COMPARATIVE CHARACTERISTICS OF CHANGES IN HEMO - AND LYMPHOMICROCIRCULATORY VESSELS OF ILEUM ACCUMULATED LYMPHOID NODES OF RATS IN THE CASE OF APPLICATION OF INFUSION SOLUTIONS IN EXPERIMENTAL BURN DISEASE

Relevance. Thermal burns of the skin cause the development of burns, the main factor of which is endogenous intoxication. The infusion of detoxification solutions is a mandatory component of the treatment of burns, as it corrects its course and prevents the development of certain stages and complications. According to the stage of the burn disease and the different direction of its links in its pathogenesis, infusion therapy should not only restore water-electrolyte balance and detoxify the body, but also contribute to the normalization and stabilization of vital (including immune) body functions. Objective: study of changes in the vessels of the hemo- and lymphomicrocirculatory system of Peyer's patches in burnt rats at the stages of burn disease, under conditions of intravenous infusion of isotonic sodium chloride solution and combined colloidal-hyperosmolar solutions (lactoprotein and sorbitolum). Materials and methods. The experiment was performed on 72 white rats. Experimental animals were divided into 4 groups (18 animals in each group). I, II, III - rats with skin burn trauma, which received a separate infusion of isotonic sodium chloride (I), lactoprotein with sorbitol (II) and hecoton (III), at a dose of 10 ml / kg. IV - intact animals (control group). Simulation of burn disease was performed by inflicting burn injury by applying to the lateral surfaces of the body of animals four copper plates, which were previously kept for 6 minutes in water with a constant temperature of 100 ° C. Histological and electron microscopic examination were performed. Light microscopy was used. Results. Intravenous administration of the applied infusion solutions caused various phase changes of the hemo- and lymphomicrocirculatory tract of Peyer's patches of the ileum of burnt rats, depending on the applied solution. In the case of infusion of burnt rats with 0.9% sodium chloride solution, the negative effects of burn disease were exacerbated, which were manifested by damage to the vascular wall of the hemo- and lymphocapillary channels, resulting in plasma and lymph seepage through the affected areas into the perivascular space. This process was accompanied by a violation of the rheological properties of blood, the formation of edema. The established "membrane-plastic effect" of lactoprotein with sorbitol revealed clear organ-specific features, which had manifestations of penetration through the damaged wall of microvascular electron-dense impregnations, which contributed to a significant thickening of the basement membrane in the wall of the blood capillary formation and its gradual formation of rounded membranous structure. This structure of variable electron density not only strengthened the vascular wall, but also served as a closure, helping to close the vascular lumen at the site of largest damage. The difference between the perinodal lymphatic capillaries in burnt rats infused with lactoprotein and sorbitol is characterized by the phenomenon of "overflow" of the lymphocapillary channel with cells in different functional states. In the case of infusion of hecoton solution, the effect of "overflow" of the lymphocapillary channel was not observed, which indicates adequate implementation of the immune function of immunocompetent cells. Conclusions. Intravenous infusion of colloid-hyperosmolar solutions causes various changes in the hemo- and lymphomicrocirculatory tract of Peyer's patches. Infusion of a 0.9% sodium chloride solution leads to a deepening of the negative consequences of burn disease, which manifests itself in the form of damage to the vascular wall of the hemo- and lymphocapillary channels. Infusion of solutions of lactoprotein with sorbitol and hecoton helps to preserve the vascular wall of the nodular lymphatic capillaries. When a solution of lactoprotein with sorbitol is applied around the damaged vessels of blood capillaries and venules, annular membrane formations are formed, which promote selective recirculation of structurally intact lymphocytes.

An Audit and Comparison of pH, Measured Concentration, and Particulate Matter in Mannitol and Hypertonic Saline Solutions

Background: The preferred hyperosmolar therapy remains controversial. Differences in physical properties such as pH and osmolality may be important considerations in hyperosmolar agent selection. We aimed to characterize important physical properties of commercially available hyperosmolar solutions.Methods: We measured pH and concentration in 37 commonly-used hyperosmolar solutions, including 20 and 25% mannitol and 3, 5, 14.6, and 23.4% hypertonic saline. pH was determined digitally and with litmus paper. Concentration was determined by freezing point and vapor pressure osmometry. Salinity/specific gravity was measured with portable refractometry. Particulate matter was analyzed with filtration and light microscopy and with dynamic light scattering nephelometry.Results: pH of all solutions was below physiological range (measured range 4.13–6.80); there was no correlation between pH and solution concentration (R2 = 0.005, p = 0.60). Mannitol (mean 5.65, sd 0.94) was less acidic than hypertonic saline (5.16, 0.60). 14/59 (24%) pH measurements and 85/111 concentration measurements were outside manufacturer standards. All 36/36 mannitol concentration measurements were outside standards vs. 48/72 (67%) hypertonic saline (p < 0.0001). All solutions examined on light microscopy contained crystalline and/or non-crystalline particulate matter up to several hundred microns in diameter. From nephelometry, particulate matter was detected in 20/22 (91%) solutions.Conclusion: We present a novel characterization of mannitol and hypertonic saline. Further research should be undertaken, including research examining development of acidosis following hyperosmolar therapy, the relevance of our findings for dose-response, and the clinical relevance of particulate matter in solution.

