Chronicle
EXPERIMENTAL STUDIES
The purpose of the study is to compare the structural and functional state of neuro-glio-vascular microstructural complexes of the somatosensory cortex (SSC), CA1 of the hippocampus and amygdala of the brain of white rats under normal conditions and after acute ischemia caused by a 20-minute occlusion of common carotid arteries.
Materials and methods. In this experiment, neurons, astrocytes, endotheliocytes, pericytes, basal membrane of the microvessels were studied in the normal (n=5) and the reperfusion period (1, 3, 7, 14, 21 and 30 days, n=30) using electron and fluorescence microscopy (DAPI staining). The morphometric analysis was carried out using the ImageJ 1.46 software.
Results. During the recovery period after ischemia was noted reactive (edema-swelling, tinctorial properties of cells) and compensatory-restoration (hyperplasia, hypertrophy, proliferation, increased transcytosis) changes in neuro-glia-vascular complexes. After ischemia, the number of neurons decreased (by 8.7%—55,3%), and the glial cell count 2—3 fold increased. Increasing neuroglial index (NGI) was accompanied by: 1) the emergence of microvessels with numerous branched processes of pericytes, 2) the complication of the spatial organization of basal membranes, and 3) the structural features of activation of transcytosis processes (large number of caveolae, smooth and clathrin vesicles, large vesicles) in pericytes and endothelial cells.
Conclusion.These findings indicate the compensatory-restoration changes in the components of neuro-gliovascular complexes SSC, CA1 of the hippocampus and amygdala of white rat’s brain after a 20-minute occlusion of the common carotid arteries. The most complete implementation of mechanisms for the protection and repair of damaged neurons occurs in the SSC and amygdala exhibiting high NGI values.
Objective. Using laser Doppler flowmetry (LDF) and wavelet-analysis of microvascular blood flow oscillations to determine the features of regulation of cutaneous and cerebral microhemocirculation at early stages of acute fixed volume blood loss.
Materials and methods.Experiments were carried out on 31 male outbred rats weighing 300 g to 400 g. The animals were anesthetized by intraperitoneal injection of pentobarbital (45 mg/kg). The tail artery was catheterized for invasive measurement of mean blood pressure (BP) and blood withdrawal. The LDF method (ЛАКК-02 device, LAZMA, Russia) was used to record microvascular blood flow simultaneously in the right ear and the pial vessels of the left parietal region. An acute fixed-volume hemorrhage model was used. The target blood loss volume was 30% of the total blood volume (TBV). Within 10 minutes after the end of hemorrhage (posthemorrhagic period), the blood pressure and the LDF-gram were recorded. The following LDF-gram parameters were analyzed: the mean value of IP; the maximum amplitude of blood flow oscillations (Amax) and the corresponding frequency (Fmax) in the frequency band 0.01—0.4 Hz. Statistical processing of the data was performed using Statistica 7.0.
Results. At baseline, the values of IP, Аmax and Fmax in the brain were higher than in the skin. At posthemorrhagic period, BP decreased, on average, from 105 to 41 mm Hg. Against this background, IP in the skin decreased by 65%, while in the brain it reduced only by 17%, as compared with the baseline values (P0,0001). In the same time these organs were characterized by a unidirectional dynamics of patterns of fluxmotion. In both investigated organs, Amax increased sharply, and Fmax decreased. In posthemorrhagic period, fluxmotion not only «slowed down», but was also synchronized in a relatively narrow frequency band: for the skin Fmax was about 0.04 Hz (at the border of the endothelial and neurogenic band), for the brain about 0.09 Hz (neurogenic range).
Conclusion. Acute blood loss at a volume of 30% of TBV is accompanied by the unidirectional dynamics of changes in the amplitude and frequency characteristics of cutaneous and cerebral blood flow oscillations: an increase in the amplitude, slowing down and synchronization of the fluxmotion in a narrow frequency band. The results of present study and literature data allow assuming that during hypotension, the mechanisms for reducing the dominant fluxmotion pattern frequency are associated with a decrease in pressure on the vessel walls, while an increase in amplitude is associated with the activation of the sympathoadrenal system.
ETHICAL AND LEGAL ISSUES
The purpose of the study: to assess legally justified measures concerning the rights of a patient with life-threatening conditions.
Materials and methods. Federal Law N 323-FZ «On The Fundamentals of Health Protection in the Russian Federation» as of 11/21/2011 and a number of current normative legal acts (NLA) regulating patient's rights were analyzed including those related to the ICU setting.
Results. It has been determined that the state of health of a patient who is being treated in the intensive care unit of a healthcare institution involves restriction of some of his rights. We found out that the existing restrictive measures related to the patient's rights under life-threatening conditions are established in order to ensure timely medical care in cases, when the result of activities undertaken depends on the time of its delivery.
