Incidence of Barotrauma in Patients With COVID-19 Pneumonia During Prolonged Invasive Mechanical Ventilation – A Case-Control Study
Journal of Intensive Care Medicine 1-7
a The Author(s) 2020
Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/0885066620954364 journals.sagepub.com/home/jic
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Josefina Udi1,2 ￼ ￼, Corinna N. Lang1,2, Viviane Zotzmann1,2, Kirsten Krueger1,2, Annabelle Fluegle1,2, Fabian Bamberg3, Christoph Bode1,2, Daniel Duerschmied1,2, Tobias Wengenmayer1,2, and Dawid L. Staudacher1,2
Background: SARS-CoV2 can cause pulmonary failure requiring prolonged invasive mechanical ventilation (MV). Lung protective ventilation strategies are recommended in order to minimize ventilator induced lung injury. Whether patients with COVID-19 have the same risk for complications including barotrauma is still unknown. Therefore, we investigated barotrauma in patients with COVID-19 pneumonia requiring prolonged MV. Methods: All patients meeting diagnosis criteria for ARDS according to the Berlin Definition, with PCR positive SARS-CoV2 infection and prolonged mechanical ventilation, defined as 2 days, treated at our ARDS referral center between March and April 2020 were included in a retrospective registry analysis. Complications were detected by manual review of all patient data including respiratory data, imaging studies, and patient files. Results: A total of 20 patients with severe COVID-19 pulmonary failure (Overall characteristics: median age: 61 years, female gender 6, median duration of MV 22 days) were analyzed. Eight patients (40%) developed severe barotrauma during MV (after median 18 days, range: 1-32) including pneumothorax (5/20), pneumomediastinum (5/20), pneumopericard (1/20), and extended subcutaneous emphysema (5/20). Median respirator settings 24 hours before barotrauma were: Peak inspiratory pressure (Ppeak) 29 cm H2O (range: 27-35), positive end-expiratory pressure (PEEP) 14 cm H2O (range: 5-24), tidal volume (VT) 5.4ml/kg predicted body weight (range 0.4-8.6), plateau pressure (Pplateau) 27 cm H2O (range: 19-30). Mechanical ventilation was significantly more invasive on several occasions in patients without barotrauma. Conclusion: Barotrauma in COVID-19 induced respiratory failure requiring mechanical ventilation was found in 40% of patients included in this registry. Our data suggest that barotrauma in COVID-19 may occur even when following recommendations for lung protective MV.
SARS-CoV2, COVID-19, mechanical ventilation, complication, barotrauma
The novel COVID-19 causes pulmonary failure, in some cases, requiring prolonged invasive mechanical ventilation (MV). It is well known that MV by itself may lead to specific complica- tions including bacterial and fungal superinfections and barotrauma.1
The primary objective of the present case-control study was therefore to determine the incidence of barotrauma in a cohort of patients with COVID-19 pneumonia under invasive MV for at least 2 days (inclusion criteria). Identified cases were patients with barotrauma under invasive MV (n 1⁄4 8), controls were patients under invasive MV without barotrauma (n 1⁄4 12). Besides, we analyzed MV characteristics during the last 24 hours before the occurrence of barotrauma, and compared MV settings in patients without vs. with barotrauma in order to assess potential risk factors.
All patients with COVID-19 pneumonia on MV for at least 2 days treated at our intensive care unit (ICU), between March
1 Department of Cardiology and Angiology I, Heart Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
2 Department of Internal Medicine III, Medical Intensive Care, Medical Center, University of Freiburg, Freiburg, Germany
3 Department of Radiology, University of Freiburg, Faculty of Medicine, Freiburg, Germany
Received May 20, 2020. Received revised August 04, 2020. Accepted August 12, 2020.
Josefina Udi, Department of Cardiology and Angiology I, Heart Center, Faculty of Medicine, University of Freiburg, Freiburg 79106, Germany.
Journal of Intensive Care Medicine XX(X)
and April 2020 were included. If barotrauma secondary to MV was suspected, chest radiography was immediately obtained in order to detect pneumothorax, pneumomediastinum or subcu- taneous emphysema. In selected cases, computed tomography (CT) of the chest or even full-body CT was performed.
