Initial emergency department mechanical ventilation strategies for COVID-19 hypoxemic respiratory failure and ARDS

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging viral pathogen that causes the novel coronavirus disease of 2019 (COVID-19) and may result in hypoxemic respiratory failure necessitating invasive mechanical ventilation in the most severe cases.ObjectiveThis narrative review provides evidence-based recommendations for the treatment of COVID-19 related respiratory failure requiring invasive mechanical ventilation.DiscussionIn severe cases, COVID-19 leads to hypoxemic respiratory failure that may meet criteria for acute respiratory distress syndrome (ARDS). The mainstay of treatment for ARDS includes a lung protective ventilation strategy with low tidal volumes (4–8 mL/kg predicted body weight), adequate positive end-expiratory pressure (PEEP), and maintaining a plateau pressure of < 30 cm H₂O. While further COVID-19 specific studies are needed, current management should focus on supportive care, preventing further lung injury from mechanical ventilation, and treating the underlying cause.ConclusionsThis review provides evidence-based recommendations for the treatment of COVID-19 related respiratory failure requiring invasive mechanical ventilation.     

High flow nasal cannula for adult acute hypoxemic respiratory failure in the ED setting

IntroductionHigh flow nasal cannula (HFNC) is a noninvasive ventilation (NIV) system that has demonstrated promise in the emergency department (ED) setting.ObjectiveThis narrative review evaluates the utility of HFNC in adult patients with acute hypoxemic respiratory failure in the ED setting.DiscussionHFNC provides warm (37 °C), humidified (100% relative humidity) oxygen at high flows with a reliable fraction of inspired oxygen (FiO₂). HFNC can improve oxygenation, reduce airway resistance, provide humidified flow that can flush anatomical dead space, and provide a low amount of positive end expiratory pressure. Recent literature has demonstrated efficacy in acute hypoxemic respiratory failure, including pneumonia, acute respiratory distress syndrome (ARDS), coronavirus disease 2019 (COVID-19), interstitial lung disease, immunocompromised states, the peri-intubation state, and palliative care, with reduced need for intubation, length of stay, and mortality in some of these conditions. Individual patient factors play an important role in infection control risks with respect to the use of HFNC in patients with COVID-19. Appropriate personal protective equipment, adherence to hand hygiene, surgical mask placement over the HFNC device, and environmental controls promoting adequate room ventilation are the foundation for protecting healthcare personnel. Frequent reassessment of the patient placed on HFNC is necessary; those with severe end organ dysfunction, thoracoabdominal asynchrony, significantly increased respiratory rate, poor oxygenation despite HFNC, and tachycardia are at increased risk of HFNC failure and need for further intervention.ConclusionsHFNC demonstrates promise in several conditions requiring respiratory support. Further randomized trials are needed in the ED setting.     

Emergency Department Management of Severe Hypoxemic Respiratory Failure in Adults With COVID-19

BackgroundWhile emergency physicians are familiar with the management of hypoxemic respiratory failure, management of mechanical ventilation and advanced therapies for oxygenation in the emergency department have become essential during the coronavirus disease 2019 (COVID-19) pandemic.ObjectiveWe review the current evidence on hypoxemia in COVID-19 and place it in the context of known evidence-based management of hypoxemic respiratory failure in the emergency department.DiscussionCOVID-19 causes mortality primarily through the development of acute respiratory distress syndrome (ARDS), with hypoxemia arising from shunt, a mismatch of ventilation and perfusion. Management of patients developing ARDS should focus on mitigating derecruitment and avoiding volutrauma or barotrauma.ConclusionsHigh flow nasal cannula and noninvasive positive pressure ventilation have a more limited role in COVID-19 because of the risk of aerosolization and minimal benefit in severe cases, but can be considered. Stable patients who can tolerate repositioning should be placed in a prone position while awake. Once intubated, patients should be managed with ventilation strategies appropriate for ARDS, including targeting lung-protective volumes and low pressures. Increasing positive end-expiratory pressure can be beneficial. Inhaled pulmonary vasodilators do not decrease mortality but may be given to improve refractory hypoxemia. Prone positioning of intubated patients is associated with a mortality reduction in ARDS and can be considered for patients with persistent hypoxemia. Neuromuscular blockade should also be administered in patients who remain dyssynchronous with the ventilator despite adequate sedation. Finally, patients with refractory severe hypoxemic respiratory failure in COVID-19 should be considered for venovenous extracorporeal membrane oxygenation.     

