Pulse Oximetry and Arterial Saturation Difference in Pediatric COVID-19 Patients: Retrospective Analysis by Race.

OBJECTIVES: Pulse oximetry (Sp o2 ) may overestimate arterial oxygen saturation (Sa o2 ) in blood laboratory testing. This study aimed to assess Sp o2 -Sa o2 difference in relation to race (i.e., patient self-reporting as Black or White), occult hypoxemia, and length of stay (LOS) in pediatric patients with COVID-19. DESIGN: Single-center retrospective study in pediatric COVID-19 patients. We used multivariable linear regressions to examine the association between race and oximetry measurements and between occult hypoxemia and LOS. Oximetry bias was defined using Sp o2 and Sa o2 data according to approved comparisons. Occult hypoxemia was defined as Sp o2 greater than 92% and Sa o2 less than 88%. SETTING: Quaternary pediatric hospital. PATIENTS: Pediatric COVID-19 patients admitted to Texas Children's Hospital between May 2020 and December 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 2713 patients with complete physiological data in the analysis. Of the total, 61% were Black, and 39% were White. Oximetry bias was greater in Black compared with White patients ( p < 0.001), and this bias increased as the oxygen saturations decreased ( p < 0.001). Black and White patients had a 12% and 4% prevalence of occult hypoxemia, respectively ( p < 0.001). LOS was not associated with oximetry bias or occult hypoxemia once controlled for the level of support (intensive care, respiratory, circulatory). CONCLUSIONS: We found an oximetry bias in the measurement of Sp o2 with respect to Sa o2 in symptomatic hospitalized pediatric patients with the diagnosis of COVID-19. Furthermore, race is related to an increased oximetry bias. However, we did not find a relationship between oximetry bias and the LOS in the hospital in this cohort of patients.

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.

Res-SE-ConvNet: A Deep Neural Network for Hypoxemia Severity Prediction for Hospital In-Patients Using Photoplethysmograph Signal.

Determining the severity level of hypoxemia, the scarcity of saturated oxygen (SpO2) in the human body, is very important for the patients, a matter which has become even more significant during the outbreak of Covid-19 variants. Although the widespread usage of Pulse Oximeter has helped the doctors aware of the current level of SpO2 and thereby determine the hypoxemia severity of a particular patient, the high sensitivity of the device can lead to the desensitization of the care-givers, resulting in slower response to actual hypoxemia event. There has been research conducted for the detection of severity level using various parameters and bio-signals and feeding them in a machine learning algorithm. However, in this paper, we have proposed a new residual-squeeze-excitation-attention based convolutional network (Res-SE-ConvNet) using only Photoplethysmography (PPG) signal for the comfortability of the patient. Unlike the other methods, the proposed method has outperformed the standard state-of-art methods as the result shows 96.5% accuracy in determining 3 class severity problems with 0.79 Cohen Kappa score. This method has the potential to aid the patients in receiving the benefit of an automatic and faster clinical decision support system, thus handling the severity of hypoxemia.

Hypoxic pulmonary vascular response can screen subclinical lifestyle disease in healthy population.

OBJECTIVE: Subclinical life style disease can cause endothelial dysfunction associated with perfusion abnormalities and reduced vascular compliance. Subclinical elevated beta type natriuretic peptide (BNP) has been associated with altered fluid shift from extra to intracellular space during acute hypoxia. Therefore we measured vascular response and BNP levels during acute hypoxia to study endothelial functions among healthy individuals. METHODS: Individuals were exposed to acute normobaric hypoxia of FiO2 = 0.15 for one hour in supine position and their pulmonary and systemic vascular response to hypoxia was compared. Individuals were divided into two groups based on either no response (Group 1) or rise in systolic pulmonary artery pressure to hypoxia (Group 2) and their BNP levels were compared. RESULTS: BNP was raised after hypoxia exposure in group 2 only from 18.52 ± 7 to 21.56 ± 10.82 picogram/ml, p < 0.05. Group 2 also showed an increase in mean arterial pressure and no fall in total body water in response to acute hypoxia indicating decreased endothelial function compared to Group 1. CONCLUSION: Rise in pulmonary artery pressure and BNP level in response to acute normobaric hypoxia indicates reduced endothelial function and can be used to screen subclinical lifestyle disease among healthy population.

