Covid-19: A systemic disease treated with a wide-ranging approach: A case report.

Novel Coronavirus COVID-19: Current Evidence and Evolving Strategies.

Role of Helmet-Delivered Noninvasive Pressure Support Ventilation in COVID-19 Patients

High-flow nasal cannula (HFNC) and ventilator-delivered non-invasive mechanical ventilation (NIV) were used to treat acute respiratory distress syndrome (ARDS) due to COVID-19 pneumonia, especially in low- and middle-income countries (LMICs), due to lack of ventilators and manpower resources despite the paucity of data regarding their efficacy. This prospective study aimed to analyse the efficacy of HFNC versus NIV in the management of COVID-19 ARDS. A total of 88 RT-PCR-confirmed COVID-19 patients with moderate ARDS were recruited. Linear regression and generalized estimating equations (GEEs) were used for trends in vital parameters over time. A total of 37 patients were on HFNC, and 51 were on NIV. Patients in the HFNC group stayed slightly but not significantly longer in the ICU as compared to their NIV counterparts (HFNC vs. NIV: 8.00 (4.0-12.0) days vs. 7.00 (2.0-12.0) days; p = 0.055). Intubation rates, complications, and mortality were similar in both groups. The switch to HFNC from NIV was 5.8%, while 37.8% required a switch to NIV from HFNC. The resolution of respiratory alkalosis was better with NIV. We conclude that in patients with COVID-19 pneumonia with moderate ARDS, the duration of treatment in the ICU, intubation rate, and mortality did not differ significantly with the use of HFNC or NIV for respiratory support.

