Impact of cumulative fluid balance on the pharmacokinetics of extended infusion meropenem in critically ill patients with sepsis.

BACKGROUND: Meropenem dosing for septic critically patients is difficult due to pathophysiological changes associated with sepsis as well as supportive symptomatic therapies. A prospective single-center study assessed whether fluid retention alters meropenem pharmacokinetics and the achievement of the pharmacokinetic/pharmacodynamic (PK/PD) targets for efficacy. METHODS: Twenty-five septic ICU patients (19 m, 6f) aged 32-86 years with the mean APACHE II score of 20.2 (range 11-33), suffering mainly from perioperative intra-abdominal or respiratory infections and septic shock (n = 18), were investigated over three days after the start of extended 3-h i.v. infusions of meropenem q8h. Urinary creatinine clearance (CLcr) and cumulative fluid balance (CFB) were measured daily. Plasma meropenem was measured, and Bayesian estimates of PK parameters were calculated. RESULTS: Eleven patients (9 with peritonitis) were classified as fluid overload (FO) based on a positive day 1 CFB of more than 10% body weight. Compared to NoFO patients (n = 14, 11 with pneumonia), the FO patients had a lower meropenem clearance (CLme 8.5 ± 3.2 vs 11.5 ± 3.5 L/h), higher volume of distribution (V1 14.9 ± 3.5 vs 13.5 ± 4.1 L) and longer half-life (t1/2 1.4 ± 0.63 vs 0.92 ± 0.54 h) (p < 0.05). Over three days, the CFB of the FO patients decreased (11.7 ± 3.3 vs 6.7 ± 4.3 L, p < 0.05) and the PK parameters reached the values comparable with NoFO patients (CLme 12.4 ± 3.8 vs 11.5 ± 2.0 L/h, V1 13.7 ± 2.0 vs 14.0 ± 5.1 L, t1/2 0.81 ± 0.23 vs 0.87 ± 0.40 h). The CLcr and Cockroft-Gault CLcr were stable in time and comparable. The correlation with CLme was weak to moderate (CLcr, day 3 CGCLcr) or absent (day 1 and 2 CGCLcr). Dosing with 2 g meropenem q8h ensured adequate concentrations to treat infections with sensitive pathogens (MIC 2 mg/L). The proportion of pre-dose concentrations exceeding the MIC 8 mg/L and the fraction time with a target-exceeding concentration were higher in the FO group (day 1-3 f Cmin > MIC: 67 vs 27%, p < 0.001; day 1%f T > MIC: 79 ± 17 vs 58 ± 17, p < 0.05). CONCLUSIONS: These findings emphasize the importance of TDM and a cautious approach to augmented maintenance dosing of meropenem to patients with FO infected with less susceptible pathogens, if guided by population covariate relationships between CLme and creatinine clearance.

Endothelial glycocalyx in acute care surgery - what anaesthesiologists need to know for clinical practice.

The endothelial glycocalyx (EG) is the thin sugar-based lining on the apical surface of endothelial cells. It has been linked to the physiological functioning of the microcirculation and has been found to be damaged in critical illness and after acute care surgery. This review aims to describe the role of EG in severely injured patients undergoing surgery, discuss specific situations (e.G. major trauma, hemorrhagic shock, trauma induced coagulopathy) as well as specific interventions commonly applied in these patients (e.g. fluid therapy, transfusion) and specific drugs related to perioperative medicine with regard to their impact on EG.EG in acute care surgery is exposed to damage due to tissue trauma, inflammation, oxidative stress and inadequate fluid therapy. Even though some interventions (transfusion of plasma, human serum albumin, hydrocortisone, sevoflurane) are described as potentially EG protective there is still no specific treatment for EG protection and recovery in clinical medicine.The most important principle to be adopted in routine clinical practice at present is to acknowledge the fragile structure of the EG and avoid further damage which is potentially related to worsened clinical outcome.

Does Neuraxial Anesthesia as General Anesthesia Damage DNA? A Pilot Study in Patients Undergoing Orthopedic Traumatological Surgery.