Coronavirus Disease (COVID-19): A primer for emergency physicians

IntroductionRapid worldwide spread of Coronavirus Disease 2019 (COVID-19) has resulted in a global pandemic.ObjectiveThis review article provides emergency physicians with an overview of the most current understanding of COVID-19 and recommendations on the evaluation and management of patients with suspected COVID-19.DiscussionSevere Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for causing COVID-19, is primarily transmitted from person-to-person through close contact (approximately 6 ft) by respiratory droplets. Symptoms of COVID-19 are similar to other viral upper respiratory illnesses. Three major trajectories include mild disease with upper respiratory symptoms, non-severe pneumonia, and severe pneumonia complicated by acute respiratory distress syndrome (ARDS). Emergency physicians should focus on identifying patients at risk, isolating suspected patients, and informing hospital infection prevention and public health authorities. Patients with suspected COVID-19 should be asked to wear a facemask. Respiratory etiquette, hand washing, and personal protective equipment are recommended for all healthcare personnel caring for suspected cases. Disposition depends on patient symptoms, hemodynamic status, and patient ability to self-quarantine.ConclusionThis narrative review provides clinicians with an updated approach to the evaluation and management of patients presenting to the emergency department with suspected COVID-19.     

Clinical efficacy of casirivimab-imdevimab antibody combination treatment in patients with COVID-19 Delta variant

IntroductionCasirivimab-imdevimab, an antibody cocktail containing two severe acute respiratory syndrome coronavirus 2 neutralizing antibodies, reduces the viral load and the risk of coronavirus disease 2019 (COVID-19)-related hospitalization or death. The objective of this study was to evaluate the clinical efficacy of casirivimab-imdevimab in patients with COVID-19 Delta variant in Japan.MethodsThis study was conducted at five institutions and assessed a total of 461 patients with COVID-19 who met the inclusion criteria. The treatment group received a dose of casirivimab-imdevimab consisting of a cocktail of two monoclonal antibodies, (casirivimab 600 mg and imdevimab 600 mg intravenously). The control consisted of age- and sex-matched COVID-19 patients (n = 461) who sufficed the inclusion criteria but did not receive casirivimab-imdevimab. The outcome was the requirement of oxygen therapy.ResultsIn the treatment group, patients received oxygen therapy (n = 30), nasal canula (n = 23), high flow nasal cannula (n = 5), and mechanical ventilation (n = 2). In the control group, patients received oxygen therapy (n = 56), nasal canula (n = 45), high flow nasal cannula (n = 8), and mechanical ventilation (n = 3). The administration of oxygen therapy was significantly lower in the treatment group than the control group (6.5% vs. 12.1%, P = 0.0044). All these patients admitted to our hospitals and received additional therapy and recovered.ConclusionsOur results demonstrate that the casirivimab-imdevimab combination antibody treatment is associated with reduced rates of requiring oxygen therapy among high-risk patients with COVID-19 Delta variant.     

