Pulmonary barotrauma as a complication of mechanical ventilation for management of COVID-19 associated acute respiratory distress syndrome (CARDS)

Objective: To identify that incidence of pulmonary barotrauma secondary to mechanical ventilation for the management of acute respiratory distress syndrome associated with coronavirus-disease-2019, and to compare it with the incidence of pulmonary barotrauma trauma secondary to mechanical ventilation associated with all the other causes. Method: The retrospective case-control study was conducted at the Aga Khan University Hospital, Karachi, and comprised data from October 2020 to March 2021 of patients who underwent mechanical ventilation. The data was divided into two groups. Data of acute respiratory distress syndrome associated with coronavirus-disease-2019 was in group 1, and that of acute respiratory distress syndrome associated with any other cause in control group 2. Medical records were reviewed to obtain demographic and clinical data, while the institutional picture archiving and communication system was used to review radiological images. Data was analysed using SPSS 24. Results: Of the 261 cases, 115(44%) were in group 1; 87(75.6%) males and 28(24.3%) females. There were 146(56%) controls in group 2; 96(65.7%) males and 50(34.2%) females. There were 142(54.4%) subjects aged >60 years; 61(43%) in group 1 and 81(57%) in group 2. The incidence of pulmonary barotrauma in group 1 was 39(34%) and 8(5.5%) in group 2 ( p <0.0001). Conclusion: Mechanical ventilation in the management of acute respiratory distress syndrome associated with coronavirus-disease-2019 was found to be associated with a significantly higher incidence of pulmonary barotrauma than acute respiratory distress syndrome associated with any other cause.


Introduction
Acute respiratory distress syndrome (ARDS) is a critical condition characterised by acute hypoxaemia accompanied by reduced compliance and non-cardiogenic pulmonary oedema. 1 Since the beginning of the coronavirus disease-2019 (COVID-19) pandemic, a rapid surge of ARDS cases was reported in healthcare centres across the globe, and the condition was labelled as COVID-19-related ARDS (CARDS).Most of these patients ended up requiring mechanical ventilation (MV). 2 Barotrauma is defined as tissue injury that occurs as a consequence of the pressure difference between a poorlyventilated body cavity and the surrounding air, fluid interface or across a tissue plane.Pulmonary barotrauma can manifest in a variety of ways, including spontaneous pneumothorax (PTX), subcutaneous emphysema (SE), pneumopericardium and pneumomediastinum. 3lmonary barotrauma is a known complication of MV with ARDS, and COVID-19 was an independent risk factor for increasing the possibility of developing this complication. 4,5However, exact incidence of pulmonary barotrauma injury secondary to MV for the management of CARDS is not well documented.
The current study was planned to fill the gap by documenting the incidence of various manifestations of pulmonary barotrauma secondary to MV for CARDS management, and to compare it with the incidence of pulmonary barotrauma secondary to MV related to any other cause.

Materials and Methods
The retrospective case-control study was conducted at the Aga Khan University Hospital (AKUH), Karachi, and comprised patient data from October 1, 2020, to March 31, 2021.
After obtaining exemption from the institutional ethics review committee, the sample was raised using convenience sampling method.Data was extracted from the hospital information and management system (HIMS), using key word 'mechanical ventilation' and also the International Classification of Diseases-10 (ICD-10) coding system. 6Data included was related to patients of either gender, aged 18 and above, who underwent MV for any reason.Data was excluded in cases where there was evidence of pulmonary barotrauma on first radiological image, as the identification of MV as being the cause of pulmonary barotrauma could not be ascertained.System (PACS).Both radiologists were blinded to the clinical indication for MV at the time of image interpretation.The panel documented its findings on a predesigned chart, including type of MV, presence of pulmonary barotrauma on radiographs acquired postinitiation of MV till radiological evidence of discontinuation of MV, and the day of pulmonary barotrauma occurrence post-initiation of MV.
Data was analysed using SPSS 24.Qualitative variables were expressed as frequencies and percentages, while quantitative parameters were expressed as mean±standard deviation (SD).Two tailed Fisher's exact test was used to compare the associations.P<0.05 was considered statistically significant.
Within group 1, the difference between patients who developed pulmonary barotrauma after non-invasive MV and those who developed it after invasive MV was significant (p<0.01).
The mean serum ferritin values and length of hospital stay was higher while serum CRP level was lower in group A patients with pulmonary barotrauma compared to overall group 1 values (Table 3) In group 1, overall mortality was 65(56.5%);27(69%) in the pulmonary barotrauma subset compared to 38(50%) of those who did not have pulmonary barotrauma.

