Department of Internal Medicine. University Hospital of Patras. Patras.

Introduction: Oxygen therapy remains the cornerstone for managing patients with severe SARS-CoV-2 infection and several modalities of non-invasive ventilation are used worldwide. High-flow oxygen via nasal canula is one therapeutic option which may in certain cases prevent the need of mechanical ventilation. The aim of this review is to summarize the current evidence on the use of high-flow nasal oxygen in patients with severe SARS-CoV-2 infection.Material and Methods: We conducted a systematic literature search of the databases PubMed and Cochrane Library until April 2021 using the following search terms: “high flow oxygen and COVID-19” and “high flow nasal and COVID-19’’.Results: Twenty-three articles were included in this review, in four of which prone positioning was used as an adjunctive measure. Most of the articles were cohort studies or case series. High-flow nasal oxygen therapy was associated with a reduced need for invasive ventilation compared to conventional oxygen therapy and led to an improvement in secondary clinical outcomes such as length of stay. The efficacy of high-flow nasal oxygen therapy was comparable to that of other non-invasive ventilation options, but its tolerability is likely higher. Failure of this modality was associated with increased mortality.Conclusion: High flow nasal oxygen is an established option for respiratory support in COVID-19 patients. Further investigation is required to quantify its efficacy and utility in preventing the requirement of invasive ventilation.

Observational study of changes in utilization and outcomes in mechanical ventilation in COVID-19

Background The role of non-invasive ventilation (NIV) in severe COVID-19 remains a matter of debate. Therefore, the utilization and outcome of NIV in COVID-19 in an unbiased cohort was determined. Aim The aim was to provide a detailed account of hospitalized COVID-19 patients requiring non-invasive ventilation during their hospital stay. Furthermore, differences of patients treated with NIV between the first and second wave are explored. Methods Confirmed COVID-19 cases of claims data of the Local Health Care Funds with non-invasive and/or invasive mechanical ventilation (MV) in the spring and autumn pandemic period in 2020 were comparable analysed. Results Nationwide cohort of 17.023 cases (median/IQR age 71/61–80 years, 64% male) 7235 (42.5%) patients primarily received IMV without NIV, 4469 (26.3%) patients received NIV without subsequent intubation, and 3472 (20.4%) patients had NIV failure (NIV-F), defined by subsequent endotracheal intubation. The proportion of patients who received invasive MV decreased from 75% to 37% during the second period. Accordingly, the proportion of patients with NIV exclusively increased from 9% to 30%, and those failing NIV increased from 9% to 23%. Median length of hospital stay decreased from 26 to 21 days, and duration of MV decreased from 11.9 to 7.3 days. The NIV failure rate decreased from 49% to 43%. Overall mortality increased from 51% versus 54%. Mortality was 44% with NIV-only, 54% with IMV and 66% with NIV-F with mortality rates steadily increasing from 62% in early NIV-F (day 1) to 72% in late NIV-F (>4 days). Conclusions Utilization of NIV rapidly increased during the autumn period, which was associated with a reduced duration of MV, but not with overall mortality. High NIV-F rates are associated with increased mortality, particularly in late NIV-F.

Awake Prone Positioning, High-Flow Nasal Oxygen and Non-Invasive Ventilation as Non-Invasive Respiratory Strategies in COVID-19 Acute Respiratory Failure: A Systematic Review and Meta-Analysis

Background: Acute respiratory failure is the most important organ dysfunction of COVID-19 patients. While non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) oxygen are frequently used, efficacy and safety remain uncertain. Benefits and harms of awake prone positioning (APP) in COVID-19 patients are unknown. Methods: We searched for randomized controlled trials (RCTs) comparing HFNC vs. NIV and APP vs. standard care. We meta-analyzed data for mortality, intubation rate, and safety. Results: Five RCTs (2182 patients) were identified. While it remains uncertain whether HFNC compared to NIV alters mortality (RR: 0.92, 95% CI 0.65–1.33), HFNC may increase rate of intubation or death (composite endpoint; RR 1.22, 1.03–1.45). We do not know if HFNC alters risk for harm. APP compared to standard care probably decreases intubation rate (RR 0.83, 0.71–0.96) but may have little or no effect on mortality (RR: 1.08, 0.51–2.31). Conclusions: Certainty of evidence is moderate to very low. There is no compelling evidence for either HFNC or NIV, but both carry substantial risk for harm. The use of APP probably has benefits although mortality appears unaffected.

High-Flow Nasal Cannula

Conventionally, oxygen is given at 4 to 6 L/min through nasal cannula for supplementation of oxygen. The FiO2 achieved through this can be up to 0.4. Flows more than this can cause dryness to the nasal mucosa without much increase in the FiO2. High-flow nasal cannula (HFNC) uses flow up to 60 L/min. Positive end-expiratory pressure is created in the nasopharynx and it is also conducted to the lower airways. Studies have shown HFNC improves washout of CO2 and decreases respiratory rate. Patient compliance also improves due to the comfort of the cannula compared to the non-invasive ventilation through a mask.

Evidence-Based Mechanical Ventilatory Strategies in ARDS

Acute respiratory distress syndrome (ARDS) remains one of the leading causes of morbidity and mortality in critically ill patients despite advancements in the field. Mechanical ventilatory strategies are a vital component of ARDS management to prevent secondary lung injury and improve patient outcomes. Multiple strategies including utilization of low tidal volumes, targeting low plateau pressures to minimize barotrauma, using low FiO2 (fraction of inspired oxygen) to prevent injury related to oxygen free radicals, optimization of positive end expiratory pressure (PEEP) to maintain or improve lung recruitment, and utilization of prone ventilation have been shown to decrease morbidity and mortality. The role of other mechanical ventilatory strategies like non-invasive ventilation, recruitment maneuvers, esophageal pressure monitoring, determination of optimal PEEP, and appropriate patient selection for extracorporeal support is not clear. In this article, we review evidence-based mechanical ventilatory strategies and ventilatory adjuncts for ARDS.

