ImportanceMeropenem is a widely prescribed β-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes.ObjectiveTo determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis.Design, Setting, and ParticipantsA double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022.InterventionsPatients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304).Main Outcomes and MeasuresThe primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events.ResultsAll 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients).Conclusions and RelevanceIn critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28.Trial RegistrationClinicalTrials.gov Identifier: NCT03452839

Федеральный дистанционный консультативный центр анестезиологии и реаниматологии на базе Первого МГМУ им. И.М. Сеченова

Цель. Изучение летальности и факторов риска смерти больных с COVID-19, госпитализированных для респираторной поддержки в отделения реанимации и интенсивной терапии (ОРИТ) лечебных учреждений Российской Федерации. Материал и методы. Ретроспективное исследование было выполнено в Федеральном дистанционном консультативном центре анестезиологии и реаниматологии для взрослых пациентов с COVID-19 на базе Первого МГМУ им. И.М. Сеченова. В исследование включали всех пациентов с известными исходами (смерть от любых причин или выздоровление) SARS-CoV-2 пневмонии, осложнившейся острым респираторным дистресс синдромом (ОРДС), которые были проконсультированы с 16 марта по 3 мая 2020 г. Факторы риска смерти анализировали с помощью многофакторной регрессионной модели Кокса. Результаты. В исследование были включены 1522 пациента, 864 (56,8%) мужчины и 658 (43,2%) женщин. Медиана возраста-62 года. 922 (60,6%) больных находились в ОРИТ стационаров Москвы и Московской области, 600 (39,4%)-лечебных учреждений в 70 регионах Российской Федерации. У 995 (65,4%) больных диагноз SARS-CoV-2 инфекции был подтвержден с помощью ПЦР. Умерли 995 (65,4%) пациентов, выжили 527 (34,6%). Основными причинами смерти были ОРДС (93,2%), сер

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Background Data on the lung respiratory mechanics and gas exchange in the time course of COVID-19-associated respiratory failure is limited. This study aimed to explore respiratory mechanics and gas exchange, the lung recruitability and risk of overdistension during the time course of mechanical ventilation. Methods This was a prospective observational study in critically ill mechanically ventilated patients (n = 116) with COVID-19 admitted into Intensive Care Units of Sechenov University. The primary endpoints were: «optimum» positive end-expiratory pressure (PEEP) level balanced between the lowest driving pressure and the highest SpO2 and number of patients with recruitable lung on Days 1 and 7 of mechanical ventilation. We measured driving pressure at different levels of PEEP (14, 12, 10 and 8 cmH2O) with preset tidal volume, and with the increase of tidal volume by 100 ml and 200 ml at preset PEEP level, and calculated static respiratory system compliance (CRS), PaO2/FiO2, alveolar dead space and ventilatory ratio on Days 1, 3, 5, 7, 10, 14 and 21. Results The «optimum» PEEP levels on Day 1 were 11.0 (10.0–12.8) cmH2O and 10.0 (9.0–12.0) cmH2O on Day 7. Positive response to recruitment was observed on Day 1 in 27.6% and on Day 7 in 9.2% of patients. PEEP increase from 10 to 14 cmH2O and VT increase by 100 and 200 ml led to a significant decrease in CRS from Day 1 to Day 14 (p < 0.05). Ventilatory ratio was 2.2 (1.7–2,7) in non-survivors and in 1.9 (1.6–2.6) survivors on Day 1 and decreased on Day 7 in survivors only (p < 0.01). PaO2/FiO2 was 105.5 (76.2–141.7) mmHg in non-survivors on Day 1 and 136.6 (106.7–160.8) in survivors (p = 0.002). In survivors, PaO2/FiO2 rose on Day 3 (p = 0.008) and then between Days 7 and 10 (p = 0.046). Conclusion Lung recruitability was low in COVID-19 and decreased during the course of the disease, but lung overdistension occurred at «intermediate» PEEP and VT levels. In survivors gas exchange improvements after Day 7 mismatched CRS. Trial registration ClinicalTrials.gov, NCT04445961. Registered 24 June 2020—Retrospectively registered.

Aim. In a retrospective study, we evaluated factors associated with the early development of septic shock in patients with severe COVID-19. Materials and methods. We collected medical records of the intensive care unit patients submitted by the local COVID-19 hospitals across Russia to the Federal Center for the Critical Care at the Sechenov First Moscow State Medical University (Sechenov University). Septic shock in crticially ill patients requiring mechanical ventilation was defined as a need in vasopressors to maintain blood pressure. Results. We studied 1078 patients with severe COVID-19 who were admitted to the intensive care units for respiratory support. There were 611 males and 467 females. The mean age was 61.013.7 years. Five hundred twenty five medical records (48.7%) were received from the Moscow hospitals, 159 (14.7%) from the Moscow region, and 394 (36.5%) from the hospitals located in 58 regions of the Russian Federation. In 613 (56.9%) patients, diagnosis of SARS-CoV-2 infection was confirmed by PCR, and in the other cases it was established on the basis of the clinical picture and the results of the chest CT scan. Septic shock developed in 214 (19.9%) of 1078 patients. In the logistic regression model, the risk of septic shock in patients older than 50 years was higher than in patients of a younger age (OR 2.34; 95% CI 1.533.67; p0.0001). In patients with more severe SARS-CoV-2 infection, there was an increase in the prevalence of cardiovascular diseases, including coronary heart disease and atrial fibrillation, type 2 diabetes and malignant tumors. The risk of septic shock in patients with three or more concomitant diseases was higher than in patients without any concomitant chronic diseases (OR 1.76; 95% CI 1.762.70). Conclusion. The risk of septic shock in patients with acute respiratory distress syndrome induced by SARS-CoV-2 is higher in patients older than 50 years with concomitant diseases, although a severe course of the disease is also possible in younger patients without any concomitant disorders.

Currently, there is no uniform respiratory support strategy during cardiopulmonary bypass (CPB) in cardiac anesthesiology.The aim of the study was to examine possible variants of respiratory support during CPB and determine the most effective technique capable to reduce the incidence of postoperative pulmonary complications.Material and methods. Ninety cardiac surgery patients were enrolled in the pilot study and divided into groups (CPAP, VC, and apnea). In the CPAP group, positive airway pressure of + 5 cm H2O was maintained during CPB. The VC group patients underwent mechanical ventilation during CPB with a reduced tidal volume of 3 mL/kg, respiratory rate of 6/min, and REER of + 5 cm H2O. In the apnea group, patients received no respiratory support (non-rebreathing system).Results. In both the apnea and CPAP (constant positive airway pressure) group, there was a decrease in oxygenation index (OI) at the end of the CPB compared with baseline values. In the apnea group, the OI dropped from 316.31±81.76 to 230.10±102.48, while in the CPAP group it decreased from 319.37±80.01 to 223.17±152.36 (P<0.001). No significant changes in this parameter were observed in the VC group. The frequency of recruitment maneuvers after CPB to correct the impaired respiratory oxygenation was maximal in patients from apnea group (22 cases (73%) versus 13 cases (43%) in the CPAP group and 5 cases (16%) in the VC group) (P<0.001). Frequency of pulmonary atelectasis on chest radiology in postoperative period was 47, 37, 10% in apnea, CPAP, and VC groups, respectively, and the difference was also significant (P=0.006).Conclusion. Low-volume ventilation is the preferable method of respiratory support in cardiac surgery patients during CPB.

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