Objectives To describe polymyxin B pharmacokinetics in patients receiving veno-venous extracorporeal membrane oxygenation (ECMO) in comparison with critically ill patients without ECMO support and to explore potential covariates that could affect the pharmacokinetics in this group of patients. Patients and methods In 13 critically ill patients on ECMO and in 21 critically ill patients without ECMO support, 6–8 blood samples were collected during 12 h intervals after reaching steady state. Polymyxin B concentration in serum was determined using a previously developed ELISA. Protein binding was assessed by rapid equilibrium dialysis. Results In 13 critically ill patients on ECMO who received polymyxin B, the median area under the concentration–time curve over 12 h (AUC0–12h) was 48.38 mg/h/L for the total drug and 14.08 mg/h/L for the free drug. The unbound fraction was 0.35. Total body clearance was 1.16 L/h. In non-ECMO patients, the median AUC0–12h was 34.7 mg/h/L and the median CL was 1.76 L/h. The volume of distribution was significantly lower in ECMO patients (19.7 versus 30.4 L, respectively). We found a moderate negative correlation between the ECMO blood flow rate and AUC0–12h, a strong negative correlation between SOFA score and polymyxin B clearance and a moderate correlation between polymyxin B clearance and renal function in ECMO patients. Conclusions Currently recommended polymyxin B dosage regimens are sufficient for patients receiving ECMO and no dosage increase is required. In our study, polymyxin B exposure was higher in ECMO patients compared with the control group.

Introduction Defects of platelet functional responses in COVID-19 were reported, but their origin and pathophysiological significance are unclear. The objective of this study was to characterize the thrombocytopathy in COVID-19. Materials and methods Analysis of platelet functional responses to activation by flow cytometry and aggregometry in 46 patients with confirmed COVID-19 of different severity (non-ICU, ICU, and ECMO) over the course of hospitalization alongside with plasma coagulation, inflammatory markers (CRP, fibrinogen, NETosis assays in smears) was performed. Results and conclusions All patients had increased baseline percentage of procoagulant platelets (healthy: 0.9 ± 0.5%; COVID-19: 1.7 ± 0.6%). Patients had decreased agonist-induced platelet GPIb shedding (1.8 ± 0.7 vs 1.25 ± 0.4), P-Selectin exposure (1.51 ± 0.21 vs 1.1 ± 0.3) and aggregation. The values of these parameters among the non-ICU and ICU cohorts differed modestly, while the ECMO cohort differed significantly. Only ECMO patients had pronounced thrombocytopenia. While inflammatory markers improved over time, the observed platelet functional responses changed only moderately. SARS-CoV-2 RNA was found in 8% of blood samples and it did not correlate with platelet counts or responses. All patients had increased NETosis that moderately correlated with platelet dysfunction. High cumulative dosages of LMWH (average > 12,000 IU/day over 5 days) resulted in an improvement in platelet parameters. The observed pattern of platelet refractoriness was reproduced by in vitro pre-treatment of washed platelets with subnanomolar thrombin or perfusion of blood through a collagen-covered flow chamber. We conclude that platelet dysfunction in COVID-19 is consistent with the intravascular-coagulation-induced refractoriness rather than with an inflammation-induced mechanism or a direct activation by the virus.

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The article provides the main statements of the guidelines for the anesthesia and intensive care of patients with the coronavirus disease (COVID-19), developed by the Federation of Anesthesiologists and Reanimatologists of Russia. In the process of developing the recommendations, the publications of the official websites of the Russian Federation, the electronic databases of the RSCI, PubMed, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) were analyzed by the developers independently of each other. The date of the last search query was February 01, 2021. To develop the recommendations for the Guidelines, were used documents directly describing the features of the management of patients with NCI COVID-19 (guidelines - 34; randomized clinical trials and Cochrane Reviews - 13; observational and comparative studies - 107; other documents, notes and comments - 64), and documents describing anesthesia and intensive care in the general population of patients. Compared to the previous 4th version of the guidelines, the recommendations in 8 sections have been corrected; new subsections “Chronic kidney disease”, “Rehabilitation treatment of patients with COVID-19 in the intensive care unit”, “Routing of patients with COVID-19 to the stages of rehabilitation” were created; revised 1 Appendix, additionally developed 7 Appendices; the section “Quality criteria” has been supplemented. The provisions of the current version of the guidelines highlight the specifics of anesthesia, intensive care, rehabilitation, resuscitation measures, manipulation, transportation, prevention of the spread of COVID-19 in the implementation of these activities. Methods of protecting personnel from infection with COVID-19 during manipulations, anesthesia and intensive care are considered. The features of respiratory support, extracorporeal detoxification, extracorporeal membrane oxygenation, thromboprophylaxis, drug interactions are described. The features of management of pregnant women, children of different age groups, patients with concomitant diseases, the principles of the formation of stocks of drugs and consumables are considered.

The article provides the main statements of the guidelines for the anesthesia and intensive care of patients with the coronavirus disease (COVID-19), developed by the Federation of Anesthesiologists and Reanimatologists of Russia. In the process of developing the recommendations, the publications of the official websites of the Russian Federation, the electronic databases of the RSCI, PubMed, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) were analyzed by the developers independently of each other. The date of the last search query was June 29, 2020. To develop the Guidelines for the recommendations, were used documents that directly describing the features of the management of patients with coronavirus disease COVID-19 (guidelines and guidelines - 16; randomized clinical trials and Cochrane Reviews - 8; observational and comparative studies - 77; other documents, notes and comments - 54) and describing anesthetic and resuscitation support in the general population of patients. The provisions of the recommendations highlight the specifics of anesthesia, intensive care, resuscitation, manipulation, and prevention of the spread of COVID-19 in the implementation of these activities. Methods of protecting personnel from infection with COVID-19 during manipulations, anesthesia and intensive care are considered. The features of respiratory support, extracorporeal detoxification, extracorporeal membrane oxygenation, thromboprophylaxis are described. The features of the management of pregnant women, children of different age, patients with concomitant diseases, issues of transportation of patients are considered.