Extracorporeal Membrane Oxygenation Settings Research Articles

A randomized embedded multifactorial adaptive platform for extra corporeal membrane oxygenation (REMAP ECMO) – design and rationale of the left ventricular unloading trial domain

BackgroundThe use of Extracorporeal Membrane Oxygenation (ECMO) remains associated with high rates of complications, weaning failure and mortality which can be partly explained by a knowledge gap on how to properly manage patients on ECMO support. To address relevant patient management issues, we designed a “Randomized Embedded Multifactorial Adaptive Platform (REMAP)” in the setting of ECMO (REMAP ECMO) and a first embedded randomized controlled trial (RCT) investigating the effects of routine early left ventricular (LV) unloading through intra-aortic balloon pumping (IABP). MethodsREMAP ECMO describes a registry-based platform allowing for the embedding of multiple response adaptive RCTs (trial domains) which can perpetually address the effect of relevant patient management issues on ECMO weaning success. A first trial domain studies the effects of LV unloading by means of an IABP as an adjunct to veno-arterial (V-A) ECMO versus V-A ECMO alone on ECMO weaning success at 30 days in adult cardiogenic shock patients admitted to the Intensive Care Unit (ICU). The primary outcome of this trial is “successful weaning from ECMO” being defined as a composite of survival without the need for mechanical circulatory support, heart transplantation, or left ventricular assist device (LVAD) at 30 days after initiation of ECMO. Secondary outcomes include the need for interventional escalation of LV unloading strategy, mechanistic endpoints, survival characteristics until one year after ECMO initiation, and quality of life. Trial data will be analysed using a Bayesian statistical framework. The adaptive design allows for a high degree of flexibility, such as response adaptive randomization and early stopping of the trial for efficacy or futility. The REMAP ECMO LV unloading study is approved by the Medical Ethical Committee of the Erasmus Medical Center and is publicly registered. ConclusionThis REMAP ECMO trial platform enables the efficient roll-out of multiple RCTs on relevant patient management issues. A first embedded trial domain will compare routine LV unloading by means of an IABP as an adjunct to V-A ECMO versus V-A ECMO alone. Trial registrationClinicalTrials.gov, NCT05913622

Complete thrombosis of a bioprosthetic mitral valve and left atrium in a patient on venoarterial extracorporeal membrane oxygenation with favorable outcome

Intra-cardiac thrombosis is a potentially devastating complication of extracorporeal membrane oxygenation (ECMO) mechanical circulatory support. We present here a patient who suffered complete thrombosis of a fresh mitral prosthesis and left atrium in the setting of ECMO with aortic insufficiency who was treated with repeat valve replacement and thrombectomy. To our knowledge, she is the only patient in the reported literature to have survived this complication.

Use of point-of-care ultrasound (POCUS) to monitor neonatal and pediatric extracorporeal life support.

Extracorporeal membrane oxygenation (ECMO) is an invasive life support technique that requires a blood pump, an artificial membrane lung, and vascular cannulae to drain de-oxygenated blood, remove carbon dioxide, oxygenate, and return it to the patient. ECMO is generally used to provide advanced and prolonged cardiopulmonary support in patients with refractory acute cardiac and/or respiratory failure. After its first use in 1975 to manage a severe form of meconium aspiration syndrome with resultant pulmonary hypertension, the following years were dominated by the use of ECMO to manage neonatal respiratory failure and limited to a few centers across the world. In the 1990s, evidence for neonatal respiratory ECMO support increased; however, the number of cases began to decline with the use of newer pharmacologic therapies (e.g., inhaled nitric oxide, exogenous surfactant, and high-frequency oscillatory ventilation). On the contrary, pediatric ECMO sustained steady growth. Combined advances in ECMO technology and bedside medical management have improved general outcomes, although ECMO-related complications remain challenging. Point-of-care ultrasound (POCUS) is an essential tool to monitor all phases of neonatal and pediatric ECMO: evaluation of ECMO candidacy, ultrasound-guided ECMO cannulation, daily evaluation of heart and lung function and brain perfusion, detection and management of major complications, and weaning from ECMO support. Conclusion: Based on these considerations and on the lack of specific guidelines for the use of POCUS in the neonatal and pediatric ECMO setting, the aim of this paper is to provide a systematic overview for the application of POCUS during ECMO support in these populations. What is Known: • Extracorporeal membrane oxygenation (ECMO) provides advanced cardiopulmonary support for patients with refractory acute cardiac and/or respiratory failure and requires appropriate monitoring. • Point-of-care ultrasound (POCUS) is an accessible and adaptable tool to assess neonatal and pediatric cardiac and/or respiratory failure at bedside. What is New: • In this review, we discussed the use of POCUS to monitor and manage at bedside neonatal and pediatric patients supported with ECMO. • We explored the potential use of POCUS during all phases of ECMO support: pre-ECMO assessment, ECMO candidacy evaluation, daily evaluation of heart, lung and brain function, detection and troubleshooting of major complications, and weaning from ECMO support.

