Time dependency and unique etiology of barotrauma in COVID-19: A retrospective cohort study with landmark analysis and pathological approach.

BACKGROUND: Barotrauma frequently occurs in coronavirus disease 2019. Previous studies have reported barotrauma to be a mortality-risk factor; however, its time-dependent nature and pathophysiology are not elucidated. To investigate the time-dependent characteristics and the etiology of coronavirus disease 2019-related-barotrauma. METHODS AND FINDINGS: We retrospectively reviewed intubated patients with coronavirus disease 2019 from March 2020 to May 2021. We compared the 90-day survival between the barotrauma and non-barotrauma groups and performed landmark analyses on days 7, 14, 21, and 28. Barotrauma within seven days before the landmark was defined as the exposure. Additionally, we evaluated surgically treated cases of coronavirus disease 2019-related pneumothorax. We included 192 patients. Barotrauma developed in 44 patients (22.9%). The barotrauma group's 90-day survival rate was significantly worse (47.7% vs. 82.4%, p < 0.001). In the 7-day landmark analysis, there was no significant difference (75.0% vs. 75.7%, p = 0.79). Contrastingly, in the 14-, 21-, and 28-day landmark analyses, the barotrauma group's survival rates were significantly worse (14-day: 41.7% vs. 69.1%, p = 0.044; 21-day: 16.7% vs. 62.5%, p = 0.014; 28-day: 20.0% vs. 66.7%, p = 0.018). Pathological examination revealed a subpleural hematoma and pulmonary cyst with heterogenous lung inflammation. CONCLUSIONS: Barotrauma was a poor prognostic factor for coronavirus disease 2019, especially in the late phase. Heterogenous inflammation may be a key finding in its mechanism. Barotrauma is a potentially important sign of lung destruction.

High incidence of barotrauma in patients admitted with COVID-19 to ICU and associated mortality in rural Appalachia: An observational study.

OBJECTIVES: To assess the incidence of barotrauma and its impact on mortality in COVID-19 patients admitted to ICU. DESIGN: Single-center retrospective study of consecutive COVID-19 patients admitted to a rural tertiary-care ICU. The primary outcomes were incidence of barotrauma in COVID-19 patients and all-cause 30-day mortality. Secondary outcomes were the length of stay (LOS) in the hospital and ICU. Kaplan-Meier method and log-rank test were used in the survival data analysis. SETTING: Medical ICU, West Virginia University Hospital (WVUH), USA. PATIENTS: All adult patients were admitted to the ICU for acute hypoxic respiratory failure due to coronavirus disease 2019 between September 1, 2020, and December 31, 2020. Historical controls were ARDS patients admitted pre-COVID. INTERVENTION: Not applicable. MEASUREMENTS AND MAIN RESULTS: One hundred and sixty-five consecutive patients with COVID-19 were admitted to the ICU during the defined period, compared to 39 historical non-COVID controls. The overall incidence of barotrauma in COVID-19 patients was 37/165 (22.4%) compared to 4/39 (10.3%) in the control group. Patients with COVID-19 and barotrauma had a significantly worse survival (HR = 1.56, p = 0.047) compared to controls. In those requiring invasive mechanical ventilation, the COVID group also had significantly higher rates of barotrauma (OR 3.1, p = 0.03) and worse all-cause mortality (OR 2.21, p = 0.018). COVID-19 with barotrauma had significantly higher LOS in the ICU and the hospital. CONCLUSIONS: Our data on critically ill COVID-19 patients admitted to the ICU shows a high incidence of barotrauma and mortality compared to the controls. Additionally, we report a high incidence of barotrauma even in non-ventilated ICU patients.

Clinical use of Macklin-like radiological sign (Macklin effect): A systematic review.

INTRODUCTION: Recent studies suggested that Macklin sign is a predictor of barotrauma in patients with acute respiratory distress syndrome (ARDS). We performed a systematic review to further characterize the clinical role of Macklin. METHODS: PubMed, Scopus, Cochrane Central Register and Embase were searched for studies reporting data on Macklin. Studies without data on chest CT, pediatric studies, non-human and cadaver studies, case reports and series including <5 patients were excluded. The primary objective was to assess the number of patients with Macklin sign and barotrauma. Secondary objectives were: occurrence of Macklin in different populations, clinical use of Macklin, prognostic impact of Macklin. RESULTS: Seven studies enrolling 979 patients were included. Macklin was present in 4-22% of COVID-19 patients. It was associated with barotrauma in 124/138 (89.8%) of cases. Macklin sign preceded barotrauma in 65/69 cases (94.2%) 3-8 days in advance. Four studies used Macklin as pathophysiological explanation for barotrauma, two studies as a predictor of barotrauma and one as a decision-making tool. Two studies suggested that Macklin is a strong predictor of barotrauma in ARDS patients and one study used Macklin sign to candidate high-risk ARDS patients to awake extracorporeal membrane oxygenation (ECMO). A possible correlation between Macklin and worse prognosis was suggested in two studies on COVID-19 and blunt chest trauma. CONCLUSIONS: Increasing evidence suggests that Macklin sign anticipate barotrauma in patients with ARDS and there are initial reports on use of Macklin as a decision-making tool. Further studies investigating the role of Macklin sign in ARDS are justified.

