TO CHARACTERISTICS OF THE ETIOLOGICAL STRUCTURE AND ANTIBIOTIC SENSITIVITY PATHOGENSOF INFECTIOUS RESPIRATORY ORGANS IN NEWBORN AFTER ARTIFICIAL PULMONARY VENTILATION

Objective. The study of the etiological structure, properties of pathogens of the Vinnytsia National Medical University named after E. Pirogova, respiratory process in newborns who have underwent artificial mechanical lung ventilation (MLV) and their resistance to antibacterial agents is especially relevant in modern conditions, expands the search for new approaches to pathogens, improves treatment and reduces mortality from this pathology. The purpose of the study - to determine the etiological structure, sensitivity to antibiotics of the leading pathogens of the infectious process of the respiratory system in newborns who were on mechanical ventilation. Materials and methods. In total, the species composition of the leading microorganisms that colonized the airways of 180 newborns treated in the Neonatal Intensive Care Unit (VAITN) of Vinnytsia Regional Children’s Clinical Hospital (VRCCH) was studied in 2020. A total of 285 isolates of microorganisms were isolated. 62 patients who underwent mechanical ventilation were involved in a prospective microbiological study, 86 clinical strains of microorganisms were isolated. The susceptibility of microorganisms to 30 antibacterial agents was determined according to the generally accepted method (order of the Ministry of Health of Ukraine №167; recommendations). Research results. The etiological significance of opportunistic pathogens (Enterobacter cloacae - 29%, Staphylococcus aureus - 24.4%, Pseudomonas aeruginosa - 18.6%, Candida albicans) was proved in patients who were on mechanical ventilation in VAITN VRCCH in 2020 for pneumonia. Clinical strains of S. aureus are sensitive to vancomycin, oxacillin and clindamycin. Conclusions. Pathogens of the respiratory process in newborns who have been on mechanical ventilation, are resistant to a number of antibiotic drugs (cefepime, gentamicin amikacin, piperacillin).

ASSESSMENT OF RISK FACTORS FOR DEATH OF PATIENTS WITH COVID-19 REQUIRING MECHANICAL LUNG VENTILATION

Relevance: with the increasing incidence of COVID-19, it is clear that early detection of the risk of death in patients on mechanical lung ventilation can help ensure proper treatment planning and optimize health resources.Objectives of our study was to identify predictors of the risk of death in patients with COVID-19 who required mechanical ventilation.Material and methods: research design – retrospective, observational, multicenter. Inclusion criteria: clinical, laboratory, and radiological criteria for severe viral pneumonia. Exclusion criteria: death in the first 12 hours of hospitalization. End points: need for mechanical ventilation and death. One hundred and sixty-eight patients met the inclusion criteria. The number of patients who were given a ventilator was 69 (41,1%), 47 (68,1%) of them died. Risk factors were determined by calculating the odds ratio with a 95% confidence interval. The discriminative ability of factors was evaluated using ROC analysis with the calculation of the area under the curve (AUC ROC).Results: the most significant risk factors for require of mechanical ventilation in patients with COVID-19 were a large extent of changes in the lung parenchyma, more than 5 points of the SOFA scale and blood D-dimers >3000 ng/ml. Deceased patients were more likely to be men and initially had statistically significantly higher points of the SOFA scale, neutrophil-to-lymphocyte ratio, and blood interleukin 6 (IL-6) count >186 ng/ml. However, the discriminative ability of these risk factors was moderate (AUC ROC from 0.69 to 0.76). In deceased patients, there were no changes in the PaO2/FiO2 ratio, blood D-dimer count, and SOFA severity assessment in the first three days of intensive care.Conclusion: Predictors of the development of an unfavorable outcome of the disease with moderate discriminative ability in patients with severe COVID-19 on mechanical ventilation are an increased score on the SOFA scale, an increase of the neutrophil-lymphocyte ratio, high levels of D-dimers and IL-6 in the blood.