Positive association between arterial blood lactate level before extra-corporeal membrane oxygenation and 30-day mortality in pediatric patients with severe cardiopulmonary failure.

This study aimed to investigate the relationship between blood lactate level and mortality in pediatric patients receiving extracorporeal membrane oxygenation (ECMO) for severe cardiopulmonary failure. A retrospective observational study was conducted on pediatric patients who received ECMO from January 2013 to December 2021 at the Seventh Medical Center of PLA General Hospital. Patient demographic characteristics, arterial blood lactate level prior to ECMO (pre-ECMO), ECMO settings, ECMO duration, and 30-days mortality were retrieved from patients' medical records. The relationships between pre-ECMO blood lactate level and mortality were interpreted using the logistic regression analysis and Kaplan-Meier survival analysis. A total of 160 pediatric patients who had either refractory respiratory failure (n = 89) or circulatory failure (n = 71) and received ECMO were included in this study. In both the respiratory failure and circulatory failure groups, the non-survivors showed a higher mean pre-ECMO arterial blood lactate level than the survivors. In the respiratory failure group, a pre-ECMO lactate concentration at ≥11.6mmol/L had a sensitivity of 51% and a specificity of 82% for predicting mortality. In the circulatory failure group, a pre-ECMO lactate concentration at ≥7.2mmol/L had a sensitivity of 90% and a specificity of 57% for predicting mortality. The Kaplan-Meier survival curves showed that respiratory failure patients with a pre-ECMO lactate level over 11.6mmol/L or circulatory failure patients with a pre-ECMO lactate level over 7.2mmol/L had a higher 30-days mortality rate than those with a lower lactate level. High pre-ECMO arterial blood lactate level serves as an independent risk factor for mortality in pediatric patients who receive ECMO for severe cardiopulmonary failure.

Case of successful treatment of acute respiratory distress syndrome in the parturient woman with systemic lupus erythematosus and cerebral cyst of the third ventricular complicated by posterior reversible encephalopathy syndrome

Pregnancy and the postpartum period provoke an exacerbation of systemic lupus erythematosus (SLE), which requires aggressive cytostatic therapy that can cause life-threatening conditions for the fetus and complications for the mother, one of which is posterior reversible encephalopathy syndrome (PRES- syndrome). The article describes a clinical case of successful treatment of acute respiratory distress syndrome (ARDS) in a 22-year-old woman in labor with high activity of SLE during pregnancy complicated by the development of PRES syndrome. Also, for the first time in the postpartum period, the patient was diagnosed with occlusive periventricular hydrocephalus, a giant cyst of the third ventricle. An emergency endoscopic cyst ventriculocisternostomy was performed. In the future, the development of severe ARDS against the background of sepsis, which required the setting of extracorporeal membrane oxygenation (ECMO). A multidisciplinary approach and timely therapy saved the life of a young mother.

Is it time to switch to bivalirudin for ECMO anticoagulation?

For decades, unfractionated heparin (hereafter, heparin) has been the primary anticoagulant used for extracorporeal membrane oxygenation (ECMO) support. More recently, however, bivalirudin, a direct thrombin inhibitor, has emerged as an alternative. This systematic review based on PRISMA guidelines, aims to summarize 16 comparative studies and 8 meta-analysis and review articles published from January, 2011 till May, 2023 which directly compares ECMO courses using heparin versus bivalirudin as the anticoagulant. While this comparison is complicated by the lack of a standardized definition of major bleeding or thrombosis, our overall findings suggest there is no statistical difference between heparin and bivalirudin in incidence of bleeding and thrombosis. That said, some studies found a statistical significance favoring bivalirudin in reducing major bleeding, thrombosis, and the need for transfusions. We also offer essential guidance for appropriately selecting an anticoagulant and monitoring its effect in ECMO settings.