Our ICU is located at a university hospital offering a 24/7 ECMO center specialized in the treatment of acute respiratory distress syndrome (ARDS). ARDS treatment is performed according to current guidelines focusing on prevention of ven- tilator induced lung injury (VILI), including early mobilization or prone positioning, early spontaneous breathing in patients without desynchronization with the ventilator. In case of severe pulmonary failure, extracorporeal membrane oxygenation (ECMO) is discussed by a multidisciplinary team including at least the intensivist in charge, an ECMO specialist, a regis- tered nurse and a perfusionist in order to prevent VILI.
Detection of Patients and Complications
pressure (PEEP), tidal volume (TV) in ml and in ml/kg predicted body weight (PBW) and respiratory frequency (RF) and plateau pressure (Pplateau). In order to exclude false mea- surements, only parameters stable over at least 1 hour were recorded. According to the method proposed by Anzueto et al.,3 we compared the airway pressures and tidal volumes in patients with barotrauma of the day before the detection of barotrauma with the highest pressures and tidal volumes at any time during the duration of mechanical ventilation in patients without barotrauma.
Tidal volumes are given in ml/kg optimal body weight as estimated by registered nurses routinely for every patient admitted to our intensive care unit. In order to investigate the adherence to lung protective ventilation protocols, respirator settings were recorded as proposed by “The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network.”1
Baseline demographic characteristics, predisposing lung pathology and treatment parameters were recollected retro- spectively using electronic files. MV characteristics during the last 24 hours before any complication were recorded and MV parameters are displayed as median values with their corre- sponding interquartile range. In patients who developed baro- trauma, we compared MV parameters (Ppeak, PEEP, Pplateau and TV) of the 24 hours before the detection of barotrauma with the highest measured pressures and tidal volumes at any time in patients without barotrauma. ICU survival was defined as discharge from the ICU to a weaning facility or to a regular ward. No patient was discharged to a hospice. The local ethics committee approved the study protocol (Ethik-Kommission der Albert-Ludwigs-Universita ̈t Freiburg im Breisgau 234/20).
Statistics were performed using SPSS (version 23, IBM) using two-sample Kolmogorov-Smirnov test for the comparison of MV parameters of the patients without and with barotrauma. A p-value <0.05 was considered statistically significant.
A total of 20 patients with COVID-19 pneumonia and invasive mechanical ventilation for at least 2 days were included in our case-control study (Overall patients’ characteristics: median age: 61 years, female gender 6, median duration of mechanical ventilation 22 days, 55% on V-V ECMO). Of these, 8/20 (40%) developed severe barotrauma while on MV. The proportion of patients receiving V-V ECMO therapy, specifically 5/8 1⁄4 62% of patients in the barotrauma group and 6/12 1⁄4 50% of patients in the non-barotrauma-group was statistically similar. Patients’ characteristics of the case-group (patients with barotrauma) are displayed in detail in Table 1. Patients’ characteristics of the control group (patients without barotrauma) are displayed in Table 2.
In the present case-control study, we included all COVID-19 patients on mechanical ventilation treated at the medical ICU between 03/2020 and 04/2020 that fulfilled criteria for the diagnosis of ARDS according to the “Berlin Definition of ARDS”: 1.) Onset within 1 week of a known clinical insult or new or worsening respiratory symptoms; 2.) Presence of bilateral opacities in the chest imaging; 3.) Respiratory failure not fully explained by cardiac failure or fluid overload; 4) Hypoxemia (with the corresponding subclassification in mild, moderate and severe ARDS).2 Only patients with PCR-confirmed SARS-CoV-2 infection were considered, with PCR (polymerase chain reaction) tests either processing nasopharyngeal swabs or tracheal secretion. Patients with high clinical probability of COVID-19 infection but negative SARS-CoV-2 PCR testing were therefore excluded. Within this time period, a total of 198 SARS-CoV-2 positive patients were treated at our hos- pital, from which 67 patients were on intensive care unit and 56 underwent mechanical ventilation for COVID-19 ARDS. Of these 56 ARDS patients, 25 were transferred from a smaller hospital to our ARDS center. Barotrauma was detected by manual review of all radiological investi- gations performed in our COVID-19 patients. We defined presence of pneumothorax, pneumomediastinum or pneumo- pericard in absence of a preceding intervention with the risk of pulmonary complications (like cannulation for a central venous catheter) as barothauma or VILI.