The human organism is exposed daily to many endogenous and exogenous substances that are the source of oxidative damage. Oxidative damage is one of the most frequent types of cell component damage, leading to oxidation of lipids, proteins, and the DNA molecule. The predominance of these damaging processes may later be responsible for human diseases such as cancer, neurodegenerative disease, or heart failure. Anesthetics undoubtedly belong to the group of substances harming DNA integrity. The goal of this pilot study is to evaluate the range of DNA damage by general and neuraxial spinal anesthesia in two groups of patients undergoing orthopedic traumatological surgery. Each group contained 20 patients, and blood samples were collected before and after anesthesia; the degree of DNA damage was evaluated by the comet assay method. Our results suggest that general anesthesia can cause statistically significant damage to the DNA of patients, whereas neuraxial anesthesia has no negative influence.

Targeting the endothelial glycocalyx in acute critical illness as a challenge for clinical and laboratory medicine.

The purpose of this manuscript is to review the role of endothelial glycocalyx (EG) in the field of critical and perioperative medicine and to discuss possible future directions for investigations in this area. Under physiological conditions, EG has several well-defined functions aimed to prevent the disruption of vessel wall integrity. Under pathological conditions, the EG represent one of the earliest sites of injury during inflammation. EG structure and function distortion contribute to organ dysfunction related to sepsis, trauma, or global ischemia of any origin. Discovering new therapeutic approaches (either pharmacological or non-pharmacological) aimed to protect the EG against injury represents a promising direction in clinical medicine. Further, the currently-used common interventions in the acutely ill - fluids, blood products, nutritional support, organ-supporting techniques (e.g. continuous renal replacement therapy, extracorporeal circulation), temperature modulation and many others - should be re-evaluated during acute illness in terms of their EG "friendliness". To assess new therapies that protect the EG, or to evaluate the effect of currently-used interventions on EG integrity, a relevant marker or method to determine EG damage is needed. Such marker or method should be available to clinicians within hours, preferably in the form of a point-of-care test at the bedside. Collaborative research between clinical disciplines and laboratory medicine is warranted, and targeting the EG represents major challenges for both.

Effects of hypertonic saline and mannitol on cortical cerebral microcirculation in a rabbit craniotomy model.

BACKGROUND: Hyperosmolar solutions have been used in neurosurgery to modify brain bulk and prevent neurological deterioration. The aim of this animal study was to compare the short-term effects of equivolemic, equiosmolar solutions of mannitol and hypertonic saline (HTS) on cerebral cortical microcirculation in a rabbit craniotomy model. METHODS: Rabbits (weight, 2.0-3.0 kg) were anesthetized, ventilated mechanically, and subjected to a craniotomy. The animals were allocated randomly to receive a 3.75 ml/kg intravenous infusion of either 3.2% HTS (group HTS, n = 8) or 20% mannitol (group MTL, n = 8). Microcirculation in the cerebral cortex was evaluated using sidestream dark-field (SDF) imaging before and 20 min after the end of the 15-min HTS infusion. Global hemodynamic data were recorded, and blood samples for laboratory analysis were obtained at the time of SDF image recording. RESULTS: No differences in the microcirculatory parameters were observed between the groups before the use of osmotherapy. After osmotherapy, lower proportions of perfused small vessel density (P = 0.0474), perfused vessel density (P = 0.0457), and microvascular flow index (P = 0.0207) were observed in the MTL group compared with those in the HTS group. CONCLUSIONS: Our findings suggest that an equivolemic, equiosmolar HTS solution better preserves perfusion of cortical brain microcirculation compared to MTL in a rabbit craniotomy model.

Exogenous surfactant for lung contusion causing ARDS: A systematic review of clinical and experimental reports.

This systematic review aimed to summarize the available data on the treatment of pulmonary contusions with exogenous surfactants, determine whether this treatment benefits patients with severe pulmonary contusions, and evaluate the optimal type of surfactant, method of administration, and drug concentration. Three databases (MEDline, Scopus, and Web of Science) were searched using the following keywords: pulmonary surfactant, surface-active agents, exogenous surfactant, pulmonary contusion, and lung contusion for articles published between 1945 and February 2023, with no language restrictions. Four reviewers independently rated the studies for inclusion, and the other four reviewers resolved conflicts. Of the 100 articles screened, six articles were included in the review. Owing to the limited number of papers on this topic, various types of studies were included (two clinical studies, two experiments, and two case reports). In all the studies, surfactant administration improved the selected ventilation parameters. The most frequently used type of surfactant was Curosurf® in the concentration of 25 mg/kg of ideal body weight. In most studies, the administration of a surfactant by bronchoscopy into the segmental bronchi was the preferable way of administration. In both clinical studies, patients who received surfactants required shorter ventilation times. The administration of exogenous surfactants improved ventilatory parameters and, thus, reduced the need for less aggressive artificial lung ventilation and ventilation days. The animal-derived surfactant Curosurf® seems to be the most suitable substance; however, the ideal concentration remains unclear. The ideal route of administration involves a bronchoscope in the segmental bronchi.