Effects of adding the second drainage cannula in severely hypoxemic patients supported with VV ECMO due to COVID-19-associated ARDS.

Extracorporeal membrane oxygenation (ECMO) is a recognized method of support in patients with severe and refractory acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 infection. While veno-venous (VV) ECMO is the most common type, some patients with severe hypoxemia may require modifications to the ECMO circuit. In this study, we aimed to investigate the effects of adding a second drainage cannula to the circuit in patients with refractory hypoxemia, on their gas exchange, mechanical ventilation, ECMO settings, and clinical outcomes. We conducted an observational retrospective study based on a single-center institutional registry including all consecutive cases of COVID-19 patients requiring ECMO admitted to the Centre of Extracorporeal Therapies in Warsaw between March 1, 2020 and March 1, 2022. We selected patients who had an additional drainage cannula inserted. Changes in ECMO and ventilator settings, blood oxygenation, and hemodynamic parameters, as well as clinical outcomes were assessed. Of 138 VV ECMO patients, 12 (9%) patients met the inclusion criteria. Ten patients (83%) were men, and mean age was 42.2 ± 6.8. An addition of drainage cannula resulted in a significant raise in ECMO blood flow (4.77 ± 0.44 to 5.94 ± 0.81 [L/min]; p = 0.001), and the ratio of ECMO blood flow to ECMO pump rotations per minute (RPM), whereas the raise in ECMO RPM alone was not statistically significant (3432 ± 258 to 3673 ± 340 [1/min]; p = 0.064). We observed a significant drop in ventilator FiO2 and a raise in PaO2 to FiO2 ratio, while blood lactates did not change significantly. Nine patients died in hospital, one was referred to lung transplantation center, two were discharged uneventfully. The use of an additional drainage cannula in severe ARDS associated with COVID-19 allows for an increased ECMO blood flow and improved oxygenation. However, we observed no further improvement in lung-protective ventilation and poor survival.

Sustaining Life versus Altering Life-Saving Drugs: Insights to Explain the Paradoxical Effect of Extracorporeal Membrane Oxygenation on Drugs.

There has been a substantial increase in the use of extracorporeal membrane oxygenation (ECMO) support in critically ill adults. Understanding the complex changes that could affect drugs' pharmacokinetics (PK) and pharmacodynamics (PD) is of suitable need. Therefore, critically ill patients on ECMO represent a challenging clinical situation to manage pharmacotherapy. Thus, clinicians' ability to predict PK and PD alterations within this complex clinical context is fundamental to ensure further optimal and, sometimes, individualized therapeutic plans that balance clinical outcomes with the minimum drug adverse events. Although ECMO remains an irreplaceable extracorporeal technology, and despite the resurgence in its use for respiratory and cardiac failures, especially in the era of the COVID-19 pandemic, scarce data exist on both its effect on the most commonly used drugs and their relative management to achieve the best therapeutic outcomes. The goal of this review is to provide key information about some evidence-based PK alterations of the drugs used in an ECMO setting and their monitoring.

The Influence of Extracorporeal Membrane Oxygenation on Antibiotic Pharmacokinetics.

Extracorporeal membrane oxygenation (ECMO) is becoming increasingly utilized to support critically ill patients who experience life-threatening cardiac or pulmonary compromise. The provision of this intervention poses challenges related to its complications and the optimization of medication therapy. ECMO's mechanical circulatory support is facilitated via various devices and equipment that have been shown to sequester lipophilic- and protein-bound medications, including anti-infectives. Since infectious outcomes are dependent on achieving specific anti-infectives' pharmacodynamic targets, the understanding of these medications' pharmacokinetic parameters in the setting of ECMO is important to clinicians. This narrative, non-systematic review evaluated the findings of the most recent and robust pharmacokinetic analyses for commonly utilized anti-infectives in the setting of ECMO. The data from available literature indicates that anti-infective pharmacokinetic parameters are similar to those observed in other non-ECMO critically ill populations, but considerable variability in the findings was observed between patients, thus prompting further evaluation of therapeutic drug monitoring in this complex population.

