Alina Davydenko

The number of patients requiring mechanical ventilation is increasing in parallel with improved survival of critically ill individuals and population aging. The costs associated with the care of these patients are substantial, with intensive care unit (ICU) bed costs being significantly higher than those in general hospital wards. One of the key factors contributing to prolonged ICU stay is the persistence of the need for ventilatory support despite stabilization of the patient’s overall condition and positive dynamics of the underlying disease. Objective: To systematize global evidence on the principles of weaning patients from mechanical ventilation, develop an algorithmic approach to these principles, and create a standardized protocol for weaning from mechanical ventilation in order to shorten the duration of ventilatory support and patients’ length of stay in the intensive care unit, reduce the incidence and severity of complications, and thereby significantly decrease mortality and the cost of intensive care. Currently, a variety of methods and algorithms for ventilator weaning have been proposed, incorporating different modes of respiratory support and approaches to assess readiness for spontaneous breathing. Contemporary strategies aimed at reducing the duration of the weaning process include the gradual reduction of ventilatory assistance combined with increasing the frequency and duration of spontaneous breathing efforts. The primary goal of any weaning protocol is the restoration of respiratory muscle strength and endurance. Early rehabilitation plays a crucial role in facilitating timely transition to spontaneous breathing. In particular, respiratory muscle training and adequate nutritional support are essential components of successful weaning. Strict adherence to criteria for assessing readiness for weaning, a stepwise transition from controlled or assisted ventilation modes to supportive modes with a gradual reduction in ventilatory parameters, implementation of spontaneous breathing trials, minimization of sedation during ventilatory support, early initiation of rehabilitation, respiratory muscle strengthening exercises, and appropriate nutritional support have been shown to reduce the duration of mechanical ventilation and ICU length of stay, decrease complication rates and mortality, and, importantly, ensure a safer and more comfortable transition to spontaneous breathing.

Circadian rhythm and sleep disturbances are frequently observed in patients admitted to intensive care units (ICUs) and are recognized as components of Post-Intensive Care Syndrome. These disorders arise from both the discomfort associated with ICU stay and the effects of the underlying disease. Sleep disruption, in turn, contributes to significant cognitive impairments, most notably delirium. Therefore, awareness of this issue, along with timely diagnosis and preventive interventions, is essential for optimizing therapeutic strategies and improving clinical outcomes. Routine ICU-related factors contributing to circadian rhythm disruption and altered sleep architecture include artificial lighting, environmental noise, mechanical ventilation, pharmacotherapy, prolonged immobilization, and continuous medical interventions. At present, there is insufficient evidence to suggest that critically ill patients can adapt to ICU conditions through circadian rhythm regulation alone. Disruption of circadian rhythms is influenced by both the severity of illness and environmental characteristics of the ICU. Although a direct causal relationship between circadian rhythm disruption, altered sleep architecture, and disease severity has not been definitively established, several studies indicate a correlation between the degree of organ dysfunction and the extent of sleep fragmentation. Preventive strategies aimed at reducing sleep disturbances in ICU patients should be incorporated into standardized care protocols, with the goal of restoring circadian rhythm balance. In Ukraine, there are currently no clinical guidelines for ICU rehabilitation that address the preservation of sleep architecture. Despite growing attention to this issue in international literature and the development of related clinical recommendations, the implementation of sleep-promoting protocols remains challenging in specific healthcare settings. Successful integration requires institutional commitment, increased staff awareness, and adaptation to local ICU infrastructure, all of which are essential for improving the quality of intensive care.