Impact of anesthetics on rat hippocampus and neocortex: A comprehensive proteomic study based on label-free mass spectrometry.

Anesthesia is regarded as an important milestone in medicine. However, the negative effect on memory and learning has been observed. In addition, the impact of anesthetics on postoperative cognitive functions is still discussed. In this work, in vivo experiment simulating a general anesthesia and ICU sedation was designed to assess the impact of two intravenous (midazolam, dexmedetomidine) and two inhalational (isoflurane, desflurane) agents on neuronal centers for cognition (neocortex), learning, and memory (hippocampus). More than 3600 proteins were quantified across both neocortex and hippocampus. Proteomic study revealed relatively mild effects of anesthetics, nevertheless, protein dysregulation uncovered possible different effect of isoflurane (and midazolam) compared to desflurane (and dexmedetomidine) to neocortical and hippocampal proteins. Isoflurane induced the upregulation of hippocampal NMDAR and other proteins of postsynaptic density and downregulation of GABA signaling, whereas desflurane and dexmedetomidine rather targeted mitochondrial VDAC isoforms and protein regulating apoptotic activity.

Pyelovesicostomy as an Alternative Surgical Treatment for Complex Ureteral Lesions After Kidney Transplant.

OBJECTIVES: We evaluated the feasibility, safety, and long-term outcomes of pyelovesicostomy as an alternative surgical treatment for complex ureteral lesions after kidney transplant. MATERIALS AND METHODS: A single-center, retrospective, observational cohort study was conducted on 5 adult kidney transplant recipients who underwent pyelovesicostomy between January 2000 and June 2023. The collected data included patient demographics, surgery indication, time from transplant to pyelovesicostomy, procedure details, and kidney function at various time points after surgery. Primary outcomes were allograft function and complications. RESULTS: The 5 patients (4 female, 1 male) had a mean age of 65.8 years and mean body mass index of 26.8. Indications were complex ureteral lesions. The time between transplant and reoperation ranged from 4 days to 12 years. Renal function improved for all patients, with a progressive decrease in mean serum creatinine concentration. The mean follow-up period extended to 7 years. One patient died with the graft still functional at 20 years after the operation, whereas the remaining 4 patients continue to live with functional grafts. CONCLUSIONS: Our study suggests that pyelovesicostomy may provide a potent alternative for the management of complex ureteral lesions after kidney transplant. We have observed good short-term and long-term outcomes in specific patients, pointing toward a promising avenue oftreatment worth further exploration. This reaffirms the importance of a personalized approach in medicine, to consider each patient's unique conditions and characteristics during therapeutic decisions.

Lipid emulsions prevent postoperative abdominal adhesions.

INTRODUCTION: Adhesions are the most common cause of long-term morbidity after abdominal surgery and most often cause various forms of intestinal passage disorders ranging from partial obstruction to complete, life-threatening intestinal obstruction. The aim of the present study was to evaluate the protective effect of intraperitoneally administered lipid emulsions on the formation of adhesions in larger animal model, as the lubricating effect of phospholipids and the mechanical barrier of the lipid component are combined with the anti-inflammatory effect of fish oil. METHODS: Thirty-one female domestic pigs were randomly divided into three groups. At the end of the surgical procedure, a lipid emulsion or saline solution was applied intraperitoneally. After 14 days, an independent macroscopic, histological and immunohistochemical evaluation of the adhesions were performed. RESULTS: Intraperitoneal administration of lipid emulsions significantly reduced the incidence of intra-abdominal adhesions. Microscopic examination demonstrated a significant reduction in the number of inflammatory elements and the amount of collagen in the adhesions, especially after administration of the fish oil-based emulsion. A simultaneous decrease in neovascularization was observed in the adhesions. Evaluation of the intestinal anastomosis did not reveal significant differences in healing between the groups. CONCLUSION: Intraperitoneal administration of lipid emulsions can reduce the development of postoperative intra-abdominal adhesions by the combined action of phospholipids as important lubricants and lipids as a mechanical barrier. Their effect is caused by a reduction in proinflammatory and profibrotic mediators. At the same time, intraperitoneal administration of lipid emulsions does not impair healing of the anastomosis in larger animal model.