Barotrauma in COVID 19: Incidence, pathophysiology, and effect on prognosis.

OBJECTIVES: To investigate the incidence, risk factors, and outcomes of barotrauma (pneumomediastinum and subcutaneous emphysema) in mechanically ventilated COVID-19 patients. To describe the chest radiography patterns of barotrauma and understand the development in relation to mechanical ventilation and patient mortality. METHODS: We performed a retrospective study of 363 patients with COVID-19 from March 1 to April 8, 2020. Primary outcomes were pneumomediastinum or subcutaneous emphysema with or without pneumothorax, pneumoperitoneum, or pneumoretroperitoneum. The secondary outcomes were length of intubation and death. In patients with pneumomediastinum and/or subcutaneous emphysema, we conducted an imaging review to determine the timeline of barotrauma development. RESULTS: Forty three out of 363 (12%) patients developed barotrauma radiographically. The median time to development of either pneumomediastinum or subcutaneous emphysema was 2 days (IQR 1.0-4.5) after intubation and the median time to pneumothorax was 7 days (IQR 2.0-10.0). The overall incidence of pneumothorax was 28/363 (8%) with an incidence of 17/43 (40%) in the barotrauma cohort and 11/320 (3%) in those without barotrauma (p ≤ 0.001). In total, 257/363 (71%) patients died with an increase in mortality in those with barotrauma 33/43 (77%) vs. 224/320 (70%). When adjusting for covariates, barotrauma was associated with increased odds of death (OR 2.99, 95% CI 1.25-7.17). CONCLUSION: Barotrauma is a frequent complication of mechanically ventilated COVID-19 patients. In comparison to intubated COVID-19 patients without barotrauma, there is a higher rate of pneumothorax and an increased risk of death.

Macklin effect on baseline chest CT scan accurately predicts barotrauma in COVID-19 patients.

PURPOSE: To validate the role of Macklin effect on chest CT imaging in predicting subsequent occurrence of pneumomediastinum/pneumothorax (PMD/PNX) in COVID-19 patients. MATERIALS AND METHODS: This is an observational, case-control study. Consecutive COVID-19 patients who underwent chest CT scan at hospital admission during the study time period (October 1st, 2020-April 31st, 2021) were identified. Macklin effect accuracy for prediction of spontaneous barotrauma was measured in terms of sensitivity, specificity, positive (PPV) and negative predictive values (NPV). RESULTS: Overall, 981 COVID-19 patients underwent chest CT scan at hospital arrival during the study time period; 698 patients had radiological signs of interstitial pneumonia and were considered for further evaluation. Among these, Macklin effect was found in 33 (4.7%), including all 32 patients who suffered from barotrauma lately during hospital stay (true positive rate: 96.9%); only 1/33 with Macklin effect did not develop barotrauma (false positive rate: 3.1%). No barotrauma event was recorded in patients without Macklin effect on baseline chest CT scan. Macklin effect yielded a sensitivity of 100% (95% CI: 89.1-100), a specificity of 99.85% (95% CI: 99.2-100), a PPV of 96.7% (95% CI: 80.8-99.5), a NPV of 100% and an accuracy of 99.8% (95% CI: 99.2-100) in predicting PMD/PNX, with a mean advance of 3.2 ± 2.5 days. Moreover, all Macklin-positive patients developed ARDS requiring ICU admission and, in 90.1% of cases, invasive mechanical ventilation. CONCLUSIONS: Macklin effect has high accuracy in predicting PMD/PNX in COVID-19 patients; it is also an excellent predictor of disease severity.

Outcomes of Barotrauma in Critically Ill COVID-19 Patients With Severe Pneumonia.

BACKGROUND: Pneumomediastinum and pneumothorax are complications which may be associated with barotrauma in mechanically ventilated patients. The current literature demonstrates unclear outcomes regarding barotrauma in critically ill patients with severe COVID-19. The purpose of this study was to examine the incidence of barotrauma in patients with severe COVID-19 pneumonia and its influence on survival. STUDY DESIGN AND METHODS: A retrospective cohort study was performed from March 18, 2020 to May 5, 2020, with follow-up through June 18, 2020, encompassing critically ill intubated patients admitted for COVID-19 pneumonia at an academic tertiary care hospital in Brooklyn, New York. Critically ill patients with pneumomediastinum, pneumothorax, or both (n = 75) were compared to those without evidence of barotrauma (n = 206). Clinical characteristics and short-term patient outcomes were analyzed. RESULTS: Barotrauma occurred in 75/281 (26.7%) of included patients. On multivariable analysis, factors associated with increased 30-day mortality were elevated age (HR 1.015 [95% CI 1.004-1.027], P = 0.006), barotrauma (1.417 [1.040-1.931], P = 0.027), and renal dysfunction (1.602 [1.055-2.432], P = 0.027). Protective factors were administration of remdesivir (0.479 [0.321-0.714], P < 0.001) and receipt of steroids (0.488 [0.370-0.643], P < 0.001). CONCLUSION: Barotrauma occurred at high rates in intubated critically ill patients with COVID-19 pneumonia and was found to be an independent risk factor for 30-day mortality.