Noninvasive ventilation for acute hypoxemic respiratory failure in patients with COVID-19

AimNoninvasive ventilation (NIV) is known to reduce intubation in patients with acute hypoxemic respiratory failure (AHRF). We aimed to assess the outcomes of NIV application in COVID-19 patients with AHRF.Materials & methodsIn this retrospective cohort study, patients with confirmed diagnosis of COVID-19 and AHRF receiving NIV in general wards were recruited from two university-affiliated hospitals. Demographic, clinical, and laboratory data were recorded at admission. The failure of NIV was defined as intubation or death during the hospital stay.ResultsBetween April 8 and June 10, 2020, 61 patients were enrolled into the final cohort. NIV was successful in 44 out of 61 patients (72.1%), 17 patients who failed NIV therapy were intubated, and among them 15 died. Overall mortality rate was 24.6%. Patients who failed NIV were older, and had higher respiratory rate, PaCO₂, D-dimer levels before NIV and higher minute ventilation and ventilatory ratio on the 1-st day of NIV. No healthcare workers were infected with SARS-CoV-2 during the study period.ConclusionsNIV is feasible in patients with COVID-19 and AHRF outside the intensive care unit, and it can be considered as a valuable option for the management of AHRF in these patients.     

The impact of timing of initiating invasive mechanical ventilation in COVID-19-related respiratory failure

PurposeOptimal timing of initiating invasive mechanical ventilation (IMV) in coronavirus disease 2019 (COVID-19)-related respiratory failure is unclear. We hypothesized that a strategy of IMV as opposed to continuing high flow oxygen or non-invasive mechanical ventilation each day after reaching a high FiO2 threshold would be associated with worse in-hospital mortality.MethodsUsing data from Kaiser Permanente Northern/Southern California's 36 medical centers, we identified patients with COVID-19-related acute respiratory failure who reached ≥80% FiO2 on high flow nasal cannula or non-invasive ventilation. Exposure was IMV initiation each day after reaching high FiO2 threshold (T₀). We developed propensity scores with overlap weighting for receipt of IMV each day adjusting for confounders. We reported relative risk of inpatient death with 95% Confidence Interval.ResultsOf 28,035 hospitalizations representing 21,175 patient-days, 5758 patients were included (2793 received and 2965 did not receive IMV). Patients receiving IMV had higher unadjusted mortality (63.6% versus 18.2%, P < 0.0001). On each day after reaching T₀ through day >10, the adjusted relative risk was higher for those receiving IMV compared to those not receiving IMV (Relative Risk>1).ConclusionsInitiation of IMV on each day after patients reach high FiO2 threshold was associated with higher inpatient mortality after adjusting for time-varying confounders. Remaining on high flow nasal cannula or non-invasive ventilation does not appear to be harmful compared to IMV. Prospective evaluation is needed.     

Distinctive features of severe SARS-CoV-2 pneumonia

The coronavirus disease 2019 (COVID-19) pandemic is among the most important public health crises of our generation. Despite the promise of prevention offered by effective vaccines, patients with severe COVID-19 will continue to populate hospitals and intensive care units for the foreseeable future. The most common clinical presentation of severe COVID-19 is hypoxemia and respiratory failure, typical of the acute respiratory distress syndrome (ARDS). Whether the clinical features and pathobiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia differ from those of pneumonia secondary to other pathogens is unclear. This uncertainty has created variability in the application of historically proven therapies for ARDS to patients with COVID-19. We review the available literature and find many similarities between patients with ARDS from pneumonia attributable to SARS-CoV-2 versus other respiratory pathogens. A notable exception is the long duration of illness among patients with COVID-19, which could result from its unique pathobiology. Available data support the use of care pathways and therapies proven effective for patients with ARDS, while pointing to unique features that might be therapeutically targeted for patients with severe SARS-CoV-2 pneumonia.     