Modulation of the capillary leakage by exogenous albumin in a rat model of endothelial glycocalyx damage.

BACKGROUND: Endothelial glycocalyx (EG) plays a crucial role in maintaining the plasma proteins within the intravascular space. OBJECTIVE: We studied whether exogenous albumin protects the EG in an experimental model of EG enzymatic damage in rats. METHODS: Rats were divided into three groups of 10 animals that received (1) Evans blue (2) Evans blue + hyaluronidase, or (3) Evans blue + hyaluronidase + 20% human albumin via the tail vein. Spectrophotometric analysis was performed 2 h later to quantify the leakage of Evans blue-labeled albumin into the heart, lungs, brain, kidneys, liver, small intestine, spleen, and skeletal muscle. RESULTS: Administration of hyaluronidase numerically increased the capillary leakage of Evans blue in all examined tissues. Co-administration of albumin decreased the leakage of albumin in all tissues except the heart. In the lungs, the ratio between the absorbance and dry organ weight decreased from 5.3 ± 2.4 to 1.7 ± 0.5 (mean ± SD) (P <  0.002), and in the liver, the absorbance decreased from 2.2 ± 0.7 to 1.5 ± 0.4 (P <  0.011). CONCLUSION: Exogenous albumin decreased the capillary leakage of albumin which was interpreted as a sign of maintained EG integrity.

Protection of the endothelium and endothelial glycocalyx by hydrogen against ischaemia-reperfusion injury in a porcine model of cardiac arrest.

BACKGROUND: Hydrogen is a potent antioxidant agent that can easily be administered by inhalation. The aim of the study was to evaluate whether hydrogen protects the endothelial glycocalyx layer after successful cardiopulmonary resuscitation (CPR). METHODS: Fourteen anesthetized pigs underwent CPR after induced ventricular fibrillation. During CPR and return of spontaneous circulation, 2% hydrogen gas was administered to seven pigs (hydrogen group) and seven constituted a control group. Biochemistry and sublingual microcirculation were assessed at baseline, during CPR, at the 15th, 30th, 60th, 120th minute. RESULTS: All seven subjects from the hydrogen group and six subjects in the control group were successfully resuscitated after 6-10 minutes. At baseline, there were no statistically significant differences in examined variables. After the CPR, blood pH, base excess, and lactate showed significantly smaller deterioration in the hydrogen group than in the control group. By contrast, plasma syndecan-1 and the measured variables obtained via sublingual microcirculation did not change after the CPR; and were virtually identical between the two groups. CONCLUSION: In pigs, hydrogen gas inhalation during CPR and post-resuscitation care was associated with less pronounced metabolic acidosis compared to controls. However, we could not find evidence of injury to the endothelium or glycocalyx in any studied groups.

Endothelial glycocalyx damage in patients with severe COVID-19 on mechanical ventilation - A prospective observational pilot study.

BACKGROUND: Coronavirus disease (COVID-19) associated endotheliopathy and microvascular dysfunction are of concern. OBJECTIVE: The objective of the present single-center observational pilot study was to compare endothelial glycocalyx (EG) damage and endotheliopathy in patients with severe COVID-19 (COVID-19 group) with patients with bacterial pneumonia with septic shock (non-COVID group). METHODS: Biomarkers of EG damage (syndecan-1), endothelial cells (EC) damage (thrombomodulin), and activation (P-selectin) were measured in blood on three consecutive days from admission to the intensive care unit (ICU). The sublingual microcirculation was studied by Side-stream Dark Field (SDF) imaging with automatic assessment. RESULTS: We enrolled 13 patients in the non-COVID group (mean age 70 years, 6 women), and 15 in the COVID-19 group (64 years old, 3 women). The plasma concentrations of syndecan-1 were significantly higher in the COVID-19 group during all three days. Differences regarding other biomarkers were not statistically significant. The assessment of the sublingual microcirculation showed improvement on Day 2 in the COVID-19 group. Plasma levels of C-reactive protein (CRP) were significantly higher on the first two days in the COVID-19 group. Plasma syndecan-1 and CRP were higher in patients suffering from severe COVID-19 pneumonia compared to bacterial pneumonia patients. CONCLUSIONS: These findings support the role of EG injury in the microvascular dysfunction in COVID-19 patients who require ICU.