Mechanical Ventilator Setting
Mechanical ventilator characteristics are recorded online by the electronic patients file (COPRA6Live) every 30 min. For this research, we investigated inspiratory oxygen fraction (FiO2) peak inspiratory pressure (Ppeak), positive end-expiratory
Udi et al 3 Table 1. Patient Characteristics of COVID-19 Affected Subjects With Barotrauma (n 1⁄4 8) During Mechanical Ventilation (MV).
Patient # COVID-19
1 þ 2 þ
3 þ 4 þ 5 þ
6 þ 7 þ
8 þ Median 100%
Gender lung (f/m) Age (y) pathology
m 52 – m 58 –
m 76 – m 69 – f 61 –
f 47 –
m 62 COPD
m 67 –
post-IMV post-IMV post-IMV
10 19 32
ECMO Type of complication
þ Pneumothorax, pneumomediastinum
þ Pneumothorax, pneumomediastinum
– Tension pneumothorax
þ Subcutaneous emphysema,
– Subcutaneous emphysema,
pneumomediastinum, þ Pneumomediastinum
IMV duration before
18 (1-32) 62%
Abbreviations: f 1⁄4 female; m 1⁄4 male; y 1⁄4 years; d 1⁄4 days; MV 1⁄4 mechanical ventilation; V-V ECMO 1⁄4 veno-venous extracorporeal membrane oxygenation, COPD 1⁄4 chronic obstructive pulmonary disease.
Table 2. Patient Characteristics of COVID-19 Affected Subjects Without Barotrauma (n 1⁄4 12) during Mechanical Ventilation (MV). Predisposing Complication Total IMV V-V Type of
Patient # COVID-19 Gender (f/m) Age (y) lung pathology (pre-/post-MV) duration (d)* ECMO complication
1 þ f 60 – – 19 þ – 2 þ f 77 – – 21 – – 3 þ f 70 – – 17 – – 4 þ m 59 – – 17 þ – 5 þ m 73 COPD – 38 – – 6 þ m 53 – – 8 – – 7 þ f 59 – – 14 þ – 8 þ m 49 – – 7 þ – 9 þ m 61 – – 7 – – 10 þ f 65 – – 63 – – 11 þ m 38 – – 41 þ – 12 þ m 66 Asthma – 80 þ – Median 100% 61 (38-77) 18 (7-80) 50%
Abbreviations: ARDS 1⁄4 acute respiratory distress syndrome; f 1⁄4 female; m 1⁄4 male; y 1⁄4 years; d 1⁄4 days; MV 1⁄4 invasive mechanical ventilation; V-V ECMO 1⁄4 veno-venous extracorporeal membrane oxygenation, COPD 1⁄4 chronic obstructive pulmonary disease.
*Total MV duration until extubation, transfer to a weaning ward or an external intensive care unit or death.
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In all 8 patients, barotrauma developed during invasive MV. Only 1 patient in the barotrauma group (patient #7) had a pre- disposing lung disease (chronic obstructive pulmonary dis- ease). Median MV duration before complication occurred was 18 days (range: 1-32 days). Survival rate of patients with barotrauma was 75% (6/8).
Five patients developed a pneumothorax, 5 patients a pneu- momediastinum, 1 patient a pneumopericard and 2 patients an extended subcutaneous emphysema, with some patients show- ing more than 1 type of complication. In all 5 patients with
pneumothorax, complication management included chest tube insertion.
Figure 1 shows the full-body CT scan of a patient, who developed an extended subcutaneous emphysema, pneumome- diastinum and pneumopericard 1 day after invasive MV was started.
