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Pneumothorax/pneumomediastinum in non-intubated COVID-19 patients: Differences between first and second Italian pandemic wave

  • Author Footnotes
    ⁎ These authors equally contributed to the manuscript
    Diego Palumbo
    Footnotes
    ⁎ These authors equally contributed to the manuscript
    Affiliations
    Department of Radiology, IRCCS San Raffaele Scientific Institute, Milan, Italy
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  • Author Footnotes
    ⁎ These authors equally contributed to the manuscript
    Corrado Campochiaro
    Footnotes
    ⁎ These authors equally contributed to the manuscript
    Affiliations
    Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
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  • Author Footnotes
    ⁎ These authors equally contributed to the manuscript
    Alessandro Belletti
    Correspondence
    Corresponding author Dr. Alessandro Belletti, Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
    Footnotes
    ⁎ These authors equally contributed to the manuscript
    Affiliations
    Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
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  • Alessandro Marinosci
    Affiliations
    Department of General Medicine and Advanced Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
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  • Lorenzo Dagna
    Affiliations
    Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy

    School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
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  • Alberto Zangrillo
    Affiliations
    Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy

    School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
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  • Francesco De Cobelli
    Affiliations
    Department of Radiology, IRCCS San Raffaele Scientific Institute, Milan, Italy

    School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
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  • for the COVID-BioB Study Group
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    1 Covid-BioB Study Group CollaboratorsGiovanni Landoni
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    ⁎ These authors equally contributed to the manuscript
    1 Covid-BioB Study Group CollaboratorsGiovanni Landoni
Published:March 18, 2021DOI:https://doi.org/10.1016/j.ejim.2021.03.018

      Keywords

      Pneumothorax (PNX) and pneumomediastinum (PMD) have been frequently observed in mechanically ventilated patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS), with a reported rate up to 24% [
      • Belletti A.
      • Palumbo D.
      • Zangrillo A.
      • et al.
      Predictors of pneumothorax/pneumomediastinum in mechanically ventilated COVID-19 patients.
      ]. No study has evaluated so far the exact rate of these events in non-intubated COVID-19 patients. We therefore decided to perform an observational study to investigate the rate of PNX/PMD in non-intubated COVID-19 patients and to compare the rate of PNX/PMN between patients admitted during the first and second Italian pandemic wave.
      Under our Institutional Review Board-approved protocol (protocol number 34/int/2020; ClinicalTrials.gov no. NCT04318366), we identified all patients with pneumothorax and/or pneumomediastinum documented at chest X-ray  or computed tomography (CT) between March 1st, 2020 and June 1st, 2020 (first Italian wave) and between October 1st, 2020 and January 1st, 2021 (second Italian wave) (Fig. 1). Patients were included in the analysis if not invasively ventilated before PNX/PMD diagnosis. Details on hospital organization and clinical management have been previously published [
      • Zangrillo A.
      • Beretta L.
      • Scandroglio A.M.
      • et al.
      Characteristics, treatment, outcomes and cause of death of invasively ventilated patients with COVID-19 ARDS in Milan, Italy.
      ,
      • Ramirez G.A.
      • Bozzolo E.P.
      • Castelli E.
      • et al.
      Continuous positive airway pressure and pronation outside the intensive care unit in COVID 19 ARDS.
      ,
      • Zangrillo A.
      • Beretta L.
      • Silvani P.
      • et al.
      Fast reshaping of intensive care unit facilities in a large metropolitan hospital in Milan, Italy: facing the COVID-19 pandemic emergency.
      ,
      • Sartini C.
      • Tresoldi M.
      • Scarpellini P.
      • et al.
      Respiratory Parameters in Patients with COVID-19 after Using Noninvasive Ventilation in the Prone Position Outside the Intensive Care Unit.
      ]. The main change in patients’ management between first and second pandemic wave was the administration of dexamethasone to all patients requiring oxygen supplementation during the second wave and the avoidance of hydroxychloroquine [
      Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report.
      ]. We collected data as per Table 1. Categorical variables are expressed as numbers and percentages; continuous variables are presented as median and interquartile range. Continuous measures were compared using Wilcoxon matched pairs signed rank test, while dichotomous data were compared using χ2 or Fisher's exact. Two-sided p-value < 0.05 defined statistical significance.
      Fig. 1
      Fig. 1Number of Coronavirus Disease 2019 patients presenting to San Raffaele Scientific Institute per day, from February 25th, 2020 to February 9th, 2021.
      Table 1Patients’ characteristics and treatment details. .
      VariableFirst wave(N = 1)Second wave(N = 13)
      Age, years7572 (65 – 76)
      Male sexMale12 (92.3)
      CPAPYes7 (53.8)
      Steroid therapy
      • -
        Dexamethasone
      • -
        Prednisone
      No13 (100)
      • -
        12 (92.3)
      • -
        1 (7.7)
      LMWH (4000 IU enoxaparin)Yes13 (100)
      Antibiotic therapyYes9 (69.2)
      HCQ (400 mg daily)Yes0 (0.0)
      Biologics
      • -
        Tocilizumab (400 mg)
      • -
        Anakinra (10 mg/kg)
      No5 (38.5)
      • -
        1 (7.7)
      • -
        4 (30.8)
      Comorbidities
      • -
        COPD
      • -
        ILD
      • -
        DM
      • -
        Cancer
      Yes:
      • -
        Yes
      • -
        No
      • -
        No
      • -
        No
      3 (23.1)
      • -
        1 (7.7)
      • -
        0 (0.0)
      • -
        1 (7.7)
      • -
        2 (13.4)
      Continuous variables are presented as median and interquartile range, while categorical variables are presented as number and percentages.
      CPAP: continuous positive airway pressure; COPD: chronic obstructive pulmonary disease; DM: type-2 diabetes mellitus; HCQ: hydroxychloroquine; ILD: interstitial lung disease; IU: international units; LMWH: low molecular weight heparin.
      All the 1151 patients of the first wave and 1484 patients of the second wave did multiple chest X-ray examinations and 813 non-intubated COVID-19 patients underwent at least one CT scan (418, first pandemic wave; 395, second pandemic wave). Fourteen non-intubated patients with radiologically proven PNX/PMD were identified: one patient during the first wave and 13 during the second wave (p = 0.005 when using all patients at denominator and p<0.001 when using only patients who underwent CT scan at denominator). Specifically, eight patients had PMD, two PNX, whereas the remaining three had both. Patients’ characteristics are summarized in Table 1. At the time of PNX/PMD development, eight patients were on CPAP, whereas six patients were on supplemental oxygen therapy only. All but the patient of the first wave were on steroid therapy (dexamethasone 6 mg daily in 12 cases and prednisone 60 mg daily in one case, p = 0.071). Median time from symptoms onset to PNX/PMD was 18 (17–24.5) days; median time form corticosteroid start to PNX/PMD was 15 (13–17) days. After PNX/PMD onset, four (29%) patients were admitted to ICU and seven (50%) patients died.
      The rate of PNX/PMD in non-intubated COVID-19 was significantly higher in the second pandemic wave as compared with the first pandemic wave. To the best of our knowledge, this is the first report comparing incidence of PNX/PMD in non-intubated COVID-19 ARDS patients in the first and second pandemic wave.
      As the only difference in treatment between the two waves was dexamethasone administration and hydroxychloroquine avoidance, it could be hypothesized that dexamethasone might have induced lung frailty and increased the risk of PNX/PMD, as already suggested in patients with interstitial inflammatory lung diseases [
      • Nishimoto K.
      • Fujisawa T.
      • Yoshimura K.
      • et al.
      Pneumothorax in connective tissue disease-associated interstitial lung disease.
      ]. Future studies are needed to confirm a different rate of PNX/PMD when using or not corticosteroids in COVID-19 patients.