A porcine model of endothelial glycocalyx damage by enzymatic digestion: A pilot study.

BACKGROUND: The endothelial glycocalyx (EG) plays a vital role in the physiology and pathophysiology of human microcirculation. Having relevant EG damage model would be important tool for testing new interventions aiming at EG protection and recovery. We describe the first in vivo EG damage model in pig. OBJECTIVE: To investigate the course of animal EG damage induced by specific enzymes. MATERIAL AND METHODS: Four anesthetized piglets received enzymes: 1g hyaluronidase and 25 IU heparanase I intravenously. Blood and urine samples were collected at baseline and 20/40/60/80/100/120 min for detecting markers of endothelial and EG function. Sublingual microcirculation and EG thickness were assessed by Side-stream Dark Field (SDF) imaging and Perfused Boundary Region (PBR) respectively. EG of the mesentery artery was visualized in fluorescent microscopy. RESULTS: Biochemical marker of EG damage syndecan-1 showed temporary increase with return to baseline and was reflected by PBR values. Albumin levels suggested brief period of capillary leakage (decrease in the serum, increase in the urine) with a trend to normalization. Urine glycosaminoglycans peaked at 120 minutes. Microcirculatory perfusion parameter showed significant alteration. Diffusion parameters were altered with no statistical significance. CONCLUSION: EG damage induced by specific enzymes was reflected by temporary changes of biochemical makers together with alteration of microcirculation and changes in fluorescent microscopy of EG layer. Our results support to further validate presented model of EG damage on a larger number of animals.

Clinical physiology aspects of chloremia in fluid therapy: a systematic review.

BACKGROUND: This systematic review discusses a clinical physiology aspect of chloride in fluid therapy. Crystalloid solutions are one of the most widely used remedies. While generally used in medicine for almost 190 years, studies focused largely on their safety have only been published since the new millennium. The most widely used solution, normal saline, is most often referred to in this context. Its excessive administration results in hyperchloremic metabolic acidosis with other consequences, including higher mortality rates. METHODS: Original papers and review articles eligible for developing the present paper were identified by searching online in the electronic MEDLINE database. The keywords searched for included hyperchloremia, hypochloremia, and compound words containing the word "chloride," infusion therapy, metabolic acidosis, renal failure, and review. RESULTS: A total of 21,758 papers published before 31 May 2020 were identified; of this number, 630 duplicates were removed from the list. Upon excluding articles based on their title or abstract, 1850 papers were screened, of which 63 full-text articles were assessed. CONCLUSIONS: According to the latest medical concepts, dyschloremia (both hyperchloremia and hypochloremia) represents a factor indisputably having a negative effect on selected variables of clinical outcome. As infusion therapy can significantly impact chloride homeostasis of the body, the choice of infusion solutions should always take into account the potentially adverse impact of chloride content on chloremia and organ function.

Evaluation of endothelial glycocalyx in healthy volunteers - An observational study.

BACKGROUND: Endothelial glycocalyx (EG) is a carbohydrate-rich gel-like mesh covering the apical surface of endothelial cells. It has been linked to the microvascular pathophysiology and tissue metabolism. However, little is known about its condition in young healthy adults. OBJECTIVE: We aimed to describe the condition of EG in young healthy adults by in vivo EG imaging and measurement of syndecan-1, a plasma marker of EG integrity in order to obtain reference values. METHODS: For in vivo EG studies we used Side-stream Dark Field imaging of the sublingual microcirculation. Recordings were analysed automatically by GlycoCheck software providing the Perfused Boundary Region (PBR) as a marker of EG thickness. Levels of syndecan-1 were analysed in plasma samples by ELISA. RESULTS: 21 volunteers were included in the study. Median of the PBR value was 1.82 µm (interquartile range 1.69-2.01, 95% CI 1.79-1.97). Median concentration of syndecan-1 was 0.3 ng/ml (interquartile range 0.23-0.39, 95% CI 0.27-0.49). CONCLUSION: This study provides a comparison for cohorts of patients with a particular disease where the EG is presumably damaged. Our findings do not entirely comply with already published data in healthy individuals.

Neuraxial anesthesia is less harmful to the endothelial glycocalyx during elective joint surgery compared to general anesthesia.