The Risk of Necrotizing Enterocolitis following the Administration of Hyperosmolar Enteral Medications to Extremely Preterm Infants

<b><i>Introduction:</i></b> Necrotizing enterocolitis (NEC) is a disease predominantly affecting preterm infants. The administration of hyperosmolar solutions could lead to the development of NEC. The objective of this study was to measure the osmolality of enteral medications used in clinical practice and to assess the risk of NEC following exposure to hyperosmolar medications. <b><i>Methods:</i></b> A retrospective cohort study in extremely preterm infants (gestational age &#x3c;28 weeks) born between 2010 and 2016 at a tertiary neonatal intensive care unit in Sweden. 465 infants were identified via the Swedish Neonatal Quality register. Data relating to enteral administrations received during a two-week period were collected from the medical records. The osmolalities of medications were measured using an osmometer. Logistic regression was used to calculate the odds ratio of developing NEC. <b><i>Results:</i></b> A total of 253 patients met the inclusion criteria. The osmolalities of 5 commonly used medications significantly exceeded the recommended limit of 450 mOsm/kg set by the American Academy of Paediatrics (AAP). Most patients (94%) received at least one hyperosmolar medication. No significant risk of developing NEC could be found. <b><i>Conclusion:</i></b> The medications used in clinical practice can significantly exceed the limit set by the AAP. This study does not indicate an increased risk of developing NEC in extremely preterm infants following exposure to hyperosmolar medications. Further studies in larger cohorts are needed to determine the specific cut-off level of osmolality in relation to the pathogenesis of NEC.

The role of hyperosmolar solutions in the physician’s practice

Background. The goal of infusion therapy (IT) is to maintain central euvolemia without excess sodium and water. The term “restrictive IT”, which allows hypovolemia, should be replaced by the term “IT with a zero balance”. Individualized targeted IT involves monitoring cardiac output, optimizing stroke volume, and preventing episodes of hypovolemia. Less stringent restrictions on preoperative nutrition contribute to better control of hemodynamic parameters. Objective. To describe the role of hyperosmolar solutions in the physician’s practice. Materials and methods. Analysis of literature sources on this issue. Results and discussion. Support of perioperative euvolemia is the basis of the concept of enhanced recovery and improvement of the surgery outcomes. Clinical indices of tissue perfusion adequacy include mean blood pressure, central and abdominal perfusion pressure, diuresis, consciousness level, skin perfusion, lactate and blood pH, etc. Each patient with suspected hypovolemia should be physically examined with an emphasis on searching for bleeding, dehydration, and other causes of hypovolemia. Fluid deficiency should be compensated before surgery. Hyperhydration must also be detected and eliminated timely, as the diagnosis and prediction of pulmonary edema are difficult. There are 4 phases in IT of shock: rescue (achieving blood pressure and cardiac output required for survival), optimization (ensuring sufficient oxygen delivery and lactate control), stabilization (preventing organ dysfunction after achieving hemodynamic stability), and de-escalation (ensuring negative fluid balance). In resuscitation of patients with sepsis and septic shock, the use of hydroxyethyl starch (HES) is not recommended; crystalloids should be preferred over gelatin. If HES were still prescribed, their introduction should be stopped if there are signs of kidney damage or signs of coagulopathy. It is also proposed not to administer hyperoncotic solutions to critically ill patients outside of clinical trials. New colloidal solutions should be introduced into clinical practice only after the establishment of safety for the patient. Following an appeal by HES-manufacturing companies, the Pharmacovigilance and Risk Assessment Committee of the European Medicines Agency stated that HES could be used for massive bleeding at the discretion of the chief physician. Continued use of HES in the postoperative period should be further investigated, including monitoring of renal function for 90 days. In general, the use of HES in clinical practice remains relevant in conditions such as massive bleeding or penetrating trauma, as well as for preloading before regional anesthesia and IT of critical conditions without the risk of bleeding. Modern HES should be used and the dose should not exceed 30 ml/kg. The benefits of preoperative targeted preload optimization using HES are beyond doubt, while recommendations for the overall hazard of these solutions are debatable and inconclusive. The volume of injected solutions should be monitored during IT, as infusion of large volumes of crystalloids may cause pulmonary edema and large volumes of 0.9 % NaCl may lead to the development of hyperchloremic metabolic acidosis. Hypertonic solutions have been shown to be effective in reducing the number of abdominal complications of pancreatoduodenectomy, reducing the length of stay on mechanical ventilation in patients with hemorrhagic shock, and in a number of other interventions. Fluid resuscitation with a small volume of hypertonic saline after damage control operations significantly reduces the length of stay in the intensive care unit, decreases the likelihood of acute respiratory distress syndrome, sepsis and multiple organ failure, reduces 30-day mortality. In patients with brain injuries, hypertonic solutions reduce intracranial pressure and help to balance the fibrinolysis system by reducing secondary brain damage. Unfortunately, most (60 %) of the solutions on the market are unbalanced (Hohn R., 2014). The reasons for this include lower cost of the latter, the lack of understanding of the benefits of alternatives by doctors, the lack of awareness of the seriousness of these solutions’ disadvantages. Due to the risk of acidosis on the background of unbalanced solutions, chloride-restrictive IT should be followed. Hyperosmolar balanced solution Reosorbilact (“Yuria-Pharm”) helps to activate the sympathetic nervous system, which leads to increased blood pressure, decreased diuresis, adrenaline release and increase of circulating blood volume by contracting the spleen. Reosorbilact quickly normalizes hemodynamic parameters, microcirculation, laboratory and biochemical parameters, stabilizes and normalizes the function of external respiration and blood circulation. The use of osmotic drugs Reosorbilact and Xylate (“Yuria-Pharm”) is indicated for plasma volume replacement in hypovolemia of various origins. Conclusions. 1. Perioperative euvolemia is the main principle of perioperative IT. 2. It is not recommended to use HES in intensive care. 3. HES remain relevant in acute hypovolemia and blood loss. 4. Balanced hyperosmolar solutions (Reosorbilact) are an alternative to HES in the treatment of patients with multiple organ failure in intensive care units.

