In our study, we observed a high incidence of air leak syndromes in patients with COVID 19 related ARDS requiring intensive care. We prefer the terminology ‘Air leak syndrome’ over ‘Barotrauma’ as not all patients were on positive pressure ventilation when they were found to have pneumo-mediastinum, pneumothorax or subcutaneous emphysema. A total of 16(20.2%) patients developed ALS, which is significantly higher when compared with ALS incidence in other ARDS patient populations (5-8%).16,17 Out of the 16 patients, 6 patients were on non-invasive ventilation, 7 patients were on invasive mechanical ventilation were as 3 patients were found to have spontaneous pneumo-mediastinum.
Multiple cases have reported spontaneous pneumo-mediastinum in patients with COVID-19. 18–22 Many of these reports indicate that patients were not on mechanical ventilation and did not have history of prior pneumothorax. Thus, the cause of spontaneous air leak syndromes and specifically pneumo-mediastina in the realm of Covid-19 ARDS remains an enigma. The predominant mechanism of air leak may not be barotrauma or related to ventilatory pressures, although positive pressure may be contributory to their development. The high incidence of ALS in critically ill COVID 19 patients may be related to excessive lung inflammation. Indeed high plasma levels of inflammatory mediators like IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα have been observed in ICU patients as compared to non-ICU patients with COVID-19.23 It is plausible that excessively inflamed lung tissue may be friable and prone to lung tears. Alternatively, there also may be a predisposition to fibrosis and worsening of swings in transpulmonary pressures with respiratory efforts of mechanical ventilation. Macklin and Macklin first noticed that air released from alveolar rupture centripetally dissects through the interstitium of the lungs, along the broncho vascular sheaths toward the pulmonary hila and into the mediastinum.24 Macklin effect is commonly seen in patients with blunt chest trauma.12 The Macklin effect has been observed in COVID-19 patients and could explain the high incidence of spontaneous pneumo-mediastinum often leading to pneumothorax.13,14,25,26 We studied D-dimer, CRP and Ferritin at admission to assess the role of inflammation. Admission D-dimer in ALS group was observed to be higher and reached statistical significance. Both baseline hypoxia and low PF ratio at presentation were significantly lower in ALS group, which may indicate that severity of disease has a role in the tendency for air leak.
Prior to COVID 19, air leak syndromes in ARDS have been known not only to increase hospital stay but also be associated with morbidity and mortality.4 In our cohort of patients, the requirement of prolonged ventilation in the ALS group was associated with higher incidence of ventilator associated pneumonia in these patients which may have adversely impacted their outcome.
Ventilatory management of COVID-19 patients has been a tough challenge throughout the pandemic. Different ventilatory management has been suggested based on the COVID phenotypes: L-type pneumonia and H-type pneumonia.27 Some previously done studies have found relationship between PEEP and barotrauma28, whereas others have found no relation between airway pressures and barotrauma29–31. In our study, higher PEEP was observed in the ALS group which was statistically significant. The pressure support, driving pressures and peak airway pressures were found to be higher in the ALS group. However, this trend was not found to be statistically significant. The higher PEEP settings in the ALS group may have set by clinicians in order to tackle poorer oxygenation and severity of disease in that group relative to the non-ALS group (and therefore may be a confounder)
Use of corticosteroids has shown reduction in severity of ARDS, increase in ventilator free days and reduction in mortality32. An observational study showed better results with high dose methylprednisolone as compared with conventional dose dexamethasone in COVID 19 patients in terms of progression of ARDS.33 In our study we observed that patients who received Inj. Dexamethasone were less likely to develop ALS as opposed to patients who received Inj. methylprednisolone. Although this could be chance finding, it is possible that fluid retention associate with the mineralocorticoid properties of methylprednisolone may have rendered the lung more friable or amenable to injury as opposed to Dexamethasone. Further studies need to be done to understand difference in effect of dexamethasone and methylprednisolone on outcome in COVID 19 patients.
A limitation of our study is a small sample size from a single center, however our study adds to the volume of data available on this topic as well as supports results from other settings. Another key limitation was out inability to capture tidal volume data from our cohort appropriately. However, the classic teaching is that pressure is the chief variable involved in air leak. Also other studies have not demonstrated that volume is a predictor of ALS 8. The unique incidence and pattern of ALS in Covid-19 patients, such as predisposition to pneumomediastina, gives us a window into understanding the pathophysiology and course of COVID 19 ARDS. Prospective studies need to continue to look into how to mitigate ALS so as to improve outcomes. With early recognition and emerging treatment options there could be reduced level of inflammation and severity of disease leading to less incidence of ALS and perhaps better outcomes.