.99). However, there was a moderate agreement between the two PLR tests (morning and evening) (kappa = 0.429, p = 0.012). There was a moderate correlation between the changes in SV between the two PLR tests (rs = 0.50, p < 0.001). CONCLUSION: In young, healthy individuals, we observed no change in the systemic hemodynamic responsiveness to the PLR test between the morning and evening, without restriction of fluid and food intake.

AI-Enabled Public Surveillance Cameras for Rapid Emergency Medical Service Activation in Out-of-Hospital Cardiac Arrests.

This study aims to evaluate the potential usefulness of a novel artificial intelligence (AI)-based video processing algorithm for rapidly activating ambulance services (EMS) in unwitnessed out-of-hospital cardiac arrest (OHCA) cases in public places. We hypothesized that AI should activate EMS using public surveillance cameras after detecting a person fallen due to OHCA. We created an AI model based on our experiment performed at the Lithuanian University of Health Sciences, Kaunas, Lithuania, in Spring 2023. Our research highlights the potential benefits of AI-based surveillance cameras for rapidly detecting and activating EMS during cardiac arrests.

Early course of microcirculatory perfusion in eye and digestive tract during hypodynamic sepsis.

INTRODUCTION: The aim of the study was to evaluate and compare the microcirculatory perfusion during experimental sepsis in different potentially available parts of the body, such as sublingual mucosa, conjunctiva of the eye, and mucosa of jejunum and rectum. METHODS: Pigs were randomly assigned to sepsis (n = 9) and sham (n = 4) groups. The sepsis group received a fixed dose of live Escherichia coli infusion over a 1-hour period (1.8 × 10(9)/kg colony-forming units). Animals were observed 5 hours after the start of E. coli infusion. In addition to systemic hemodynamic assessment, we performed conjunctival, sublingual, jejunal, and rectal evaluation of microcirculation by using Sidestream Dark Field (SDF) videomicroscopy at the same time points: at baseline, and at 3 and 5 hours after the start of live E. coli infusion. Assessment of microcirculatory parameters of convective oxygen transport (microvascular flow index (MFI) and proportion of perfused vessels (PPV)), and diffusion distance (perfused vessel density (PVD) and total vessel density (TVD)) was done by using a semiquantitative method. RESULTS: Infusion of E. coli resulted in a hypodynamic state of sepsis associated with low cardiac output and increased systemic vascular resistance despite fluid administration. Significant decreases in MFI and PPV of small vessels were observed in sublingual, conjunctival, jejunal, and rectal locations 3 and 5 hours after the start of E. coli infusion in comparison with baseline variables. Correlation between sublingual and conjunctival (r = 0.80; P = 0.036), sublingual and jejunal (r = 0.80; P = 0.044), and sublingual and rectal (r = 0.79; P = 0.03) MFI was observed 3 hours after onset of sepsis. However, this strong correlation between the sublingual and other regions disappeared 5 hours after the start of E. coli infusion. Overall, the sublingual mucosa exhibited the most-pronounced alterations of microcirculatory flow in comparison with conjunctival, jejunal, and rectal microvasculature (P < 0.05). CONCLUSIONS: In this pig model, a time-dependent correlation exists between sublingual and microvascular beds during the course of a hypodynamic state of sepsis.

Microvascular distribution in the ocular conjunctiva and digestive tract in an experimental setting.

UNLABELLED: Recently improved microcirculatory imaging techniques, such as orthogonal polarization spectral (OPS) and its technical successor sidestream dark field (SDF) imaging, in handheld devices have allowed a direct observation of the microcirculation at the bedside. Usually a cut-off of 20 µm in diameter is used to differentiate small vessels (mainly capillaries) from large vessels (mainly venules) during this technique. We hypothesized that it was possible to measure the small vessels with a considerably smaller inner diameter. MATERIAL AND METHODS: Images of the sublingual, conjunctival, jejunal, and rectal mucosa microcirculation were obtained with SDF videomicroscopy (Microscan®, Microvision Medical, Amsterdam, the Netherlands). Using the validated software, the length and diameter of microvessels were manually traced with a computer-generated line. All vessels were divided into the groups according to the inner diameter. RESULTS: A total of 156 SDF images of the sublingual, ocular conjunctival, jejunal, and rectal mucosa were taken in 13 pigs. The length of microscopic vessels progressively increased with a decrease in the vessel diameter less than 8 mm in all the lodges, such as sublingual (80.6% of total vessel length), ocular conjunctival (76.5% of total vessel length), jejunal (99.8% of total vessel length), and rectal (97.8% of total vessel length), due to capillary network formation. There was no significant difference in the distribution of vessels from 0 to 10 µm in diameter comparing sublingual and eye conjunctival as well as jejunal and rectal mucosa. CONCLUSION: In pigs, small-diameter microscopic vessels (<10 µm) dominated in all the studied lodges (sublingual, ocular conjunctival, jejunal, and rectal mucosa), and this is evidence to establish a new cut-off for capillaries in microcirculatory analysis of SDF imaging in experimental and clinical studies.