BACKGROUND: Damage of the endothelial glycocalyx (EG) has been described during surgery, but the effect of different anesthesia techniques remains unknown. Perfused boundary region (PBR) evaluated by side-stream dark field (SDF) imaging of the sublingual microcirculation enables in vivo EG assessment. PBR values are inversely related to the EG thickness. OBJECTIVE: The aim of the observational study was to evaluate the changes of PBR in patients undergoing elective joint surgery under general (GA) vs. neuraxial anesthesia (NA). Our hypothesis was that PBR will be lower in patients in NA. METHODS: Sixty consecutive patients (ASA 1-3) undergoing elective total knee or hip replacement under GA or NA were included in this prospective observational cohort study. PBR in the sublingual microcirculation was recorded in each patient using SDF at two time points - before surgery and 2 hours after surgery. RESULTS: Before surgery, there was no significant difference in baseline PBR between groups (NA: 1.95 µm (±0.24); GA: 2.02 µm (±0.26); p = 0.098). Postoperatively (2 hours after surgery) PBR was significantly increased in both groups with respect to baseline values (NA: 2.09 µm (±0.19), GA: 2.20 µm (±0.25); p < 0.001). In the GA group, postoperative PBR values were significantly higher than in the NA group (p = 0.006). CONCLUSION: Joint surgery led to significant increases of PBR. Patients in the GA group had significantly higher PBR values 2 hours after surgery compared to NA group. This might implicate that NA is associated with less EG damage then GA in elective hip/knee surgery.

Effect of short-term administration of lipid emulsion on endothelial glycocalyx integrity in ICU patients - A microvascular and biochemical pilot study.

BACKGROUND: Endothelial glycocalyx (EG) is a carbohydrate-rich vascular lining of the apical surface of endothelial cells. It has been proved to have an essential role in vascular homeostasis. Lipid emulsions as part of parenteral nutrition (PN) are widely used in patients in the setting of critical care and perioperative medicine. Due to their structure, lipids may potentially interact with EG. The aim of the study was to evaluate the effect of lipid emulsion on EG. OBJECTIVE: To assess the influence of lipid emulsion on EG integrity in ICU patients using a videomicroscopic and biochemical methods. METHODS: Patients in surgical ICU after major abdominal surgery or cardio surgery and in general ICU were assessed for eligibility for this pilot observational study in University Hospital. The study was performed during the first day of adding lipids as a part of their PN. The patients were given the SMOFlipid 20% for 6 hours in prescribed dose of approx. 1 g/kg of body weight. EG integrity was measured indirectly by automated sublingual videomicroscopy calculating a parameter PBR which describes the amount of lateral deviation of red blood cells from the central column and by levels of syndecan-1 and syndecan-4 in plasma as EG degradational products. Measurements were performed before lipid administration (T0) and 30 minutes after (T6) the infusion of lipid emulsion was completed. The statistical analysis was performed at the level of significance p < 0.05, data are expressed as mean ± standard deviation (SD) and for PBR as median and interquartile range (IQR). RESULTS: Fifteen patients were studied, from them 9 included in final analysis. PBR (expressed in µm) increased after the lipid infusion with no statistical significance (T0 = 2.10; 1.97-2.33 vs. 2.28; 2.11-2.45, p = 0.13). At T6 both syndecans showed statistically significant decrease in their particular levels. Syndecan-1 at T0 = 2580±1013 ng/l, resp. at T6 = 2365±1077 ng/l, p = 0.02; syndecan-4 at T0 = 134±29 ng/l, resp. at T6 = 123±43 ng/l, p = 0.04. CONCLUSION: In our study, we showed that six hours long SMOFlipid 20% infusion had no detrimental effect on the EG integrity as assessed by PBR value and by syndecan-1 and syndecan-4 plasmatic levels. Observed decrease of syndecans shortly after lipid infusion allows us to hypothesize even possibly protecting effect of lipids on EG.

The Effect of Fluid Loading and Hypertonic Saline Solution on Cortical Cerebral Microcirculation and Glycocalyx Integrity.

