Use of almitrine in spontaneously breathing patients with COVID-19 treated with high-flow nasal cannula oxygen therapy and with persistent hypoxemia.

BACKGROUND: Almitrine, a selective pulmonary vasoconstrictor in hypoxic area, improves oxygenation in mechanically ventilated patients with COVID-19 but its effects in spontaneously breathing patients with COVID-19 remain to be determined. METHODS: We prospectively studied the effects of almitrine (16 µg/kg/min over 30 min followed by continuous administration in responders only) in 62 patients (66% of male, 63 [53-69] years old) with COVID-19 treated with high-flow nasal cannula oxygen therapy (HFNO) and with persistent hypoxemia, defined as a PaO2/FiO2 ratio < 100 with FiO2 > 80% after a single awake prone positioning session. Patients with an increase in PaO2/FiO2 ratio > 20% were considered as responders. RESULTS: Overall, almitrine increased the PaO2/FiO2 ratio by 50% (p < 0.01), decreased the partial arterial pressure of carbon dioxide by 7% (p = 0.01) whereas the respiratory rate remained unchanged and 46 (74%) patients were responders. No patient experienced right ventricular dysfunction or acute cor pulmonale. The proportion of responders was similar regardless of the CT-Scan radiological pattern: 71% for the pattern with predominant ground-glass opacities and 76% for the pattern with predominant consolidations (p = 0.65). Responders had lower intubation rate (33 vs. 88%, p < 0.01), higher ventilator-free days at 28-day (28 [20-28 ] vs. 19 [2-24] days, p < 0.01) and shorter ICU length of stay (5 [3-10] vs.12 [7-30] days, p < 0.01) than non-responders. CONCLUSIONS: Almitrine could be an interesting therapy in spontaneously breathing patients with COVID-19 treated with HFNO and with persistent hypoxemia, given its effects on oxygenation without serious adverse effects regardless of the CT-Scan pattern, and potentially on intubation rate. These preliminary results need to be confirmed by further randomized studies.

Platypnea-orthodeoxia syndrome in SARS-CoV-2 related ARDS: a case report.

Platypnea-Orthodeoxia Syndrome (POS) is an often misdiagnosed clinical condition characterized by dyspnea and hypoxia in sitting or semi-sitting position, reversible in supine position. Although POS is typically associated with intracardiac shunts, it seems frequent also in SARS-CoV-2 related Acute Respiratory Distress Syndrome (ARDS). In fact, the prevalent involvement of the lung bases due to interstitial pneumonia can determine refractory positional hypoxemia, with marked desaturation in the sitting position and regression or improvement in the supine position, configuring the clinical picture of the POS. We present a clinical case of POS associated with acute respiratory distress from SARS-CoV-2 pneumonia in which refractory hypoxia would have required support by invasive mechanical ventilation if the syndrome had not been identified.

The Use of Wearable Pulse Oximeters in the Prompt Detection of Hypoxemia and During Movement: Diagnostic Accuracy Study.

BACKGROUND: Commercially available wearable (ambulatory) pulse oximeters have been recommended as a method for managing patients at risk of physiological deterioration, such as active patients with COVID-19 disease receiving care in hospital isolation rooms; however, their reliability in usual hospital settings is not known. OBJECTIVE: We report the performance of wearable pulse oximeters in a simulated clinical setting when challenged by motion and low levels of arterial blood oxygen saturation (SaO2). METHODS: The performance of 1 wrist-worn (Wavelet) and 3 finger-worn (CheckMe O2+, AP-20, and WristOx2 3150) wearable, wireless transmission-mode pulse oximeters was evaluated. For this, 7 motion tasks were performed: at rest, sit-to-stand, tapping, rubbing, drinking, turning pages, and using a tablet. Hypoxia exposure followed, in which inspired gases were adjusted to achieve decreasing SaO2 levels at 100%, 95%, 90%, 87%, 85%, 83%, and 80%. Peripheral oxygen saturation (SpO2) estimates were compared with simultaneous SaO2 samples to calculate the root-mean-square error (RMSE). The area under the receiver operating characteristic curve was used to analyze the detection of hypoxemia (ie, SaO2<90%). RESULTS: SpO2 estimates matching 215 SaO2 samples in both study phases, from 33 participants, were analyzed. Tapping, rubbing, turning pages, and using a tablet degraded SpO2 estimation (RMSE>4% for at least 1 device). All finger-worn pulse oximeters detected hypoxemia, with an overall sensitivity of ≥0.87 and specificity of ≥0.80, comparable to that of the Philips MX450 pulse oximeter. CONCLUSIONS: The SpO2 accuracy of wearable finger-worn pulse oximeters was within that required by the International Organization for Standardization guidelines. Performance was degraded by motion, but all pulse oximeters could detect hypoxemia. Our findings support the use of wearable, wireless transmission-mode pulse oximeters to detect the onset of clinical deterioration in hospital settings. TRIAL REGISTRATION: ISRCTN Registry 61535692; http://www.isrctn.com/ISRCTN61535692. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-034404.

