Secondary pneumomediastinum and pneumopericardium are most often associated with chest trauma, esophageal perforation, cardiothoracic surgery or mechanical ventilation. SPM and SPP, however, are less common phenomena . During the severe acute respiratory syndrome (SARS) outbreak in 2002–2003, a study from Hong Kong reported an incidence of 11.6% of SPM in infected patients . The incidence of SPM and SPP in patients with COVID-19 pneumonia is unknown.
The pathophysiology of SPM in SARS patients is thought to be related to diffuse alveolar damage (DAD) which leads to gas leak into the pulmonary interstitium causing pneumomediastinum . This concept is supported by postmortem studies on SARS lungs revealing extensive features of acute exudative alveolar and vascular injury . Like the SARS virus, the novel COVID-19 virus causes ARDS in a sizable percentage of infected patients, but the mechanisms of alveolar injury are still under investigation. However, emerging autopsy reports of COVID-19 patients from Italy and the United States revealed that DAD appears to also be the predominate pathologic pattern of pulmonary injury in COVID-19 patients [9, 10].
Pulmonary barotrauma from mechanical ventilation, especially with high positive end-expiratory end pressure (PEEP), is a well-known risk factor for pneumomediastinum and pneumopericardium. High intra-alveolar pressure causes susceptible alveoli to rupture allowing air to dissect along the bronchovascular sheaths towards the mediastinum . Occasionally, pressure accumulation in the mediastinum causes air to escape into the pleural space (pneumothorax) or through weaknesses of the parietal pericardium (pneumopericardium). Air can also travel towards the thoracic inlet and into the neck soft tissue causing cervico-facial subcutaneous emphysema .
HFNC is a relatively newer form of ventilation used in the management of ARDS. HFNC generally delivers PEEPs lower than mechanical ventilation and some of this pressure escapes with mouth opening . A few published cases described SPM in patients managed with HFNC, including that of a 77-year-old woman with influenza A and underlying chronic obstructive and interstitial lung disease after 4 days of HFNC at 60 L/min . Similar incidents were noted in the pediatric population as well . Both of our patients were on HFNC for several days prior to the development of SPM. It is unclear if HFNC causes barotrauma that contributed to the occurrence of SPM in our patients. Another therapy that has been used in the management of ARDS in COVID-19 patients is steroids . Steroid’s use in the treatment of connective tissue diseases, such as dermatomyositis, has been postulated to contribute to the development of SPM by weakening the pulmonary interstitial tissue causing alveolar air leak . Each of our patients received a cumulative dose of < 1 g methylprednisolone prior to the development of SPM. Although this is a small dose, further investigation is needed to determine if steroid use and cumulative dose play a role in the pathogenesis of SPM in COVID-19 patients.
Cough is a forceful expiration of air that causes sudden transient alveolar over-distention and occasionally rupture. It is a well-known risk factor for pneumomediastinum and pneumothorax . Both of our patients had significant cough upon presentation to the hospital and during the early part of their hospital stay. The coughing spells, exerting strain upon the already damaged and weakened alveoli from COVID-19 pneumonia, could have directly contributed to the development of pneumomediastinum in our two patients.
Notably, both of our patients had history of underlying lung disease as well as obesity, which have been shown predispose patients to severe COVID-19 . When COVID-19 outbreak data from Wuhan, China were examined, obese patients appeared to have higher severity of illness, and all-cause mortality . Prior studies found obesity (BMI ≥30 kg/m2) to be an independent risk for pulmonary edema, DAD, and alveolar capillary hemosiderosis . Taken together, one can postulate that obese COVID-19 patients, who are at risk for DAD, are also at higher risk for developing SPM.
In addition to identifying patient characteristics as potential risk factors for SPM, laboratory evaluation may have a predictive value. Lactate dehydrogenase (LDH) levels reflect the level of cell death due to plasma membrane damage. In the SARS outbreak, higher peak LDH was associated with SPM (mean 863 U/L) as compared with those without SPM (mean 583 U/L) . Similarly, our two patients had high LDH peak prior to the onset of SPM (953 U/L and 1664 U/L for patient 1 and 2, respectively). If further study support this correlation, trending LDH levels may have a prognostic value in patients with COVID-19 pneumonia.
An interesting observation in our cases is the delayed appearance of SPM from onset of symptomatic infection (day 27 and day 18 for patient 1 and 2, respectively). SARS patients who developed SPM also showed similar delay, with a mean of 19.6 ± 4.6 days from symptom onset . Therefore, clinicians should consider SPM in the differential diagnosis of new-onset pleuritic chest pain or unexpected respiratory deterioration after 2 weeks of illness in COVID-19 patients.
There are noteworthy diagnostic difficulties relating to SPM, especially in COVID-19 patients. Curvilinear radiolucency outlining the cardiac border is typical of pneumomediastinum on frontal CXR. This view, however, may only identify 50% of pneumomediastinum cases . A lateral CXR, where gas is seen in the retrosternal space, is more sensitive . When the diagnosis of pneumomediastinum remains uncertain, a chest CT is the modality of choice. Both lateral CXR and CT scans require transferring patients to and from the radiology suite. When applied to COVID-19 patients, these episodes of intra-hospital transport create potential breaches in infection control measures, a decision which must be weighed against the risk missing a diagnosis of SPM .
Finally, while SPM is usually self-limited in healthy individuals, patients with SARS and SPM had worse outcomes. Of those who developed SPM, 46% had simultaneous or new bilateral pneumathorax and most required bilateral chest tube insertion . Ultimately, 38% progressed to intubation and 31% died . Both of our COVID-19 patients eventually required intubation and mechanical ventilation and both suffered significant worsening of the subcutaneous emphysema on the ventilator and eventually expired. It is prudent to keep in mind that significantly elevated pressure in the mediastinal cavity (tension pneumomediastinum) and in the pericardium (tension pneumopericardium) can cause compression of intrathoracic structures leading to rapid respiratory and hemodynamic instabilities, complications that are more likely to occur with the use of positive pressure ventilation . In such situations, a mediastinotomy with insertion of a drainage catheter should be strongly considered . Although neither of our patients required immediate surgical intervention, the balance of maintaining adequate oxygenation while preventing exacerbation of the mediastinal emphysema while on mechanical ventilation proved to be challenging.