SARS-CoV-2 infection, pulse oximetry, and interpretive caveats.

Hypoxaemia in COVID-19 does not necessarily imply COVID pneumonia or post-COVID lung fibrosis, and the caveats of finger pulse oximetry should be remembered. Drug-induced methaemoglobinemia should be considered in individuals with unexplained cyanosis, refractory hypoxaemia, or the presence of a saturation gap. Here, we share our recent encounter of 'spurious hypoxia' in a patient with COVID-19 and methaemoglobinemia.

Predictors of silent hypoxia in hospitalized patients with COVID-19 in Japan.

INTRODUCTION: Silent hypoxia (SH) is common in patients with coronavirus disease (COVID-19) in Japan and other countries. Early identification of SH is important as more treatment options for COVID-19 have become available. This study aimed to identify predictors of SH using a nationwide COVID-19 registry of hospitalized patients. METHODS: Adult patients who were admitted to hospital with COVID-19 between January 2020 and June 2021 and who were hypoxic on admission (SpO2: 70-93%), not transferred from another facility, and who did not have disturbance of consciousness, confusion, or dementia, were included. SH was defined as hypoxia in the absence of shortness of breath/dyspnea upon admission. Predictors of SH were identified using univariable and multivariable logistic regression. RESULTS: The study included 1904 patients, of whom 990 (52%) satisfied the criteria for SH. Compared to patients without SH, patients with SH were older, more likely to be female, and had a slightly higher SpO2 on admission. Compared to patients without SH, patients with SH had a lower prevalence of chronic lung disease (CLD) other than chronic obstructive pulmonary disease (COPD), asthma, and obesity. Multivariable analysis revealed that the independent predictors of SH were older age, a shorter interval from symptom onset to admission, higher SpO2, and an absence of CLD or COPD. CONCLUSIONS: The absence of underlying lung disease and older age were important predictors of SH. The results of this study, which is the largest such study reported to date in Japan, may help clarify the mechanism of SH.

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.

Silent Hypoxia in COVID-19 Pneumonia: State of Knowledge, Pathophysiology, Mechanisms, and Management.

Patients with COVID-19 often present with life-threatening hypoxemia without dyspnea or signs of respiratory distress. Termed silent or happy hypoxia, it has puzzled clinicians and challenged and defied our understanding of normal respiratory physiology. A range of host- and pathogen-related factors appears to contribute to its development, including SARS-CoV-2's ability to produce different COVID-19 phenotypes; induce endothelial damage and elicit a vascular distress response; invade cells of the central nervous system and disrupt normal interoception and response; and modulate transcription factors involved in hypoxic responses. Because hypoxemia in COVID-19 is associated with increased mortality risk and poorer survival, early detection and prompt treatment is essential to prevent potential complications. Interventions to prevent hypoxemia and improve oxygen delivery to the blood and the tissues include home pulse-oximetry monitoring, optimization of patient positioning, judicious use of supplemental oxygen, breathing control exercises, and timely and appropriate use of ventilatory modalities and adjuncts.

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.

BACKGROUND: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. METHODS: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg-800 mg (depending on weight) given intravenously. A second dose could be given 12-24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). FINDINGS: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76-0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12-1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77-0·92; p<0·0001). INTERPRETATION: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. FUNDING: UK Research and Innovation (Medical Research Council) and National Institute of Health Research.

Soluble ST2 concentrations associate with in-hospital mortality and need for mechanical ventilation in unselected patients with COVID-19.