The impact of different targeted temperatures on out-of-hospital cardiac arrest outcomes in patients receiving extracorporeal membrane oxygenation: a nationwide cohort study

BackgroundTargeted temperature management (TTM) is recommended in the management of out-of-hospital cardiac arrest (OHCA) when coma persists after the return of spontaneous circulation. In the setting of extracorporeal membrane oxygenation (ECMO) for OHCA patients, TTM is associated with good neurological outcomes and is recommended in the Extracorporeal Life Support Organization guidelines. However, the optimal targeted temperature for these patients has not yet been adequately investigated. This study aimed to compare the impact of different targeted temperatures on the outcomes in OHCA patients receiving ECMO.MethodsThis was a retrospective analysis of data from the Japanese Association for Acute Medicine (JAAM)-OHCA Registry, a multicentre nationwide prospective database in Japan in which 103 institutions providing emergency care participated. OHCA patients aged ≥ 18 years who required ECMO with TTM between June 2014 and December 2019 were included in our analysis. The primary outcome was 30-day survival with favourable neurological outcomes, defined as a Glasgow–Pittsburgh cerebral performance category score of 1 or 2. Patients were divided into two groups according to their targeted temperature: normothermic TTM (n-TTM) (35–36 °C) and hypothermic TTM (h-TTM) (32–34 °C). We compared the outcomes between the two targeted temperature groups using multivariable logistic regression and inverse probability weighting (IPW).ResultsA total of 890 adult OHCA patients who received ECMO and TTM were eligible for our analysis. Of these patients, 249 (28%) and 641 (72%) were treated with n-TTM and h-TTM, respectively. The proportions of patients with 30-day favourable neurological outcomes were 16.5% (41/249) and 15.9% (102/641), in the n-TTM and h-TTM groups, respectively. No difference in neurological outcomes was observed in the multiple regression analysis [adjusted odds ratio 0.91, 95% confidence interval (CI) 0.58–1.43], and the result was constant in the IPW (odds ratio 1.01, 95% CI 0.67–1.54).ConclusionNo difference was observed between n-TTM and h-TTM in OHCA patients receiving TTM with ECMO. The current understanding that changes to the targeted temperature have little impact on the outcome of patients may remain true regardless of ECMO use.

Surviving White-out: How to Manage Severe Noninfectious Acute Lung Allograft Dysfunction of Unknown Etiology.

Surviving White-out: How to Manage Severe Noninfectious Acute Lung Allograft Dysfunction of Unknown Etiology.

Extracorporeal membrane oxygenation circuits in parallel for refractory hypoxemia in patients with COVID-19

ObjectivesRefractory hypoxemia can occur in patients with acute respiratory distress syndrome from COVID-19 despite support with venovenous (VV) extracorporeal membrane oxygenation (ECMO). Parallel ECMO circuits can be used to increase physiologic support. We report our clinical experience using ECMO circuits in parallel for select patients with persistent severe hypoxemia despite the use of a single ECMO circuit. MethodsWe performed a retrospective cohort study of all patients with COVID–19-related acute respiratory distress syndrome who received VV-ECMO with an additional circuit in parallel at Vanderbilt University Medical Center between March 1, 2020, and March 1, 2022. We report demographic characteristics and clinical characteristics including ECMO settings, mechanical ventilator settings, use of adjunctive therapies, and arterial blood gas results after initial cannulation, before and after receipt of a second ECMO circuit in parallel, and before removal of the circuit in parallel, and outcomes. ResultsOf 84 patients with COVID-19 who received VV-ECMO during the study period, 22 patients (26.2%) received a circuit in parallel. The median duration of ECMO was 40.0 days (interquartile range, 31.6-53.1 days), of which 19.0 days (interquartile range, 13.0-33.0 days) were spent with a circuit in parallel. Of the 22 patients who received a circuit in parallel, 16 (72.7%) survived to hospital discharge and 6 (27.3%) died before discharge. ConclusionsIn select patients, the additional use of an ECMO circuit in parallel can increase ECMO blood flow and improve oxygenation while allowing for lung-protective mechanical ventilation and excellent outcomes.

