key: cord-1033667-r9ykilbe
authors: Elsaaran, Hussein; AlQinai, Shamlan; AlTarrah, Dana; Abdulrasoul, Mahdi; Al-Youha, Sarah; Almazeedi, Sulaiman; Al-Haddad, Mohannad; Jamal, Mohammad H.; Al-Sabah, Salman
title: Prevalence and risk factors of barotrauma in Covid-19 patients admitted to an intensive care unit in Kuwait; a retrospective cohort study
date: 2021-02-05
journal: Ann Med Surg (Lond)
DOI: 10.1016/j.amsu.2021.01.089
sha: 1e8511508f1b5f377846f06ba269cf7f585eef7b
doc_id: 1033667
cord_uid: r9ykilbe

BACKGROUND: The development of barotrauma has been suggested to complicate the management of mechanically ventilated COVID-19 patients admitted to the intensive care unit (ICU). This study aims to identify potential risk factors associated with the development of barotrauma related complications in COVID-19 patients receiving mechanical ventilation. METHODS: A retrospective cohort study was carried out in a single COVID-19 designated center in Kuwait. Three hundred and forty-three confirmed COVID-19 patients transferred and/or admitted to our institution between February 26, 2020 and June 20, 2020 were included in the study. All patients were admitted into the ICU with the majority being mechanically ventilated (81.3%). RESULTS: Fifty-four (15.4%) patients developed barotrauma, of which 49 (90.7%) presented with pneumothorax, and 14.8% and 3.7% due to pneumomediastinum and pneumopericardium respectively. Of those that developed barotrauma, 52 (96.3%) patients were in acute respiratory distress syndrome (ARDS). Biochemically, the white blood cells (p = 0.001), neutrophil percentage (p = 0.012), lymphocyte percentage (p = 0.014), neutrophil: lymphocyte ratio (NLR) (p=<0.001) and lactate dehydrogenase (LDH) (p = 0.002) were found to be significantly different in patients that developed barotrauma. Intubation due to low level of consciousness (p = 0.007), a high admission COVID-GRAM score (p = 0.042), and a positive-end expiratory pressure (PEEP) higher than the control group (p = 0.016) were identified as potential risk factors for the development of barotrauma. CONCLUSION: Patients infected with COVID-19 have a significant risk of developing barotrauma when receiving invasive mechanical ventilation. This poses a substantial impact on the hospital course of the patients and clinical outcome, correlating to a higher mortality rate in this cohort of patients.

The novel coronavirus has become a global pandemic (1) . This highly transmissible and infectious disease is found to affect multiple systems, particularly the respiratory tract. The prevalence of pneumothorax among COVID-19 patients in the intensive care unit (ICU) has been reported to be 2% (1, 2) . More recently, studies have found that barotrauma-related complications due to invasive mechanical ventilation is increasingly reported, as incidence in COVID-19 patients was reported to be as high as 15% (3) .

The association of acute respiratory distress syndrome (ARDS) and the development of secondary pneumothorax in mechanically ventilated patients is well documented as an independent risk factor of mortality (4, 5, 6) . The majority of patients that contract COVID-19 experience symptoms of a mild upper respiratory tract infection (7, 8, 9) , however a small proportion of patients are found to develop severe pneumonia and sepsis with the potential development of ARDS and multi-system organ failure (9, 10, 11, 12) .

The development of ARDS and its associated complications, which include septic shock, thrombotic complications, acute kidney injury (AKI), derangement of liver enzymes, cardiac injury and barotrauma are associated with poor clinical outcomes in COVID-19 patients (9, 10, 11) . There are a limited number of studies that have focused on the epidemiology and the potential risk factors associated with developing barotrauma in COVID-19 patients (11, 12, 13) .

In our single-center study we aimed to identify clinical features and risk factors associated with the potential development of barotrauma in mechanically ventilated COVID-19 patients. The study also aims to investigate the impact in terms of clinical course and prognosis of COVID-19 when barotrauma related complications occur.

J o u r n a l P r e -p r o o f

The present retrospective study included the first 343 confirmed COVID-19 patients transferred and/or admitted to our institution between 26 th February 2020 and 20 th of June 2020. Our institution, located in the State of Kuwait, was dedicated solely to COVID-19 patients, predominantly for patients who were deemed critical and may require further support in the form of extracorporeal membrane oxygenation (ECMO) in the ICU.

Inclusion criteria were patients of all ages diagnosed with COVID-19 using PCR testing, in accordance with the World Health Organization (WHO) interim guidance. COVID-GRAM predictive risk score developed and internally validated in China was used to predict the risk of critical illness in hospitalized COVID-19 patients (14) . Ten variables at admission were used to predict critical illness. These include age, unconsciousness, hemoptysis, dyspnea, number of comorbidities, cancer history, chest X-ray abnormality, neutrophil to lymphocyte ratio, lactate dehydrogenase and direct bilirubin. The risk of developing critical illness was further categorized into three categories: low, medium and high.

