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Physiological effects and subjective tolerability of prone positioning in COVID-19 and healthy hypoxic challenge

Akhilesh Jha, Fangyue Chen, Sam Mann, Ravi Shah, Randa Abu-Youssef, Holly Pavey, Helen Lin-Jia-Qi, Josh Cara, Daniel Cunningham, Kate Fitzpatrick, Celine Goh, Renee Ma, Souradip Mookerjee, Vaitehi Nageshwaran, Timothy Old, Catherine Oxley, Louise Jordon, Mayurun Selvan, Anna Wood, Andrew Ying, Chen Zhang, Dariusz Wozniak, Iain Goodhart, Frances Early, Marie Fisk, Jonathan Fuld
ERJ Open Research 2022 8: 00524-2021; DOI: 10.1183/23120541.00524-2021
Akhilesh Jha
1Dept of Medicine, University of Cambridge, Cambridge, UK
2Dept of Respiratory Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
6These authors contributed equally
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  • ORCID record for Akhilesh Jha
  • For correspondence: aj580@cam.ac.uk
Fangyue Chen
2Dept of Respiratory Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
6These authors contributed equally
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Sam Mann
3School of Clinical Medicine, University of Cambridge, Cambridge, UK
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Ravi Shah
2Dept of Respiratory Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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Randa Abu-Youssef
1Dept of Medicine, University of Cambridge, Cambridge, UK
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Holly Pavey
1Dept of Medicine, University of Cambridge, Cambridge, UK
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Helen Lin-Jia-Qi
3School of Clinical Medicine, University of Cambridge, Cambridge, UK
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  • ORCID record for Helen Lin-Jia-Qi
Josh Cara
3School of Clinical Medicine, University of Cambridge, Cambridge, UK
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Daniel Cunningham
4Dept of Anaesthesia and Critical Care, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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Kate Fitzpatrick
3School of Clinical Medicine, University of Cambridge, Cambridge, UK
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Celine Goh
3School of Clinical Medicine, University of Cambridge, Cambridge, UK
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Renee Ma
3School of Clinical Medicine, University of Cambridge, Cambridge, UK
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Souradip Mookerjee
3School of Clinical Medicine, University of Cambridge, Cambridge, UK
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Vaitehi Nageshwaran
2Dept of Respiratory Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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Timothy Old
2Dept of Respiratory Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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Catherine Oxley
3School of Clinical Medicine, University of Cambridge, Cambridge, UK
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Louise Jordon
2Dept of Respiratory Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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Mayurun Selvan
2Dept of Respiratory Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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Anna Wood
3School of Clinical Medicine, University of Cambridge, Cambridge, UK
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Andrew Ying
3School of Clinical Medicine, University of Cambridge, Cambridge, UK
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Chen Zhang
3School of Clinical Medicine, University of Cambridge, Cambridge, UK
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Dariusz Wozniak
5Respiratory Support and Sleep Centre, Royal Papworth Hospital, Cambridge, UK
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Iain Goodhart
4Dept of Anaesthesia and Critical Care, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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Frances Early
2Dept of Respiratory Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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Marie Fisk
1Dept of Medicine, University of Cambridge, Cambridge, UK
2Dept of Respiratory Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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Jonathan Fuld
2Dept of Respiratory Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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  • Article
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  • FIGURE 1
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    FIGURE 1

    Summary flowchart of study recruitment.

  • FIGURE 2
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    FIGURE 2

    Change in oxygen saturation measured by pulse oximetry (SpO2) in different body positions in coronavirus disease 2019 (COVID-19) pneumonia and healthy hypoxic challenge. Boxplots showing SpO2 measured in a) COVID-19 patients (n=24, one dataset unavailable due to technical loss) and b) healthy volunteers (n=10) in different body positions. Boxes represent 25th percentile, median and 75th percentile. The lower and upper whiskers extend to 1.5 times the interquartile range from the 25th and 75th percentile, respectively. The overlaid dot plots show each SpO2 value that was measured (every 2 s). Dot plot and LOESS smooth curve showing the absolute change in SpO2 (percentage points) over time in prone position for c) COVID-19 patients and d) healthy volunteers. The SpO2 at each timepoint in prone position was corrected for every individual's baseline SpO2 (in supine position) – each dot represents the mean corrected SpO2 in all individuals for every minute in prone position.

  • FIGURE 3
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    FIGURE 3

    Visual analogue scales (VAS) for subjective breathlessness and discomfort in coronavirus disease 2019 (COVID-19) patients and healthy volunteers. Breathlessness (SOB) score for a) COVID-19 patients (n=25) and b) healthy volunteers (n=10). Discomfort score for c) COVID-19 patients and d) healthy volunteers. Lines represent median (IQR). Compared using Friedman's test and Dunn's multiple correction. *: p<0.05; **: p<0.005.