OBJECTIVE: Soluble ST2 (sST2) reflects inflammation, endothelial dysfunction and myocardial fibrosis, is produced in the lungs and is an established biomarker in heart failure. We sought to determine the role of sST2 in COVID-19 by assessing pathophysiological correlates and its association to in-hospital outcomes. METHODS: We enrolled 123 consecutive, hospitalised patients with COVID-19 in the prospective, observational COVID-19 MECH study. Biobank samples were collected at baseline, day 3 and day 9. The key exposure variable was sST2, and the outcome was ICU treatment with mechanical ventilation or in-hospital death. RESULTS: Concentrations of sST2 at baseline was median 48 (IQR 37-67) ng/mL, and 74% had elevated concentrations (>37.9 ng/mL). Higher baseline sST2 concentrations were associated with older age, male sex, white race, smoking, diabetes, hypertension and chronic kidney disease. Baseline sST2 also associated with the presence of SARS-CoV-2 viraemia, lower oxygen saturation, higher respiratory rate and increasing concentrations of biomarkers reflecting inflammation, thrombosis and cardiovascular disease. During the hospitalisation, 8 (7%) patients died and 27 (22%) survivors received intensive care unit (ICU) treatment. Baseline sST2 concentrations demonstrated a graded association with disease severity (median, IQR): medical ward 43 (36-59) ng/mL; ICU 67 (39-104) ng/mL and non-survivors 107 (72-116) ng/mL (p<0.001 for all comparisons). These associations persisted at day 3 and day 9 . CONCLUSIONS: sST2 concentrations associate with SARS-CoV-2 viraemia, hypoxaemia and concentrations of inflammatory and cardiovascular biomarkers. There was a robust association between baseline sST2 and disease severity that was independent of, and superior to, established risk factors. sST2 reflects key pathophysiology and may be a promising biomarker in COVID-19. TRIAL REGISTRATION NUMBER: NCT04314232.

High-Flow Nasal Oxygen for Severe Hypoxemia: Oxygenation Response and Outcome in Patients with COVID-19.

Rationale: The "Berlin definition" of acute respiratory distress syndrome (ARDS) does not allow inclusion of patients receiving high-flow nasal oxygen (HFNO). However, several articles have proposed that criteria for defining ARDS should be broadened to allow inclusion of patients receiving HFNO. Objectives: To compare the proportion of patients fulfilling ARDS criteria during HFNO and soon after intubation, and 28-day mortality between patients treated exclusively with HFNO and patients transitioned from HFNO to invasive mechanical ventilation (IMV). Methods: From previously published studies, we analyzed patients with coronavirus disease (COVID-19) who had PaO2/FiO2 of ⩽300 while treated with ⩾40 L/min HFNO, or noninvasive ventilation (NIV) with positive end-expiratory pressure of ⩾5 cm H2O (comparator). In patients transitioned from HFNO/NIV to invasive mechanical ventilation (IMV), we compared ARDS severity during HFNO/NIV and soon after IMV. We compared 28-day mortality in patients treated exclusively with HFNO/NIV versus patients transitioned to IMV. Measurements and Main Results: We analyzed 184 and 131 patients receiving HFNO or NIV, respectively. A total of 112 HFNO and 69 NIV patients transitioned to IMV. Of those, 104 (92.9%) patients on HFNO and 66 (95.7%) on NIV continued to have PaO2/FiO2 ⩽300 under IMV. Twenty-eight-day mortality in patients who remained on HFNO was 4.2% (3/72), whereas in patients transitioned from HFNO to IMV, it was 28.6% (32/112) (P < 0.001). Twenty-eight-day mortality in patients who remained on NIV was 1.6% (1/62), whereas in patients who transitioned from NIV to IMV, it was 44.9% (31/69) (P < 0.001). Overall mortality was 19.0% (35/184) and 24.4% (32/131) for HFNO and NIV, respectively (P = 0.2479). Conclusions: Broadening the ARDS definition to include patients on HFNO with PaO2/FiO2 ⩽300 may identify patients at earlier stages of disease but with lower mortality.

