Safety and efficacy of methylprednisolone versus dexamethasone in critically ill patients with COVID-19 acute respiratory distress syndrome: a retrospective study.

Background: Corticosteroids (CSs), specifically dexamethasone (DEX), are the treatment of choice for severe acute respiratory distress syndrome (ARDS) due to COVID-19 pneumonia (CARDS). However, data from both ARDS and relatively small CARDS clinical trials have suggested improved outcomes with methylprednisolone (MP) versus DEX. The objective of this retrospective cohort study was to compare the safety and effectiveness of MP and DEX in critically ill CARDS patients. Methods: The study cohort included CARDS patients admitted to a tertiary referral intensive care unit (ICU) between April and September 2020 who received at least 5 days of CSs for CARDS. Results: The cohort was notable for a high severity of illness (overall, 88.5% of patients required mechanical ventilation and 16% required vasopressors on admission). The DEX group (n = 62) was significantly older with a higher illness severity [Sequential Organ Failure Assessment (SOFA) 6 (4.75-8) versus 4.5 (3-7), p = 0.008], while the MP group (n = 51) received significantly more loading doses [19 (37.3%) versus 4 (6.5%), p < 0.0001]. MP was associated with a shorter time to intubation and more rapid progression to mortality [days to death: 18 (15-23) versus 27 (15-34), p = 0.026]. After correction for baseline imbalances in age and SOFA score, DEX was associated with improved mortality at 90 days compared with MP [hazard ratio (HR) = 0.43, 95% confidence interval (CI) = 0.23-0.80, p = 0.008]. However, there were no differences between rates of secondary infections during hospitalization or insulin requirements at 7 and 14 days. Conclusion: In this cohort of critically ill CARDS, choice of CS was associated with mortality but not adverse event profile, and thus warrants further investigation.

WHO recommends corticosteroids for patients with severe or critical COVID-19.

SOURCE CITATION: Lamontagne F, Agoritsas T, Macdonald H, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020;370:m3379. 32887691.

Inhaled Antibiotic Therapy in Chronic Respiratory Diseases.

The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF) and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus, Burkholderia species and non-tuberculous Mycobacteria (NTM). These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases.

Suspecting non-cystic fibrosis bronchiectasis: What the busy primary care clinician needs to know.

AIMS: Non-cystic fibrosis bronchiectasis (NCFB) is a chronic, progressive respiratory disorder characterised by irreversibly and abnormally dilated airways, persistent cough, excessive sputum production and recurrent pulmonary infections. In the last several decades, its prevalence has increased, making it likely to be encountered in the primary care setting. The aim was to review the clinical presentation and diagnosis of NCFB, with an emphasis on the role of computed tomography (CT). METHODS: For this review, trials and reports were identified from PubMed/Medline and ClinicalTrials.gov from the US NIH and the Cochrane Register of Controlled Trials. The search used keywords: bronchiectasis, non-cystic fibrosis bronchiectasis, chronic pulmonary infection and computed tomography. No date/language restrictions were used. RESULTS: Non-cystic fibrosis bronchiectasis often coexists with other respiratory conditions, such as chronic obstructive pulmonary disease. The prevalence of NCFB is increasing, particularly in women and older individuals, possibly as a result of increased physician awareness and widespread use of CT, which is the gold standard for the diagnosis of NCFB. CT can assist in identifying an underlying cause of NCFB and determining the extent and severity of the disease. DISCUSSION: Non-cystic fibrosis bronchiectasis should be suspected in the primary care setting in patients with chronic cough, purulent sputum and frequent respiratory infections that tend to resolve slowly or partially. Early diagnosis and determination of the extent and severity of the disease by CT and other tests are critical to establish therapy to improve quality of life and potentially slow progressive decline of lung function in patients with NCFB.

Use of ultrasound guidance for central venous catheterization: a national survey of intensivists and hospitalists.

PURPOSE: The purpose of the study is to evaluate the frequency and barriers to use of ultrasound guidance for central venous catheter (CVC) insertion by physicians specializing in critical care and hospital medicine. MATERIALS AND METHODS: A national cross-sectional electronic survey of intensivists and hospitalists was administered from November 2014 to January 2015. RESULTS: The survey response rate was 5.9% (1013/17 233). Moderate to very frequent use of ultrasound guidance varied by site: internal jugular vein (80%), subclavian vein (31%), and femoral vein (45%). Nearly all physicians (99%) who insert internal jugular CVCs daily use ultrasound guidance, whereas only 46% of physicians who insert subclavian CVCs daily use ultrasound guidance. Use of real-time ultrasound guidance varied by insertion site: internal jugular vein (73%), subclavian vein (28%), and femoral vein (42%). Most physicians (59%) reported not being comfortable with real-time needle tracking at the subclavian site. The most frequently reported barriers to use of ultrasound guidance were (1) limited availability of ultrasound equipment (28%), (2) perception of increased total procedure time (22%), and (3) concern for loss of landmark skills (13%). CONCLUSIONS: Most intensivists routinely use ultrasound guidance to insert internal jugular CVCs but not subclavian CVCs. The most commonly reported barrier to ultrasound use was limited access to an ultrasound machine.