Modern strategies of adaptation to the respiratory support as a way to reduce self-induced lung injury (SILI)

Background. The success of respiratory support depends on the effectiveness of improving gas exchange, reducing lung damage, and adaptation of the respirator. Reduction of lung damage has previously been reported in the context of ventilator-associated injury: barotrauma in case of high plateau pressure and driving pressure, volume trauma in case of large tidal volume, atelectasis trauma due to the cyclic collapse of lungs on exhalation and opening on inspiration. Objective. To describe the features of lung damage during mechanical lung ventilation (MLV) and the possibility of its prevention. Materials and methods. Analysis of literature sources on this topic. Results and discussion. The main causes of “air hunger” breathing type and shortness of breath include hypoxia, acidosis, increased anatomical and functional dead space, psychomotor agitation and fear. Metabolic acidosis is compensated by hyperventilation and respiratory alkalosis, but it is treated by improving oxygenation. High-flow oxygenation helps to leach CO2 from the dead space. Psychomotor agitation and pain aggravate shortness of breath, so all components of these processes should be influenced by effective analgesia, providing the patient with a comfortable body position (especially obese people), ensuring the absence of hunger and thirst, creating conditions for night sleep and more. If all these measures are taken, but the patient’s agitation is maintained, sedation should be considered. Propofol and dexmedetomidine are increasingly used for short-term sedation. Approaches to sedation have been changing abroad in recent years. First, non-pharmacological methods are used and only then – pharmacological ones. First of all, it is recommended to achieve analgesia, and then – sedation. It is advisable to maintain moderate sedation (from 0 to -2 on the RASS scale) and avoid deep sedation (from -3 to -5 points on the RASS scale). Sedation should be stopped each morning for the wake-up test and the respirator quitting test. To improve the immediate consequences of treatment (duration of MLV and stay in the intensive care unit), it is advisable to minimize the use of benzodiazepines and prefer propofol or dexmedetomidine. The depth of sedation should be constantly monitored, however, even experienced physicians may not always be able to detect asynchrony and excessive sedation. Asynchrony is associated with the increased mortality and prolonged weaning. To assess the intensity of the patient’s respiratory effort, the index of rapid shallow breathing, the maximum vacuum in the airways and the pressure in 0.1 second after the start of the breathing attempt are used. If the latter exceeds 3.5 cm H2O, it indicates the excessive respiratory effort of the patient (Telias I. et al., 2020). Conclusions. 1. The term “self-induced lung injury” has become widely used in the practice of anesthesiologists. 2. The need for respiratory support is determined primarily by the patient’s breathing efforts. 3. The ability to timely identify and respond to asynchrony helps to avoid self-induced lung damage.

Patients of risk groups in the perioperative period: the review of modern guidelines