BACKGROUND: Fluid loading and hyperosmolar solutions can modify the cortical brain microcirculation and the endothelial glycocalyx (EG). This study compared the short-term effects of liberal fluid loading with a restrictive fluid intake followed by osmotherapy with hypertonic saline (HTS) on cerebral cortical microcirculation and EG integrity in a rabbit craniotomy model. METHODS: The experimental rabbits were allocated randomly to receive either <2 mL/kg/h (group R, n=14) or 30 mL/kg/h (group L, n=14) of balanced isotonic fluids for 1 hour. Then, the animals were randomized to receive 5 mL/kg intravenous infusion of either 3.2% saline (group HTS, n=14) or 0.9% saline (group normal saline, n=13) in a 20-minute infusion. Microcirculation in the cerebral cortex based on sidestream dark-field imaging, a morphologic index of glycocalyx damage to sublingual and cortical brain microcirculation (the perfused boundary region), and serum syndecan-1 levels were evaluated. RESULTS: Lower cortical brain perfused small vessel density (P=0.0178), perfused vessel density (P=0.0286), and total vessel density (P=0.0447) were observed in group L, compared with group R. No differences were observed between the HTS and normal saline groups after osmotherapy. Cerebral perfused boundary region values (P=0.0692) and hematocrit-corrected serum syndecan-1 levels (P=0.0324) tended to be higher in group L than in group R animals. CONCLUSIONS: Liberal fluid loading was associated with altered cortical cerebral microcirculation and EG integrity parameters. The 3.2% saline treatment did not affect cortical cerebral microcirculation or EG integrity markers.

Effect of acute hypernatremia induced by hypertonic saline administration on endothelial glycocalyx in rabbits.

BACKGROUND AND OBJECTIVE: The endothelial glycocalyx (EG) is fragile and sensitive to damage such as exposure to hypernatremia. Our aim was to describe the influence of hypernatremia on the EG in sublingual and brain microcirculation in rabbits. METHODS: Hypernatremia was induced by intravenous administration of 10% NaCl solution. The sublingual and brain microcirculation were evaluated by the Side-stream Dark Field imaging before (T1) and 20 minutes after infusion of 10% saline (T2). Damage to the EG was quantified by automated analysis of Perfused Boundary Region (PBR) indicating the amount of penetration of red blood cells into the EG. Syndecan-1 levels were also measured. RESULTS: Hypernatremia was reached in all 20 animals, the PBR values of the sublingual area raised from 1,98 (0,3) to 2,17 (0,18) µm (p = 0,05). The levels of syndecan-1 (1,23 (0,36); 1,31 (0,33) ng/l, p = 0,3) did not mirror PBR changes. CONCLUSIONS: Hypernatremia increased the PBR within the sublingual microcirculation in our animal model, probably due to compression of the EG related to temporary intravascular hypervolemia and changes of the EG charge in RBC instead of direct damaging effect on EG, which has been excluded by rather unchanged levels of syndecan-1.

Inhalation of molecular hydrogen prevents ischemia-reperfusion liver damage during major liver resection.

BACKGROUND: Liver resection is a surgical procedure associated with a high risk of hepatic failure that can be fatal. One of the key mechanisms involves ischemia-reperfusion damage. Building on the well-known positive effects of hydrogen at mitigating this damage, the goal of this work was to demonstrate the antioxidant, anti-inflammatory, and anti-apoptotic effects of inhaled hydrogen in domestic pigs during major liver resection. METHODS: The study used a total of 12 domestic pigs, 6 animals underwent resection with inhaled hydrogen during general anesthesia, and 6 animals underwent the same procedure using conventional, unsupplemented, general anesthesia. Intraoperative preparation of the left branch of the hepatic portal vein and the left hepatic artery was performed, and a tourniquet was applied. Warm ischemia was induced for 120 minutes and then followed by liver reperfusion for another 120 minutes. Samples from the ischemic and non-ischemic halves of the liver were then removed for histological and biochemical examinations. RESULTS: An evaluation of histological changes was based on a numerical expression of damage based on the Suzuki score. Liver samples in the group with inhaled hydrogen showed a statistically significant reduction in histological changes compared to the control group. Biochemical test scores showed no statistically significant difference in hepatic transaminases, alkaline phosphatase (ALP), lactate dehydrogenase (LD), and lactate. However, a surprising result was a statistically significant difference in gamma-glutamyl-transferase (GMT). Marker levels of oxidative damage varied noticeably in plasma samples. CONCLUSIONS: In this experimental study, we showed that inhaled hydrogen during major liver resection unquestionably reduced the level of oxidative stress associated with ischemia-reperfusion damage. We confirmed this phenomenon both histologically and by direct measurement of oxidative stress in the organism.