Introduction Pneumonia caused by a novel coronavirus known as 2019 novel coronavirus disease (COVID-19)[1] appeared in Wuhan, China in December 2019, and approximately 15% to 30% of patients developed acute respiratory distress syndrome within a short period of time.[2,3] To reduce respiratory symptoms and improve prognosis, respiratory support is the most important means of life support,[1] and non-invasive respiratory support systems,[2] including various conventional oxygen therapies, non-invasive positive pressure ventilation (NPPV), and high-flow nasal cannula (HFNC), are most commonly used. However, their efficacy and safety remain unclear, and whether they increase the risk of aerosol dispersion and disease transmission is particularly controversial.[4,5] Given that there are many similarities between COVID-19 pneumonia and severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS),[6] this study primarily discusses clinical indications and provides details regarding the prevention of nosocomial infections during NPPV and HFNC treatment of COVID-19 pneumonia based on previous clinical data on the use of these two therapies for SARS and MERS and our experience with the treatment of COVID-19 pneumonia. Clinical Efficacy of NPPV NPPV can reduce the rate of tracheal intubation; therefore, theoretically, it can significantly reduce the risk of infection of medical personnel during tracheal intubation and artificial airway management for COVID-19 pneumonia patients.[7] A recent retrospective epidemiological study of 99 COVID-19 pneumonia patients in China[2] revealed that NPPV is the most commonly used mechanical ventilation method for acute respiratory failure. The rates of using non-invasive and invasive mechanical ventilation are 13% and 4%, respectively; however, the efficacies of these ventilation methods need to be further investigated. There are little clinical data on NPPV for SARS,[4,5] of which most are small-sample, single-center retrospective studies from China, and the NPPV failure rate is approximately 20% to 40%. Cheung et al[8] in their study of 20 Hong Kong patients with SARS and acute respiratory failure (oxygen flow >6 L/min, pulse oxygen saturation [SpO2] 93–96%) revealed that NPPV could prevent tracheal intubation in 70% of patients and significantly reduce the time spent in the intensive care unit. Reports on NPPV for the treatment of MERS are also limited.[9] Because the degree of lung and extra-pulmonary injuries in patients with MERS is significantly higher than that in patients without MERS,[9] the failure rate of NPPV is relatively high (60–70%). In addition, current evidence and clinical guideline[10] do not recommend NPPV for treating acute hypoxic respiratory failure and pandemic viral illness. Therefore, we believe that NPPV should currently not be used as a first-line treatment to correct respiratory failure in patients with COVID-19 pneumonia. For strictly selected early-stage patients with mild-to-moderate (partial pressure of arterial oxygen [PaO2]/fraction of inspired oxygen [FiO2] >200 mmHg) hypoxic respiratory failure and especially for units with limited numbers of invasive ventilators, it is recommended that NPPV be attempted for short periods of time (1–2 h)[1,8,11] and intubation be performed immediately if no improvement is observed. In addition, early-stage identification of high-risk factors (shock, metabolic acidosis; multiple organ failure; PaO2/FiO2 ≤175 mmHg at 1 h after NPPV treatment; severe hypoxemia with PaO2/FiO2 ≤147 mmHg; Simplified Acute Physiology Score II >34; tidal volume >9.5 mL/kg; elevated partial pressure of arterial carbon dioxide (PaCO2); respiratory rate >30 breaths/min) for NPPV failure in the treatment of hypoxic respiratory failure can improve the safety of NPPV treatment.[11] NPPV should be avoided in patients with hemodynamic instability, multiple organ failure, disorders of consciousness, or mucus drainage disorders.[1] NPPV Aerosol Dispersion and Disease Transmission Problems Notably, NPPV can lead to aerosol transmission during use. In vitro simulation experiments have shown that NPPV can lead to the dispersion of exhaled aerosols within 1 m of patients. In addition, the dispersion range increases with increased air leakage and increased inspiratory pressure,[12,13] such that the World Health Organization considers NPPV to be an important form of aerosol transmission in patient wards. However, clinical studies on the use of NPPV for SARS did not clearly demonstrate that NPPV increases the risk of infection transmission between infected patients and medical staffs.[4,8] Conversely, NPPV masks may also reduce aerosol exhalation during coughing and talking.[4,5] Recent studies have shown that NPPV is a low-risk airborne route with good interface fitting.[1,14] Therefore, it is still unclear whether NPPV increases the risk of aerosol diffusion and disease transmission, especially with respect to transmission to medical personnel.[4] The use of NPPV for COVID-19 pneumonia still requires strict control of the medical environment and vigilance and monitoring of the infection risk to medical personnel. Table 1 shows specific prevention and control measures for preventing aerosol production and disease transmission in patient wards during NPPV.[7,15]Table 1: Nosocomial infection prevention and control measures during non-invasive positive pressure ventilation treatment of 2019 novel coronavirus disease (COVID-19).Clinical Efficacy of HFNC HFNC is a new form of non-invasive respiratory support[16] that can be adjusted to a maximum gas flow of 60 to 80 L/min and an FiO2 of 0.21 to 1.0. No clinical data exist regarding the use of HFNC for SARS, MERS, or COVID-19, and the clinical efficacy of HFNC needs to be further investigated. However, for patients with non-infectious mild-to-moderate hypoxic respiratory failure, compared with conventional oxygen therapy, HFNC can reduce the rate of tracheal intubation and mortality.[17] Therefore, HFNC treatment for COVID-19 pneumonia can be attempted when hypoxemia cannot be treated using conventional oxygen therapy devices, NPPV cannot be tolerated, or in the following situations[1]: mild-to-moderate hypoxemia (100 mmHg ≤ PaO2/FiO2 < 300 mmHg); no indications for emergency tracheal intubation; and relatively stable vital signs. HFNC should be avoided in patients with hemodynamic instability, multiple organ failure, or disorders of consciousness. The therapeutic response should be closely monitored (1–2 h) after HFNC treatment. The patient should be switched to non-invasive or invasive positive pressure ventilation if the following conditions persist: respiratory rate >30 breaths/min; SpO2 <88% to 90%; paradoxical breathing and/or continuous assisted respiratory muscle activity; pH <7.35; or PaCO2 >45 mmHg.[18] Nosocomial Infection Prevention and Control During HFNC Therapy To prevent and control the nosocomial infection during HFNC therapy, we provide the following suggestions based on our experience: (1) disposable, single-use high-flow nasal plugs and tubing should be used during HFNC treatment; (2) patients should be instructed to breathe with the mouth closed as much as possible while wearing surgical masks or oxygen mask; (3) condensation in the circuit should be cleaned in a timely manner to avoid production of aerosols caused by high flow gas and condensed water entering the nasal cavity, stimulating coughing in patients; (4) recent evidence shows that the dispersion distance of exhaled gases during HFNC treatment is limited, and the risk of airborne transmission is low.[14,19] However, loose connections between HFNC and nasal plugs significantly increase the dispersion distance of exhaled gases (from 172 to 620 mm).[14,19] Therefore, attention should be paid to correct the positioning and wearing of high-flow nasal plugs. Funding This study was supported by grants from the National Key Research and Development Program of China (No. 2016YFC1304300), Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (No. 2018- I2M-1-003), Non-profit Central Research Institute Fund of CAMS (No. 2019TX320006), and the National Natural Science Foundation of China (No. 81870072). Conflicts of interest None.

SARS-CoV-2 & influenza A virus co-infection in an elderly patient with pneumonia.