Background. According to the Decree of the Ministry of Health of Ukraine № 275 issued on 11.09.2018, there is a list of measures to ensure surgical safety and patient’s safety. These measures can be divided into those that should be performed 1) before anesthesia; 2) before skin dissection; 3) before the patient leaves the operating room. Perioperative medicine (POM) is a patient-centered and interdisciplinary perioperative care for surgical patients. Objective. To describe the current recommendations for POM. Materials and methods. Review of available guidance documents. Results and discussion. The pathophysiology of postoperative complications (infectious processes, intestinal paralysis, respiratory failure, kidney damage, etc.) includes the following factors: triggers (anxiety, pain, surgical trauma), patient factors (age, comorbid conditions), the consequences of general operative stress (autonomous system imbalance, inflammation, coagulopathy, metabolic imbalance). Clinical evaluation or biomarkers should be used to identify high-risk patients in the perioperative period. Measures to improve postoperative rehabilitation should be carried out in the pre-, intra- and postoperative period. Thus, in the preoperative period it is necessary to examine the patient, to provide the carbohydrate load 2 hours before the intervention, to conduct antibiotic prophylaxis, to correct or stabilize the comorbid diseases (especially cardiovascular and renal diseases, diabetes, anemia). In the intraoperative period it is necessary to maintain normovolemia and normothermia, to use protective mechanical lung ventilation, to limit the use of opioids, to perform extubation immediately after the intervention. In the postoperative period early activation, early enteral nutrition and early removal of drainages and catheters should be used. The key components of POM include the identification of low-risk patients in order to save resources, the identification of high-risk patients with the possible use of alternative management strategies, and the frequent risk reassessment. The main components of the success of anesthesia include preoperative assessment of the patient’s somatic status and risk, use of controlled hypnotics and effective and predictable muscle relaxant, use of analgesics that break down quickly and have no ability to accumulate, control of the hemodynamics stability, blood gases and acid-base balance. To prevent the perioperative myocardial ischemia, it is advisable to use esmolol – a cardioselective β-blocker of ultrashort action. Preoperative anxiety, intubation and extubation, surgical manipulations lead to the excessive adrenergic response, which justifies the use of β-blockers. The pharmacological effects of esmolol (Biblok, “Yuria-Pharm”) include the reduction of myocardial oxygen consumption, increase of the diastole duration, limitation of the free radicals’ production, control of the activity of metalloproteinases, and the reduction of inflammation around atherosclerotic plaques. In addition, esmolol (Biblok) is able to reduce intra- and postoperative use of opioids, and therefore its use as a component of multimodal total intravenous anesthesia has been proposed. Preoperative administration of esmolol may also be an effective and safe method of myocardial protection in patients undergoing cardiac surgery. β-blockers are well tolerated in patients with acute hypovolaemia during anesthesia, however, episodes of hypercapnia should be avoided during their use. Conclusions. 1. For the optimal POM, the individual risk of perioperative complications should be determined. 2. POM includes a number of pre-, intra- and postoperative measures. 3. The use of ultrashort-acting β-blocker esmolol prevents intraoperative myocardial ischemia, has antioxidant and anti-inflammatory effects, reduces the need for opioids.

