Barotrauma in COVID-19 acute respiratory distress syndrome: retrospective analysis of the COVADIS prospective multicenter observational database.

BACKGROUND: Despite evidence suggesting a higher risk of barotrauma during COVID-19-related acute respiratory distress syndrome (ARDS) compared to ARDS due to other causes, data are limited about possible associations with patient characteristics, ventilation strategy, and survival. METHODS: This prospective observational multicenter study included consecutive patients with moderate-to-severe COVID-19 ARDS requiring invasive mechanical ventilation and managed at any of 12 centers in France and Belgium between March and December 2020. The primary objective was to determine whether barotrauma was associated with ICU mortality (censored on day 90), and the secondary objective was to identify factors associated with barotrauma. RESULTS: Of 586 patients, 48 (8.2%) experienced barotrauma, including 35 with pneumothorax, 23 with pneumomediastinum, 1 with pneumoperitoneum, and 6 with subcutaneous emphysema. Median time from mechanical ventilation initiation to barotrauma detection was 3 [0-17] days. All patients received protective ventilation and nearly half (23/48) were in volume-controlled mode. Barotrauma was associated with higher hospital mortality (P < 0.001) even after adjustment on age, sex, comorbidities, PaO2/FiO2 at intubation, plateau pressure at intubation, and center (P < 0.05). The group with barotrauma had a lower mean body mass index (28.6 ± 5.8 vs. 30.3 ± 5.9, P = 0.03) and a higher proportion of patients given corticosteroids (87.5% vs. 63.4%, P = 0.001). CONCLUSION: Barotrauma during mechanical ventilation for COVID-19 ARDS was associated with higher hospital mortality.

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.

The Macklin effect closely correlates with pneumomediastinum in acutely ill intubated patients with COVID-19 infection.

PURPOSE: Patients with COVID-19 infection are frequently found to have pulmonary barotrauma. Recent work has identified the Macklin effect as a radiographic sign that often occurs in patients with COVID-19 and may correlate with barotrauma. METHODS: We evaluated chest CT scans in COVID-19 positive mechanically ventilated patients for the Macklin effect and any type of pulmonary barotrauma. Patient charts were reviewed to identify demographic and clinical characteristics. RESULTS: The Macklin effect on chest CT scan was identified in a total of 10/75 (13.3%) COVID-19 positive mechanically ventilated patients; 9 developed barotrauma. Patients with the Macklin effect on chest CT scan had a 90% rate of pneumomediastinum (p < 0.001) and a trend toward a higher rate of pneumothorax (60%, p = 0.09). Pneumothorax was most frequently omolateral to the site of the Macklin effect (83.3%). CONCLUSION: The Macklin effect may be a strong radiographic biomarker for pulmonary barotrauma, most strongly correlating with pneumomediastinum. Studies in ARDS patients without COVID-19 are needed to validate this sign in a broader population. If validated in a broad population, future critical care treatment algorithms may include the Macklin sign for clinical decision making and prognostication.

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.

Venovenous Extracorporeal Membrane Oxygenation in Awake Non-Intubated Patients With COVID-19 ARDS at High Risk for Barotrauma.

OBJECTIVES: To assess the efficacy of an awake venovenous extracorporeal membrane oxygenation (VV-ECMO) management strategy in preventing clinically relevant barotrauma in patients with coronavirus disease 2019 (COVID-19) with severe acute respiratory distress syndrome (ARDS) at high risk for pneumothorax (PNX)/pneumomediastinum (PMD), defined as the detection of the Macklin-like effect on chest computed tomography (CT) scan. DESIGN: A case series. SETTING: At the intensive care unit of a tertiary-care institution. PARTICIPANTS: Seven patients with COVID-19-associated severe ARDS and Macklin-like radiologic sign on baseline chest CT. INTERVENTIONS: Primary VV-ECMO under spontaneous breathing instead of invasive mechanical ventilation (IMV). All patients received noninvasive ventilation or oxygen through a high-flow nasal cannula before and during ECMO support. The study authors collected data on cannulation strategy, clinical management, and outcome. Failure of awake VV-ECMO strategy was defined as the need for IMV due to worsening respiratory failure or delirium/agitation. The primary outcome was the development of PNX/PMD. MEASUREMENTS AND MAIN RESULTS: No patient developed PNX/PMD. The awake VV-ECMO strategy failed in 1 patient (14.3%). Severe complications were observed in 4 (57.1%) patients and were noted as the following: intracranial bleeding in 1 patient (14.3%), septic shock in 2 patients (28.6%), and secondary pulmonary infections in 3 patients (42.8%). Two patients died (28.6%), whereas 5 were successfully weaned off VV-ECMO and were discharged home. CONCLUSIONS: VV-ECMO in awake and spontaneously breathing patients with severe COVID-19 ARDS may be a feasible and safe strategy to prevent the development of PNX/PMD in patients at high risk for this complication.

