Pneumomediastinum in Mechanically Ventilated Coronavirus Disease 2019 Patients.

To the Editor:

Currently, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is a global health threat that has resulted in more than 300,000 deaths. Severe acute respiratory syndrome coronavirus 2 primarily targets the pulmonary system and causes hypoxemic respiratory failure and acute respiratory distress syndrome (ARDS). Pneumomediastinum is a well-known life-threatening complication related to the use of mechanical ventilation, especially in ARDS patients. However, publications highlighting the characteristics and outcomes of COVID-19 patients who develop pneumomediastinum after intubation and mechanical ventilation are very limited. Herein, we present our institution's experience with 4 patients (Table 1 ). The median age of the patients was 56 years (range 41-74 y). Two were male, and 2 were female. All patients had significant risk factors for developing severe COVID-19, including comorbidities, obesity, and the elevation of inflammatory markers. None was a smoker or had any underlying lung diseases. All patients were intubated using direct laryngoscopy, due to acute hypoxemic respiratory failure from COVID-19 pneumonia. Assist volume- control ventilation was implemented in all patients. The positive end-expiratory pressure (PEEP) values and tidal volume before the patients developed pneumomediastinum ranged from 16- to- 20 cmH2O and 350- to- 520 mL, respectively. One patient underwent prone intervention for 6 days on and off. The diagnosis of pneumomediastinum was confirmed by chest x-ray (Fig 1 ). Due to their persistent hypoxemia from severe ARDS, we could not decrease the ventilator settings of any of the patients after they had developed pneumomediastinum. All patients ultimately died due to septic shock and multiorgan failure from severe COVID-19. We did not perform autopsies.

Table 1

Patient characteristics and hospital courses

Case	1	2	3	4
Age/ Sex	74/ female	48/ female	41/ male	64/ male
Comorbidities	HTN, DM, HLD	Obesity (BMI 47)	Obesity (BMI 35)	Obesity (BMI 34)
Smoking status	Non-smoker	Non-smoker	Non-smoker	Non-smoker
Presenting symptoms	Fever, cough, diarrhea, vomiting	Dyspnea, cough	Dyspnea, cough, fever	Dyspnea, fever, cough, diarrhea, vomiting
Inflammatory markers	CRP 16, DD 303, IL6 75	CRP 35, DD 1084, IL6 159	CRP 7, DD 866, IL6 10	CRP 20, DD 3009
COVID-19 treatment	Hydroxychloroquine, IL6 inhibitor trial	Hydroxychloroquine	Hydroxychloroquine	Hydroxychloroquine, convalescent plasma
Day of intubation	D 1	D 0	D 4	D 2
ETT size	7.5	7 (2 attempts)	7.5	8
Highest PEEP	16	20	15	18
Highest Tidal Volume	350	350	520	400
Prone intervention	No	No	No	Yes
Day from intubation	13	4	2	6
CXR	Massive pneumomediastinum and subcutaneous emphysema	Right-sided tension pneumothorax, pneumomediastinum	Small left pneumothorax, pneumomediastinum, marked subcutaneous emphysema	Large right pneumothorax (70%)
Severity	Severe	Severe	Mild	Severe
Management	Left intrapleural chest drain	Needle decompression, Right intrapleural chest drain	Left intrapleural chest drain	Needle decompression, Right intrapleural chest drain
Outcome	Death (LOS 17 days)	Death (LOS 6 days)	Death (LOS 30 days)	Death (LOS 10 days)

Endotracheal tube (ETT), positive end-expiratory pressure (PEEP), Chest x-ray (CXR), C-reactive protein (CRP (mg/dl), normal <0.4 mg/dl), D-dimer (DD (ng/ml) normal < 230 ng/ml), interleukin-6 (IL6 (pg/mL), normal < 15.5 pg/mL), length of stay (LOS)

Figure 1

CXR of the patients

We searched the Medline database for pneumomediastinum in mechanically ventilated COVID-19 patients and discovered 1 previously reported case series from the United Kingdom. Wali et al. described 5 COVID-19 patients who developed pneumomediastinum after tracheal intubation and mechanical ventilation and proposed that the pneumomediastinum was at least partly due to large-bore tracheal tubes (initially used size 9 in all patients) leading to tracheobronchial injury. However, our patients were intubated with a smaller size of tracheal tubes (median 7.5, ranges 7-8). We hypothesized that the primary mechanism of pneumomediastinum in these patients was barotrauma, as evident by the high requirement of PEEP in all patients. The positive correlations of high PEEP values, barotrauma, and the risks of developing pneumomediastinum are well-recognized. None of our patients or those in the Wali et al. reported had underlying lung pathology. None of our patients had ever smoked. The lack of preexisting pulmonary abnormalities may support the hypothesis that the destruction of alveoli from cytokine storm in patients with severe COVID-19 is a significant predisposing factor for the development of barotrauma and pneumomediastinum. We also found substantially higher inflammatory markers in all patients, validating the occurrence of the cytokine storm. However, whether immunosuppressive agents will help in decreasing the destruction of alveoli and the risks of developing pneumomediastinum needs to be determined.

Prone positioning has shown proven benefits in patients with ARDS. , Recent evidence also suggested that prone positioning improves oxygenation in nonmechanically ventilated COVID-19 patients. In contrast, the risks and complications of prone intervention, especially in COVID-19 patients, are not well-elucidated. From our institution's experience, prone positioning may lead to an increased incidence of tracheal tube cuff leakage, tracheal tube dislodgement, and a decrease in blood pressure. In addition, repositioning intervention may cause tracheobronchial injury and pneumomediastinum in intubated patients. Our 4th patientand 1 patient in the Wali et al. case series developed pneumomediastinum after prone positioning. Studies to determine the risks related to prone intervention will be worthwhile.

Adjustment of mechanical ventilation, management of lung injury and barotrauma, and treatment of pneumomediastinum in invasively ventilated COVID-19 patients, pose great challenges to all relevant health-care professionals. Studies to explore the respiratory pathophysiology and possible treatment interventions in invasively ventilated COVID-19 patients are needed urgently to solve these issues.