Four D concept of fluid therapy

Background. D (definition): the daily fluid balance is the sum of all the amounts of consumed and excreted fluid. Assessment of fluid accumulation per day allows to detect fluid overload. At early stages (the first 1-3 hours) of infusion therapy (IT) targeted administration of necessary drugs should be carried out. The volume of infusion is 10-30 ml/kg of body weight. Subsequently, during the first week of treatment in the intensive care unit (ICU) it is necessary to achieve two consecutive days with a negative fluid balance. In the later stages of treatment, active fluid removal is performed with diuretics or renal replacement therapy. The concept of four D IT actually includes seven D: definitions, diagnosis, drug, dose, duration, de-escalation, discharge. Objective. To describe the basic principles of modern IT. Materials and methods. Analysis of literature sources on this topic. Results and discussion. The improvement and proper application of the existing IT techniques and drugs is an important step in improving treatment outcomes. Frequent mistakes include too long IT, wrong choice of drug or dose. Hypervolemia as a result of excessive infusions is even more dangerous than hypovolemia because it can lead to the interstitial edema. To address the issue of IT, it is advisable to focus on preload – the degree of stretching of a cardiomyocyte before contraction. Echocardiographic indicators of preload include end-diastolic volume and end-diastolic pressure of left ventricle. When choosing a solution for IT, it is necessary to take into account its tonicity and osmolality, as it depends on whether the solution will remain in the vessels or enter the intercellular space. Choosing an optimal IT, one should take into account the choice of solution or combination of solutions, the optimal time and duration of its introduction, the pathological condition of the patient. Thus, in case of trauma, blood and crystalloids are prescribed, in case of sepsis – crystalloids, and later albumin, in the perioperative period – hydroxyethyl starch (HES) and crystalloids. When choosing an antibiotic for IT, you should pay attention to the recent history of hospitalizations, length of stay in a medical institution (term >5 days increases the likelihood that the patient’s infection is nosocomial), comorbid conditions, history of steroid use, previous antibiotic therapy (ABT), duration of mechanical lung ventilation. Dose is another important aspect of IT. In ABT, too high dose can be toxic to the macroorganism, and too low dose can be ineffective and cause bacterial resistance. When selecting the dose of the antibiotic, attention should be paid to the distribution volume of the drug, the liver and kidney function and the peculiarities of the drug clearance, albumin level, ability to penetrate into tissues, minimal inhibitory concentration. In turn, when selecting the dose of solutions for IT, it is necessary to take into account the volume of distribution, type of solution, osmolality, tonicity, and the condition of renal function. In most cases, the maintenance volume of solutions is 1 ml/kg/h (25 ml/kg/day), and the volume required for resuscitation is 30 ml/kg in the first 3 hours, the fluid bolus is 4 ml/kg / 15 min. Some fluids (HES) are toxic for the kidneys (maximum dose is 30 ml/kg/h). However, lack of control over shock is also not beneficial for the kidneys, so the benefit/risk balance should always be assessed. Static surrogate parameters of preload (central venous pressure, average arterial pressure, urine volume, volumetric indicators) are often used for IT titration. However, it is more appropriate to use dynamic functional parameters of hemodynamics: pulse pressure variations, stroke volume variations, passive leg raise test. The duration of optimal IT has not yet been established, although there is evidence of a downward trend. After eliminating shock and normalizing blood lactate, it is advisable to stop IT. It is advisable to reduce the duration of ABT to a minimum and to remember that the goal is to treat the infection, not to treat fever, infiltrates or elevated C-reactive protein. Therefore, ABT should be discontinued when the signs and symptoms of active infection disappear. In future, biomarkers (procalcitonin or cystatin C, citrulline, respectively) will be used to determine the need to discontinue ABT or IT. Timely de-escalation of IT is no less important than its timely start. It is advisable to follow the ROSE concept (R – resuscitation; O – organ support; S – stabilization; E – evacuation). Conclusions. 1. The concept of four D IT includes definitions, diagnosis, drug, dose, duration, de-escalation, and discharge. 2. For IT titration it is reasonable to use dynamic functional parameters of hemodynamics: pulse pressure and shock volume variation, passive leg raise test. 3. It is advisable to follow the concept of ROSE.

Features of infusion therapy in patients of the therapeutic profile during the COVID-19 pandemic