Among neonates, 2 per 1,000 experience hypoxia/ischemia at birth, resulting in hypoxic-ischemic encephalopathy (HIE) and subsequent neurodevelopmental disorders, which impose a lifelong burden on families and society. Infants with stage 3 HIE exhibit a high incidence of convulsive syndrome and severe neurodevelopmental delay. Even in the absence of profound impairments, affected children may present with motor, cognitive, or behavioral abnormalities. The aim of our study was to analyze and identify maternal and neonatal risk factors associated with psychomotor developmental delay. Materials and methods of the study. The study enrolled 45 infants born to mothers with metabolic syndrome who were diagnosed with moderate or severe HIE in the early neonatal period; among them, 30 were preterm and 15 were full-term. Follow-up of infants continued until 9 months of age; сontinued observation was possible in 27 (17 preterm, 10 full-term) of the 45 infants diagnosed with moderate or severe HIE. Statistical analysis was performed using standard descriptive methods and simple and multiple logistic regression, including Poisson regression. The predictive value of maternal history, metabolic parameters, and other variables was evaluated using receiver operating characteristic (ROC) curve analysis with calculation of the area under the curve (AUC) in STATA 14.0. According to the decision of the Bioethics Commission of Poltava State Medical University No. 217 dated 12.06.2023, the study adhered to ethical standards for the humane treatment of patients, as defined by the Tokyo Declaration of the World Medical Association, the Helsinki Declaration, the Universal Declaration of Human Rights, the Council of Europe Convention on Human Rights and Biomedicine, current Ukrainian legislation, orders of the Ministry of Health, and the Code of Ethics for Physicians of Ukraine. Informed consent was obtained from all parents. The study was conducted as part of the scientific research project of the Department of Pediatrics No. 1 with Neonatology, Poltava State Medical University, No. 0120U102856: “Development of clinical and laboratory criteria and methods for predicting and preventing metabolic disorders in young children.” Research results. Most infants included in the study were diagnosed with moderate asphyxia at birth. The Apgar scores at 1 and 5 minutes were 5.83 ± 0.23 and 6.7 ± 0.14 points, respectively, in preterm infants, and 5.8 ± 0.52 and 7.2 ± 0.34 points in full-term infants. Mechanical ventilation was required immediately after birth in 16.7% of preterm infants with HIE and 46.7% of full-term infants; the duration of mechanical ventilation was 4.26 ± 0.7 days in preterm infants and 5.47 ± 1.26 days in full-term infants. The most common neurological conditions at 9 months of age were hypoxic-ischemic CNS injury and psychomotor delay. The frequency of hypoxic-ischemic CNS injury was 88.2% in preterm infants and 60% among full-term infants. The incidence of psychomotor delay was 20.0% in preterm infants and 17.6% in full-term infants. Multivariate logistic regression analysis, adjusted for gestational age at birth, was used to develop predictive models for psychomotor delay. The Apgar score and duration of mechanical ventilation were identified as the strongest prognostic factors. . The predictive model including the duration of mechanical ventilation demonstrated a reliable predictive coefficient (β = 0.31; 95% CI, 0.11–0.50) with an area under the ROC curve of 0.9180. Conclusion. Approximately 20% of infants with HIE, both preterm and full-term, exhibited delayed neurodevelopment at 9 months of age. Multivariate logistic analysis identified low Apgar scores and prolonged mechanical ventilation as the most significant prognostic factors, with the predictive model incorporating ventilation duration demonstrating the highest predictive accuracy. These findings highlight the need to optimize medical monitoring and follow-up of infants with HIE born to mothers with metabolic syndrome.