Conclusion. The current legislation of the Russian Federation provided further guarantees for patients in the intensive care units, namely, the terms for the admission of relatives, lawyers, and clergymen. However, further mechanisms to implement the rights of patients in cases when they are unconscious or their will can be misinterpreted are required.
PREDICTORS, MARKERS AND MONITORING OF CRITICAL STATES
Mental illnesses in patients with sepsis occur in 23—32% of cases and are an unfavorable prognostic sign. At present, the causes of these disorders are adequately explained by the theory of neuroinflammation that takes into account the pathogenic influence of the systemic inflammatory reaction and related endothelial dysfunction on the central nervous system function.
The purpose of the study was to evaluate the relevance of the severity of the systemic inflammatory response, the intensity of oxidative stress and the severity of patient's general state to prediction of the duration of delirium and therapy outcomes in patients with sepsis-associated delirium.
Materials and methods. A pilot, single-center, prospective, cohort study was performed in 187 adult patients diagnosed with sepsis who were treated in the intensive care unit of L. A.Vorokhobov Municipal Clinical Hospital No. 67. The following tests and examinations were performed: Vasoactive-Inotropic Score (VIS), Sepsis-related Organ Failure Assessment score (SOFA), Intensive Care Delirium Screening Checklist (ICDSC); plasma levels of carbonylated peptides, procalcitonin (PCT), and neuromarkers were monitored; and a correlation analysis with the severity of the sepsis, its duration and therapy outcomes was performed.
Results. A moderate correlation (R=0.68; P<0.05) between the plasma concentration of carbonylated peptides and the duration of delirium was found. The S100b protein level, a marker of neuronal damage, also closely correlated (R=0.75; P<0.05) with the duration of delirium. In the group of ICDSC, SOFA, and VIS, the latter turned out to be the most significant predictor of the delirium duration (P=0.02). In the group in which SOFA, carbonylated peptides and PCT levels monitored, the organ failure scale was the leading one (P=0.02).
Conclusion. The vasoactive-inotropic score (VIS) is a more relevant predictor of the delirium duration than ICDSC and SOFA; the organ failure scale assessment has a greater correlation with the delirium duration than carbonylated peptides and PCT level monitoring; the VIS is the best predictor of the mortality in patients with sepsis.
The purpose of the study is to investigate the effect of epidural block on the functional state of the kidneys in patients with localized cancer during kidney resection under the conditions of warm ischemia.
Materials and methods. We examined 45 patients (25 men and 20 women) with a localized kidney cancer (T1N0M0) aged 56.5±8.7 years. All the patients underwent kidney resection performed under conditions of warm ischemia (15—20 minutes). Patients were divided into 2 groups: the main group (25 subjects) in which the perioperative epidural block was applied and the reference group (20 patients) without the epidural block. The following parameters were tested in blood and urine using the ELISA technique: cystatin C, L-FABP, KIM-1 , IL-18, and GFR. The test was carried out 1 hour prior to surgery, 20 minutes after the warm ischemia stage, and on Days 1 and 3. Based on the baseline cystatin С level, the patients in each group were divided into 2 subgroups: subgroup 1 —cystatin C is 1000 ng/ml and lower; subgroup 2 — more than 1000 ng/ml. The statistical processing of the findings was performed using the Statistica 6.0 software based on the t-test for two independent samples. Differences were considered to be statistically significant at P<0.05.
Results. It has been demonstrated that functional parameters of kidneys were recovered to the baseline values by the 3rd day after the kidney resection under the warm ischemia due to perioperative epidural block. Impairment of the tubulointerstitium and glomerular apparatus were observed in the reference group. GFR values in the patients of the main group were within normal limits by Day 3, whereas in the patients of the GFR was lower by 38.8% as compared to the baseline (P<0.05).
Conclusion. The use of the perioperative epidural block in patients with localized kidney cancer who underwent the organ resection under the warm ischemia demonstrated the nephroprotective effect, while maintaining the functional parameters of kidneys at the baseline level.
The systemic inflammatory response syndrome is a typical systemic reaction to tissue injury and an important factor for structural and functional regeneration of the damaged tissue. The systemic inflammatory response syndrome developed in patients in the postoperative period after cardiac surgeries is a natural body reaction; however, in some cases there is an excessive generation of pro-inflammatory factors that can change the nature of inflammation and worsen the tissue damage. The massive release of inflammatory mediators leads to dysfunction of various organs and systems and can become one of main causes of lethal outcomes in the postoperative period. There is evidence of the contribution of the systemic inflammation to the pathogenesis of atherosclerosis. Therefore, an assessment of patient’s susceptibility to the systemic inflammatory response may contribute to predicting disease risks and severity as well as choosing a specific therapy for a given patient. This review analyzes the information about the contribution of the polymorphism of genes encoding cytokines and proteins involved in the pathogenesis of the systemic inflammatory response in the development of individual susceptibility to the non-infectious systemic inflammatory response in patients after cardiac surgeries, as well as in modification of its severity and consequences.