Veno-venous extracorporeal membrane oxygenation allocation in the COVID-19 pandemic

Rapid global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resultant clinical illness, coronavirus disease 2019 (COVID-19), drove the World Health Organization to declare COVID-19 a pandemic. Veno-venous Extra-Corporeal Membrane Oxygenation (VV-ECMO) is an established therapy for management of patients demonstrating the most severe forms of hypoxemic respiratory failure from COVID-19. However, features of COVID-19 pathophysiology and necessary length of treatment present distinct challenges for utilization of VV-ECMO within the current healthcare emergency. In addition, growing allocation concerns due to capacity and cost present significant challenges. Ethical and legal aspects pertinent to triage of this resource-intensive, but potentially life-saving, therapy in the setting of the COVID-19 pandemic are reviewed here. Given considerations relevant to VV-ECMO use, additional emphasis has been placed on emerging hospital resource scarcity and disproportionate representation of healthcare workers among the ill. Considerations are also discussed surrounding withdrawal of VV-ECMO and the role for early communication as well as consultation from palliative care teams and local ethics committees. In discussing how to best manage these issues in the COVID-19 pandemic at present, we identify gaps in the literature and policy important to clinicians as this crisis continues.     

The effectiveness of high-dose intravenous vitamin C for patients with coronavirus disease 2019: A systematic review and meta-analysis

ObjectivesVitamin C has anti-inflammatory effects. This review aimed to investigate the therapeutic effect of high-dose intravenous vitamin C (HDIVC) in patients with coronavirus disease 2019 (COVID-19).MethodsThe following key phrases were searched for article inclusion: “Vitamin C OR ascorbic acid” AND “COVID-19 OR coronavirus disease 2019 OR severe acute respiratory syndrome coronavirus 2 OR SARS-CoV-2″. Articles that utilized HDIVC for the management of patients with COVID-19 were included, whereas review articles and case reports were excluded from this review. Moreover, we performed a meta-analysis to evaluate whether HDIVC can reduce the length of hospital stay and in-hospital mortality rate of patients with severe COVID-19.ResultsIn total, eight articles were included in this review, and five studies were included in the meta-analysis. The length of hospital stay was not significantly different between the HDIVC and control groups. Also, although our meta-analysis showed a tendency for HDIVC to reduce the in-hospital mortality rate in patients with severe COVID-19, the in-hospital mortality rate was not significantly different between patients treated with HDIVC and those who did not receive HDIVC.ConclusionsEvidence supporting the therapeutic use of HDICV in COVID-19 patients is lacking. Further studies are required for drawing a clear conclusion on this topic.     

Mechanical ventilation and mortality among 223 critically ill patients with coronavirus disease 2019: A multicentric study in Germany

BackgroundThere are large uncertainties with regard to the outcome of patients with coronavirus disease 2019 (COVID-19) and mechanical ventilation (MV). High mortality (50–97%) was proposed by some groups, leading to considerable uncertainties with regard to outcomes of critically ill patients with COVID-19.ObjectivesThe aim was to investigate the characteristics and outcomes of critically ill patients with COVID-19 requiring intensive care unit (ICU) admission and MV.MethodsA multicentre retrospective observational cohort study at 15 hospitals in Hamburg, Germany, was performed. Critically ill adult patients with COVID-19 who completed their ICU stay between February and June 2020 were included. Patient demographics, severity of illness, and ICU course were retrospectively evaluated.ResultsA total of 223 critically ill patients with COVID-19 were included. The majority, 73% (n = 163), were men; the median age was 69 (interquartile range = 58–77.5) years, with 68% (n = 151) patients having at least one chronic medical condition. Their Sequential Organ Failure Assessment score was a median of 5 (3–9) points on admission. Overall, 167 (75%) patients needed MV. Noninvasive ventilation and high-flow nasal cannula were used in 31 (14%) and 26 (12%) patients, respectively. Subsequent MV, due to noninvasive ventilation/high-flow nasal cannula therapy failure, was necessary in 46 (81%) patients. Renal replacement therapy was initiated in 33% (n = 72) of patients, and owing to severe respiratory failure, extracorporeal membrane oxygenation was necessary in 9% (n = 20) of patients. Experimental antiviral therapy was used in 9% (n = 21) of patients. Complications during the ICU stay were as follows: septic shock (40%, n = 90), heart failure (8%, n = 17), and pulmonary embolism (6%, n = 14). The length of ICU stay was a median of 13 days (5–24), and the duration of MV was 15 days (8–25). The ICU mortality was 35% (n = 78) and 44% (n = 74) among mechanically ventilated patients.ConclusionIn this multicentre observational study of 223 critically ill patients with COVID-19, the survival to ICU discharge was 65%, and it was 56% among patients requiring MV. Patients showed high rate of septic complications during their ICU stay.     

