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ObjectTo evaluate the clinical efficacy and safety of α-Lipoic acid (ALA) for critically ill patients with coronavirus disease 2019 (COVID-19).MethodsA randomized, single-blind, group sequential, active-controlled trial was performed at JinYinTan Hospital, Wuhan, China. Between February 2020 and March 2020, 17 patients with critically ill COVID-19 were enrolled in our study. Eligible patients were randomly assigned in a 1:1 ratio to receive either ALA (1200 mg/d, intravenous infusion) once daily plus standard care or standard care plus equal volume saline infusion (placebo) for 7 days. All patients were monitored within the 7 days therapy and followed up to day 30 after therapy. The primary outcome of this study was the Sequential Organ Failure Estimate (SOFA) score, and the secondary outcome was the all-cause mortality within 30 days.ResultNine patients were randomized to placebo group and 8 patients were randomized to ALA group. SOFA score was similar at baseline, increased from 4.3 to 6.0 in the placebo group and increased from 3.8 to 4.0 in the ALA group (P = 0.36) after 7 days. The 30-day all-cause mortality tended to be lower in the ALA group (3/8, 37.5%) compared to that in the placebo group (7/9, 77.8%, P = 0.09).ConclusionIn our study, ALA use is associated with lower SOFA score increase and lower 30-day all-cause mortality as compared with the placebo group. Although the mortality rate was two-folds higher in placebo group than in ALA group, only borderline statistical difference was evidenced due to the limited patient number. Future studies with larger patient cohort are warranted to validate the role of ALA in critically ill patients with COVID-19.Clinical Trial Registrationhttp://www.chictr.org.cn/showproj.aspx?proj=49534.

Background: To find the optimal positive end expiratory pressure (PEEP) in mechanical ventilated patients without Acute Respiratory Distress Syndrome (ARDS), we conducted a Bayesian network meta-analysis and systematic review of randomized controlled trials (RCTs) comparing different level of PEEP based on a novel classification of PEEP level: ZEEP group (PEEP = 0 cm H2O); lower PEEP group (PEEP = 1–6 cm H2O); intermediate PEEP group (PEEP = 7–10 cm H2O); higher PEEP group (PEEP > 10 cm H2O).Result: Twenty eight eligible studies with 2,712 patients were included. There were no significant differences in the duration of mechanical ventilation between higher and intermediate PEEP (MD: 0.020, 95% CI: −0.14, 0.28), higher and lower PEEP (MD: −0.010, 95% CI: −0.23, 0.22), higher PEEP and ZEEP (MD: 0.010, 95% CI: −0.40, 0.22), intermediate and lower PEEP (MD: −0.040, 95% CI: −0.18, 0.040), intermediate PEEP and ZEEP (MD: −0.010, 95% CI: −0.42, 0.10), lower PEEP and ZEEP (MD: 0.020, 95% CI: −0.32, 0.13), respectively. Higher PEEP was associated with significantly higher PaO2/FiO2 ratio(PFR) when compared to ZEEP (MD: 73.24, 95% CI: 11.03, 130.7), and higher incidence of pneumothorax when compared to intermediate PEEP, lower PEEP and ZEEP (OR: 2.91e + 12, 95% CI: 40.3, 1.76e + 39; OR: 1.85e + 12, 95% CI: 29.2, 1.18e + 39; and OR: 1.44e + 12, 95% CI: 16.9, 8.70e + 38, respectively). There was no association between PEEP levels and other secondary outcomes.Conclusion: We identified higher PEEP was associated with significantly higher PFR and higher incidence of pneumothorax. Nonetheless, in terms of other outcomes, no significant differences were detected among four levels of PEEP.Systematic Review Registration: The study had registered on an international prospective register of systematic reviews, PROSPERO, on 09 April 2021, identifier: [CRD42021241745].