Discussion
The study reported pulmonary barotrauma in 39/115 (34%) hospitalised adult patients who underwent MV for CARDS compared to only 8/146 (5.5%) such events in cases of pulmonary barotrauma secondary to MV for all other causes.][10] The incidence of pulmonary   barotrauma among patients undergoing MV for causes others CARDS has been reported to be about 6.5%. 11The 34% frequency of pulmonary barotrauma in CARDS reported in the study was much higher than the reported frequency of pulmonary barotrauma in ARDS cases. 12,13In the current study, pneumomediastinum was the most common type of pulmonary barotrauma in CARDS (74%) while its occurrence 37.5% in the control group.This pattern is similar to earlier reports; 13.6% versus 1.9%. 8The increased incidence of pulmonary barotrauma secondary to MV in CARDS patients can be multifactorial.One possible explanation is fragility of the lung parenchyma as a consequence of the infection resulting in increased susceptibility to rupture secondary to positive-pressure ventilation. 14In the current cohort, the subset of CARDS patients who received non-invasive positive-pressure ventilation (NIPPV) demonstrated higher incidence of pulmonary barotrauma (77%) versus the incidence in IPPV cases (30%).Jones et al. and Hamouri et al. have also reported similar findings. 15,16The increased incidence of pulmonary barotrauma secondary to NIPPV is multifactorial.One possible explanation is that the tidal volumes and transpulmonary pressure in NIPPV are dependent on patient's spontaneous respiratory effort, control of which can help in reducing the risk of pulmonary barotrauma. 17The spontaneous effort results in fluctuant pressure gradients, thereby increasing the incidence of pulmonary barotrauma with NIPPV. 18,19The higher incidence of pulmonary barotrauma in NIPPV might be also attributed to the limited use of sedation and muscle relaxant compared to IPPV which impacts patientventilator dys-synchrony, and subsequently higher risk of developing pulmonary barotrauma. 20,21Many clinical and laboratory variables were investigated in the current cohort, looking for predictors associated with a higher risk of developing pulmonary barotrauma in patients receiving MV.Some studies have speculated the role of inflammatory markers as possible predictors of poor outcomes.Hamouri et al. 16 found that the pulmonary barotrauma group had higher levels of ferritin (p=0.07) and no significant difference in CRP levels, which is concordant with the current results.Inflammatory markers may help identify patients at the highest risk of developing ARDS, assess response to therapy and the risk of pulmonary barotrauma.Subsequently, they may also be useful in improving risk stratification. 22,23However, a larger sample size will be needed to study general trends and the likelihood of complications.
The current study has limitations because of single-centre data which limits generalisability of the findings.An assessment of patients' comorbid and extensive laboratory investigations may help in better understanding the causative factors that lead to pulmonary barotrauma.The current study was based on a reductionist perspective to correlate the two factors.A better understanding can be developed if the other factors, like comorbidities, could be made more consistent to minimise the impact of potential confounding factors.

Conclusion
The management of CARDS using MV was found to be associated with increased incidence of pulmonary barotrauma.Physician must be aware of this critical complication that will allow prevention, early detection and management of the condition and help reduce associated mortality.

Figure- 1 :
Figure-1:A 60 year old female presented to emergency room (ER) with a 7-day history of fever and worsening shortness of breath.On investigation, she was found to be positive for coronavirus disease-2019 (COVID-19) on polymerase chain reaction (PCR) assay.Chest radiograph obtained at presentation (a) revealed patchy consolidations in bilateral mid and lower lung fields typical of viral pneumonia secondary to COVID-19 infection.Her radiographs obtained on day 10 of admission (b) showed worsening of inhomogeneous shadowing along with increased oxygen dependence clinically.Therefore, she was intubated and positive-pressure mechanical ventilation (MV) started (c).On the 4th MV day(d), the patient developed suspicion of lucency within the mediastinal soft tissue planes, extending along the descending thoracic aortic interface and into the neck soft tissues (white arrows), indicating pneumomediastinum.On the 7th MV day (e), a large lucency devoid of vascular markings was noted along the right lateral hemithorax with underlying lung collapse, indicating pneumothorax.The patient was subsequently managed with multiple chest tubes for barotrauma, but due to worsening airspace disease (f), the patient eventually expired on the 19th day of admission.

Figure- 2 :
Figure-2: Multiple patients with radiographic findings consistent with coronavirus disease-2019 (COVID-19) pneumonia.(a) A shadow of the external respirator device is seen (white arrow), which was reconfirmed to be a bilevel positive airway pressure (BiPAP) device.Such patients were managed with (b) invasive positive-pressure ventilation through endotracheal tube, and (c) tracheostomy.

Table - 2
: Association of MV and pulmonary barotrauma for management of CARDS.

Table - 3
: Inflammatory markers and length of hospital stay in CARDS group.