e-ISSN 1941-5923 © Am J Case Rep, 2020; 21: e920453 DOI: 10.12659/AJCR.920453 Received: Accepted: 2019.10.02 2019.11.11 A Case of Persistent Air Leak Managed by Published: 2020.01.06 Selective Left Main Bronchus Intubation in an Infant with Pulmonary Tuberculosis Authors’ Contribution: BEF 1 Laura Vargas-Pons 1 Pediatric Pneumology Unit, Parc Taulí University Hospital, Institute of Research Study Design A EF 1 Laura Valdesoiro Navarrete and Annovation, Autonomous University of Barcelona, Sabadell, Spain Data Collection B 2 Pediatric Intensive Care Unit, Parc Taulí University Hospital, Institute of Research Statistical Analysis C EF 2 Sílvia Sánchez Pérez and Annovation, Autonomous University of Barcelona, Sabadell, Spain Data Interpretation D EF 3 Elisabet Guijarro Casas 3 Pediatric Pneumology Unit, Althaia – Xarxa University Assistance of Manresa, Manuscript Preparation E EF 4 Nuria Brun Lozano Manresa, Spain Literature Search F 4 Department of Pediatric Surgery, Parc Taulí University Hospital, Institute of Funds Collection G EF 2 Luis Renter Valdovinos Research and Annovation, Autonomous University of Barcelona, Sabadell, Spain EFG 5 Raquel Corripio Collado 5 Department of Pediatric Endocrinology, Parc Taulí University Hospital, Autonomous University of Barcelona, Sabadell, Spain Corresponding Author: Raquel Corripio Collado, e-mail: raquelcorripio@gmail.com, rcorripio@tauli.cat Conflict of interest: None declared Patient: Male, 3-month-old Final Diagnosis: Pulmonary tuberculosis Symptoms: Respiatory distress Medication: — Clinical Procedure: Selective left main bronchus intubation Specialty: Pediatrics and Neonatology Objective: Unusual clinical course Background: Persistent air leak, or persistent pneumothorax, is defined as a pneumothorax that persists beyond the first week, or air leak through a chest drain for more than 48 hours. The most common findings in pediatric pul- monary tuberculosis are parenchymal disease and mediastinal lymphadenopathy, but airway obstruction can cause emphysema and pneumothorax. A case is presented of persistent air leak in a 3-month-old infant with pulmonary tuberculosis that was managed by selective left main bronchus intubation. Case Report: A 3-month-old boy presented with respiratory distress and fever. Imaging findings suggested pulmonary tu- berculosis, and first-line anti-tuberculous treatment was initiated with isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE). He was discharged home after eight days, but was admitted four days later with respira- tory distress. Chest X-rays showed a tension pneumothorax that required drainage and chest computed to- mography (CT) showed right lung emphysema. Bronchoscopy found extrinsic obstruction of both main bronchi. Chest drains continued to leak air leak after 48 h. Right middle and lower lobectomy and drainage of multi- ple lymph nodes resulted in significant improvement. He developed pneumonia and acute respiratory distress syndrome, which prevented mechanical ventilation. The left main bronchus was selectively intubated to allow the air leak to heal and to ventilate the lung. He was extubated 10 days later and recovered completely. Conclusions: This case highlights that when medical management of persistent air leak associated with tuberculosis is not effective, surgery, active ventilation, and selective main bronchus intubation should be considered. MeSH Keywords: Pneumonectomy • Pneumothorax • Pulmonary Emphysema • Tuberculosis Full-text PDF: https://www.amjcaserep.com/abstract/index/idArt/920453 2846   —   6   19 This work is licensed under Creative Common Attribution- Indexed in: [PMC] [PubMed] [Emerging Sources Citation Index (ESCI)] NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) e920453-1 [Web of Science by Clarivate] Vargas-Pons L. Et al.: Management of persistent air leak in an infant with TB © Am J Case Rep, 2020; 21: e920453 Background Case Report Tuberculosis in neonates and children is an important pub- A 3-month-old male infant was admitted to our pediatric emer- lic health issue, with an estimated incidence in Spain of 4.3 gency department from a small local hospital in a neighboring cases per 100,000 persons per year [1,2]. The diagnosis of pe- town. He was in acute respiratory distress due to a mediastinal diatric tuberculosis can be challenging, as clinical and radio- mass. His family explained that he had developed increasing logical signs can be variable, resulting in delayed treatment. difficulties in breathing and had a fever of up to 38.5°C dur- In Europe, pediatric mortality due to tuberculosis is rare, but in ing the previous five days. He had no remarkable past medical cases with severe pulmonary or extrapulmonary disease, com- history. He was born at full-term, and newborn screening tests plications can result in increased morbidity and mortality [3]. were negative. He had been asymptomatic from birth, and he had no previous infections. He had no syndromic features and The most common findings in pediatric pulmonary tuberculosis