The impact of different ventilatory support modalities and timing of intubation on longitudinal lung recovery trajectories in patients with severe coronavirus disease 2019 (COVID-19) is unknown. This was a multicentre, prospective observational study conducted in 52 Spanish intensive care units (ICUs) involving critically ill COVID-19 patients admitted between 25 February 2020 and 8 February 2021. 1854 COVID-19 patients were followed after hospital discharge at 3, 6 and 12 months with diffusing capacity of the lung for carbon monoxide (D LCO) measurements and chest imaging. Patients were classified regarding the ventilatory support received during the ICU stay: noninvasive mechanical ventilation (NIMV), high-flow nasal cannula (HFNC) and invasive mechanical ventilation (IMV), divided into early IMV (intubation within 24 h) and late IMV (intubation after 24 h). The primary objective was to evaluate the impact of the different respiratory support modalities during the ICU stay and the time of intubation on D LCO measurements and their recovery trajectories over a 1-year follow-up. Secondary outcomes included other pulmonary function parameters and chest imaging findings. A total of 360 (19.4%) and 290 (15.6%) patients received HFNC and NIMV, respectively. 1204 (64.9%) patients underwent IMV; 966 received early IMV and 238 received late IMV. The latter exhibited a significantly worse percentage predicted D LCO during the 1-year follow-up with adjusted differences of 6.9 (95% CI 3.9-10; p<0.001), 4.2 (95% CI 1.1-7.2; p=0.007) and 4.9 (95% CI 1.7-8.2; p=0.003) at 3, 6 and 12 months compared with early IMV. NIMV patients exhibited greater lung damage at follow-up than those under HFNC with an adjusted difference of percentage predicted D LCO of 5.2 (95% CI 1.7-8.7; p=0.003) at 6 months and greater presence of radiological abnormalities during follow-up. Matched and sensitivity analysis showed results consistent with those reported. Delay in intubation implies the worst outcomes; however, patients with NIMV exhibited a slower lung recovery in terms of D LCO measurements and more radiological abnormalities compared with HFNC patients. These results should be used to optimise follow-up protocols for COVID-19 acute respiratory distress syndrome (ARDS) survivors.