Ethnopharmacology for Skin Diseases and Cosmetics during the COVID-19 Pandemic in Lithuania.

The documentation of ethnopharmaceutical knowledge has always been important for the preservation of countries' cultural, social, and economic identity. The COVID-19 pandemic with the collapse of healthcare, which has left the individual health to self-care, has also forced us to look back at ethnopharmacology from a practical point of view. This is the first study in Lithuania, dedicated entirely to ethnopharmaceuticals used for skin diseases and cosmetics, and the first study to analyse ethnopharmacology as a Lithuanian phenomenon during the ongoing COVID-19 pandemic. The main purpose of this study was to collect and evaluate ethnopharmaceutical knowledge regarding skin diseases and cosmetics in Siauliai District, Lithuania during the COVID-19 pandemic from July 2020 to October 2021. This study surveyed 50 respondents; the survey was conducted using the deep interview method. The respondents mentioned 67 species of medicinal plants from 37 different families used for skin diseases (64.18%), cosmetics (13.44%) and cosmeceuticals (22.38%). Of the 67 plant species, 43 (64%) were not included in the European Medicines Agency monographs and only 14 species (21%) of all included species were used with European Medicines Agency approved medical indications for skin diseases. In terms of public health, the safety of "self-treatment" and recovery rituals for skin diseases are no less important than ethnopharmacological knowledge and its application, this being especially relevant during the COVID-19 pandemic.

Microcirculatory changes during open label magnesium sulphate infusion in patients with severe sepsis and septic shock.

BACKGROUND: Microcirculatory alterations play a pivotal role in sepsis and persist despite correction of systemic hemodynamic parameters. Therefore it seems tempting to test specific pro-microcirculatory strategies, including vasodilators, to attenuate impaired organ perfusion. As opposed to nitric oxide donors, magnesium has both endothelium-dependent and non-endothelium-dependent vasodilatory pathways. METHODS: In a single-center open label study we evaluated the effects of magnesium sulphate (MgS) infusion on the sublingual microcirculation perfusion in fluid resuscitated patients with severe sepsis and septic shock within the first 48 hours after ICU admission. Directly prior to and after 1 hour of magnesium sulphate (MgS) infusion (2 gram) systemic hemodynamic variables, sublingual SDF images and standard laboratory tests, were obtained. RESULTS: Fourteen patients (12 septic shock, 2 severe sepsis) with a median APACHE II score of 20 were enrolled. No significant difference of the systemic hemodynamic variables was found between baseline and after MgS infusion. We did not observe any significant difference pre and post MgS infusion in the primary endpoint microvascular flow index (MFI) of small vessels: 2.25(1.98-2.69) vs. 2.33(1.96-2.62), p = 0.65. Other variables of microcirculatory perfusion were also unaltered. In the overall unchanged microvascular perfusion there was a non-significant trend to an inverse linear relationship between the changes of MFI and its baseline value (y = -0.7260 × + 1.629, r2 = 0.270, p = 0.057). The correlation between baseline Mg concentrations and the change in MFI pre- and post MgS infusion was non-significant (rs = -0.165, p = 0.67). CONCLUSIONS: In the setting of severe sepsis and septic shock sublingual microcirculatory alterations were observed despite fulfillment of sepsis resuscitation guidelines. After infusion of a limited and fixed dose of MgS, microcirculatory perfusion did not improve over time. TRIAL REGISTRATION: ClinicalTrials.gov NTC01332734.