Global impact of bronchiectasis and cystic fibrosis.

EDUCATIONAL AIMS: To recognise the clinical and radiological presentation of the spectrum of diseases associated with bronchiectasis.To understand variation in the aetiology, microbiology and burden of bronchiectasis and cystic fibrosis across different global healthcare systems.Bronchiectasis is the term used to refer to dilatation of the bronchi that is usually permanent and is associated with a clinical syndrome of cough, sputum production and recurrent respiratory infections. It can be caused by a range of inherited and acquired disorders, or may be idiopathic in nature. The most well recognised inherited disorder in Western countries is cystic fibrosis (CF), an autosomal recessive condition that leads to progressive bronchiectasis, bacterial infection and premature mortality. Both bronchiectasis due to CF and bronchiectasis due to other conditions are placing an increasing burden on healthcare systems internationally. Treatments for CF are becoming more effective leading to more adult patients with complex healthcare needs. Bronchiectasis not due to CF is becoming increasingly recognised, particularly in the elderly population. Recognition is important and can lead to identification of the underlying cause, appropriate treatment and improved quality of life. The disease is highly diverse in its presentation, requiring all respiratory physicians to have knowledge of the different "bronchiectasis syndromes". The most common aetiologies and presenting syndromes vary depending on geography, with nontuberculous mycobacterial disease predominating in some parts of North America, post-infectious and idiopathic disease predominating in Western Europe, and post-tuberculosis bronchiectasis dominating in South Asia and Eastern Europe. Ongoing global collaborative studies will greatly advance our understanding of the international impact of bronchiectasis and CF.

Profile of lebrikizumab and its potential in the treatment of asthma.

Interleukin (IL)-13 has been associated with multiple inflammatory features of asthma. It affects multiple cellular lines in asthma and is a key mediator in airway hyperreactivity and remodeling. Periostin, an extracellular protein, has been used as a surrogate marker of IL-13 activity and has been linked to airway remodeling by inducing subepithelial fibrosis. Lebrikizumab is a humanized monoclonal antibody that targets IL-13. Studies have demonstrated promising results with lebrikizumab therapy in asthma with regard to pulmonary function and exacerbation rates, especially on those patients with surrogate markers of T helper cell type 2-driven inflammation (ie, elevated immunoglobulin E levels, eosinophil counts, periostin levels). Lebrikizumab appears to be a safe therapy, but there are ongoing studies evaluating its efficacy and safety profile. Other therapies that target IL-13 and the receptor of IL-4/IL-13 have been studied, but future studies are needed to determine their role in the treatment of asthma.

Aerosolized Antibiotics.

Administration of medications via aerosolization is potentially an ideal strategy to treat airway diseases. This delivery method ensures high concentrations of the medication in the targeted tissues, the airways, with generally lower systemic absorption and systemic adverse effects. Aerosolized antibiotics have been tested as treatment for bacterial infections in patients with cystic fibrosis (CF), non-CF bronchiectasis (NCFB), and ventilator-associated pneumonia (VAP). The most successful application of this to date is treatment of infections in patients with CF. It has been hypothesized that similar success would be seen in NCFB and in difficult-to-treat hospital-acquired infections such as VAP. This review summarizes the available evidence supporting the use of aerosolized antibiotics and addresses the specific considerations that clinicians should recognize when prescribing an aerosolized antibiotic for patients with CF, NCFB, and VAP.

Prevention of ventilator-associated pneumonia in the intensive care unit: a review of the clinically relevant recent advancements.

Ventilator-associated pneumonia (VAP) is one of the most commonly encountered hospital-acquired infections in intensive care units and is associated with significant morbidity and high costs of care. The pathophysiology, epidemiology, treatment and prevention of VAP have been extensively studied for decades, but a clear prevention strategy has not yet emerged. In this article we will review recent literature pertaining to evidence-based VAP-prevention strategies that have resulted in clinically relevant outcomes. A multidisciplinary strategy for prevention of VAP is recommended. Those interventions that have been shown to have a clinical impact include the following: (i) Non-invasive positive pressure ventilation for able patients, especially in immunocompromised patients, with acute exacerbation of chronic obstructive pulmonary disease or pulmonary oedema, (ii) Sedation and weaning protocols for those patients who do require mechanical ventilation, (iii) Mechanical ventilation protocols including head of bed elevation above 30 degrees and oral care, and (iv) Removal of subglottic secretions. Other interventions, such as selective digestive tract decontamination, selective oropharyngeal decontamination and antimicrobial-coated endotracheal tubes, have been tested in different studies. However, the evidence for the efficacy of these measures to reduce VAP rates is not strong enough to recommend their use in clinical practice. In numerous studies, the implementation of VAP prevention bundles to clinical practice was associated with a significant reduction in VAP rates. Future research that considers clinical outcomes as primary endpoints will hopefully result in more detailed prevention strategies.