Two Years Into COVID-19: Complications in Patients Requiring Extracorporeal Life Support Highlight the Need for Vascular Expertise

Early adoption of extracorporeal membrane oxygenation (ECMO) for the management of refractory respiratory and cardiopulmonary failure associated with coronavirus disease 2019 (COVID-19) has resulted in a growing use of this highly technical modality. The prothrombotic state associated with severe COVID-19 presents unique challenges to management. In the setting of ECMO, characterized by large-cannula instrumentation, patients with both arterial and venous thrombosis may be recalcitrant to traditional anticoagulation therapy requiring expertise of vascular subspecialists for diagnosis and management.

Abstract 199: Use Of Hybrid Veno-venous-pulmonary Artery ECMO In A Patient With Respiratory Failure Secondary To COVID-19

Background: Extracorporeal membrane oxygenation (ECMO) is a form of cardio-pulmonary life support used for patients with respiratory and/or cardiac failure. Hybrid ECMO is a sophisticated circuit to match the exact hemodynamic demands in patients who are refractory to traditional ECMO settings. Case: A 43-year-old male presented with dyspnea for four days. On physical examination, he exhibited increased work of breathing and decreased breath sounds bilaterally. Pulse oximetry was 70% on room air, minimally improved to 75% on maximum high flow nasal cannula. He was found to be COVID-19 positive and demonstrated diffuse bilateral lung consolidation on CT chest consistent with severe acute respiratory distress syndrome. Patient was intubated but continued to show poor oxygenation with P/F ratio of 71 (Normal: >400). Veno-Venous (VV) ECMO was started with cannulations into the right femoral vein (RFV) and right internal jugular vein (RIJV); this resulted in an initial improvement of partial pressure of oxygen (pO2) in arterial blood gas. However, within a few days, pO2 started to decrease with visual evidence of recirculation of oxygenated blood into the venous drainage line. A transthoracic echocardiography revealed severe pulmonary artery (PA) hypertension secondary to respiratory failure with PA pressure of 116mmHg (Normal: 18-25mmHg). This prompted a revision of the ECMO circuit to offload the right ventricle. Revised circuit included a cannula in the RFV for venous drainage and oxygenated venous return through two pathways: cannula in the RIJV (approximately 1 liter return), and a third cannula inserted through the left subclavian vein terminating into the main PA (approximately 4 liters return). Hereon, patient was able to maintain adequate pO2 for the remainder of his hospital stay until he was transferred to a lung transplant center. Conclusion: Our case illustrates the clinical sophistication of hybrid VV-PA ECMO - especially in patients with PA hypertension and impending right-sided heart failure. As respiratory failure secondary to COVID-19 becomes more prevalent, hybrid ECMO may provide a practical solution to protect the right heart in the journey to lung transplant.

Poor Outcomes of Pediatric Acute Compartment Syndrome in the Setting of Extracorporeal Membrane Oxygenation: A Multicenter Case Series.

Acute compartment syndrome (ACS) is a well-described condition that merits emergent surgical decompression. Peripheral arterial cannulation can increase the likelihood of ACS in patients requiring extracorporeal membranous oxygen (ECMO). Comorbidities in these critically ill patients may portend negative consequences of decompressive fasciotomy. This study investigated the clinical short-term and mid-term outcomes in pediatric patients with ECMO-associated ACS. This is a retrospective case series at 3 pediatric hospitals from 2006 to 2019, including children ages 0 to 19 years who underwent peripheral arterial cannulation and developed ACS. Eighteen patients developed ACS after receiving peripheral cannulation ECMO. Mean time to diagnosis after cannulation was 63.1 hours. All patients were diagnosed clinically; the most common findings were tight compartments, swelling, and loss of peripheral pulses. Eight patients (44%) died due to underlying illness. Treating physicians decided against decompression for 5 patients due to their underlying illness, instability, and concern for infection. Thirteen patients (72%) underwent decompressive fasciotomies. Ten surgical patients required subsequent surgeries and 6 (33%) developed surgical site infections. Of the 7 surviving surgical patients, 4 (57%) required extremity amputations and 4 had lower extremity neurological deficits on follow-up. Two of 3 nonsurgical patients (66%) had functional lower extremity motor deficits on follow-up. No surviving nonoperative patients developed infections or required amputations. ACS on ECMO is associated with high rates of complications including neurologic deficits, infection, and amputation. Patients treated nonoperatively avoided complications such as infection and amputation, but had more functional neurological deficits than surgical patients. Orthopaedic surgeons should consider the high morbidity of compartment release in these critically ill patients and, with critical care teams, assess whether the potential benefits of surgery outweigh expected risks. Level IV.