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.

Incidence, clinical characteristics and outcome of barotrauma in critically ill patients with COVID-19: a systematic review and meta-analysis.

INTRODUCTION: Barotrauma is rare in patients with acute respiratory distress syndrome undergoing mechanical ventilation. Its incidence seems increased among critically ill COVID-19 patients. We performed a systematic review and meta-analysis to investigate the incidence, risk factors and clinical outcomes of barotrauma among critically ill COVID-19 patients. EVIDENCE ACQUISITION: PubMed was searched from March 1st, 2020 to August 31st, 2021; case series and retrospective cohort studies concerning barotrauma in adult critically ill COVID-19 patients, either hospitalized in the Intensive Care Unit (ICU) or invasively ventilated were included. Primary outcome was the incidence of barotrauma in COVID-19 versus non-COVID-19 patients. Secondary outcomes were clinical characteristics, ventilator parameters, mortality and length of stay between patients with and without barotrauma. EVIDENCE SYNTHESIS: We identified 21 studies (six case series, 15 retrospective cohorts). The overall incidence of barotrauma was 11 [95% CI: 8-14]% in critically ill COVID-19 patients, vs. 2 [1-3]% in non-COVID-19, P<0.001; the incidence in mechanically ventilated patients was 14 [11-17]% vs. 4 [2-5]% non-COVID-19 patients, P<0.001. There were no differences in demographic, clinical, ventilatory parameters between patients who did and did not develop barotrauma, while, on average, protective ventilation criteria were always respected. Among COVID-19 patients, those with barotrauma had a higher mortality (60 [55-66] vs. 48 [42-54]%, P<0.001) and a longer ICU length of stay (20 [14-26] vs. 13 [10,5-16] days, P=0.03). CONCLUSIONS: Barotrauma is a frequent complication in critically ill COVID-19 patients and is associated with a poor prognosis. Since lung protective ventilation was delivered, the ventilatory management might not be the sole factor in the development of barotrauma.

Barotrauma in critically ill COVID-19 patients: a retrospective case-control study.

BACKGROUND: There is increased incidence of barotrauma in COVID-19 patients, probably due to disease pathology, oxygen therapy and coughing. We aimed to retrospectively compare the characteristics, associations and outcomes of COVID-19 patients with and without barotrauma in the intensive care unit (ICU). METHODS: All adults admitted between October 1st and December 31st 2020 in the ICUs of a COVID-19 hospital were retrospectively analysed for presence of a 'barotrauma event' (presence of at least one of pneumothorax, pneumomediastinum, subcutaneous emphysema or bronchopleural fistula). A control group was formed by matching each case to a patient belonging to the same gender and age range from the remaining patients in the cohort, i.e., those without barotrauma. Demographic details, ICU stay details, details of oxygen therapy and ventilation, and outcomes were noted and compared. RESULTS: Of 827 patients, 30 patients (3.6%) developed barotrauma events. The typical patient was middle aged (median age 55.5 years) and male (73.3%). The mortality rate was significantly higher in the barotrauma group (83.3% vs. 43.3%, P < 0.001), and odds of survival decreased by 85% if barotrauma occurred (OR 0.15; 95% CI: 0.46-0.51). Patients who developed barotrauma spent a longer time on a high-flow nasal cannula (median 6.7 vs. 1.73 days, P = 0.04), and mechanical ventilation (median 9.54 vs. 0.867 days, P < 0.001), and had a longer ICU stay (median 15.5 vs. 9 days, P = 0.014). The most common event was pneumothorax (26/30). CONCLUSIONS: Barotrauma in the COVID-19 ICU is associated with prolonged ICU stay, higher odds of mortality and longer duration spent on mechanical ventilation and a high-flow nasal cannula. Key words: barotrauma, ICU, COVID-19, mortality, pneumothorax.