Background. An analysis of 44,415 Chinese patients with COVID-19 found a critical condition defined as severe hypoxemia and/or other organ damage or shock in 2087 (5 %) (Wu Z. et al., 2020). In inpatients, the frequency of shock is likely to be higher and can reach 20-35 % (Yang X. et al., 2020). Risk factors for shock and unstable hemodynamics in COVID-19 are older age, the presence of comorbidities, lymphopenia, higher levels of D-dimer. Objective. To describe the features of infusion therapy (IT) in patients of the therapeutic profile during the COVID-19 pandemic. Materials and methods. Analysis of literature sources on this topic. Results and discussion. The Surviving Sepsis guidelines state that crystalloids, not colloids, should be used for acute resuscitation of patients with COVID-19. The recommendation is based on indirect data on critically ill patients (Cochrane review by S.R. Lewis et al.). It is advisable to use buffered/balanced crystalloids. Such solutions include Reosorbilact (“Yuria-Pharm”), which has such effects as hemodynamic, detoxifying, microcirculatory, and diuretic. Reosorbilact corrects fluid-electrolyte and acid-base balance, improves the rheological properties of blood, reduces the need for sympathomimetics. The use of hydroxyethyl starch, gelatin and albumin in COVID-19 is not recommended. In the treatment of coronavirus pneumonia, IT is significantly limited due to the risk of fluid overload and the development of pulmonary edema. The use of conservative rather than liberal IT strategy is recommended, including for patients with acute respiratory distress syndrome (ARDS) who are on mechanical lung ventilation (MLV). In severe pneumonia, the use of vasopressors is recommended. Noradrenaline is used as a first-line vasoactive agent. The use of hyperosmolar solutions reduces the volume of infusion required to maintain stable hemodynamics in patients with severe sepsis. Hypertonic solutions also reduce the length of MLV in patients with shock. For adults with COVID-19 and refractory shock, low-dose corticosteroid therapy (bolus doses or infusion of prednisolone at a dose of 200 mg per day) has been suggested. Systemic corticosteroids should also be used in ARDS. In the absence of the latter, routine use of systemic corticosteroids is not recommended. Empirical use of antibacterial drugs is advisable in patients on ARDS, as superinfections in this group of patients are extremely common. The advantages of levofloxacin (Leflocin 750, “Yuria-Pharm”) include high efficiency against all respiratory pathogens, good penetration into the inflammatory focus, and active influence on microorganisms in biofilms. Leflocin 750 mg is administered once a day intravenously for 5-14 days. It is recommended to use paracetamol (Infulgan, “Yuria-Pharm”) to control fever. The advantages of the latter are lowering the temperature within 30 minutes after administration, antipyretic effect lasting up to 6 hours, safety for patients with gastrointestinal and hematological diseases. Infulgan is administered intravenously (1 g up to 4 times a day). Conclusions. 1. Balanced IT holds a leading position in the treatment of severe coronavirus infection. 2. Preference should be given to balanced solutions of crystalloids. 3. The IT program should be designed taking into account the quality of life and creating maximum patient comfort.

Vitamin D for prevention of sternotomy healing complications: REINFORCE-D trial

Background Most cardiac surgery patients undergo median sternotomy during open heart surgery. Sternotomy healing is an arduous, very complex, and multifactorial process dependent on many independent factors affecting the sternum and the surrounding soft tissues. Complication rates for median sternotomy range from 0.5 to 5%; however, mortality rates from complications are very variable at 7–80%. Low calcidiol concentration below 80 nmol/L results in calcium absorptive impairment and carries a risk of bone loss, which is considered as a risk factor in the sternotomy healing process. The primary objective of this clinical trial is to compare the incidence of all postoperative sternotomy healing complications in two parallel patient groups administered cholecalciferol or placebo. The secondary objectives are focused on general patient recovery process: sternal bone healing grade at the end of the trial, length of hospitalization, number of days spent in the ICU, number of days spent on mechanical lung ventilation, and number of hospital readmissions for sternotomy complications. Methods This clinical trial is conducted as monocentric, randomized, double-blind, placebo-controlled, with planned enrollment of 600 patients over 4 years, approximately 300 in the placebo arm and 300 in the treatment arm. Males and females from 18 to 95 years of age who fulfill the indication criteria for undergoing cardiac surgery with median sternotomy can be included in this clinical trial, if they meet the eligibility criteria. Discussion REINFORCE-D is the first monocentric trial dividing patients into groups based on serum calcidiol levels, and with dosing based on serum calcidiol levels. This trial may help to open up a wider range of postoperative healing issues. Trial registration EU Clinical Trials Register, EUDRA CT No: 2016-002606-39. Registered on September 8, 2016.

