Pneumothorax is a fatal complication in patients with ARDS, especially those undergoing invasive mechanical ventilation . In a previous study in which 84 severe ARDS patients were examined, the pneumothorax rate was 48.8%, and the mortality (66% vs 46%) was higher in patients with pneumothorax . In the presence of COVID-19 and ARDS, This rate was found to be 80% . Since our intensive care is one of our country's reference centers, severe patients were accepted from other intensive care units and hospitals. Hence, our mortality rate was 43.4% in all patients, 52.8% in patients with ARDS. This rate was found as 87% in the case of pneumothorax with ARDS occurrence. Therefore, we believe that preventing pneumothorax in a tertiary intensive care unit will significantly reduce mortality rates.
In a case series conducted on SARS patients in Hong Kong, it was observed that high neutrophil count and LDH level increased the tendency to pneumothorax . It was also thought that high-dose methylprednisolone administration affected the improvement of the lung tissue and contributed to the pneumothorax occurrence . Hameed et al. reported that high LDH and acute phase reactants were higher in COVID-19 patients who received high-dose prednisolone and developed pneumothorax . We used high dose methylprednisolone in all our patients. We found a significant difference between the baseline LDH level of our patients and the LDH levels at the time of pneumothorax occurrence. In the same manner, we observed that acute phase reactants increased significantly. Increases in acute phase reactants and LDH may be an early indicator for pneumothorax. Besides, we think that it would be beneficial to reconsider high-dose methylprednisolone treatment in this respect in the patient group requiring intensive care.
The duration of ARDS can explain the incidence of pneumothorax in ARDS. ARDS consists of three phases: exudative phase (1–7 days), proliferative phase (8–21 days), and fibrotic phase (> 21 days) . Gattinoni L et al. found the incidence of pneumothorax in late ARDS (longer than two weeks) patients as 87% and early ARDS (less than seven days) as 30% . Wang et al. reported that pneumothorax occurred two weeks after symptom onset in 5 COVID-19 patients with ARDS . In line with the literature, we found that pneumothorax's occurrence time was 17.4 ± 4.8 days in our patients. We did not find a significant relationship between pneumothorax occurrence time and mortality.
ARDS development is one of the most important prognostic factors in COVID-19 patients. In ARDS pathophysiology, neutrophil count is characterized by increased activation of proinflammatory cytokines and complement cascade, which results in microvascular permeability and fluid exudation . Eventually, fluid accumulation, alveolar atelectasis, and fibrin accumulation are seen in the lung . The occurrence of pneumothorax in mechanically ventilated patients is closely related to the underlying pulmonary pathology, and ARDS has been proven to be closely related to the occurrence of this complication . As it has been marvelously described by computed tomographic studies in patients with ARDS, the affected lung parenchyma, seems to have a remarkable heterogenic distribution which causes a multi-compartmental lung, with patchy infiltrates interspersed with normal-appearing lung areas . We performed tomography on our patients in the 1st week of their follow-up (table 4, Fig. 1–2). As seen in the literature, we observed common ground-glass opacities, heterogenic distribution with patch infiltrates, alveolar exudates in our patients' tomographic images. Interstitial thickening was observed in patients, although the computed tomography was performed in the early period. Emphysematous appearance and bullous formations occur in the affected lung areas in the late period, explaining the increase in pneumothorax incidence in this period .
Patients with ARDS who are under mechanical ventilation are at the highest risk for pneumothorax development . Many ventilation parameters, such as tidal volume, PIP, PEEP, and respiratory rate are considered important in the development of barotrauma. It was shown that there is a high correlation between the development of end-inspiratory pressure [P(plat)], especially when exceeding 35 cm H2O and pneumothorax . Furthermore, large tidal volume might elicit injury to the pulmonary epithelium; therefore tidal volume reduction is another parameter presented for the prevention of ventilator-induced injury in ARDS . Pplat pressure did not exceed 35 cm H2O in the patients we followed up. Pplat pressure was aimed to be kept below 30 cm H2O, and only four patients were observed to have over 30 cm H2O pressure at the time of pneumothorax occurrence. Also, VT was aimed to be kept between 4–6 ml/kg to prevent pulmonary epithelium damage. Neuromuscular blockers and fentanyl were used to minimize oxygen consumption and provide lung-protective settings. High PEEP levels are associated with the persistence of lung air leaks as well as the occurrence of pneumothorax. PEEP level was kept at 5–9 cm H2O level in our patients. In conclusion, we applied AC protective ventilation in almost all ARDS patients who developed pneumothorax in ICU, but we still could not avoid pneumothorax occurrence.
Data on pneumothorax treatment in ARDS patients are limited. Tube thoracostomy, open thoracotomy, pleurodesis, and thoracoscopic surgical methods are among the treatment methods. It was shown in the previous studies that thoracotomy increases mortality in patients with ARDS . A limited number of successful results have been published using thoracoscopic surgical methods, but further studies are needed on this subject . We placed chest tubes in all of our patients during the treatment, except for five patients with subcutaneous emphysema together with pneumothorax. Also, ECMO was used in one severe ARDS patient whose oxygenation could not be achieved. The patient's survival time who had diffuse lung involvement was extended, but mortality could not be avoided. Nevertheless, we think that administering ECMO can be one of the most promising options in patients who develop ARDS and pneumothorax due to COVID-19 since it reduces lung effort and provides a time gap for the treatment of pneumothorax and the elimination of the virus.
This study had some limitations. The study was conducted retrospectively, and further studies may fill some of the deficiencies of this study. First of all, the number of patients was limited. A multi-center study with a larger sample size may contribute to treatment improvement. Second, the risk factors can be compared by expanding the study population with patients who do not require intensive care conditions, who do not have ARDS, and who have a milder manifestation. Third, since it is difficult to use CT scan as an imaging method in the patients' follow-up, bedside X-ray criteria or USG administration methods can be defined for follow-up. Besides, it can be discussed to administer early treatment to patients to reduce mortality. Also, the relationship between high-dose methylprednisolone treatment and pneumothorax can be examined.
In conclusion, although lung-protective ventilation parameters were applied, we found that mortality was high in our COVID-19 patients with ARDS. We have seen that the pneumothorax tendency was more common in patients after two weeks. We also observed that acute phase reactants and LDH increased significantly on the day of pneumothorax occurrence. According to our findings, pneumothorax with ARDS increased mortality, and we believe that the prevention of pneumothorax will make an important contribution to reducing mortality. Therefore, more comprehensive studies are needed on this subject in the future to prevent and treatment pneumothorax occurrence in critically ill COVID-19 patients.