No SARS-CoV-2 RNA detected in the convalescent plasma of COVID-19 patients with different disease severity

IntroductionConvalescent plasma transfusion (CPT), a potential therapy for coronavirus disease 2019 (COVID-19), requires strict quality control of the donor blood. Whether to confirm the disappearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA (RNAemia) in convalescent donor blood or not is unclear. Reports recommending the proof of viral disappearance from the blood are controversial. Foreseeing CPT in treating COVID-19 patients in Japan, we investigated RNAemia in 100 convalescent donors with mild, moderate, and severe COVID-19.MethodsBetween April 30 and July 30, 2020, we measured RNAemia in the plasma samples of donors with resolved COVID-19. Data on patients’ demographics, comorbidities, pneumonia, treatment, and real-time polymerase chain reaction results for SARS-CoV-2 were collected. Date of onset of initial symptoms or date of positive testing (for asymptomatic patients) were self-reported by the patients. Disease severity was defined as: no, mild, moderate oxygen demand, or severe (requiring mechanical ventilation).ResultsOf 100 donors (58 males [58.0%]; median age, 47 [range 22–69] years) screened as of July 30, 2020, 77 (77.0%); 19 (19.0%); and 4 (4.0%) had mild, moderate, and severe disease, respectively. Median time between onset and testing was 68.5 (range, 21–167) days. SARS-CoV-2 RNA was not detected in any of the plasma samples.ConclusionRNAemia was not found in recovered COVID-19 patients at least 21, 27, and 57 days after the onset of mild, moderate, and severe symptoms. Our study may contribute to determining a suitable time for collecting convalescent plasma from COVID-19 patients and to future CPT use.     

Healthy neonate born to a SARS-CoV-2 infected woman: A case report and review of literature

BACKGROUNDSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly discovered coronavirus that has generated a worldwide outbreak of infections. Many people with coronavirus disease-2019 (COVID-19) have developed severe illness, and a significant number have died. However, little is known regarding infection by the novel virus in pregnant women. We herein present a case of COVID-19 confirmed in a woman delivering a neonate who was negative for SARS-CoV-2 and related it to a review of the literature on pregnant women and human coronavirus infections.CASE SUMMARYThe patient was a 36-year-old pregnant woman in her third trimester who had developed progressive clinical symptoms when she was confirmed as infected with SARS-CoV-2. Given the potential risks for both the pregnant woman and the fetus, an emergency cesarean section was performed, and the baby and his mother were separately quarantined and cared for. As a result, the baby currently shows no signs of SARS-CoV-2 infection (his lower respiratory tract samples were negative for the virus), while the mother completely recovered from COVID-19.CONCLUSIONAlthough we presented a single case, the successful result is of great significance for pregnant women with SARS-CoV-2 infection and with respect to fully understanding novel coronavirus pneumonia.     

COVID-19 in gastroenterology and hepatology: Lessons learned and questions to be answered

BACKGROUNDAlthough coronavirus disease 2019 (COVID-19) presents primarily as a lower respiratory tract infection, increasing data suggests multiorgan, including the gastrointestinal (GI) tract and liver, involvement in patients who are infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).AIMTo provide a comprehensive overview of COVID-19 in gastroenterology and hepatology.METHODSRelevant studies on COVID-19 related to the study aim were undertaken through a literature search to synthesize the extracted data.RESULTSWe found that digestive symptoms and liver injury are not uncommon in patients with COVID-19 and varies in different individuals. The most common GI symptoms reported are diarrhea, nausea, vomiting, and abdominal discomfort. Other atypical GI symptoms, such as loss of smell and taste and GI bleeding, have also been reported along with the evolvement of COVID-19. Liver chemistry abnormalities mainly include elevation of aspartate transferase, alanine transferase, and total bilirubin. It is postulated to be related to the binding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus to the angiotensin converting enzyme-2 receptor located on several different human cells. CONCLUSIONStandardized criteria should be established for diagnosis and grading of the severity of GI symptoms in COVID-19 patients. Gastroenterology and hepatology in special populations, such as children and elderly, should be the focus of further research. Future long-term data regarding GI symptoms should not be overlooked.     