Median MV parameters from all 8 patients during the last 24 hours before barotrauma occurred were recorded. Specif- ically, median inspiratory oxygen fraction (FiO2) was 60% (range: 35-90%), median Ppeak 29 cm H2O, PEEP 14 cm
4 Journal of Intensive Care Medicine XX(X)
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Figure 1. Full-body CT scan of a patient with COVID-19 pneumonia, showing an extended subcutaneous emphysema, pneumomediastinum and pneumopericard 1 day after invasive MV was started.
Table 3. Median Mechanical Ventilation (MV) Parameters in Patients With Barotrauma (n 1⁄4 8) 24 Hours Before Complication.
Ppeak PEEP Spontaneous Prone FiO2 (cm (cm
breathing positioning (%) H2O) H2O)
Pplateau (cm H2O)
Compliance (cm H2O/ml)
VT (ml/kg RF
(ml) PBW) (/min)
– – 55 27 12 19 49 428 5.4 15 þþ502916273410.430 þ–35n.k.5n.k.n.k.4536.018 þ–70271530437758.622 þþ90352420304505.332 – þ 45 31 15 28 22 268 3.6 16 þ–65321026596737.526 þþ662910276670.726
60 29 14 27 30 439 5.4 24 (35-90) (27-35) (5-24) (19-30) (3-59) (41-775) (0.4-8.6) (15-32)
Abbreviations: FiO2 1⁄4 inspiratory oxygen fraction; PEEP 1⁄4 positive end-expiratory pressure; Ppeak 1⁄4 peak inspiratory pressure; TV 1⁄4 tidal volume; RF 1⁄4 respiratory frequency; n.k. 1⁄4 not known (MV parameters before barotrauma development and admission to our center were not documented); Pplateau 1⁄4 plateau pressure; kg BW 1⁄4 kilograms predicted body weight.
H2O, tidal volume 5.4ml/kg PBW, Pplateau 27 cm H2O, and RF 24/min. A total of 63% (5/8) were on spontaneous breathing mode, 50% (4/8) were prone positioned. In patients with barotrauma, lung compliance was low, with a median of 30 cm H2O/ml. The MV parameters (median and range), as well as the presence/absence of spontaneous breathing and prone positioning 24 hours before any com- plication are summarized in Table 3. A comprehensive anal- ysis of MV parameters over the first week is given in the supplementary material.
In order to investigate whether selected MV parameters were associated to the development of barotrauma in patients with COVID-19 pneumonia, we compared median peak inspiratory parameters of patients with barotrauma (n 1⁄4 8) during the last 24 hours before complication occurred, to the highest parameter at any time during the duration of MV in patients without barotrauma (n 1⁄4 12).
In patients without barotrauma throughout the entire ICU stay, the maximal measured Ppeak, PEEP, Pplateau and VT were in median 37 cm H2O (range: 31-49), 15 cm H2O (range:
Udi et al
Table 4. Comparison of MV Parameters Between Patients Without and With Barotrauma.
Ppeak (cm H2O) PEEP (cm H2O) Pplateau (cm H2O) TV (ml/kg PBW)
Patients without barotrauma (n 1⁄4 12) Whole duration of MV (19 days)
37 (31-49) 15 (7-18) 32 (22-36)
Patients with barotrauma (n 1⁄4 8) 24 hours before complication
27 (19-30) 5.4 (0.4-8.6)
0.009 0.80 0.01 0.005
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Parameters of mechanical ventilation of patients with barotrauma (highest values within 24 hours to diagnosis of the barotrauma) were compared to patients without (highest values within the whole ICU stay), as suggested by Anzueto A. et al. . Abbreviations: MV: mechanical ventilation; PEEP 1⁄4 positive end-expiratory pressure; Ppeak 1⁄4 peak inspiratory pressure; TV 1⁄4 tidal volume; ml/kg PBW 1⁄4 kilograms predicted body weight.
Figure 2. Graphical summary of our main findings, including incidence of barotrauma in patients with COVID-19 pneumonia and prolonged mechanical ventilation (MV), type of complication and MV parameters in patients with vs. without barotrauma. Abbreviations: MV 1⁄4 mechanical ventilation; PEEP 1⁄4 positive end-expiratory pressure; ppeak 1⁄4 peak inspiratory pressure; TV1⁄4 tidal volume; Pplateau 1⁄4 plateau pressure; p 1⁄4 p- value.