had shown normal weight gain. He had received the first dose are parenchymal disease and mediastinal lymphadenopathy, but of the pediatric combination hexavalent vaccine (DTaP/HepB/ airway obstruction can cause emphysema and pneumothorax. IPV/Hib) containing diphtheria toxoid, tetanus toxoid, acellular pertussis, inactivated poliovirus, and recombinant hepatitis B Following the diagnosis of pulmonary tuberculosis, medical virus (HBV) surface antigen. He had not received the Bacillus treatment is the first-line treatment option. When emphysema Calmette-Guérin (BCG) vaccine because it does not form part results in pneumothorax and air leak, the management op- of the routine national vaccination schedule. tions include conservative treatment, drainage, or thoracen- tesis. Surgery is rarely performed and is usually reserved for Chest X-rays performed at the primary care center showed lung pulmonary emphysema that results in persistent air leak [4]. hyperinflation and a left displacement of the trachea. Chest Persistent air leak, or persistent pneumothorax, is defined as computed tomography (CT) showed collapse of the bronchus in- a pneumothorax that persists beyond the first week, or an air termedius and air trapping in the right middle and lower lobes. leak through a chest drain for more than 48 hours. A case is Although he did not need respiratory support, it was decided presented of persistent air leak in a 3-month-old infant with to move him to our hospital, which had an intensive care unit. pulmonary tuberculosis that was managed by selective left main bronchus intubation. On admission, he was admitted to the pediatric ward. A con- trast-enhanced chest CT was performed, which showed find- ings suggestive of pulmonary tuberculosis (Figure 1). A B Figure 1. Contrast-enhanced chest computed tomography (CT) imaging of a 3-month-old infant with pulmonary tuberculosis and persistent air leak. (A) Chest CT shows parenchymal lesions in the right upper lobe and the left lung. (B) There is emphysema in the right middle lobe and inferior right lower lobe and multiple mediastinal lymph nodes. This work is licensed under Creative Common Attribution- Indexed in: [PMC] [PubMed] [Emerging Sources Citation Index (ESCI)] NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) e920453-2 [Web of Science by Clarivate] Vargas-Pons L. Et al.: Management of persistent air leak in an infant with TB © Am J Case Rep, 2020; 21: e920453 Laboratory tests showed microcytic anemia with a hemoglo- bin of 73 g/L, a mean corpuscular volume (MCV) of 76.5 fL, and an elevated C-reactive protein (CRP) of 4.2 mg/dL. Anemia was attributed to chronic inflammation and iron deficiency. Because the patient was hemodynamically stable, oral treat- ment with iron supplements was initiated. Three gastric aspi- rates were collected, and Ziehl–Neelsen staining for acid-fast bacilli was negative. The result of the interferon-g release assay (IGRA) was positive, which supported a diagnosis of tubercu- losis. The cerebrospinal fluid analysis was negative. A neutro- phil oxidative burst assay for chronic granulomatous disease and a human immunodeficiency virus (HIV) test were negative. However, because pulmonary tuberculosis was strongly sus- pected, first-line treatment with isoniazid, rifampicin, pyrazin- amide, and ethambutol (HRZE) was initiated. After 48 hours of supplemental oxygen, the fraction of inspired oxygen in air (FiO2) of 30% was delivered through a nasal cannula, and his Figure 2. Chest X-ray imaging of a 3-month-old infant with respiratory distress resolved. The nasal cannula was withdrawn, pulmonary tuberculosis and persistent air leak. Chest and the chest X-ray confirmed no complications. Oral treat- radiographs show a right residual pneumothorax and partial collapse of the right upper lobe. ment was initiated and was well tolerated. The patient was dis- charged eight days later with no signs of respiratory distress. However, four days later, he was readmitted to the small lo- cal hospital where he was initially treated for signs of respi- ratory distress and because vomiting made it impossible for his mother to manage his oral treatment. Chest X-ray showed pulmonary changes that raised the possibility of a reaction to medical treatment. He had signs of moderate respiratory dis- tress, and so a high-flow nasal cannula was used, and his re- spiratory status improved. Anti-emetic treatment was also ini- tiated, and the patient resumed oral treatment and remained stable for 11 days. On the 12th day of hospitalization, he pre- sented with sudden worsening respiratory distress with de- saturation and tachycardia, absent breath sounds over the right hemithorax, and severe respiratory acidosis. Chest X-ray showed a right tension pneumothorax. Needle thoracentesis was performed, and 100 cc of air was aspirated from the pleu- ral space. However, there was no clinical improvement, and a chest tube was inserted. Because tachycardia, respiratory dis- Figure 3. Chest computed tomography (CT) imaging of a