COVID-19 and the heart

An outbreak of coronavirus disease 2019 (COVID-19) occurred in December 2019 due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is a strain of SARS-CoV. Patients infected with the virus present a wide spectrum of manifestations ranging from mild flu-like symptoms, cough, fever and fatigue to severe lung injury, appearing as bilateral interstitial pneumonia or acute respiratory failure. Although SARS-CoV-2 infection predominantly offends the respiratory system, it has been associated with several cardiovascular complications as well. For example, patients with COVID-19 may either develop type 2 myocardial infarction due to myocardial oxygen demand and supply imbalance or acute coronary syndrome resulting from excessive inflammatory response to the primary infection. The incidence of COVID-19 related myocarditis is estimated to be accountable for an average of 7% of all COVID-19 related fatal cases, whereas heart failure (HF) may develop due to infiltration of the heart by inflammatory cells, destructive action of pro-inflammatory cytokines, micro-thrombosis and new onset or aggravated endothelial and respiratory failure. Lastly, SARS-CoV-2 can engender arrhythmias through direct myocardial damage causing acute myocarditis or through HF decompensation or secondary, through respiratory failure or severe respiratory distress syndrome. In this comprehensive review we summarize the COVID-19 related cardiovascular complications (acute coronary syndromes, myocarditis, HF, arrhythmias) and discuss the main underlying pathophysiological mechanisms.     

Nutrition management for critically and acutely unwell hospitalised patients with coronavirus disease 2019 (COVID-19) in Australia and New Zealand

Coronavirus disease 2019 (COVID-19) results from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical features and subsequent medical treatment, combined with the impact of a global pandemic, require specific nutritional therapy in hospitalised adults. This document aims to provide Australian and New Zealand clinicians with guidance on managing critically and acutely unwell adult patients hospitalised with COVID-19. These recommendations were developed using expert consensus, incorporating the documented clinical signs and metabolic processes associated with COVID-19, the literature from other respiratory illnesses, in particular acute respiratory distress syndrome, and published guidelines for medical management of COVID-19 and general nutrition and intensive care. Patients hospitalised with COVID-19 are likely to have preexisting comorbidities, and the ensuing inflammatory response may result in increased metabolic demands, protein catabolism, and poor glycaemic control. Common medical interventions, including deep sedation, early mechanical ventilation, fluid restriction, and management in the prone position, may exacerbate gastrointestinal dysfunction and affect nutritional intake. Nutrition care should be tailored to pandemic capacity, with early gastric feeding commenced using an algorithm to provide nutrition for the first 5–7 days in lower-nutritional-risk patients and individualised care for high-nutritional-risk patients where capacity allows. Indirect calorimetry should be avoided owing to potential aerosole exposure and therefore infection risk to healthcare providers. Use of a volume-controlled, higher-protein enteral formula and gastric residual volume monitoring should be initiated. Careful monitoring, particularly after intensive care unit stay, is required to ensure appropriate nutrition delivery to prevent muscle deconditioning and aid recovery. The infectious nature of SARS-CoV-2 and the expected high volume of patient admissions will require contingency planning to optimise staffing resources including upskilling, ensure adequate nutrition supplies, facilitate remote consultations, and optimise food service management. These guidelines provide recommendations on how to manage the aforementioned aspects when providing nutrition support to patients during the SARS-CoV-2 pandemic.