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7-18), 32 cm H2O (22-36) and TV 11.7 ml/kg PBW (range: 4.2-22), respectively, see Table 4.
Median PEEP recorded in patients who developed baro- trauma did not significantly differ from the highest PEEP in patients without barotrauma. Interestingly, in patients with barotrauma median Ppeak, median Pplateau and median VT 24 hours previous to complication were significantly lower than in patients without barotrauma (p-value: 0.009, 0.01 and 0.005, respectively) (Table 4).
A graphical summary of our main findings is displayed in Figure 2.
In our registry, we detected severe barotrauma in 40% of patients with COVID-19. This is considerably higher than reported from larger registries of non-COVID-19 patients.
MyGuinness et al. reported a rate of barotrauma of 15% in a mixed collective of invasive ventilated COVID-19 patients.4
However, this publication mainly focused on radiological find- ings and did not investigate a possible association between barotrauma and respirator settings.
Anzueto et al. carried out an exhaustive prospective study including over 5000 patients with MV for more than 12 hours and found barotrauma in 2.9% (6.5% in patients with ARDS).3 In the retrospective single-center study performed by Chen N. et al. including a total of 99 patients with COVID-19 pneumo- nia, pneumothorax occurred only in 1 patient.5 Since baro- trauma detection frequently requires computed tomography, barotrauma might be under diagnosed if only less sensitive chest radiography is obtained. Moreover, there are many case reports of barotrauma, which might suggest underreporting cases of barotrauma in large registries.
Mansbridge C. T. nicely presented the case of a 33-year old previously healthy man with Influenza A (H1N1) infection with perihilar opacities in both lungs and pneumomediasti- num.6 Another case of pneumomediastinum and subcutaneous emphysema associated with Influenza A (H1N1) was described
Journal of Intensive Care Medicine XX(X)
by Luis BAL. et al.7 Two particularities of the case report by Niehaus M. et al. are firstly that the patient had both influenza A and asthma, and secondly the development not only of mas- sive pneumomediastinum and small apical pneumothoraces, but also of retropharyngeal emphysema leading to airway compromise.8
Only single cases of complications in general and in partic- ular of barotrauma have been previously described in patients with COVID-19 pneumonia. Sun R. et al recently reported the case of a 38-year old man who developed mediastinal emphy- sema, giant bulla and pneumothorax. Analog to our patient’s cohort, this patient had no previous history of pneumothorax and no underlying lung disease. In the initial CT scan, no abnormalities (small bulla, emphysema) were evident. In this case report, the authors postulated the diffuse alveolar damage in severe COVID-19 pneumonia and the intense cough as prob- able predisposing factors for a sudden increase in alveolar pressure and consecutively for alveolar rupture leading to the release of air into the lung parenchyma, the mediastinum and the subcutaneous tissue.9
We found lower MV pressures and tidal volumes in patients with barotrauma compared to patients without barotrauma, reaching statistical significance for the comparison of Ppeak and TV. This might suggest no direct association between the development of barotrauma and the applied MV parameters when following recommendations for lung protective ventilation.
Whether the development of barotrauma during invasive MV is associated or not with MV parameters has been contro- versially discussed. Anzueto A. et al. found no correlation between barotrauma and MV settings.3 While some authors argued that the development of barotrauma is not related to the ventilator airway pressures and tidal volumes,10 other groups like Eisner et al.11 found that higher PEEP was related to an increased risk of barotrauma. While it seems counterintuitive that barotrauma is not associated with increased positive pres- sure ventilation, it can be argued that high pressures for exam- ple during coughing are triggers for barotrauma and not recorded adequately. It has also been proposed that develop- ment of spontaneous pneumomediastinum and subcutaneous emphysema might be a disease specific complication of viral pneumonia.8 Survival rate from all 20 patients was 65%, whereas survival rate from patients with barotrauma was 75%, indicating that in most cases barotrauma could success- fully be managed and was not an inevitable cause of death in our cohort of patients.