Background: Extracorporeal membrane oxygenation (ECMO) is a rapidly evolving therapy for acute lung and/or heart failure. However, the information on the application of ECMO in severe coronavirus disease 2019 (COVID-19) is limited, such as the initiation time. Especially in the period and regions of ECMO instrument shortage, not all the listed patients could be treated with ECMO in time. This study aimed to investigate and clarify the timing of ECMO initiation related to the outcomes of severe patients with COVID-19. The results show that ECMO should be initiated within 24 h after the criteria are met.Methods: In this retrospective, multicenter cohort study, we enrolled all ECMO patients with confirmed COVID-19 at the three hospitals between December 29, 2019 and April 5, 2020. Data on the demographics, clinical presentation, laboratory profile, clinical course, treatments, complications, and outcomes were collected. The primary outcomes were successful ECMO weaning rate and 60-day mortality after ECMO. Successful weaning from ECMO means that the condition of patients improved with adequate oxygenation and gas exchange, as shown by the vital signs, blood gases, and chest X-ray, and the patient was weaned from ECMO for at least 48 h.Results: A total of 31 patients were included in the analysis. The 60-day mortality rate after ECMO was 71%, and the ECMO weaning rate was 26%. Patients were divided into a delayed ECMO group [3 (interquartile range (IQR), 2–5) days] and an early ECMO group [0.5 (IQR, 0–1) days] based on the time between meeting the ECMO criteria and ECMO initiation. In this study, 14 and 17 patients were included in the early and delayed treatment groups, respectively. Early initiation of ECMO was associated with decreased 60-day mortality after ECMO (50 vs. 88%, P = 0.044) and an increased ECMO weaning rate (50 vs. 6%, P = 0.011).Conclusions: In ECMO-supported patients with COVID-19, delayed initiation of ECMO is a risk factor associated with a poorer outcome.Trial Registration: Clinical trial submission: March 19, 2020. Registry name: A medical records-based study for the clinical application of extracorporeal membrane oxygenation in the treatment of severe respiratory failure patients with novel coronavirus pneumonia (COVID-19). Chinese Clinical Trial Registry: https://www.chictr.org.cn/showproj.aspx?proj=51267,identifier:~ChiCTR2000030947.

Background: Patients with coronavirus disease 2019 (COVID-19) may develop severe acute respiratory distress syndrome (ARDS). The aim of the study was to explore the lung recruitability, individualized positive end-expiratory pressure (PEEP), and prone position in COVID-19-associated severe ARDS.Methods: Twenty patients who met the inclusion criteria were studied retrospectively (PaO2/FiO2 68.0 ± 10.3 mmHg). The patients were ventilated under volume-controlled mode with tidal volume of 6 mL/kg predicted body weight. The lung recruitability was assessed via the improvement of PaO2, PaCO2, and static respiratory system compliance (Cstat) from low to high PEEP (5–15 cmH2O). Patients were considered recruitable if two out of three parameters improved. Subsequently, PEEP was titrated according to the best Cstat. The patients were turned to prone position for further 18–20 h.Results: For recruitability assessment, average value of PaO2 was slightly improved at PEEP 15 cmH2O (68.0 ± 10.3 vs. 69.7 ± 7.9 mmHg, baseline vs. PEEP 15 cmH2O; p = 0.31). However, both PaCO2 and Cstat worsened (PaCO2: 72.5 ± 7.1 vs. 75.1 ± 9.0 mmHg; p < 0.01. Cstat: 17.5 ± 3.5 vs. 16.6 ± 3.9 ml/cmH2O; p = 0.05). Only four patients (20%) were considered lung recruitable. Individually titrated PEEP was higher than the baseline PEEP (8.0 ± 2.1 cmH2O vs. 5 cmH2O, p < 0.001). After 18–20 h of prone positioning, investigated parameters were significantly improved compared to the baseline (PaO2: 82.4 ± 15.5 mmHg. PaCO2: 67.2 ± 6.4 mmHg. Cstat: 20.6 ± 4.4 ml/cmH2O. All p < 0.001 vs. baseline).Conclusions: Lung recruitability was very low in COVID-19-associated severe ARDS. Individually titrated PEEP and prone positioning might improve lung mechanics and blood gasses.