Prone Positioning of Patients With Coronavirus Disease 2019 Who Are Nonintubated in Hypoxic Respiratory Distress: Single-Site Retrospective Health Records Review.

INTRODUCTION: In March and April 2020 of the coronavirus disease 2019 pandemic, site clinical practice guidelines were implemented for prone positioning of patients with suspected coronavirus disease 2019 in hypoxic respiratory distress who are awake, alert, and spontaneously breathing. The purpose of this pandemic disaster practice improvement project was to measure changes in pulse oximetry associated with prone positioning of patients with coronavirus disease 2019 infection in adult acute respiratory distress or adult respiratory distress syndrome, who are awake, alert, spontaneously breathing, and nonintubated. METHODS: A retrospective chart review of patients who were coronavirus disease 2019 positive in the emergency department from March 30, 2020 to April 30, 2020 was conducted for patients with a room air pulse oximetry <90% and a preprone position pulse oximetry ≤94% who tolerated prone positioning for at least 30 minutes. The primary outcome was the change in pulse oximetry associated with prone positioning, measured on room air, with supplemental oxygen, and approximately 30 minutes after initiating prone positioning. Median and mean differences were compared with the Wilcoxon signed-rank test and paired t-test. RESULTS: Of the 440 patients with coronavirus disease 2019, 31 met inclusion criteria. Median pulse oximetry increased as 83% (interquartile range, 75%-86%) on room air, 90% (interquartile range, 89%-93%) with supplemental oxygen, and 96% (interquartile range, 94%-98%) with prone positioning (z = -4.48, P < .001). A total of 45% (n = 14) were intubated during their hospital stay, and 26% (n = 8) of the included patients died. DISCUSSION: In patients with coronavirus disease 2019 who are awake, alert, and spontaneously breathing, an initially low pulse oximetry reading improved with prone positioning. Future studies are needed to determine the association of prone positioning with subsequent endotracheal intubation and mortality.

Outcome of Children Admitted With SARS-CoV-2 Infection: Experiences From a Pediatric Public Hospital.

OBJECTIVE: To study clinical characteristics and outcome of children with admitted to a paediatric hospital in Mumbai, India. METHODS: Review of medical records of 969 children admitted between 19 March and 7 August, 2020, to assess the clinico-demographic characteristics, disease severity and factors predicting outcome in COVID-19 children. Variables were compared between children who were previously healthy (Group I) and those with co-morbidity (Group II). RESULTS: 123 (71 boys) children with median (IQR) age of 3 (0.7- 6) years were admitted, of which 47 (38%) had co-morbidities. 39 (32 %) children required intensive care and 14 (11.4%) died. Male sex, respiratory manifestation, oxygen saturation <94%; at admission, mechanical ventilation, inotrope, hospital stay of <10 days were independent predictors of mortality. Oxygen saturation <94% at admission (OR 35.9, 95% CI 1.5-856) and hospital stay <10 days (OR 9.1, 95% CI 1.04-99.1) were significant. CONCLUSION: COVID-19 in children with co-morbidities causes severe disease. Association of mortality with oxygen saturation by pulse oximeter <94% on admission, and hospital stay <10 days, needs further evaluation.

Acute Respiratory Distress Syndrome: Diagnosis and Management.

Acute respiratory distress syndrome (ARDS) is noncardiogenic pulmonary edema that manifests as rapidly progressive dyspnea, tachypnea, and hypoxemia. Diagnostic criteria include onset within one week of a known insult or new or worsening respiratory symptoms, profound hypoxemia, bilateral pulmonary opacities on radiography, and inability to explain respiratory failure by cardiac failure or fluid overload. ARDS is thought to occur when a pulmonary or extrapulmonary insult causes the release of inflammatory mediators, promoting inflammatory cell accumulation in the alveoli and microcirculation of the lung. Inflammatory cells damage the vascular endothelium and alveolar epithelium, leading to pulmonary edema, hyaline membrane formation, decreased lung compliance, and decreased gas exchange. Most cases are associated with pneumonia or sepsis. ARDS is responsible for one in 10 admissions to intensive care units and one in four mechanical ventilations. In-hospital mortality for patients with severe ARDS ranges from 46% to 60%. ARDS often must be differentiated from pneumonia and congestive heart failure, which typically has signs of fluid overload. Treatment of ARDS is supportive and includes mechanical ventilation, prophylaxis for stress ulcers and venous thromboembolism, nutritional support, and treatment of the underlying injury. Low tidal volume and high positive end-expiratory pressure improve outcomes. Prone positioning is recommended for some moderate and all severe cases. As patients with ARDS improve and the underlying illness resolves, a spontaneous breathing trial is indicated to assess eligibility for ventilator weaning. Patients who survive ARDS are at risk of diminished functional capacity, mental illness, and decreased quality of life; ongoing care by a primary care physician is beneficial for these patients.