      Funding

      None

      Declaration of Competing Interests

      None

      Acknowledgements

      We thank all the personnel of San Raffaele Scientific Institute for the dedication to these patients and for the support in data collection

      References

        • Belletti A.
        • Palumbo D.
        • Zangrillo A.
        • et al.
        Predictors of pneumothorax/pneumomediastinum in mechanically ventilated COVID-19 patients.
        J Cardiothorac Vasc Anesth. 2021; (In press)https://doi.org/10.1053/j.jvca.2021.02.008
        • Zangrillo A.
        • Beretta L.
        • Scandroglio A.M.
        • et al.
        Characteristics, treatment, outcomes and cause of death of invasively ventilated patients with COVID-19 ARDS in Milan, Italy.
        Crit Care Resusc. 2020; 22: 200-211
        • Ramirez G.A.
        • Bozzolo E.P.
        • Castelli E.
        • et al.
        Continuous positive airway pressure and pronation outside the intensive care unit in COVID 19 ARDS.
        Minerva Med. 2020; (In press)https://doi.org/10.23736/S0026-4806.20.06952-9
        • Zangrillo A.
        • Beretta L.
        • Silvani P.
        • et al.
        Fast reshaping of intensive care unit facilities in a large metropolitan hospital in Milan, Italy: facing the COVID-19 pandemic emergency.
        Crit Care Resusc. 2020; 22: 91-94
        • Sartini C.
        • Tresoldi M.
        • Scarpellini P.
        • et al.
        Respiratory Parameters in Patients with COVID-19 after Using Noninvasive Ventilation in the Prone Position Outside the Intensive Care Unit.
        JAMA. 2020; 323: 2338-2340https://doi.org/10.1001/jama.2020.7861
      1. Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report.
        N Engl J Med. 2021; 384: 693-704https://doi.org/10.1056/nejmoa2021436
        • Nishimoto K.
        • Fujisawa T.
        • Yoshimura K.
        • et al.
        Pneumothorax in connective tissue disease-associated interstitial lung disease.
        PLoS ONE. 2020; 15https://doi.org/10.1371/journal.pone.0235624