ABSTRACT
Background: The efficacy and safety of awake prone positioning (APP) in hypoxemic patients with coronavirus disease 2019 (COVID-19) is unclear. Aim(s): To evaluate the efficacy and safety of APP in non-intubated adults with COVID-19. Method(s): We performed a pragmatic, international, randomized trial at 21 centers in Canada, Saudi Arabia, Kuwait, and the United States between May 19, 2020, and May 18, 2021. Eligible patients were hospitalized adults with COVID-19 requiring >40% oxygen. Patients were randomized to APP (n=205) or usual care (n=195). The primary outcome was intubation by day 30. Secondary outcomes included mortality at 60 days, ventilation-free days at 30 days, intensive care unit (ICU) and hospital-free days at 60 days, adverse events, and serious adverse events. Result(s): Patients in the APP group proned for a median of 4.8 hours per day (IQR 1.8 to 8.0) in the first 4 days. By day 30, 70/205 patients (34.1%) in the APP group and 79/195 (40.5%) in the control group were intubated (hazard ratio [HR] 0.81;95% confidence interval [CI] 0.59 to 1.12). APP did not reduce mortality at 60 days (HR 0.93;95% CI 0.62 to 1.40) and had no effect on days alive invasively or noninvasively ventilated at 30 days, or days out of ICU or hospital at 60 days. There were no serious adverse events in either group. A prespecified subgroup analysis suggested that APP reduced intubation among patients with SpO2:FiO2 >150 (HR of 0.44, 95% CI 0.23 to 0.87) but not among patients with SpO2:FiO2 <150 (HR 1.02;95% CI 0.70 to 1.48;P-interaction= 0.03). Conclusion(s): APP did not significantly reduce intubation at 30 days or mortality at 60 days overall, but may be effective in patients with SpO2:FiO2 >150.
ABSTRACT
Background: Although commonly seen as a respiratory causing disease, COVID-19 is associated with increased coagulopathy and thrombus formation. Venovenous extracorporeal membrane oxygenation (VV-ECMO), a rescue therapy for severe acute respiratory distress syndrome (ARDS) usually requires anticoagulation. We present three patients with suspected oxygenator thrombosis that were successfully treated with a protocolized tissue plasminogen activator (Alteplase). Case Presentation: All three cases were male patients, with a median age of 42, that tested positive for SARS-CoV-2 requiring mechanical ventilation and subsequently VV-ECMO (Maquet Cardiohelp HLS HIT 7.0, Getinge, Sweden) for severe ARDS. In all patients, heparin infusion was the anticoagulation of choice. During the first 24-48 hours of starting ECMO, transmembrane pressure (delta-P) elevation started and was sustained in the range 70-100 mmHg. This was associated with a drop in blood flow rate, elevated fibrinogen, fibrinogen degradation products, and hypercoagulable state on rotational thromboelastometry (ROTEM, TEM Ltd, Germany), raising the possibility of oxygenator thrombosis. After determining low risk of bleeding, Alteplase was administered following the K-ECLS protocol, mitigating the need to change the ECMO circuit. Two patients were successfully decannulated and discharged home in good condition. Whilst, one of the patients remains on ECMO. Conclusions: Protocolized t-PA for ECMO oxygenators with suspected thrombosis is feasible and cost-effective in mitigating circuit change for patients on VV-ECMO for ARDS due to COVID-19. Such protocol might be generalizable to all ECMO patients who have low risk of bleeding. To our knowledge, this is the first case series of such therapy and protocol.