A Review of Pulmonary Arterial Hypertension Treatment in Extracorporeal Membrane Oxygenation: A Case Series of Adult Patients.

Little data is published describing the use of medications prescribed for pulmonary arterial hypertension (PAH) in patients receiving extracorporeal membrane oxygenation (ECMO). Even though many patients with PAH may require ECMO as a bridge to transplant or recovery, little is reported regarding the use of PAH medications in this setting. This retrospective case series summarizes the clinical experience of 8 patients with PAH receiving ECMO and reviews medication management in the setting of ECMO. Eight PAH patients, 5 of whom were female, ranging in age from 21 to 61 years old, were initiated on ECMO. Veno-arterial (VA) ECMO was used in 4 patients, veno-venous (VV) ECMO and hybrid ECMO configurations in 2 patients respectively. Common indications for ECMO included cardiogenic shock, bridge to transplant, and cardiac arrest. All patients were on intravenous (IV) prostacyclin therapy at baseline. Refractory hypotension was noted in 7 patients of whom 5 patients required downtitration or discontinuation of baseline PAH therapies. Three patients had continuous inhaled epoprostenol added during their time on ECMO. In patients who were decannulated from ECMO, PAH therapies were typically resumed or titrated back to baseline dosages. One patient required no adjustment in PAH therapy while on ECMO. Two patients were not able to be decannulated from ECMO. The treatment of critically ill PAH patients is challenging given a variety of factors that could affect PAH drug concentrations. In particular, PAH patients on prostacyclin analogues placed on VA ECMO appear to have pronounced systemic vasodilation requiring vasopressors which is alleviated by temporarily reducing the intravenous prostacyclin dose. Patients should be closely monitored for potential need for rapid titrations in prostacyclin therapy to maintain hemodynamic stability.

Electrical Impedance Tomography to Set Positive End Expiratory Pressure During Pediatric Extracorporeal Membrane Oxygenation for Respiratory Failure... Is it Feasible?

Electrical Impedance Tomography to Set Positive End Expiratory Pressure During Pediatric Extracorporeal Membrane Oxygenation for Respiratory Failure... Is it Feasible?

Evaluation of Bivalirudin as the Primary Anticoagulant in Patients Receiving Extracorporeal Membrane Oxygenation for SARS-CoV-2-Associated Acute Respiratory Failure.

Extracorporeal membrane oxygenation (ECMO) is a potential option for the management of severe acute respiratory failure secondary to COVID-19. Conflicting the use of this therapy is the known coagulopathy within COVID-19, leading to an incidence of venous thrombotic events of 25% to 49%. To date, limited guidance is available on optimal anticoagulation strategies in this population. The purpose of this study was to evaluate the utilization of a pharmacist-driven bivalirudin dosing protocol for anticoagulation in the setting of ECMO for COVID-19-associated respiratory failure. This was a single-center retrospective chart review over a 9-month period of patients receiving bivalirudin while on ECMO. All patients with acute respiratory failure requiring ECMO with a positive SARS-CoV-2 polymerase chain reaction were included. Bivalirudin was dosed via aPTT monitoring after a starting dose of 0.2 or 0.3 mg/kg/h. There were 33 patients included in this study, all receiving mechanical ventilation. The most common starting dose of bivalirudin was 0.2 mg/kg/h, with an average time to therapeutic range of 20 hours. Compared to previous reports, rates of bleeding were low at 15.1%, and 6.1% of patients developed a new venous thromboembolic event while on ECMO. ECMO survival was 51.5%, with an ICU mortality rate of 48.5%. In the first published report of its use within this population, bivalirudin was found to be a viable choice for anticoagulation in those patients on ECMO for severe respiratory failure secondary to COVID-19.

ELSO Interim Guidelines for Venoarterial Extracorporeal Membrane Oxygenation in Adult Cardiac Patients.

ELSO Interim Guidelines for Venoarterial Extracorporeal Membrane Oxygenation in Adult Cardiac Patients.

Diagnosis and Treatment Protocol for COVID-19 Patients (Tentative 8th Edition): Interpretation of Updated Key Points.

Diagnosis and Treatment Protocol for COVID-19 Patients (Tentative 8th Edition): Interpretation of Updated Key Points.