All related patient information and clinical data were retrieved from the hospitals electronic medical record system. These included sociodemographic factors (age, gender, nationality), clinical indicators (unconsciousness on admission i.e. Glasgow coma score of less than 8, hemoptysis and shortness of breath) and biochemical inflammatory markers (white blood count, neutrophil percentage, lymphocyte percentage, neutrophil: lymphocyte ratio, lactate dehydrogenase, CRP, ferritin, direct bilirubin and d-dimer), presence of co-morbidities (diabetes, hypertension, asthma, coronary artery disease) and COVID-GRAM score.

Written informed consent was obtained from the patient for publication of this study. A copy of the written consent is available for review by the Editor-in-Chief of this journal At our institution we utilize lung-protective ventilatory strategies, with a tidal volume of 4-6 ml/kg targeting a driving pressure of 15-17 cmH2Oo and a plateau pressure not exceeding 30 cmH2O. The Fio2 was adjusted to maintain the SpO2 between 88-92%. In unresponsive cases, prone positioning and inhaled Nitric oxide were utilized.

Additional recorded outcomes included the length of hospital, length of ICU stay, the number of days a patient was placed on a mechanical ventilator, the date patients developed barotrauma associated pneumothorax, and the incidence of death.

All 343 patients included in the study were admitted to the ICU. Patients that were mechanically ventilated or receiving non-invasive airway support were included in the study. Identified iatrogenic pneumothorax cases and patients diagnosed with a preexisting pneumothorax on admission were excluded. 

This study was registered at https://www.researchregistry.com/ (unique identifying number: researchregistry6324) and work has been reported in line with the STROCSS criteria (16) .

Data were analyzed using SPSS (IBM, version 25 There were no significant differences in demographic variables, presence of comorbidities, BMI, and length of hospital/ICU stay between patients with or without barotrauma.

The present study focused on COVID-19 patients, analyzing the associated risk factors of barotrauma and the clinical implications with respect to their clinical course. Barotrauma complications are evident among COVID-19 patients and has been widely documented in the literature (17, 18) . In this single center study, the incidence of barotrauma related complications in COVID-19 patients was 15%, which is comparable to the incidence reported by McGuinness G et al (18) . 

With respect to biochemical findings, our study found that white blood count (WBC), neutrophil count, neutrophil lymphocyte ratio (NLR) and lactate dehydrogenase (LDH)

were statistically greater among patients that developed barotrauma. These findings are similar to a study by Shioe et al that reported higher levels of LDH and neutrophils among patients infected with SARS-CoV virus, which were also found to be associated with a higher severity of lung injury. However, the study did not compare their findings to the patients that did not develop barotrauma (20) . Furthermore, we documented a statistically significant lower lymphocyte count in patients whom subsequently developed barotrauma. This finding has been found to be associated with cases of increased severity as T cells play a fundamental role in the initial and continued immune response to coronaviruses, as such T cells are unnaturally depleted (21, 22) . Acute respiratory distress syndrome (ARDS) has been recognized as an independent risk factor for developing barotrauma while receiving invasive ventilation. In the literature, the incidence of ARDS has been found to vary, reaching 15% in several previous studies (23) (24) (25) (26) (27) . In our study, of the 54 patients that developed barotrauma, 52 (96.3%) fit the criteria of ARDS within the 24 hours preceding the event.

Moreover, a higher maximum PEEP was found among patients that developed barotrauma compared to the non-barotrauma patients. Although increasing PEEP values on the ventilator is part of guideline-based 'lung recruitment' maneuvers, the underlying pathophysiology of COVID-19 lung damage has been postulated to be different than typical ARDS cases (28, 29) . The inability to adopt recruitment measures in COVID-19

induced ARDS lungs presents a unique situation where barotrauma is highly likely (28) .

Furthermore, contrary to typical ARDS, the presence of conserved lung compliance in COVID-19 induced ARDS is distinctively different (28) . In the current study, the internally validated COVID-GRAM tool was used to assess the severity of disease and care required upon admission. A higher score was found among patients that subsequently developed barotrauma related incidents (p=0.042). To our knowledge this is the first time the COVID-GRAM has been used to predict barotrauma.

We reported a higher score in the patients who developed barotrauma related incidents (P value= 0.042).

In our study, the mortality was significantly greater among patients that developed barotrauma 70.4% compared to 52.9% in the non-barotrauma group (p=0.025). These findings were echoed in the study by De Lassence et al. (30) Additionally, it should be noted that the mortality rate was also significantly high in the patients whom did not develop barotrauma related events; potentially a representation of a morbid cohort of patients.

In conclusion, there is a significant risk of developing barotrauma in mechanically ventilated COVID-19 patients. In our cohort of patients, we have identified specific variables that have been associated with the development of barotrauma related complications. Selecting the optimal ventilator parameters for lung recruitment while protecting against barotrauma is a delicate balance. In our study, we have reported that the development of barotrauma carries a considerable morbidity and mortality in COVID-19 patients. Further research may be required to support and re-produce these findings which may aid in establishing lung protective protocols tailored to the COVID-19 lung.

All authors declare no conflict of interest.

J o u r n a l P r e -p r o o f All authors contributed equally to the protocol, data collection, statistical analysis, and writing.