The Roth score as a triage tool for detecting hypoxaemia in general practice: a diagnostic validation study in patients with possible COVID-19.

AIM: To validate the Roth score as a triage tool for detecting hypoxaemia. BACKGROUNDS: The virtual assessment of patients has become increasingly important during the corona virus disease (COVID-19) pandemic, but has limitations as to the evaluation of deteriorating respiratory function. This study presents data on the validity of the Roth score as a triage tool for detecting hypoxaemia remotely in potential COVID-19 patients in general practice. METHODS: This cross-sectional validation study was conducted in Dutch general practice. Patients aged ≥18 with suspected or confirmed COVID-19 were asked to rapidly count from 1 to 30 in a single breath. The Roth score involves the highest number counted during exhalation (counting number) and the time taken to reach the maximal count (counting time).Outcome measures were (1) the correlation between both Roth score measurements and simultaneous pulse oximetry (SpO2) on room air and (2) discrimination (c-statistic), sensitivity, specificity and predictive values of the Roth score for detecting hypoxaemia (SpO2 < 95%). FINDINGS: A total of 33 physicians enrolled 105 patients (52.4% female, mean age of 52.6 ± 20.4 years). A positive correlation was found between counting number and SpO2 (rs = 0.44, P < 0.001), whereas only a weak correlation was found between counting time and SpO2 (rs = 0.15, P = 0.14). Discrimination for hypoxaemia was higher for counting number [c-statistic 0.91 (95% CI: 0.85-0.96)] than for counting time [c-statistic 0.77 (95% CI: 0.62-0.93)]. Optimal diagnostic performance was found at a counting number of 20, with a sensitivity of 93.3% (95% CI: 68.1-99.8) and a specificity of 77.8% (95% CI: 67.8-85.9). A counting time of 7 s showed the best sensitivity of 85.7% (95% CI: 57.2-98.2) and specificity of 81.1% (95% CI: 71.5-88.6). CONCLUSIONS: A Roth score, with an optimal counting number cut-off value of 20, maybe of added value for signalling hypoxaemia in general practice. Further external validation is warranted before recommending integration in telephone triage.

The PaO2/FiO2 ratio on admission is independently associated with prolonged hospitalization in COVID-19 patients.

INTRODUCTION: The early identification of factors that predict the length of hospital stay (HS) in patients affected by coronavirus desease (COVID-19) might assist therapeutic decisions and patient flow management. METHODOLOGY: We collected, at the time of admission, routine clinical, laboratory, and imaging parameters of hypoxia, lung damage, inflammation, and organ dysfunction in a consecutive series of 50 COVID-19 patients admitted to the Respiratory Disease and Infectious Disease Units of the University Hospital of Sassari (North-Sardinia, Italy) and alive on discharge. RESULTS: Prolonged HS (PHS, >21 days) patients had significantly lower PaO2/FiO2 ratio and lymphocytes, and significantly higher Chest CT severity score, C-reactive protein (CRP) and lactic dehydrogenase (LDH) when compared to non-PHS patients. In univariate logistic regression, Chest CT severity score (OR = 1.1891, p = 0.007), intensity of care (OR = 2.1350, p = 0.022), PaO2/FiO2 ratio (OR = 0.9802, p = 0.007), CRP (OR = 1.0952, p = 0.042) and platelet to lymphocyte ratio (OR = 1.0039, p = 0.036) were significantly associated with PHS. However, in multivariate logistic regression, only the PaO2/FiO2 ratio remained significantly correlated with PHS (OR = 0.9164; 95% CI 0.8479-0.9904, p = 0.0275). In ROC curve analysis, using a threshold of 248, the PaO2/FiO2 ratio predicted PHS with sensitivity and specificity of 60% and 91%, respectively (AUC = 0.780, 95% CI 0.637-0.886 p = 0.002). CONCLUSIONS: The PaO2/FiO2 ratio on admission is independently associated with PHS in COVID-19 patients. Larger prospective studies are needed to confirm this finding.