In late 2019, a novel coronavirus later named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as a cause of pneumonia in Wuhan, China. The World Health Organization named the disease coronavirus disease 2019 (COVID-19) and, on 11 March 2020, characterized COVID-19 as a pandemic. As of late July 2020, over 15 million confirmed cases have been reported globally with a case fatality rate of 4%. In the United States, as of July 23, there are nearly 4 million confirmed cases with over 140 000 deaths.1 This commentary focuses on the respiratory management of adults with COVID-19-associated hypoxaemic respiratory failure and acute respiratory distress syndrome (ARDS). The pathophysiological mechanisms in COVID-19 include airflow obstruction, ARDS and 'cytokine storm'. Gattinoni et al. described two phenotypes of ARDS: type L (low elastance, high compliance and patchy ground-glass opacities on chest imaging) and type H (high elastance, low compliance, diffuse and bilateral infiltrates on chest imaging).2 Histological examination shows diffuse alveolar damage, hyaline membrane formation, type 2 pneumocyte hyperplasia, multinucleated giant cells and platelet-fibrin thrombi in small vessels and capillaries of the lung. The most common symptoms are fever, cough and shortness of breath. The disease course is variable with an incubation period of up to 14 days (median: 5 days).3 Diagnosis of COVID-19 is made by the detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing of a nasal or nasopharyngeal swab. Laboratory findings in the acute phase include lymphopenia, elevated C-reactive protein, ferritin, d-dimer, fibrinogen and lactate dehydrogenase, and normal or low procalcitonin. The hypoxaemic respiratory failure and ARDS observed in COVID-19 range from mild to severe. Basic management principles may be applied based on the type L or H phenotype. Type L patients respond to an increase in fraction of inspired oxygen (FiO2) with nasal cannula, high-flow nasal oxygen (HFNO) or non-invasive ventilation (NIV). Type H patients who require mechanical ventilation should be managed following the traditional ARDSnet ventilator protocol.4 Hospitalized patients with mild symptomatic respiratory insufficiency require supplemental oxygen via nasal canula (up to 6 L) to maintain arterial O2 saturation greater than 90%. Bronchodilators, if needed, should be administered via metred dose inhalers instead of nebulizers to prevent aerosolization of the virus. Patients with moderate hypoxaemic respiratory failure are those requiring HFNO, non-rebreather masks or NIV. Controversy exists regarding the safety of bilevel positive pressure ventilation (BiPAP), continuous positive airway pressure ventilation (CPAP) and HFNO, given the risk of aerosolization with these devices to healthcare providers. Professional societies recommend their use with airborne precautions and appropriate personal protective equipment (PPE), preferably in a negative pressure room.5 CPAP has a theoretical benefit of being able to provide the highest mean airway pressures, thus helping with alveolar recruitment. The National Health Service (United Kingdom) recommends the use of NIV with a non-vented mask, an exhalation port and a bacterial/viral filter between the mask and oxygen, over HFNO given the lower risk of aerosolization.6 Another strategy in patients with mild to moderate respiratory failure is awake proning. Proning facilitates oxygenation by improving ventilation/perfusion mismatch with increased perfusion to the healthier alveoli in the anterior lung, improved secretion management and alveolar recruitment in the posterior lung. Larger epidemiological studies have reported rates of invasive mechanical ventilation ranging from 2.3% to 33.1% of hospitalized COVID-19 patients and 29.1% to 89.9% among patients admitted to the intensive care unit (ICU).7 Risk factors of ARDS and need for ICU admission include age >60 years, male gender and comorbidities such as heart disease, diabetes mellitus, chronic lung disease, immunocompromised state and malignancy.3 Given that COVID-19 may cause hypoxia with minimal respiratory distress ('silent hypoxia'), the threshold for intubation should be lower particularly for those patients with persistent hypoxia despite escalation to HFNO and exhibiting shortness of breath. When needed, rapid sequence intubation technique without bagging should be used. Intubation should be performed by the most experienced clinician under strict airborne precautions. Other considerations include use of dry ventilator circuits, heat moisture exchangers and bacterial/viral filters at exhalation ports. The approach to mechanical ventilation in COVID-19 patients should adhere to evidence-based practices utilized in the general population with ARDS.2, 3, 8 Ventilatory strategies to implement are low tidal volume ventilation (tidal volume 6 mL/kg of predicted body weight) and targeting plateau pressures of <30 cm H2O. There are no studies of high versus low positive end-expiratory pressure (PEEP) in patients with COVID-19 ARDS; however, previous studies on non-COVID ARDS patients showed that high PEEP strategies reduced ICU and in-hospital mortality and need for rescue measures. Prone ventilation should be considered in mechanically ventilated patients with moderate to severe ARDS. Neuromuscular blocking agents may be necessary in proned patients along with deep sedation and in patients with severe ventilator dyssynchrony, severe hypoxaemia and persistently high plateau pressures. Extracorporeal membrane oxygenation (ECMO) may serve as life-saving rescue therapy for refractory ARDS. However, it is resource intensive and not widely available. To summarize, the timing of intubation, use of high versus low PEEP, high versus low tidal volume ventilation, prone positioning and ECMO are the most important factors to consider while keeping the patient's preferences at the forefront. Table 1 provides a summary of the oxygen therapies and ventilator strategies employed by ICU globally to treat patients with COVID-19 respiratory failure.7 Most recently, based on the results of the Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial, corticosteroids (i.e. dexamethasone 6 mg per day for up to 10 days) are recommended for patients who are mechanically ventilated, and in patients who require supplemental oxygen but who are not mechanically ventilated.17 The pandemic has posed unprecedented challenges to the healthcare system, given the number of patients, illness severity and limited number of ventilators. Disaster ventilator strategies such as use of one ventilator for multiple people (splitting ventilators), home BiPAP and anaesthesia ventilators have been proposed. The challenges of splitting ventilators include the patient's interaction with the ventilator and simultaneously affecting other patients connected to the ventilator, suboptimal ventilation given increase in the dead space, increased need for deep sedation and paralysis, and cross contamination. Professional societies recently issued a joint statement advising against the use of split ventilator strategy.18 Finally, patients and front-line clinicians should be optimally prepared for extubation in an airborne isolation room and with appropriate PPE as it is usually associated with coughing and could cause aerosolization of the virus. This manuscript was supported, in part, by the Core Grant (P30 CA008748) and the Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.