Recent studies have demonstrated a direct association between hypoxic-ischemic encephalopathy (HIE) and maternal overweight or obesity. HIE remains one of the leading causes of neonatal mortality and long-term neurological impairment in newborns. It represents a systemic condition affecting not only the central nervous system but also multiple peripheral organs, including the liver. One of the indirect biochemical indicators of hypoxic injury is elevated hepatic transaminase activity — specifically, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Particular emphasis has been placed on the involvement of nitric oxide (NO) in the pathophysiology of HIE Objective: to analyze and identify risk factors for hypoxic-ischemic encephalopathy in full-term and premature infants born to mothers with metabolic syndrome, to build clinical prognostic models. Materials and methods. The study cohort consisted of 125 neonates. The study cohort consisted of 125 neonates. Group 1 included infants born to mothers with metabolic syndrome who were diagnosed with HIE (n = 45), while Group 2 included infants born to mothers without metabolic syndrome and without clinical manifestations of HIE (n = 79). ). Nitrite concentrations were measured by quantifying the diazo compounds formed via reaction with sulfanilic acid, followed by a subsequent reaction with the Griess-Ilosvai reagent. The bioethical principles of the study were confirmed by the Commission on Ethical Issues and Bioethics of Poltava State Medical University (protocol No. 233 dated 21 December 2024). Statistical analysis was conducted using the STATA 14.0 software package. Statistical analysis was performed using the STATA 14.0 software package. The work was carried out within the research project of the Department of Paediatrics No. 1 with Neonatology of Poltava State Medical University ’’To develop clinical and laboratory criteria, methods for predicting and preventing metabolic disorders in young children’’ (state registration number 0120U102856, term of completion 2020-2024). Results of the study and their discussion. Initial clinical assessments were performed immediately postnatally. Among term infants, the most frequently diagnosed conditions included neonatal depression syndrome, respiratory distress syndrome, heart failure, seizures, and muscular dystonia. In preterm infants, depression syndrome, muscular dystonia, and seizures were the predominant clinical manifestations. HIE in term neonates is typically characterized by multisystem involvement, whereas in preterm infants, clinical signs are predominantly neurological. A metabolic profile analysis confirmed the multisystemic nature of HIE. On day one of life, AST and ALT levels in preterm infants with HIE were significantly elevated compared to preterm infants without HIE (p = 0.055 and p = 0.049, respectively). The urinary nitrite level in preterm infants with HIE was significantly higher compared to that in preterm infants without HIE (p = 0.025). Similar findings were observed in term infants, where those with HIE exhibited elevated urinary nitrite levels (p = 0.042). Based on these data, we developed predictive models for the early neonatal onset of HIE. After adjusting for gestational age and ALT or AST activity, urinary nitrite concentration proved to be a reliable prognostic marker for HIE in both preterm and term neonates. The areas under the ROC curves for models incorporating urinary nitrite levels, gestational age, and either ALT or AST were 0.9952 and 0.9279, respectively. Conclusions. HIE in neonates is associated with multisystem involvement, affecting various organs in addition to the central nervous system. In light of the systemic nature of the condition, potential metabolic biomarkers were evaluated. Among these, serum ALT and AST levels, as well as urinary nitrite concentration, emerged as significant risk factors for early neonatal HIE in infants born to mothers with metabolic syndrome. Due to the heterogeneity of the cohort in terms of gestational age, multiple logistic regression analysis with obligatory adjustment for gestational age was employed to ensure accurate interpretation of the findings. A predictive model for HIE development was constructed, incorporating urinary nitrite and ALT levels. Newborns diagnosed with HIE and born to mothers with metabolic syndrome require close monitoring of ALT and AST levels during the early neonatal period. Furthermore, urinary nitrite concentration serves as an optimal biomarker for predicting HIE onset.

Aim: to determine the influence of maternal and neonatal variants of the eNOS (G894T, rs1799983) and IL1B (C3953T, rs1143634) genes and their intergenic interactions on the development of HIE in newborns.Material and methods: The study included a cohort of 105 newborns and their 99 mothers. Determination of variants of the genes eNOS (G894T, rs1799983) and IL1B (C3953T, rs1143634) was carried out for the patients of study groups.Results: The frequency of detection of the 894TT genotype by the eNOS gene was increased in newborns with severe asphyxia (p=0.018) and in their mothers (p=0,0057). Further analysis of intergenic interactions, performed in mother-child pairs, revealed an increased frequency of the neonatal 894GG (eNOS)/maternal 3953С (IL-1B) genotype combination in the comparison group versus the group of newborns with HIE (p=0.007).Conclusions: The significance of the intergenic maternal combination of 894GG/3953CT genotypes for the eNOS and IL1B genes and the intergenic combination of neonatal 894GG (eNOS)/maternal 3953CT (IL-1B) genotypes in the development of HIE in newborns has been proven. Associations of maternal and neonatal 894TT genotypes for the eNOS gene with the development of severe asphyxia, bradycardia, and respiratory failure were found in newborns with HIE.