Platypnea-orthodeoxia in a patient with severe COVID-19 pneumonia.

COVID-19 pneumonia has a significant case fatality rate and no effective antiviral drugs are available even after 9 months of the pandemic. The spectrum of COVID-19 disease ranges from asymptomatic cases to severe ARDS with myriad manifestations. Here we report a case of a male patient with severe COVID-19 ARDS who improved after receiving standard therapy but again 'deteriorated' after being stepped down to ward. He complained of worsening shortness of breath and hypoxemia which was found to be mainly positional. After ruling out other causes, he was labeled as a case of platypnea-orthodeoxia syndrome due to underlying lung involvement.  It is important to be aware of this condition in the context of COVID-19 which can be easily diagnosed bedside with pulse oximetry.

Effect of early oseltamivir on outpatients without hypoxia with suspected COVID-19.

BACKGROUND: Since December 2019 coronavirus disease 2019 (COVID-19) outbreaks have occurred in China and many countries around the world. The effectiveness of oseltamivir on COVID-19 suspected outpatients without hypoxia was evaluated. METHODS: A total of 16 COVID-19 suspected medical personnel and their cohabitation families without hypoxia, who came to the adult fever clinic from March to June 2020 were studied. All patients received antiviral therapy (oseltamivir) and antibacterial therapy together. RESULTS: Most of the infected patients were female (10, 63%), 1 had diabetes (6%) and 3 hypertension (19%). The median age was 45 years (interquartile range [IQR] 31-60 years). Oseltamivir administration made the temperature fall within 24 h in part (10, 63%). Clinical data were compared between patients receiving early treatment (ET) with oseltamivir, initiated within 24 h, and patients administered late treatment (LT), initiated after this time point. Duration of fever was shorter in the ET group than in the LT group (31 ± 21 h versus 94 ± 38 h; p < 0.001). The time from fever onset to treatment initiation correlated with duration of fever (r = 0.77; p < 0.001) and the time from peak to decline (r = 0.58; p < 0.05). CONCLUSION: These findings suggest that early oseltamivir administration may lower the duration of fever in COVID-19 suspected outpatients without hypoxia when it is used in combination with antibacterial therapy.

A Methodology Based on Expert Systems for the Early Detection and Prevention of Hypoxemic Clinical Cases.

Respiratory diseases are currently considered to be amongst the most frequent causes of death and disability worldwide, and even more so during the year 2020 because of the COVID-19 global pandemic. Aiming to reduce the impact of these diseases, in this work a methodology is developed that allows the early detection and prevention of potential hypoxemic clinical cases in patients vulnerable to respiratory diseases. Starting from the methodology proposed by the authors in a previous work and grounded in the definition of a set of expert systems, the methodology can generate alerts about the patient's hypoxemic status by means of the interpretation and combination of data coming both from physical measurements and from the considerations of health professionals. A concurrent set of Mamdani-type fuzzy-logic inference systems allows the collecting and processing of information, thus determining a final alert associated with the measurement of the global hypoxemic risk. This new methodology has been tested experimentally, producing positive results so far from the viewpoint of time reduction in the detection of a blood oxygen saturation deficit condition, thus implicitly improving the consequent treatment options and reducing the potential adverse effects on the patient's health.

Epidemiology of COVID-19 and Predictors of Outcome in Nigeria: A Single-Center Study.

There is a paucity of information regarding the epidemiology and outcome of COVID-19 from low/middle-income countries, including from Nigeria. This single-center study described the clinical features, laboratory findings, and predictors of in-hospital mortality of COVID-19 patients. Patients admitted between April 10, 2020 and June 10, 2020 were included. Forty-five patients with a mean age of 43 (16) years, predominantly male (87%), presented with fever (38%), cough (29%), or dyspnea (24%). In-hospital mortality was 16%. The independent predictors of mortality were hypoxemia (adjusted odds ratio [aOR]: 2.5; 95% CI: 1.3-5.1) and creatinine > 1.5 mg/dL (aOR: 4.3; 95% CI: 1.9-9.8).