Controversies in airway management of COVID-19 patients: updated information and international expert consensus recommendations

BackgroundCalcium release-activated calcium (CRAC) channel inhibitors block proinflammatory cytokine release, preserve endothelial integrity and may effectively treat patients with severe COVID-19 pneumonia.MethodsCARDEA was a phase 2, randomized, double-blind, placebo-controlled trial evaluating the addition of Auxora, a CRAC channel inhibitor, to corticosteroids and standard of care in adults with severe COVID-19 pneumonia. Eligible patients were adults with ≥ 1 symptom consistent with COVID-19 infection, a diagnosis of COVID-19 confirmed by laboratory testing using polymerase chain reaction or other assay, and pneumonia documented by chest imaging. Patients were also required to be receiving oxygen therapy using either a high flow or low flow nasal cannula at the time of enrolment and have at the time of enrollment a baseline imputed PaO2/FiO2 ratio > 75 and ≤ 300. The PaO2/FiO2 was imputed from a SpO2/FiO2 determine by pulse oximetry using a non-linear equation. Patients could not be receiving either non-invasive or invasive mechanical ventilation at the time of enrolment. The primary endpoint was time to recovery through Day 60, with secondary endpoints of all-cause mortality at Day 60 and Day 30. Due to declining rates of COVID-19 hospitalizations and utilization of standard of care medications prohibited by regulatory guidance, the trial was stopped early.ResultsThe pre-specified efficacy set consisted of the 261 patients with a baseline imputed PaO2/FiO2≤ 200 with 130 and 131 in the Auxora and placebo groups, respectively. Time to recovery was 7 vs. 10 days (P = 0.0979) for patients who received Auxora vs. placebo, respectively. The all-cause mortality rate at Day 60 was 13.8% with Auxora vs. 20.6% with placebo (P = 0.1449); Day 30 all-cause mortality was 7.7% and 17.6%, respectively (P = 0.0165). Similar trends were noted in all randomized patients, patients on high flow nasal cannula at baseline or those with a baseline imputed PaO2/FiO2 ≤ 100. Serious adverse events (SAEs) were less frequent in patients treated with Auxora vs. placebo and occurred in 34 patients (24.1%) receiving Auxora and 49 (35.0%) receiving placebo (P = 0.0616). The most common SAEs were respiratory failure, acute respiratory distress syndrome, and pneumonia.ConclusionsAuxora was safe and well tolerated with strong signals in both time to recovery and all-cause mortality through Day 60 in patients with severe COVID-19 pneumonia. Further studies of Auxora in patients with severe COVID-19 pneumonia are warranted.Trial registration NCT04345614.

The worldwide spread of coronavirus disease 2019 (COVID-19), caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic by the World Health Organization (WHO) in March 2020. According to clinical studies carried out in China and Italy, most patients experience mild or moderate symptoms; about a fifth of subjects develop a severe and critical disease, and may suffer from interstitial pneumonia, possibly associated with acute respiratory distress syndrome (ARDS) and death.In patients who develop respiratory failure, timely conventional oxygen therapy through nasal catheter plays a crucial role, but it can be used only in mild forms. Continuous positive airway pressure (CPAP) support or non-invasive mechanical ventilation (NIV) are uncomfortable, and require significant man–machine cooperation. Herein we describe our experience of five patients with COVID-19, who were treated with high-flow nasal cannula (HFNC) after failure of CPAP or NIV, and discuss the role of HFNC in COVID-19 patients. Our findings suggest that HFNC can be used successfully in selected patients with COVID-19-related ARDS.The reviews of this paper are available via the supplemental material section.

To investigate the value of high flow nasal cannula (HFNC) in treating a patient with Middle East respiratory syndrome (MERS). The effect of HFNC applied in the first imported MERS patient with complication of acute respiratory distress syndrome (ARDS) to China was observed. The patient was admitted to Department of Critical Care Medicine of Huizhou Municipal Central Hospital on May 28th, 2015, and the changes in various clinical parameters and their significance were analyzed. A 43-year old male was admitted to negative pressure isolation intensive care unit with the complaint of back ache for 7 days and fever for 2 days. Vital signs and saturation of pulse oximetry (SpO2) were monitored continuously. After admission, ribavirin was given orally for 12 days and α-interferon was administered once on the first day. However, after 2-week anti-virus therapy, the virus test was positive. Ceftriaxone was given on the 4th day, and it was changed to meropenem on the 3rd day for 2 weeks. Immune globulin was given on the 4th day and continued for 1 week. Thymosin-α1 was given on the 8th day and continued for 2 weeks. According to his past history, methimazole had been given continuously for hyperthyroidism and other symptomatic treatment. Oxygen inhalation (6 L/min) was given immediately after admission, but the condition of patient worsened with the following symptoms: frequent cough and obvious shortness of breath. Moreover pleural effusion gradually increased as shown by X-ray. SPO2 was maintained only at about 0.91. Oxygenation index (PaO2/FiO2) decreased to 144 mmHg (1 mmHg = 0.133 kPa). So oxygen inhalation via nasal cannula was changed to HFNC after 2 days. The parameters were set as follows: temperature 34 degrees C, flow rate 20 L/min, fraction of inspired oxygen (FiO2) 0.50. The flow was raised 5 L/min every 10 minutes, and was continued till the target value reached 60 L/min. FiO2 was modified according to SpO2 and PaO2/FiO2. FiO2 was set to 0.80 on the 5th day of admission. Shortness of breath of the patient was improved on the 7th day of admission after the application of HFNC. FiO2 was then decreased to 0.58 as PaO2/FiO2 rose. Then the flow was gradually decreased to 30 L/min. HFNC was reduced with continuous improvement in PaO2/FiO2. HFNC was changed to low flow oxygen inhalation nasal cannula (2-3 L/min) on the 20th day. Oxygen treatment was stopped on the 23rd day, and SpO2 was maintained at 0.98-1.00. Activities on bed were gradually increased. The patient was cured and discharged from hospital on June 26th. The patient showed good tolerance and high compliance during the treatment with HFNC. No nosocomial spread occurred during the treatment. HFNC could improve respiratory function of the patient with MERS obviously, and complication ARDS was prevented. HFNC might reduce nosocomial spread.

