Mortality of COVID-19 Patients Requiring Extracorporeal Membrane Oxygenation During the Three Epidemic Waves.

Clinical presentation and mortality of patients treated with extracorporeal membrane oxygenation (ECMO) for COVID-19 acute respiratory distress syndrome (CARDS) were different during the French epidemic waves. The management of COVID-19 patients evolved through waves as much as knowledge on that new viral disease progressed. We aimed to compare the mortality rate through the first three waves of CARDS patients on ECMO and identify associated risk factors. Fifty-four consecutive ECMO for CARDS hospitalized at Amiens University Hospital during the three waves were included. Patients were divided into three groups according to their hospitalization date. Clinical characteristics and outcomes were compared between groups. Pre-ECMO risk factors predicting 90 day mortality were evaluated using multivariate Cox regression. Among 54 ECMO (median age of 61[48-65] years), 26% were hospitalized during the first wave (n = 14/54), 26% (n = 14/54) during the second wave, and 48% (n = 26/54) during the third wave. Time from first symptoms to ECMO was higher during the second wave than the first wave. (17 [12-23] days vs. 11 [9-15]; p < 0.05). Ninety day mortality was higher during the second wave (85% vs. 43%; p < 0.05) but less during the third wave (38% vs. 85%; P < 0.05). Respiratory ECMO survival prediction score and time from symptoms onset to ECMO (HR 1.12; 95% confidence interval [CI]: 1.05-1.20; p < 0.001) were independent factors of mortality. After adjustment, time from symptoms onset to ECMO was an independent factor of 90 day mortality. Changes in CARDS management from first to second wave-induced a later ECMO cannulation from symptoms onset with higher mortality during that wave. The duration of COVID-19 disease progression could be selection criteria for initiating ECMO.

Almitrine for COVID-19 critically ill patients - a vascular therapy for a pulmonary vascular disease: Three case reports.

BACKGROUND: Several reports with clinical, histological and imaging data have observed the involvement of lung vascular function to explain the severe hypoxemia in coronavirus disease 2019 (COVID-19) patients. It has been hypothesized that an increased pulmonary blood flow associated with an impairment of hypoxic pulmonary vasoconstriction is responsible for an intrapulmonary shunt. COVID-19 may lead to refractory hypoxemia (PaO2/FiO2 ratio below 100 mmHg) despite mechanical ventilation and prone positioning. We hypothesized that the use of a pulmonary vasoconstrictor may help decrease the shunt and thus enhance oxygenation. CASE SUMMARY: We report our experience with three patients with refractory hypoxemia treated with almitrine to enhance oxygenation. Low dose almitrine (Vectarion®; Servier, Suresnes, France) was started at an infusion rate of 4 µg × kg/min on a central line. The PaO2/FiO2 ratio and total respiratory system compliance during almitrine infusion were measured. For the three patients, the PaO2/FiO2 ratio time-course showed a dramatic increase whereas total respiratory system compliance was unchanged. The three patients were discharged from the intensive care unit. The intensive care unit length of stay for patient 1, patient 2 and patient 3 was 30 d, 32 d and 31 d, respectively. Weaning from mechanical ventilation was performed 13 d, 18 d and 15 d after almitrine infusion for patient 1, 2 and 3, respectively. We found no deleterious effects on the right ventricular function, which was similar to previous studies on almitrine safety. CONCLUSION: Almitrine may be effective and safe to enhance oxygenation in coronavirus disease 2019 patients. Further controlled studies are required.

Microvascular flow alterations in critically ill COVID-19 patients: A prospective study.

BACKGROUND: Data on microcirculatory pattern of COVID-19 critically ill patients are scarce. The objective was to compare sublingual microcirculation parameters of critically ill patients according to the severity of the disease. METHODS: The study is a single-center prospective study with critically ill COVID-19 patients admitted in ICU. Sublingual microcirculation was assessed by IDF microscopy within 48 hours of ICU admission. Microcirculatory flow index (MFI), proportion of perfused vessel (PPV), total vessel density (TVD), De Backer score (DBS), perfused vessel density (PVD) and heterogeneity index (HI) were assessed. Patients were divided in 2 groups (severe and critical) according to the World health organization definition. FINDINGS: From 19th of March to 7th of April 2020, 43 patients were included. Fourteen patients (33%) were in the severe group and twenty-nine patients (67%) in the critical group. Patients in the critical group were all mechanically ventilated. The critical group had significantly higher values of MFI, DBS and PVD in comparison to severe group (respectively, PaCO2: 49 [44-45] vs 36 [33-37] mmHg; p<0,0001, MFI: 2.8 ± 0.2 vs 2.5 ± 0.3; p = 0.001, DBS: 12.7 ± 2.6 vs 10.8 ± 2.0 vessels mm-2; p = 0.033, PVD: 12.5 ± 3.0 vs 10.1 ± 2.4 mm.mm-2; p = 0.020). PPV, HI and TVD were similar between groups Correlation was found between microcirculatory parameters and PaCO2 levels. CONCLUSION: Critical COVID-19 patients under mechanical ventilation seem to have higher red blood cell velocity than severe non-ventilated patients.

Abnormal laboratory findings and plasma concentration monitoring of lopinavir and ritonavir in COVID-19.

It is not known whether the adverse events (AEs) associated with the administration of lopinavir and ritonavir (LPV/r) in the treatment of COVID-19 are concentration-dependent. In a retrospective study of 65 patients treated with LPV/r and therapeutic drug monitoring (TDM) for severe forms of COVID-19 (median age: 67; males: 41 [63.1%]), 33 (50.8%) displayed a grade ≥2 increase in plasma levels of hepatobiliary markers, lipase and/or triglycerides. A causal relationship between LPV/r and the AE was suspected in 9 of the 65 patients (13.8%). At 400 mg b.i.d., the plasma trough concentrations of LPV/r were high and showed marked interindividual variability (median [interquartile range]: 16,600 [11,430-20,842] ng/ml for lopinavir and 501 [247-891] ng/ml for ritonavir). The trough lopinavir concentration was negatively correlated with body mass index, while the trough ritonavir concentration was positively correlated with age and negatively correlated with prothrombin activity. However, the occurrence of abnormal laboratory values was not associated with higher trough plasma concentrations of LPV/r. Further studies will be needed to determine the value of TDM in LPV/r-treated patients with COVID-19.

Acute Cor Pulmonale in COVID-19-Related ARDS: Improvement With Almitrine Infusion.

Coronavirus disease-19 (COVID-19)-related severe acute respiratory distress syndrome can lead to acute cor pulmonale. We report a case of acute cor pulmonale secondary to severe COVID-19 acute respiratory distress syndrome diagnosed with transesophageal echocardiography. Almitrine infusion allowed rapid enhancement of right ventricular function as well as improvement in oxygenation. (Level of Difficulty: Intermediate.).