Predictors of Mortality and Orotracheal Intubation in Patients with Pulmonary Barotrauma Due to COVID-19: An Italian Multicenter Observational Study during Two Years of the Pandemic

Abstract

Introduction: Coronavirus disease 2019 (COVID-19) is a significant and novel cause of acute respiratory distress syndrome (ARDS). During the COVID-19 pandemic, there has been an increase in the incidence of cases involving pneumothorax and pneumomediastinum. However, the risk factors associated with poor outcomes in these patients remain unclear. Methods: This observational study collected clinical and imaging data from COVID-19 patients with PTX and/or PNM across five tertiary hospitals in central Italy between 1 March 2020 and 1 March 2022. This study also calculated the incidence of PTX and PNM and utilized multivariable regression analysis and Kaplan-Meier curve analysis to identify predictor factors for 28-day mortality and 3-day orotracheal intubation after PTX/PNM. This study also considered the impact of the three main variants of concern (VoCs) (alfa, delta, and omicron) circulating during the study period. Results: During the study period, a total of 11,938 patients with COVID-19 were admitted. This study found several factors independently associated with a higher risk of death in COVID-19 patients within 28 days of pulmonary barotrauma. These factors included a SOFA score ≥ 4 (OR 3.22, p = 0.013), vasopressor/inotropic therapy (OR 11.8, p < 0.001), hypercapnia (OR 2.72, p = 0.021), PaO₂/FiO₂ ratio < 150 mmHg (OR 10.9, p < 0.001), and cardiovascular diseases (OR 7.9, p < 0.001). This study also found that a SOFA score ≥ 4 (OR 3.10, p = 0.015), PCO₂ > 45 mmHg (OR 6.0, p = 0.003), and P/F ratio < 150 mmHg (OR 2.9, p < 0.042) were factors independently associated with a higher risk of orotracheal intubation (OTI) within 3 days from PTX/PNM in patients with non-invasive mechanical ventilation. SARS-CoV-2 VoCs were not associated with 28-day mortality or the risk of OTI. The estimated cumulative probability of OTI in patients after pneumothorax was 44.0% on the first day, 67.8% on the second day, and 68.9% on the third day, according to univariable survival analysis. In patients who had pneumomediastinum only, the estimated cumulative probability of OTI was 37.5%, 46.7%, and 57.7% on the first, second, and third days, respectively. The overall incidence of PTX/PNM among hospitalized COVID-19 patients was 1.42%, which increased up to 4.1% in patients receiving invasive mechanical ventilation. Conclusions: This study suggests that a high SOFA score (≥4), the need for vasopressor/inotropic therapy, hypercapnia, and PaO₂/FiO₂ ratio < 150 mmHg in COVID-19 patients with pulmonary barotrauma are associated with higher rates of intubation, ICU admission, and mortality. Identifying these risk factors early on can help healthcare providers anticipate and manage these patients more effectively and provide timely interventions with appropriate intensive care, ultimately improving their outcomes.

Keywords: COVID-19; pneumomediastinum; pneumothorax.

Figure 1

Flowchart showing study selection. PTX, pneumothorax with or without pneumomediastinum; PNM, pneumomediastinum only.

Figure 2

Stacked bar showing the percentages of cases of pneumothorax with or without pneumomediastinum (PTX) and pneumomediastinum only (PNM) categorized by respiratory support. COT, conventional oxygen therapy; HFNO, high-flow nasal cannula oxygen; CPAP, non-invasive continuous positive airway pressure; BiPAP, non-invasive bilevel positive airway pressure; IMV, invasive mechanical ventilation.

Figure 3

Kaplan–Meier survival curves within 28 days from pulmonary barotrauma, with log-rank p, stratified by (a) hypercapnia or no hypercapnia (PCO₂, arterial blood partial pressure of carbon dioxide, > or ≤ 45 mmHg) within 24 h after barotrauma; (b) P/F ratio, the ratio of arterial partial pressure to fractional inspired oxygen (< or ≥ 150 mmHg), within 24 h after barotrauma; (c) the presence or absence of cardiovascular diseases; (d) the requirement for vasopressor/inotropic therapy in continuous intravenous infusion for at least six hours within the first three days after the onset of barotrauma.

Figure 4

Kaplan–Meier curves estimating the cumulative probability of orotracheal intubation (OTI) at 3 days from the occurrence of pneumothorax (with or without pneumomediastinum) and pneumomediastinum only.