IntroductionMost hospitalized patients required invasive or non-invasive ventilation and High Flow Nasal Cannula (HFNC). Therefore, this study was conducted to describe the characteristics of patients with severe Coronavirus Disease—2019 (COVID-19) treated by HFNC and its effectiveness for reducing the rate of intubated—mechanical ventilation in the Intensive Care Unit (ICU) of Phu Chanh COVID-19 Department—Binh Duong General Hospital.MethodsIt was a cross-sectional and descriptive study. All severe patients with COVID-19 with acute respiratory failure eligible for the study were included. Patient characteristics, clinical symptoms, laboratory results, and treatment methods were collected for analysis; parameters and data related to HFNC treatment and follow-up were analysed.Results80 patients, aged of 49.7 ± 16.6 years, were treated with HFNC at admission in ICU. 14 patients had type 2 diabetes (17.5%), 3 patients had chronic respiratory disease (3.8%), 19 patients had high blood pressure (23.8%), and 5 patients with other comorbidities (7.4%). The majority of patients with severe COVID-19 had typical symptoms of COVID-19 such as shortness of breath (97.5%), intensive tired (81.3%), cough (73.7%), anosmia (48.3%), ageusia (41.3%), and fever (26.3%). The results of arterial blood gases demonstrated severe hypoxia under optimal conventional oxygen therapy (PaO2 = 52.5 ± 17.4 mmHg). Respiratory rate, SpO2, PaO2 were significantly improved after using HFNC at 1st day, 3rd day and 7th day (P < 0.05; P < 0.05; P < 0.01; respectively). Receiver operating characteristics (ROC) index was significantly increased after treating with HFNC vs before HFNC treatment (4.79 ± 1.86, 5.53 ± 2.39, and 7.41 ± 4.24 vs 2.97 ± 0.39; P < 0.05, P < 0.05 and P < 0.01, respectively). 54 (67.5%) patients were success with HFNC treatment and 26 (32.5%) patients with HFNC failure needed to treat with Continuous Positive Airway Pressure (CPAP) (13 patients; 50%) or intubated ventilation (13 patients; 50%).ConclusionHFNC therapy could be considered as a useful and effective alternative treatment for patients with acute respiratory failure. HFNC might help to delay the intubated ventilation for patients with respiratory failure and to minimise the risk of invasive ventilation complications and mortality. However, it is crucial to closely monitor the evolution of patient's respiratory status and responsiveness of HFNC treatment to avoid unintended delay of intubation—mechanical ventilation. Trial Registration: An independent ethics committee approved the study (The Ethics Committee of Binh Duong General Hospital; No. HDDD-BVDK BINH DUONG 9.2021), which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice.