Barotrauma in Coronavirus Disease 2019 Patients Undergoing Invasive Mechanical Ventilation: A Systematic Literature Review.

OBJECTIVE: There are concerns of a high barotrauma rate in coronavirus disease 2019 patients with acute respiratory distress syndrome receiving invasive mechanical ventilation. However, a few studies were published, and reported rates were highly variable. We performed a systematic literature review to identify rates of barotrauma, pneumothorax, and pneumomediastinum in coronavirus disease 2019 acute respiratory distress syndrome patients receiving invasive mechanical ventilation. DATA SOURCE: PubMed and Scopus were searched for studies reporting barotrauma event rate in adult coronavirus disease 2019 patients receiving invasive mechanical ventilation. STUDY SELECTION: We included all studies investigating adult patients with coronavirus disease 2019 acute respiratory distress syndrome requiring mechanical ventilation. Case reports, studies performed outside ICU setting, and pediatric studies were excluded. Two investigators independently screened and selected studies for inclusion. DATA EXTRACTION: Two investigators abstracted data on study characteristics, rate of pneumothorax, pneumomediastinum and overall barotrauma events, and mortality. When available, data from noncoronavirus disease 2019 acute respiratory distress syndrome patients were also collected. Pooled estimates for barotrauma, pneumothorax, and pneumomediastinum were calculated. DATA SYNTHESIS: A total of 13 studies with 1,814 invasively ventilated coronavirus disease 2019 patients and 493 noncoronavirus disease 2019 patients were included. A total of 266/1,814 patients (14.7%) had at least one barotrauma event (pooled estimates, 16.1% [95% CI, 11.8-20.4%]). Pneumothorax occurred in 132/1,435 patients (pooled estimates, 10.7%; 95% CI, 6.7-14.7%), whereas pneumomediastinum occurred in 162/1,432 patients (pooled estimates, 11.2%; 95% CI, 8.0-14.3%). Mortality in coronavirus disease 2019 patients who developed barotrauma was 111/198 patients (pooled estimates, 61.6%; 95% CI, 50.2-73.0%). In noncoronavirus disease 2019 acute respiratory distress syndrome patients, barotrauma occurred in 31/493 patients (6.3%; pooled estimates, 5.7%; 95% CI, -2.1% to 13.5%). CONCLUSIONS: Barotrauma occurs in one out of six coronavirus disease 2019 acute respiratory distress syndrome patients receiving invasive mechanical ventilation and is associated with a mortality rate of about 60%. Barotrauma rate may be higher than noncoronavirus disease 2019 controls.

Barotrauma during non-invasive ventilation for acute respiratory distress syndrome caused by COVID-19: a balance between risks and benefits.

Ventilatory support is vital for the management of severe forms of COVID-19. Non-invasive ventilation is often used in patients who do not meet criteria for intubation or when invasive ventilation is not available, especially in a pandemic when resources are limited. Despite non-invasive ventilation providing effective respiratory support for some forms of acute respiratory failure, data about its effectiveness in patients with viral-related pneumonia are inconclusive. Acute respiratory distress syndrome caused by severe acute respiratory syndrome-coronavirus 2 infection causes life-threatening respiratory failure, weakening the lung parenchyma and increasing the risk of barotrauma. Pulmonary barotrauma results from positive pressure ventilation leading to elevated transalveolar pressure, and in turn to alveolar rupture and leakage of air into the extra-alveolar tissue. This article reviews the literature regarding the use of non-invasive ventilation in patients with acute respiratory failure associated with COVID-19 and other epidemic or pandemic viral infections and the related risk of barotrauma.