Prolonged higher dose methylprednisolone versus conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS).

BACKGROUND: Dysregulated systemic inflammation is the primary driver of mortality in severe coronavirus disease 2019 (COVID-19) pneumonia. Current guidelines favour a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg daily. A comparative randomised controlled trial (RCT) with a higher dose and a longer duration of intervention was lacking. METHODS: We conducted a multicentre, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow tapering versus dexamethasone 6 mg once daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. The primary outcome was reduction in 28-day mortality. Secondary outcomes were mechanical ventilation-free days at 28 days, need for intensive care unit (ICU) referral, length of hospitalisation, need for tracheostomy, and changes in C-reactive protein (CRP) levels, arterial oxygen tension/inspiratory oxygen fraction (P aO2 /F IO2 ) ratio and World Health Organization Clinical Progression Scale at days 3, 7 and 14. RESULTS: 677 randomised patients were included. Findings are reported as methylprednisolone (n=337) versus dexamethasone (n=340). By day 28, there were no significant differences in mortality (35 (10.4%) versus 41 (12.1%); p=0.49) nor in median mechanical ventilation-free days (median (interquartile range (IQR)) 23 (14) versus 24 (16) days; p=0.49). ICU referral was necessary in 41 (12.2%) versus 45 (13.2%) (p=0.68) and tracheostomy in 8 (2.4%) versus 9 (2.6%) (p=0.82). Survivors in the methylprednisolone group required a longer median (IQR) hospitalisation (15 (11) versus 14 (11) days; p=0.005) and experienced an improvement in CRP levels, but not in P aO2 /F IO2 ratio, at days 7 and 14. There were no differences in disease progression at the prespecified time-points. CONCLUSION: Prolonged, higher dose methylprednisolone did not reduce mortality at 28 days compared with conventional dexamethasone in COVID-19 pneumonia.

Sleep apnea in morbidly obese patients: prevalence and clinical predictivity.

BACKGROUND: Little is known about the prevalence of obstructive sleep apnea-hypopnea syndrome (OSAHS) in morbidly obese patients and whether such patients show peculiar clinical findings that may make it easier to suspect and diagnose OSAHS. OBJECTIVES: To investigate prevalence of OSAHS in patients with morbid obesity and find a simple structured model for predicting the results of polysomnography. METHODS: The study enrolled a group of 101 consecutive inpatients (33 males, age range 20-80 years) with a body mass index > or =40, whose symptoms of OSAHS were not known, and a validation group of 45 patients. RESULTS: Habitual snoring, nocturnal apneas or awakening as well as diurnal sleepiness were frequent findings (90.1, 40.6, 50.5 and 61.4%, respectively). Chronic obstructive pulmonary disease, hypertension, diabetes and myocardial ischemia were also frequently associated (22.8, 56.4, 30.7 and 6.9%, respectively). OSAHS was found in 61 (60.4%) patients, in 33.7% it was of severe degree. A multivariate logistic regression model allowed to select the independent predictors of OSAHS: age, male sex, diurnal sleepiness and the value of minimum nocturnal saturation. Sensitivity of 97%, specificity of 77% as well as positive and negative predictive values of 87% and 95%, respectively, were obtained; similar results were found in the validation group. When the best obtainable cutoff on the receiver operating characteristic curve is below 40%, the instrumental diagnosis might be excluded in as many as 33% of cases, since they are not affected by OSAHS or have OSAHS of mild degree. CONCLUSIONS: OSAHS is present in almost two thirds of morbidly obese patients. By applying the prediction model we propose, one may calculate the probability of a morbidly obese patient of being affected by OSAHS.

End stage chronic obstructive pulmonary disease.

Many patients with chronic obstructive pulmonary disease (COPD) die each year as those with lung cancer but current guidelines make few recommendations on the care for the most severe patients i.e. those with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages III and IV with chronic respiratory failure. Only smoking cessation and long term oxygen therapy (LTOT) improve survival in COPD. Although non invasive positive pressure ventilation (NPPV) may have an adjunctive role in the management of chronic respiratory insufficiency there is little evidence for its use in the routine management of stable hypercapnic COPD patients. At difference, several prospective, randomised, controlled studies, systematic reviews and meta-analyses show good level of evidence for clinical efficacy of NPPV in the treatment of acute on chronic respiratory failure due to acute exacerbations of COPD. NPPV is also alternative to invasive ventilation for symptom relief in end stage COPD. Surgical interventions for end stage COPD like bullectomy, different modalities of lung volume reduction surgery and lung transplantation are likely to be of value to only a small percentage of patients. Nevertheless, there are specific indications, which, when added to pulmonary rehabilitation will further advance exercise capacity and quality of life. As in other chronic diseases when severity of disease increases along the natural history, therapy aimed to prolong life becomes less and less important in comparison to palliative therapy aimed to relieve symptoms. The most effective treatments for dyspnoea are bronchodilators, although also opiates may improve dyspnoea. Supplemental oxygen reduce exertional breathlessness and improve exercise tolerance in hypoxaemic COPD patients. There are difficulties in treating with antidepressant the frail and elderly COPD patients. Good clinical care can prevent or alleviate suffering by assessing symptoms and providing psychological and social support to the patients and their families.

A proposal of a new model for long-term weaning: respiratory intensive care unit and weaning center.

BACKGROUND: Respiratory intermediate care units (RICU) are hospital locations to treat acute and acute on chronic respiratory failure. Dedicated weaning centers (WC) are facilities for long-term weaning. AIM: We propose and describe the initial results of a long-term weaning model consisting of sequential activity of a RICU and a WC. METHODS: We retrospectively analysed characteristics and outcome of tracheostomised difficult-to wean patients admitted to a RICU and, when necessary, to a dedicated WC along a 18-month period. RESULTS: Since February 2008 to November 2009, 49 tracheostomised difficult-to wean patients were transferred from ICUs to a University-Hospital RICU after a mean ICU length of stay (LOS) of 32.6 +/- 26.6 days. The weaning success rate in RICU was 67.3% with a mean LOS of 16.6 +/- 10.9 days. Five patients (10.2%) died either in the RICU or after being transferred to ICU, 10 (20.4%) failed weaning and were transferred to a dedicated WC where 6 of them (60%) were weaned. One of these patients was discharged from WC needing invasive mechanical ventilation for less than 12h, 2 died in the WC, 1 was transferred to a ICU. The overall weaning success rate of the model was 79.6%, with 16.3% and 4.8% in-hospital and 3-month mortality respectively. The model resulted in an overall 39 845 +/- 22 578 euro mean cost saving per patient compared to ICU. CONCLUSION: The sequential activity of a RICU and a WC resulted in additive weaning success rate of difficult-to wean patients. The cost-benefit ratio of the program warrants prospective investigations.