The epidemiological history of some patients infected with novel coronavirus (2019-nCoV) is unclear, and the incubation period of the virus can last for 2 weeks, even longer. During the period of latent infection or the period of incubation following infection, the disease may be infectious. As in cases of influenza, some patients develop only upper respiratory tract infection, whereas others with a severe form of the disease develop pneumonia. Patients may not have fever, mild cough, or apparent respiratory symptoms, and headache or gastrointestinal symptoms may be present. Some patients show insidious onset and slow progression, and do not appear to be sick. Thus, they may not receive attention or be identified. Some patients with severe disease or critical illness may present with moderate-to-low-grade fever, but apparent fever may also be absent. Even though several clinical studies have assessed the use of corticosteroids in acute respiratory distress syndrome (ARDS) and severe viral pneumonia, it remains unclear whether corticosteroids treatment can decrease mortality and improve patients' outcomes. In ARDS, corticosteroids are believed to antagonize certain pathophysiologic processes, including hyperinflammation, excessive cell proliferation, and aberrant collagen deposition.[1] However, evidence-based clinical research gives us other insights. As for severe acute respiratory syndrome, a retrospective study revealed that patients receiving corticosteroids treatment had poorer outcomes, such as higher risk of intensive care unit admission and higher mortality, even though they were younger and had fewer underlying diseases.[2] Furthermore, it was found that corticosteroids did not improve mortality and could delay viral nucleic acid clearance in Middle-East respiratory syndrome, which is also caused by a coronavirus.[3] A large meta-analysis which included 16 studies on influenza A virus subtype H1N1 infection showed that corticosteroids increased mortality.[4] In contrast, other studies reported that short-term treatment with corticosteroids may decrease the risk of ARDS and shorten the length of the disease in patients with severe community-acquired pneumonia.[5] In addition, the use of corticosteroids in ARDS caused by Pneumocystis carinii pneumonia has obtained widespread acceptance, as it can improve oxygenation and patients' outcomes.[6] At present, the World Health Organization does not recommend routinely applying systemic corticosteroids for the treatment of viral pneumonia or ARDS, except in clinical trials.[7] However, the "Novel Coronavirus Pneumonia Diagnosis and Treatment Protocol (5th edition, trial)" recommended short-term (3–5 days) treatment with corticosteroids for severely and critically ill cases should be based on the comprehensive assessment of patients' dyspnea level and the progression observed on chest imaging, with the dose not exceeding a methylprednisolone equivalent dose of 1 to 2 mg/kg/day.[8] Currently, there is insufficient evidence of the value of corticosteroids in the treatment of coronavirus disease 2019 (COVID-19), and further high-quality randomized controlled trials (RCTs) are warranted. Despite the numerous RCTs on ARDS in the last 30 years, there has been no significant reduction in ARDS mortality. ARDS caused by 2019-nCoV appears to be more severe than that observed routinely. In this outbreak of COVID-19, the majority of critically ill patients have been aged 50 years and above, with a large number of them aged 70 to 80 years. These patients often had underlying diseases such as hypertension, diabetes, and coronary heart diseases, with some having multiple underlying diseases. Our previous clinical experience and observations indicated that many patients with severe illness receiving high-flow nasal cannula (HFNC) oxygen therapy or non-invasive ventilation (NIV) (fraction of inspired oxygen [FiO2] of 1.0) have oxygenation indexes (partial pressure of arterial oxygen [PaO2]/FiO2) below 150 mmHg or even lower than 100 mmHg. We observed that such oxygenation support was required for a longer time, indicating that the hypoxic duration in these patients was longer. Extended durations of hypoxia can cause irreversible organ damage. Even with the subsequent use of invasive ventilation or extracorporeal membrane oxygenation (ECMO), the rate of successful resuscitation in such patients remains very low. Therefore, we suggest that patients with an oxygenation index below 150 mmHg after being treated with NIV for 2 h with an FiO2 of 1.0 or a relatively high FiO2 should receive endotracheal intubation as soon as possible to enable invasive ventilation. WHO's interim guidance also suggested that HFNC and NIV should only be used in selected patients with hypoxemic respiratory failure, and patients treated with either HFNC or NIV should be closely monitored for clinical deterioration.[7] If oxygenation index remains below 100 mmHg after invasive ventilation for 24 h with high positive end-expiratory pressure in prone position, ECMO should be used promptly. This is consistent with the recommendations of Chinese Society of Extracorporeal Life Support.[9] The "Novel Coronavirus Pneumonia Diagnosis and Treatment Protocol (5th edition, trial)" also recommended that endotracheal intubation and invasive mechanical ventilation should be performed promptly if the condition does not improve or even deteriorate within a short period of time (1–2 h) when using HFNC or NIV, and in case invasive mechanical ventilation in prone position is ineffective, ECMO should be performed at the earliest if possible.[8] The use of personal experience to guide treatment is not recommended. Supportive treatment remains the mainstay for COVID-19. Respiratory support ensures that the patient is not hypoxic and also protects other organs. There are currently no effective anti-viral drugs, and anti-microbial drugs should be administered strictly and rationally. Shuanghuanglian and similar drugs have demonstrated inhibitory effects against the virus in in vitro experiments. However, their clinical effects are unknown, and further investigations are required to demonstrate their efficacy. Conflicts of interest None.