Tables

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  • TABLE 1

    Baseline demographic and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) and healthy volunteers

    Patients with COVID-19Healthy volunteers
    Subjects n2510
    Baseline demographics
    Age years64.0 (53.0–75.0)35.0 (22.5–44.0)
    Sex
     Female7 (28.0)8 (80.0)
     Male18 (72.0)2 (20.0)
    BMI kg·m−228.50 (25.70–31.40)23.86 (22.77–25.89)
    Smoking history
     Current smoker1 (4.0)0
     Ex-smoker9 (36.0)1 (10.0)
    Patients with COVID-19 (n=25)
    Baseline clinical variables
    FiO2 at proning0.32 (0.28–0.36)
    ABGn=10
     pH7.43 (7.40–7.47)
      PaO2 kPa8.00 (7.83–9.03)
      PaCO2 kPa4.50 (3.98–4.60)
     Lactate mmol·L−11.70 (1.50–2.10)
      FiO20.28 (0.22–0.33)
    Inflammatory markersn=25
     WCC (109·L−1)7.90 (6.00–11.10)
     CRP mg·L−177.00 (40.00–141.00)
    COVID-19 status
     SARS-CoV-2 PCR positiven=25
     Symptom onset to admission (days)9.0 (3.0–11.0)
     Admission to prone (days)2.0 (1.0–3.0)
     Radiographic severity score5 (4–7)
    COVID-19 therapeutic regimen
     Dexamethasone only10 (40.0)
     Dexamethasone+Baricitinib2 (8.0)
     Dexamethasone+Dapagliflozin+Ambrisentan3 (12.0)
     Dexamethasone+EDP1815#1 (4.0)
     Dexamethasone+Ravulizumab2 (8.0)
     Dexamethasone+Remdesivir4 (16.0)
     Dexamethasone+Tocilizumab1 (4.0)
    Comorbidities
    Respiratory
     Asthma5 (20.0)
     COPD2 (8.0)
     Interstitial lung disease1 (4.0)
     Pulmonary tuberculosis1 (4.0)
    Cardiovascular
     Atrial fibrillation2 (8.0)
     Dilated cardiomyopathy1 (4.0)
     Hypercholesterolaemia1 (4.0)
     Hypertension8 (32.0)
     Ischaemic heart disease3 (12.0)
     Peripheral vascular disease1 (4.0)
    Other significant
     Connective tissue disease2 (8.0)
     Chronic kidney disease2 (8.0)
     Haematological malignancy1 (4.0)
     Hypothyroidism2 (8.0)
     Osteoarthritis2 (8.0)
     Polymyalgia rheumatica2 (8.0)
     Raynaud's disease1 (4.0)
     Rheumatoid arthritis1 (4.0)
     Type II diabetes mellitus4 (16.0)
    Outcomes
     Death1 (4.0)
     Intubation and ventilation1 (4.0)
     Noninvasive ventilation1 (4.0)
     Discharge24 (96)
     Time from proning to discharge (days)7 (4–10.5)

    Data are n (%) or median (IQR). Radiographic severity score: semi-quantitative score indicating extent of radiographic changes with a maximum score of 8. BMI: body mass index; FiO2: fractional concentration of oxygen in inspired air at point of proning; ABG: arterial blood gas; PaO2: arterial partial pressure of oxygen; PaCO2: arterial partial pressure of carbon dioxide; WCC: white cell count; CRP: C-reactive protein; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; NA: not applicable. #: EDP1815 is an investigational immune modulator used as part of the TACTIC-E Trial: ClinicalTrials.gov Identifier: NCT04393246.

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      Supplementary material ERJ-00524-2021.supplement

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    Physiological effects and subjective tolerability of prone positioning in COVID-19 and healthy hypoxic challenge
    Akhilesh Jha, Fangyue Chen, Sam Mann, Ravi Shah, Randa Abu-Youssef, Holly Pavey, Helen Lin-Jia-Qi, Josh Cara, Daniel Cunningham, Kate Fitzpatrick, Celine Goh, Renee Ma, Souradip Mookerjee, Vaitehi Nageshwaran, Timothy Old, Catherine Oxley, Louise Jordon, Mayurun Selvan, Anna Wood, Andrew Ying, Chen Zhang, Dariusz Wozniak, Iain Goodhart, Frances Early, Marie Fisk, Jonathan Fuld
    ERJ Open Research Jan 2022, 8 (1) 00524-2021; DOI: 10.1183/23120541.00524-2021

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    Physiological effects and subjective tolerability of prone positioning in COVID-19 and healthy hypoxic challenge
    Akhilesh Jha, Fangyue Chen, Sam Mann, Ravi Shah, Randa Abu-Youssef, Holly Pavey, Helen Lin-Jia-Qi, Josh Cara, Daniel Cunningham, Kate Fitzpatrick, Celine Goh, Renee Ma, Souradip Mookerjee, Vaitehi Nageshwaran, Timothy Old, Catherine Oxley, Louise Jordon, Mayurun Selvan, Anna Wood, Andrew Ying, Chen Zhang, Dariusz Wozniak, Iain Goodhart, Frances Early, Marie Fisk, Jonathan Fuld
    ERJ Open Research Jan 2022, 8 (1) 00524-2021; DOI: 10.1183/23120541.00524-2021
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