Mid-regional proadrenomedullin (MR-proADM), C-reactive protein (CRP) and other biomarkers in the early identification of disease progression in patients with COVID-19 in the acute NHS setting

AimsThere is a lack of biomarkers validated for assessing clinical deterioration in patients with COVID-19 on presentation to secondary or tertiary care. This evaluation looked at the potential clinical application of C reactive protein (CRP), procalcitonin, mid-regional proadrenomedullin (MR-proADM) and white cell count to support prediction of clinical outcomes.Methods135 patients presenting to Hampshire Hospitals NHS Foundation Trust between April and June 2020 confirmed to have COVID-19 via reverse-transcription-qPCR were included. Biomarkers from within 24 hours of presentation were used to predict disease progression by Cox regression and area under the receiver operating characteristic curves. The endpoints assessed were 30-day all-cause mortality, intubation and ventilation, critical care admission and non-invasive ventilation (NIV) use.ResultsElevated MR-proADM was shown to have the greatest ability to predict 30-day mortality adjusting for age, cardiovascular disease, renal disease and neurological disease. A significant association was also noted between raised MR-proADM and CRP concentrations and the requirement for critical care admission and NIV.ConclusionsThe measurement of MR-proADM and CRP in patients with confirmed COVID-19 infection on admission shows significant potential to support clinicians in identifying those at increased risk of disease progression and need for higher level care, subsequently enabling prompt escalation in clinical interventions.

Safety and clinical outcomes of remdesivir in hospitalised COVID-19 patients: a retrospective analysis of active surveillance database

Background Real-world data on safety and clinical outcomes of remdesivir in COVID-19 management is scant. We present findings of data analysis conducted for assessing the safety and clinical outcomes of remdesivir treatment for COVID-19 in India. Methods This retrospective analysis used data from an active surveillance programme database of hospitalised patients with COVID-19 who were receiving remdesivir. Results Of the 2329 patients included, 67.40% were men. Diabetes (29.69%) and hypertension (20.33%) were the most common comorbidities. At remdesivir initiation, 2272 (97.55%) patients were receiving oxygen therapy. Remdesivir was administered for 5 days in 65.38% of patients. Antibiotics (64.90%) and steroids (47.90%) were the most common concomitant medications. Remdesivir was overall well tolerated, and total 119 adverse events were reported; most common were nausea and vomiting in 45.40% and increased liver enzymes in 14.28% patients. 84% of patients were cured/improved, 6.77% died and 9.16% showed no improvement in their clinical status at data collection. Subgroup analyses showed that the mortality rate was significantly lower in patients < 60 years old than in those > 60 years old. Amongst patients on oxygen therapy, the cure/improvement rate was significantly higher in those receiving standard low-flow oxygen than in those receiving mechanical ventilation, non-invasive ventilation, or high-flow oxygen. Factors that were associated with higher mortality were age > 60 years, cardiac disease, diabetes high flow oxygen, non-invasive ventilation and mechanical ventilation. Conclusion Our analysis showed that remdesivir is well tolerated and has an acceptable safety profile. The clinical outcome of cure/improvement was 84%, with a higher improvement in patients < 60 years old and on standard low-flow oxygen.

Non-invasive Respiratory Support in COVID-19: A Narrative Review

Acute respiratory failure secondary to COVID-19 pneumonia may require a variety of non-pharmacological strategies in addition to oxygen therapy to avoid endotracheal intubation. The response to all these strategies, which include high nasal flow, continuous positive pressure, non-invasive ventilation, or even prone positioning in awake patients, can be highly variable depending on the predominant phenotypic involvement. Deciding when to replace conventional oxygen therapy with non-invasive respiratory support, which to choose, the role of combined methods, definitions, and attitudes toward treatment failure, and improved case improvement procedures are directly relevant clinical questions for the daily care of critically ill COVID-19 patients. The experience accumulated after more than a year of the pandemic should lead to developing recommendations that give answers to all these questions.

Italian survey on non-intubated thoracic surgery: results from INFINITY group

Background Non-Intubated Thoracic Surgery (NITS) is becoming increasingly adopted all over the world. Although it is mainly used for pleural operations,, non-intubated parenchymal lung surgery has been less frequently reported. Recently, NITS utilization seems to be increased also in Italy, albeit there are no multi-center studies confirming this finding. The objective of this survey is to assess quantitatively and qualitatively the performance of NITS in Italy. Methods In 2018 a web-based national survey on Non-Intubated management including both thoracic surgeons and anesthesiologists was carried out. Reference centers have been asked to answer 32 questions. Replies were collected from June 26 to November 31, 2019. Results We raised feedbacks from 95% (55/58) of Italian centers. Seventy-eight percent of the respondents perform NITS but only 38% of them used this strategy for parenchymal surgery. These procedures are more frequently carried out in patients with severe comorbidities and/or with poor lung function. Several issues as obesity, previous non-invasive ventilation and/or oxygen therapy are considered contraindications to NITS. The regional anesthesia technique most used to provide intra- and postoperative analgesia was the paravertebral block (37%). Conversion to general anesthesia is not anecdotal (31% of answerers). More than half of the centers believed that NITS may reduce postoperative intensive care unit admissions. Approximately a quarter of the centers are conducting trials on NITS and, three quarters of the respondent suppose that the number of these procedures will increase in the future. Conclusions There is a growing interest in Italy for NITS and this survey provides a clear view of the national management framework of these procedures.