Links between Endothelial Glycocalyx Changes and Microcirculatory Parameters in Septic Patients.

The glycocalyx is an endothelial surface layer that is essential for maintaining microvascular homeostasis. Impaired integrity of the endothelial glycocalyx may be directly related to the development of microvascular dysfunction. To explore this hypothesis, we conducted a prospective observational study on adult patients diagnosed with sepsis. The study aimed to evaluate the degree of damage to the glycocalyx and to identify correlations between microcirculatory parameters and glycocalyx thickness based on capillary diameter. Sublingual microcirculation was examined using a handheld Cytocam-incident dark field video microscope. A sidestream dark field video microscope attached to a GlycoCheck monitor was used to determine the perfused boundary regions (PBRs) of sublingual blood vessels grouped by diameter (5-9 µm, 10-19 µm, and 20-25 µm). We identified significant damage to the glycocalyx in sublingual blood vessels of all the aforementioned diameters in septic patients compared to healthy age-matched controls. Furthermore, we found that the PBRs of the smallest capillaries (diameter class 5-9µm) correlated moderately and inversely with both total and perfused blood vessel densities. Collectively, our data suggest that there may be a functional relationship between damage to the endothelial glycocalyx of the smallest capillaries and alterations in the microcirculation observed in response to sepsis.

Effects of remote ischemic conditioning on microcirculatory alterations in patients with sepsis: a single-arm clinical trial.

BACKGROUND: Remote ischemic conditioning (RIC) is a promising technique that may protect organs and tissues from the effects of additional ischemic episodes. However, the therapeutic efficacy of RIC in humans with sepsis remains unknown. We hypothesized that RIC might improve sublingual microcirculation in patients with sepsis. METHODS: This prospective single-arm trial was performed in a mixed ICU at a tertiary teaching hospital. We included patients with sepsis or septic shock within 24 h of ICU admission. The RIC procedure comprised 3 cycles of brachial cuff inflation to 200 mmHg for 5 min followed by deflation to 0 mmHg for another 5 min. The procedure took 30 min. RIC was performed at the time of study inclusion and repeated after 12 and 24 h. Sublingual microcirculatory measurements were obtained before and after each RIC procedure using a Cytocam®-incident dark-field (IDF) device (Braedius Medical, Huizen, The Netherlands). The microcirculatory data were compared with a historical control. Data are reported as the medians along with the 25th and 75th percentiles. RESULTS: Twenty-six septic patients with a median age of 65 (57-81) years were enrolled in this study. The median Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores at admission were 20 (13-23) and 10 (9-12), respectively. All patients were receiving vasopressors. After the 1st RIC procedure, the microvascular flow index (MFI) and the proportion of perfused vessels (PPV) among small vessels were significantly higher than before the procedure, with pre- and post-treatment values of 2.17 (1.81-2.69) and 2.59 (2.21-2.83), respectively, for MFI (p = 0.003) and 87.9 (82.4-93.8) and 92.5 (87.9-96.1) %, respectively, for PPV (p = 0.026). This result was confirmed by comparison with a historical control group. We found no change in microcirculatory flow or density parameters during repeated RIC after 12 h and 24 h. CONCLUSION: In patients with sepsis, the first remote ischemic conditioning procedure improved microcirculatory flow, whereas later procedures did not affect sublingual microcirculation. Trial registration NCT04644926, http://www.clinicaltrials.gov . Date of registration: 25 November 2020. Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04644926 .

New insights for adult cardiopulmonary resuscitation. Up-coming resuscitation guidelines 2010.

Despite advances in cardiac arrest care, the overall survival to hospital discharge remains poor. The objective of this paper was to review the innovations in cardiopulmonary resuscitation that could influence survival or change our understanding about cardiopulmonary resuscitation. We have performed a search in the MEDLINE and the Cochrane databases for randomized controlled trials, meta-analyses, expert reviews from December 2005 to March 2010 using the terms cardiac arrest, basic life support, and advanced life support. The lack of randomized trials during the last 5 years remains the main problem for crucial decisions in cardiopulmonary resuscitation. Current trends in cardiopulmonary resuscitation are toward minimizing the interruptions of chest compressions and improving the quality of cardiopulmonary resuscitation. In addition, attention should be paid to all the parts of chain of survival, which remains essential in improving survival rates.