Silent hypoxia: a frequently overlooked clinical entity in patients with COVID-19.

COVID-19 caused by SARS-CoV-2 may present with a wide spectrum of symptoms ranging from mild upper respiratory tract infection like illness to severe pneumonia and death. Patients may have severe hypoxaemia without proportional features of respiratory distress, also known as 'silent' or 'apathetic' hypoxia. We present a case of a 56-year-old man with COVID-19 who presented to the fever clinic of our institution with fever and cough without any respiratory distress but low oxygen saturation. The patient deteriorated over the next 2 days but eventually recovered of his illness in due course of time. This case demonstrates 'silent hypoxia' as a possible presentation in COVID-19 and emphasises the importance of meticulous clinical examination including oxygen saturation measurements in suspected or confirmed patients.

In-Ear SpO2: A Tool for Wearable, Unobtrusive Monitoring of Core Blood Oxygen Saturation.

The non-invasive estimation of blood oxygen saturation (SpO2) by pulse oximetry is of vital importance clinically, from the detection of sleep apnea to the recent ambulatory monitoring of hypoxemia in the delayed post-infective phase of COVID-19. In this proof of concept study, we set out to establish the feasibility of SpO2 measurement from the ear canal as a convenient site for long term monitoring, and perform a comprehensive comparison with the right index finger-the conventional clinical measurement site. During resting blood oxygen saturation estimation, we found a root mean square difference of 1.47% between the two measurement sites, with a mean difference of 0.23% higher SpO2 in the right ear canal. Using breath holds, we observe the known phenomena of time delay between central circulation and peripheral circulation with a mean delay between the ear and finger of 12.4 s across all subjects. Furthermore, we document the lower photoplethysmogram amplitude from the ear canal and suggest ways to mitigate this issue. In conjunction with the well-known robustness to temperature induced vasoconstriction, this makes conclusive evidence for in-ear SpO2 monitoring being both convenient and superior to conventional finger measurement for continuous non-intrusive monitoring in both clinical and everyday-life settings.

Considerations for target oxygen saturation in COVID-19 patients: are we under-shooting?

BACKGROUND: The current target oxygen saturation range for patients with COVID-19 recommended by the National Institutes of Health is 92-96%. MAIN BODY: This article critically examines the evidence guiding current target oxygen saturation recommendation for COVID-19 patients, and raises important concerns in the extrapolation of data from the two studies stated to be guiding the recommendation. Next, it examines the influence of hypoxia on upregulation of ACE2 (target receptor for SARS-CoV-2 entry) expression, with supporting transcriptomic analysis of a publicly available gene expression profile dataset of human renal proximal tubular epithelial cells cultured in normoxic or hypoxic conditions. Finally, it discusses potential implications of specific clinical observations and considerations in COVID-19 patients on target oxygen saturation, such as diffuse systemic endothelitis and microthrombi playing an important pathogenic role in the wide range of systemic manifestations, exacerbation of hypoxic pulmonary vasoconstriction in the setting of pulmonary vascular endothelitis/microthrombi, the phenomenon of "silent hypoxemia" with some patients presenting to the hospital with severe hypoxemia disproportional to symptoms, and overburdened health systems and public health resources in many parts of the world with adverse implications on outpatient monitoring and early institution of oxygen supplementation. CONCLUSIONS: The above factors and analyses, put together, call for an urgent exploration and re-evaluation of target oxygen saturation in COVID-19 patients, both in the inpatient and outpatient settings. Until data from such trials become available, where possible, it may be prudent to target an oxygen saturation at least at the upper end of the recommended 92-96% range in COVID-19 patients both in the inpatient and outpatient settings (in patients that are normoxemic at pre-COVID baseline). Home pulse oximetry, tele-monitoring, and earlier institution of oxygen supplementation for hypoxemic COVID-19 outpatients could be beneficial, where public health resources allow for their implementation.

Use of awake proning to avoid invasive ventilation in a patient with severe COVID-19 pneumonitis.

A 60-year-old man with swab-positive COVID-19 and extensive ground-glass change seen on CT imaging was successfully managed on our COVID-19 high-dependency unit with only low-flow oxygen and strict awake proning instructions. He was successfully weaned off oxygen entirely without any requirement for non-invasive or invasive ventilation and made a recovery to be discharged home after an 18-day hospital stay.