CHANGES IN OXYGENATION IN CHILDREN WITH RESPIRATORY FAILURE

Acute respiratory failure is a component of the multiorgan dysfunction syndrome and a common cause of death among the children treated in intensive care units. Readiness to wean a patient from a mechanical ventilation is determined by a set of indices, including the data on the level of hypoxemia and its ability to regress under the influence of oxygen therapy. The indices such as the paO2/FiO2 and SpO2/FiO2 ratios are valid for determining the severity of hypoxemia. In order to study the dynamics of changes in SpO2/FiO2, paO2/FiO2, oxygenation index and the one of frequent shallow breathing in the children with acute respiratory failure as well as to substantiate the criteria for their readiness to wean from pulmonary ventilation, a prospective, observational cohort investigation in patients aged from 1 month to 18 years was performed. The patients of group I received pulmonary−protective strategy of mechanical lung ventilation, II − in addition to it received the diaphragm−protective strategy. The ratios of SpO2/FiO2 and paO2/FiO2, oxygenation index and frequent shallow respiration index were calculated. Weaning was considered successful if the patient did not require a respiratory therapy after extubation for the next 48 hours. The primary endpoint of the assessment was the duration of weaning from mechanical ventilation, the secondary ones were the SpO2 / FiO2, paO2 / FiO2, oxygenation index, the one of frequent shallow breathing. Significant differences in SpO2 / FiO2 and paO2 / FiO2 indices were found on days 5 and 9 of the study. It was found that at paO2 / FiO2 values less than 200 and SpO2 / FiO2 less than 265 the prognosis of weaning is unfavorable. Key words: children, oxygenation, mechanical ventilation.

Dynamics of Serum Cytokines During Resection Surgery for Malignant Neoplasms in the Lungs

Purpose — to carry out a comparative assessment of inflammation based on evaluation of intraoperative and early postoperative dynamics of blood serum cytokines in pulmonary malignant neoplasm patients in different anesthesia and analgesia settings.Material and methods. 24 patients of 45 to 50 years of age divided into 2 groups were examined. All patients suffered from verified new onset malignant neoplasms without true signs of metastases. Tumor differentiation by morphology was not undertaken since that was beyond the study design. Patients did not receive radio- or chemotherapy. In Group I (the main group, n=12), a multimodal combined anesthesia [1] followed by extended postoperative epidural analgesia was applied. In Group II (the comparison group, n=12), a combined general anesthesia including mechanical lung ventilation followed by morphine analgesia was used. 4 study points were determined: prior to induction, and one, 12, and 24 hours post-surgery.Results. 12 hours after surgery completion, the concentration of TNFα in the main group was lesser by 57.1% vs. the comparison group; by the end of the first 24 hours, it fell down by 64.3%. Within the same period, in both groups IL-6 turned out to be significantly higher than the upper reference limit. By the end of the first 24 hours, IL-6 tend to decrease in both groups; however, in the comparison group, this parameter was 15% higher than in the main group. Serum IL-10 was within the reference range in both groups. One hour after surgery, concentrationof IL-10 was exponentially growing in both groups and exceeded multifold the upper reference limit, whereas the content of IL-10 in the main group remained reliably higher: the difference amounted to 35.6% percent.Conclusion. During the postoperative period, patients undergone lung resection displayed significant changes in cytokines concentrations demonstrating an inflammation reaction. Inflammation was significant in patients who received epidural analgesia as evidenced by an altered content of anti-inflammatory cytokines.

Proportional assist ventilation

The idea of proportional assist ventilation, in which the patient himself sets the respiratory pattern — the frequency and depth of breathing — was suggested in 1992, but has not yet found widespread practical application. One of the possible reasons for this is the complex algorithm of regime adjustment on first-generation respiratory devices. Over time, the accumulated body of information on the early damage of the diaphragm because of its atrophy in patients on respiratory support formed the basis of the awareness of the importance of maintaining the physiological state of the diaphragm during artificial lung ventilation and led to the emergence of the term “myotrauma”.At the turn the 21st century, the idea of the maximum possible preservation of spontaneous breathing of the patient during mechanical lung ventilation realized in the formation of the concept of “diaphragm-protective ventilation”. The need for further development of assisted lung ventilation technologies designed to reduce the risk of diaphragm damage, the frequency of asynchrony in the pair “respirator-patient”, and to facilitate the process of weaning of the patient from the artificial lung ventilation became apparent. This article, based on scientific literature and own clinical experience of using proportional ventilation, describes the peculiarities of regime adjustment on different respirators, places the accents necessary for successful practical use of proportional lung ventilation. Describes key conditions for its use, advantages and limitations.