Not commissioned, externally peer-reviewed 1 28.2 (8.3) ICD duration 8.2 (9.9) PS 1 16.0 (6.9) Procedure 24 hours prior, n (%) 6 (11.1) Data presented as mean (standard deviation) for continuous variables, unless indicated for categorical variables 1 Data available for 34/54 patients 2 Data available for 50/54 patients

Director-General's remarks at the media briefing on 2019-nCoV on 11

A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster

Persons Evaluated for 2019 Novel Coronavirus -United States

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan

Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province

Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

Characteristics of and Important Lessons from the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases from the Chinese Center for Disease Control and Prevention

Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Obesity in patients younger than 60 years is a risk factor for Covid-19 hospital admission

Development and validation of a clinical risk score to predict the occurrence of critical illness in hospitalized patients with COVID-19

Acute respiratory distress syndrome

Guideline: Strengthening the reporting of cohort studies in surgery. International journal of surgery

Journal of Lung Health and Diseases

High incidence of barotrauma in patients with COVID-19 infection on invasive mechanical ventilation

Pneumothorax in the ICU: patient outcomes and prognostic factors

Severe acute respiratory syndrome complicated by spontaneous pneumothorax

Understanding the T cell immune response in SARS coronavirus infection. Emerging microbes & infections

Immune responses to Middle East respiratory syndrome coronavirus during the acute and convalescent phases of human infection

Pulmonary barotrauma in mechanical ventilation: patterns and risk factors

Acute Respiratory Distress Syndrome Network. Airway pressures and early barotrauma in patients with acute lung injury and acute respiratory distress syndrome

American journal of respiratory and critical care medicine

Clinical risk factors for pulmonary barotrauma: a multivariate analysis. American journal of respiratory and critical care medicine

The relation of pneumothorax and other air leaks to mortality in the

Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome

Lung Recruitability in COVID-19-associated Acute Respiratory Distress Syndrome: A Single-Center Observational Study. American journal of respiratory and critical care medicine

Covid-19 does not lead to a "typical" acute respiratory distress syndrome. American journal of respiratory and critical care medicine

Pneumothorax in the intensive care unit: incidence, risk factors, and outcome. The Journal of the American Society of Anesthesiologists

The development of barotrauma in mechanically COVID-19 patients complicates their management and hospital course

There is a significant incidence rate (15.4%) of developing barotrauma related complications in COVID-19

Acute respiratory distress syndrome (ARDS) is a major risk factor for the development of barotrauma related complications in mechanically ventilated COVID-19 patients

Various biochemical markers as well as a high COVID-GRAM score is associated with the development of barotrauma

The development of barotrauma in COVID-19 patients is associated with a dismal clinical outcome

Hyperlink to your specific registration

The following information is required for submission. Please note that failure to respond to these questions/statements will mean your submission will be returned. If you have nothing to declare in any of these categories then this should be stated.

All authors must disclose any financial and personal relationships with other people or organisations that could inappropriately influence (bias) their work. Examples of potential conflicts of interest include employment, consultancies, stock ownership, honoraria, paid expert testimony, patent applications/registrations, and grants or other funding.All authors declare no conflict of interest.

All sources of funding should be declared as an acknowledgement at the end of the text. Authors should declare the role of study sponsors, if any, in the collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. If the study sponsors had no such involvement, the authors should so state.

Research studies involving patients require ethical approval. Please state whether approval has been given, name the relevant ethics committee and the state the reference number for their judgement.Ethical approval for the study was granted by the Ministry of Health Ethical Review Board in Kuwait. Reference number 1402/2020 on 29/3/2020 J o u r n a l P r e -p r o o f Consent Studies on patients or volunteers require ethics committee approval and fully informed written consent which should be documented in the paper.Authors must obtain written and signed consent to publish a case report from the patient (or, where applicable, the patient's guardian or next of kin) prior to submission. We ask Authors to confirm as part of the submission process that such consent has been obtained, and the manuscript must include a statement to this effect in a consent section at the end of the manuscript, as follows: "Written informed consent was obtained from the patient for publication of this cohort study. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request".Patients have a right to privacy. Patients' and volunteers' names, initials, or hospital numbers should not be used. Images of patients or volunteers should not be used unless the information is essential for scientific purposes and explicit permission has been given as part of the consent. If such consent is made subject to any conditions, the Editor in Chief must be made aware of all such conditions. Even where consent has been given, identifying details should be omitted if they are not essential. If identifying characteristics are altered to protect anonymity, such as in genetic pedigrees, authors should provide assurance that alterations do not distort scientific meaning and editors should so note.Written informed consent was obtained from all patients included in the study.

Please specify the contribution of each author to the paper, e.g. study concept or design, data collection, data analysis or interpretation, writing the paper, others, who have contributed in other ways should be listed as contributors.All authors contributed equally in the protocol, data collection, statistical analysis, and writing.

In accordance with the Declaration of Helsinki 2013, all research involving human participants has to be registered in a publicly accessible database. Please enter the name of the registry and the unique identifying number (UIN) of your study.

The Guarantor is the one or more people who accept full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish Salman Al-Sabah salman.k.alsabah@gmail.com