Features of the composition of certain complex hyperosmolar infusion solutions

Objective. To justify the use of complex hyperosmolar solutions. Results and discussion. Today, the question of the qualitative composition and quantitative relationship between the various components of infusion-transfusion therapy remains controversial. Hypertonic solutions in various concentrations of NaCl were first used for “low-volume resuscitation” in patients with hemorrhagic shock. Administration of these solutions results in a temporary osmotic pressure gradient between the blood plasma and the interstitial space, causing fluid to move into the intravascular space, increasing cardiac output, blood pressure, and improving microcirculation. Recently, combinations of hypertonic NaCl with colloids, as well as multicomponent infusion drugs are increasingly used. These are, in particular, the drugs Rheosorbilact, Xylate, Lactoxyl, Sorbilact, Lactoprotein with sorbitol, Gecoton developed at the Institute of Blood Pathology and Transfusion Medicine of the National Academy of Medical Sciences of Ukraine. Preparations based on polyhydric alcohols of sorbitol or xylitol, alkalizing agents of sodium lactate or sodium acetate and electrolytes. Rheosorbilact, Xylate, Lactoxyl are basic solutions for detoxification therapy, including in patients with diabetes. Sorbilact used as an osmodiuretic and for the treatment of patients in the postoperative period. Protein-salt solution based on donor albumin Lactoprotein with sorbitol is a mean for intensive care in emergencies. Colloid-hyperosmolar infusion solution Gecoton based on hydroxyethyl starch is used as a mean for low-volume resuscitation in the prehospital stage, including combat victims. Specially selected substances comprising the combined drugs affect different parts of the pathological process and have several advantages compared to mono-drugs. The pharmacological action of such solutions is due to the mutual potentiation of the action of its components. This provides hemodynamic effect and can reduce the dosage of each component separately, reducing the likelihood of side effects. The use of multicomponent hyperosmolar solutions can significantly reduce the total volume of fluid administered to patients. Conclusions. Complete hyperosmolar drugs can be recommended for routine and auxiliary fluid therapy and treatment for emergency conditions.

Reactive and destructive changes of Peyer’s patches in rats with experimental burn disease under infusion of detoxification solutions