Several important limitations of the present case-control study should be considered when interpreting our results. First, we here report retrospective data from a single center. Therefore, a selection bias has to be presumed since patients were treated at a referral center for ARDS. Second, a considerable proportion of all included patients were on V-V ECMO, which makes a generalization to a non-ECMO patient collective difficult. On
the other hand, since V-V ECMO might facilitate the imple- mentation of lung protective ventilation protocols, without ECMO as a therapy option, barotrauma incidence might have been even higher. In addition, without ECMO as a therapeutic option, COVID-19 affected patients would have died earlier of severe ARDS, and the observed incidence of complications would have been lower in a non-ECMO collective. For these reasons, the results of our case-control study should be consid- ered informative and our conclusions should not be generalized to a patient collective featuring less V-V ECMO. Furthermore, since this registry features a significant proportion of severely ill patients, a selection bias with concentration of the sickest patients at our institution cannot be exclude. The Incidence of barotrauma in a less sick patient collective might be lower than reported here.
To the best of our knowledge, this is the first case-control study analyzing the incidence of barotrauma in patients with COVID-19 pneumonia and prolonged invasive MV. Baro- trauma in COVID-19 induced respiratory failure requiring mechanical ventilation was found in 40% of patients included in this registry. Our data might suggest that barotrauma in patients with COVID-19 pneumonia requiring prolonged inva- sive MV is a frequent complication and may develop even when following recommendations for lung protective MV.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
The author(s) received no financial support for the research, author- ship, and/or publication of this article.
Josefina Udi ￼https://orcid.org/0000-0002-8138-3095
Dawid L. Staudacher ￼https://orcid.org/0000-0002-9423-9682
Supplemental material for this article is available online.
1. The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher versus lower positive end-expiratory pres- sures in patients with the acute respiratory distress syndrome. N Engl J Med. 2004;351(4):327-336. doi:10.1056/NEJMoa 032193
2. The ARDS Definition Task Force. Acute respiratory distress syn- drome. JAMA. 2012;307(23):2526-2533. doi:10.1001/jama.2012. 5669
3. Anzueto A, Vivar FF, Esteban A, et al. Incidence, risk factors and outcome of barotrauma in mechanically ventilated patients. Inten- sive Care Med. 2004;30(4):612-619. doi:10.1007/s00134-004- 2187-7
Udi et al 7
4. McGuinness G, Zhan C, Rosenberg N, et al. High incidence of barotrauma in patients with COVID-19 infection on invasive mechanical ventilation. Radiology. 2020. Epub ahead of print. doi:10.1148/radiol.2020202352
5. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223): 507-513. doi:10.1016/S0140-6736(20)30211-7
6. Mansbridge CT, Kim MI. Pneumomediastinum associated with influenza A infection. N Engl J Med. 2018;378(1):e1. doi:10.1056/nejmicm1702849
7. Luis BAL, Navarro AO, Palazzos GMR. Pneumomediastinum and subcutaneos emphysema associated with influenza A (H1N1) virus. Lancet Infect Dis. 2017;17(6):671. doi:10.1016/S1473- 3099(17)30262 -1
8. Niehaus M, Rusgo A, Roth K, Jacob JL. Retropharyngeal air and pneumomediastinum: a rare complication of influenza a and asthma in an adult. Am J Emerg Med. 2016;34(2):338.e1-2. doi:10.1016/j.ajem.2015.06.020
9. Sun R, Liu H, Wang X. Mediastinal emphysema, giant bulla and pneumothorax developed during the course of COVID-19 pneu- monia. Korean J Radio. 2020;21(5):541-544.
10. Weg JG, Anzueto A, Bald RA, et al. The relation of pneu- mothorax and other air leaks to mortality in the acute respira- tory distress syndrome. N Engl J Med. 1998;338(6):341-346. doi:10.1056/NEJM199802053380601
11. Eisner MD, Thompson T, Hayden D, Anzueto A, Matthay MA. Airway pressures and early barotrauma in patients with acute lung injury and the acute respiratory distress syndrome. Am J Respir Cris Care. 2002;165(7):978-982. doi:10.1164/ajrccm.165.7.2109059