BackgroundThe ratio of partial pressure of arterial oxygen to inspired oxygen fraction (PaO2/FIO2) during invasive mechanical ventilation (MV) is used as criteria to grade the severity of respiratory failure in acute respiratory distress syndrome (ARDS). During the SARS-CoV2 pandemic, the use of PaO2/FIO2 ratio has been increasingly used in non-invasive respiratory support such as high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV). The grading of hypoxemia in non-invasively ventilated patients is uncertain. The main hypothesis, investigated in this study, was that the PaO2/FIO2 ratio does not change when switching between MV, NIV and HFNC.MethodsWe investigated respiratory function in critically ill patients with COVID-19 included in a single-center prospective observational study of patients admitted to the intensive care unit (ICU) at Uppsala University Hospital in Sweden. In a steady state condition, the PaO2/FIO2 ratio was recorded before and after any change between two of the studied respiratory support techniques (i.e., HFNC, NIV and MV).ResultsA total of 148 patients were included in the present analysis. We find that any change in respiratory support from or to HFNC caused a significant change in PaO2/FIO2 ratio. Changes in respiratory support between NIV and MV did not show consistent change in PaO2/FIO2 ratio. In patients classified as mild to moderate ARDS during MV, the change from HFNC to MV showed a variable increase in PaO2/FIO2 ratio ranging between 52 and 140 mmHg (median of 127 mmHg). This made prediction of ARDS severity during MV from the apparent ARDS grade during HFNC impossible.ConclusionsHFNC is associated with lower PaO2/FIO2 ratio than either NIV or MV in the same patient, while NIV and MV provided similar PaO2/FIO2 and thus ARDS grade by Berlin definition. The large variation of PaO2/FIO2 ratio indicates that great caution should be used when estimating ARDS grade as a measure of pulmonary damage during HFNC.

Background &amp; Objective: Acute respiratory distress syndrome (ARDS) is characterized by the acute onset of tachypnea, hypoxemia, and loss of lung compliance. Clinicians have employed various means to improve oxygenation in these patients. We evaluated the effect of self-proning with a high-flow nasal cannula in patients with ARDS on oxygenation and the incidence of intubation. Methodology: Ninety patients, aged above 18 y old, patients with BMI below 30 kg/m2, from both genders, suffering from COVID-19 and mild ARDS, participated in this prospective, randomized, double-blind clinical trial at Ain Shams University hospitals. Participants were allocated into two equal groups; Group 1: Patients were subjected to HFNC with a target SpO2 ≥ 90% with FiO2 &lt; 0.6. Group 2: Patients were subjected to HFNC with a target of SpO2 &gt; 90% with FiO2 ≤ 0.6, and combined with self proning. Upon ICU admission, age, weight, BMI, sex, baseline PcO2/FiO2 (P/F) ratio, baseline SpO2 and baseline heart rate were noted. During ICU stay, hemodynamic data and respiratory rate, ABG’s were recorded on admission and every six hours after therapy 6, 12, 24, 48, and 96 h till the patient was discharged from ICU. CXR was obtained on admission and at 24 h, and assessed by Berlin criteria. Assuming a rate of intubation of 50% in the group without prone position setting power at 80% and alpha error at 0.05, a sample size of 45 patients per group was needed. Results: HFNC with proning was effective in improving oxygenation of the mild ARDS patients and decreasing the incidence of intubation; 11 patients in Group 1 and 4 in Group 2 needed to be intubated. Regarding mortality 35 patients survived in Group 1 compared to 42 in Group 2. The median ICU stay was significantly shorter in Group II, 12 (10–12) days compared to Group I, 19 (18–21); P = 0.000. Conclusion: The use of high-flow nasal cannula and proning reduced the frequency of intubation in mild ARDS patients in ICU, and also decreased the ICU stay and improved the outcome of patients with mild ARDS. Abbreviations: ARDS: Acute Respiratory Distress Syndrome; ICU: Intensive Care Unit; HFNC: High-Flow Nasal Cannula; NIV: Non-Invasive Ventilation Key words: Acute Respiratory Distress Syndrome; COVID-19; High Flow Nasal Cannula; Proning. Nasrallah BZN, et al Patients self-proning with high-flow nasal cannula www.apicareonline.com 352 Open access attribution (CC BY-NC 4.0) Citation: Nasrallah BZN, Mahmoud MS, Abdallah ElGendy HM, Youssri Mahmoud NM, Aly ElGendy MAE. Patients self-proning with high-flow nasal cannula improves oxygenation in ARDS patients: a randomized clinical trial. Anaesth. pain intensive care 2023;27(3):351−355; DOI: 10.35975/apic.v27i3.2079 Received: November 23, 2022; Reviewed: December 22, 2022; Accepted: April 08, 2023