The pathogenesis of burn immune dysfunction and burn enteropathy needs further clarification given that the cellular lesions of lymphoid tissue associated with mucous membranes are the least studied. The purpose of the study was to establish reactive and destructive changes in Peyer’s patches of rats after burn injury of the skin with the use of intravenous infusion of isotonic sodium chloride solution and combined colloid-hyperosmolar solutions. White male rats weighing 160-200 g at 6 months of age were divided into 4 groups (18 animals in each group): I, II, III – rats with burn skin injury (grade II-III burn with an area of 23% of body surface area and the development of moderate-severity shock state) which was administered a separate intravenous infusion once a day for the first 7 days of the experiment with isotonic sodium chloride, lactoprotein with sorbitol and HAES-LX-5%, in each case at a dose of 10 ml/kg; IV – intact animals. The material was collected from rats under deep thiopental intraperitoneal anesthesia after 1, 3, 7, 14, 21 and 30 days after burn injury. Biopsies from Peyer’s patches for histological and electron microscopic examination were processed using conventional methods. Investigation of histological preparations stained with hematoxylin-eosin was performed on an Olympus BX51 microscope. Ultrathin sections were contrasted on copper support meshes with uranyl acetate and lead citrate according to Reynolds and studied using a PEM-125K electron microscope. Electron and light microscopy data indicate that intravenous infusion of colloidal-hyperosmolar solutions (lactoprotein with sorbitol and HAES-LX-5%) promotes suppression of inflammatory response, inhibits necrosis, and optimizes lymphoid apoptosis at Peyer’s patches of rats with experimental burn disease caused by burn injury to the skin of 21-23% of the body surface. Apoptotic lymphocytes and their apoptotic bodies are effectively phagocytosed by macrophages and are digestible in heterophagolysosomes. The apoptotic altered dendritic cells in Peyer’s patches are characterized by osmiophilic cytoplasm and a nucleus with high electron density amorphous nucleoplasm. In the cytoplasm are located mitochondria with enlightened matrix and destroyed cristae, irregularly expanded tubules of variable configuration of a granular endoplasmic reticulum with electronically transparent content and numerous derivatives of their vacuole transformation, which are sharply darkened. The fusion of vacuoles leads to the formation of large electron-luminous cavities filled with various residues of compacted degraded cellular structures. Vacualization promotes site segmentation of condensed cytoplasm of apoptotic dendritic cells and formation of apoptotic blebs, which are subject to entrapment and subsequent sequential degradation with the participation of neighboring macrophages. The structural changes of the organelles of the protein-synthesizing apparatus found in Peyer’s plaque cells in rats with experimental burn disease can be regarded as a manifestation caused by functional overload of the granular endoplasmic reticulum (ER-stress). The consequence of optimal development of ER-stress and subsequent unfolded protein response is the apoptotic degradation of the corresponding cell, the course of which is modified by the use of colloid-hyperosmolar solutions.

Central versus Low-Lying Umbilical Venous Catheters: A Multicenter Study of Practices and Complications

Objectives Conventional neonatology practice is to place umbilical venous catheters (UVCs) in central position and to limit the use of low-lying catheters. Our objectives were to describe the practices and complications associated with UVCs and to evaluate the type of infusates used with either UVC position. Study Design A retrospective chart review was performed at four neonatal intensive care units to identify neonates who underwent UVC placement over a 2-year period. Infant demographics, UVC position, catheter days, fluid and medication characteristics, and specific complications were extracted. Results A total of 2,011 neonates who underwent UVC placement were identified during the 2-year period. Of these, 641 UVCs (31.9%) were identified in the low-lying position. Centrally positioned UVCs were associated with lower gestational age and were left in situ for a longer duration than low-lying UVCs. Infusions of hyperosmolar solutions and vasopressors were significantly higher in central UVCs, though they were used in a significant number of low-lying UVCs. Complications, while not statistically different, were three times higher in low-lying UVCs. Conclusion Despite conventional teaching, low-lying UVCs were used in nearly one-third of infants in this cohort. Parenteral nutrition, antibiotics, and vasopressors were infused through central and low-lying UVCs. There was no statistically significant difference in complication rates between UVC positions.

Effect of Glyceraldehyde Cross-Linking on a Rabbit Bullous Keratopathy Model

Background. To evaluate the effects of corneal glyceraldehyde CXL on the rabbit bullous keratopathy models established by descemetorhexis.Methods. Fifteen rabbits were randomly divided into five groups. Group A (n=3) is the control group. The right eyes of animals in Groups B,C, D, and E (n=3, resp.) were suffered with descemetorhexis procedures. From the 8th day to the 14th day postoperatively, the right eyes in Groups C and D were instilled with hyperosmolar drops and glyceraldehyde drops, respectively; the right eyes in Group E were instilled with both hyperosmolar drops and glyceraldehyde drops. Central corneal thickness (CCT), corneal transparency score, and histopathological analysis were applied on the eyes in each group.Results. Compared with Group A, statistically significant increase in CCT and corneal transparency score was found in Groups B, C, D, and E at 7 d postoperatively (P<0.05) and in Groups C, D, and E at 14 d postoperatively (P<0.05).Conclusion. Chemical CXL technique using glyceraldehyde improved the CCT and corneal transparency of the rabbit bullous keratopathy models. Topical instillation with glyceraldehyde and hyperosmolar solutions seems to be a good choice for the bullous keratopathy treatment.