INTENSIVE CARE
The aim of the study was the assessment of aerosolized colistin (AC) efficacy as adjunctive therapy to systemic antibiotic therapy for nosocomial pneumonia (NP).
Materials and methods. This observation study included 90 NP patients under critical care. The primary criterion of therapy efficacy was NP resolution. As the secondary criteria of therapy efficacy, eradication of germs from sputum, the time to patients’ spontaneous breathing, the time in critical care unit, and mortality were evaluated. Patients were split into 2 groups: Gr.1 (n=48) — systemic antibiotics combined with AC; Gr. 2 (n=42) — systemic antibiotics cross over due to sensitivity. The groups were comparable in main characteristics. Aerosolized colistin was dosed 2 mln. U 3 times/day (Xellia Pharmaceuticals ApS, Denmark) in Gr. 1. The regimen of systemic antibiotic therapy was not changed upon AC prescription. Statistical analysis was carried out using Statistica 7.0 (M, σ, Newman—Keuls test; P<0.05).
Results. This study has demonstrated efficacy of aerosolized colistin 2 mln. U 3 times/day as adjuvant therapy to systemic antibiotic therapy for NP caused by multidrug-resistant gram-negative germs: the NP resolution rate was 75% (versus 52% in Gr. 2, P=0.0295); eradication of pathogens by therapy day 7 was achieved in 80% in Gr. 1 and 60% Gr. 2 (n=12) (P>0.05); in Gr. 1, spontaneous breathing took place earlier than in Gr. 2 — 7.6±1.6 days in Gr. 1 versus 11.7±3.4 days in Gr. 2 (P=0.0000); in Gr. 1, the critical care unit duration was shorter than in Gr. 2 — 12.0±3.4 days in Gr. 1 versus 16.3±3.4 days in Gr. 2 (P=0.0000).
Conclusions. Aerosolized colistin 2 mln. U 3 times a day is an effective adjuvant therapy combined with systemic antibiotic therapy for nosocomial pneumonia caused by multidrug-resistant gram-negative germs. This modified treatment assisted faster pneumonia resolution, earlier spontaneous breathing of patients, and shorter time in the intensive care unit. Addition of aerosolized colistin to systemic antibiotics should be regarded as a possible algorithm of treatment in a case of inefficient first-line antibiotic therapy.
The latent or mist diagnosed dysfunction of the small intestine is a common disorder in critically ill patients. Intestinal oxygenotherapy is one of the alternative ways to normalize the coordinated activity of the smooth muscles of the digestive tract.
Purpose of the study. To determine the effect of intestinal oxygenotherapy in patients with enteropathies of critical conditions on the dynamics of biomarkers of the intestinal wall permeability and ischemia.
Materials and methods. An open prospective descriptive study of 12 critically ill patients (7 adults, 5 children) with multiple organ failure and evident or saspected dysfunction of the gastrointestinal tract. Pediatric patients included children with congenital heart disease who underwent open-heart surgery for the purpose of radical or palliative correction.
Results. Complications related to the intestinal oxygenotherapy were not observed. On the contrary, its use in children coincided with the positive clinical dynamics: elimination of intestinal paresis, normalization of digestion of enteral nutrition. However, it is difficult to interpret the results unambiguously. Serum citrulline concentration in children is an objective marker of the functional state of the gastrointestinal tract: in the vast majority of the control points its level was <20 μmol/l; it means a very severe intestinal damage. Serum I-FABP concentration was<100 pg/ml in a significant number of control points, which, by contrast, does not allow to talk about the intestinal wall severe ischemic disturbances. In adults, the initial serum citrulline concentration was <20 μmol/l in the vast majority of control points; but by days 5—6 after the onset of intestinal oxygenation, in the majority of patients the citrulline levels exceeded >20 μmol/l (up to 80 μmol/l). No correlation between serum citrulline and I-FABP concentrations in adults was found.
Conclusion. Intestinal oxygenotherapy is a promising therapeutic technique for prevention and correction of enteropathies. The method may appear especially effective in treatment of anaerobic (i.e. Cl. defficile-assosiated colitis) infection. The diagnostic value of plasma citrulline and I-FABP concentrations needs further confirmation.
ISSN 2411-7110 (Online)