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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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 (r_s= -0.165, p = 0.67).</p> <p>Conclusions</p> <p>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.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NTC01332734.</p

Ethnomedicinal Uses of Honeybee Products in Lithuania: The First Analysis of Archival Sources

Lithuania has old ethnomedicine traditions, consisting of many recipes with herbal, animal, and mineral original ingredients. All these findings were mostly collected in Lithuanian language, often in local community’s dialects, and stored only in archives. We analyzed archival sources about honeybee and its products used for medicinal purposes dated from 1886 till 1992 in different parts of Lithuania. We systematized and presented the most important information about bees and their products: indication for usage, ingredients used in the recipe, their preparation techniques, and application for therapeutic purposes. Researchers in Lithuania are now looking for new evidence based indications and preparation and standardization methods of bee products. Archival sources are a foundation for studies in Lithuania. The results can be integrated into scientifically approved folk medicine practices into today’s healthcare

Ethnopharmaceutical knowledge in Samogitia region of Lithuania: where old traditions overlap with modern medicine

Abstract Background Modern ethnopharmaceutical studies are still quite unusual in Northern Europe. Data regarding the medicinal use of plants, animals, and fungi and also of spiritual rituals of healing is obtained mostly from ethnographic and folkloric sources in Lithuania. The aim of this study was to assess the ethnopharmaceutical knowledge regarding traditional use of natural substances for medicinal purposes in the Samogitia region and compare with prior research conducted 10 years prior in the same region. Methods The study was performed during 2016–2017 in the Samogitia region (Lithuania) using the conventional technique of ethnobotanical studies. Twenty-eight respondents aged between 50 and 92 years were selected for the study using snowball techniques. Information was collected using semi-structured and structured interviews. The obtained information was recorded indicating local names of plants, their preparation techniques, parts used, modes of administration, and application for therapeutic purposes. Results During the research, 125 records of raw materials of herbal origin belonging to 55 families were made. The Asteraceae family had the highest number of references, 147 (16.6%). It was stated that the most commonly used medicinal plants were the raspberry (Rubus idaeus L.) (100%), marigold (Calendula officinalis L.) (96.4%), camomile (Matricaria recutita L.) (92.9%), and small linden tree (Tilia cordata Mill.) (92.9%). The most commonly used material of animal origin was the toad (Bufo bufo) (89%). The most commonly used kind of fungi was the common stinkhorn (Phallus impudicus) (71%), and the material of the mineral origin was sand (50%). Comparative analysis of the two surveys in this region showed similar results and produced a large amount of ethnopharmaceutical information. Conclusions Lithuania belongs to the countries known for urban ethnobotany where old traditions overlap with modern healing methods. Also, because modern medical assistance is quite expensive, self-medication with home-made medicines is still popular in Lithuania. It is important to collect and systematize this information as soon as possible, to save it as a traditional Lithuanian heritage and also use it for scientific investigations

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

Abstract 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)

Microcirculatory blood flow as a tool to select ICU patients eligible for fluid therapy

The aim of this study is to assess the incidence of sublingual microcirculatory flow alterations, according to a predefined arbitrary cutoff value, in patients with "clinical signs of impaired organ perfusion". Secondary endpoints were the changes in microvascular flow index (MFI), "clinical signs of impaired organ perfusion", and stroke volume (SV) after fluid administration, and the differences between groups. Prospective, single-center, observational study in a 22-bed mixed intensive care unit (ICU). Patients a parts per thousand yen18 years with invasive hemodynamic monitoring and "clinical signs of impaired organ perfusion" as the principal reason for fluid administration were included. Before and after fluid challenge, systemic hemodynamics and direct in vivo observation of the sublingual microcirculation with sidestream dark-field imaging were obtained. Microvascular flow index (MFI) 2.6 at baseline, MFI and clinical signs changed insignificantly [2.8 (2.8-2.9) versus 2.8 (2.7-3), p = 0.45, respectively, 1 (1-2) versus 1 (1-2), p <0.32]. These changes were not restricted to patients with a rise in SV a parts per thousand yen10 %. These data add to the understanding that noninvasive assessment of microvascular blood flow may help to identify patients eligible for fluid therapy, and to evaluate its effec

Time Evolution of Sublingual Microcirculatory Changes in Recreational Marathon Runners

We aimed to evaluate changes in sublingual microcirculation induced by a marathon race. Thirteen healthy male controls and 13 male marathon runners volunteered for the study. We performed sublingual microcirculation, using a Cytocam-IDF device (Braedius Medical, Huizen, Netherlands), and systemic hemodynamic measurements four times: 24 hours prior to their participation in the Kaunas Marathon (distance: 41.2 km), directly after finishing the marathon, 24 hours after the marathon, and one week after the marathon. The marathon runners exhibited a higher functional capillary density (FCD) and total vascular density of small vessels at the first visit compared with the controls. Overall, we did not find any changes in sublingual microcirculation of the marathon runners at any of the other visits. However, in a subgroup of marathon runners with a decreased FCD compared to the subgroup with increased FCD, the subgroup with decreased FCD had shorter running time (190.37±30.2 versus 221.80±23.4 min, p=0.045), ingested less fluids (907±615 versus 1950±488 mL, p=0.007) during the race, and lost much more weight (-2.4±1.3 versus -1.0±0.8 kg, p=0.041). Recreational marathon running is not associated with an alteration of sublingual microcirculation. However, faster running and dehydration may be crucial for further impairing microcirculation

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

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. 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. NCT01396980. 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). 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 therap

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

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 x 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 sepsi