tress, and acidosis persisted, the patient was intubated nasally, 3-month-old infant with pulmonary tuberculosis and and another chest tube was inserted (Figure 2). His condition persistent air leak. Chest CT shows parenchymal emphysema in the right lung with compression of improved, and he was transferred to our hospital. the left lung. During the next four days, he remained hemodynamically sta- ble but had some episodes of respiratory failure due to recur- support modes were used. Lung ultrasound was performed rent pneumothorax that required manual aspiration through daily to detect possible complications, and medical treatment the chest tubes. Bronchoscopy was performed with a flexible with anti-tuberculosis drugs was maintained. fiberoptic bronchoscope, which showed extrinsic obstruction of both main bronchi, explaining the findings of emphysema. One week later, no improvement was seen, and chest tubes No endobronchial granulomas were seen. To prevent bron- were still draining air, suggesting a persistent air leak that was chial collapse during expiration, positive end-expiratory pres- maintained by high positive pressure. Further fiberoptic bron- sure (PEEP) was increased to 8 cmH2O, and other ventilation choscopy showed worsening of the bronchial obstruction as This work is licensed under Creative Common Attribution- Indexed in: [PMC] [PubMed] [Emerging Sources Citation Index (ESCI)] NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) e920453-3 [Web of Science by Clarivate] Vargas-Pons L. Et al.: Management of persistent air leak in an infant with TB © Am J Case Rep, 2020; 21: e920453 A B Figure 4. Chest X-ray imaging of a 3-month-old infant with pulmonary tuberculosis and persistent air leak. (A) Chest radiograph before surgery shows an anterior right pneumothorax and compression of the left lung. (B) Chest radiograph after surgery shows inflation of the right lung with no residual pneumothorax. well as obstruction of the carina. Chest CT showed that the lymph nodes had decreased in size, but severe parenchymal emphysema in the right lung was compressing the contralat- eral lung (Figure 3). Despite the emphysema, as the lymph nodes had decreased in size, conservative management was maintained, followed by first-line treatment with isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE) and con- ventional ventilation. On the 19th day of hospitalization, he presented with sudden respiratory failure with desaturation and bradycardia due to tension pneumothorax, requiring the FiO2 of 100%, volume expansion, and continuous norepinephrine infusion (maxi- mum dose, 0.6 mcg/kg/min) to maintain optimal mean blood pressure. Given the poor response to conservative treatment, urgent surgery was performed. The middle and lower right lobes were resected via a right thoracotomy. During surgery, caseating granulomas were found in the lymph nodes and in Figure 5. Chest X-ray imaging of a 3-month-old infant with the lung parenchyma, and there were also multiple granulo- pulmonary tuberculosis and persistent air leak. Chest mas distributed locally in other areas of the lung parenchyma. radiograph shows the collapse of the right lung with parenchymal infiltrates in the left lung. Acid-fast bacilli were detected, and cultures of the lymph nodes identified Mycobacterium tuberculosis complex. After vancomycin was initiated. After 24 hours, Klebsiella oxytoca surgery, his respiration improved (Figure 4). One week after was detected in the tracheal cultures. surgery, fiber-optic bronchoscopy showed no airway compres- sion or endobronchial lesions, and ventilatory support was re- In the next few hours, he developed severe acute respiratory duced. However, after 24 hours, he developed further respira- distress syndrome (ARDS), requiring high levels of positive end- tory distress and fever. Laboratory tests showed leukocytosis, expiratory pressure (PEEP) (12 cmH2O) and FiO2 up to 100% to increased C-reactive protein (CRP) (19 mg/dL), and chest X-rays maintain adequate ventilation and oxygenation. Norepinephrine showed left-sided pneumonia (Figure 5). Tracheal, urinary and infusion commenced (maximum dose, 0.7 mcg/kg/min). A ten- blood cultures were taken and treatment with meropenem and sion pneumothorax appeared in the right hemithorax, requiring This work is licensed under Creative Common Attribution- Indexed in: [PMC] [PubMed] [Emerging Sources Citation Index (ESCI)] NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) e920453-4 [Web of Science by Clarivate] Vargas-Pons L. Et al.: Management of persistent air leak in an infant with TB © Am J Case Rep, 2020; 21: e920453 Discussion Tuberculosis and its complications can be much more severe in neonates and children than in adults, and the management of tuberculosis and its complications can be difficult. This re- port has shown that selective main bronchus intubation can be used to treat cases where conventional management fails to achieve adequate oxygenation. In this case, the diagnosis of tuberculosis was strongly suspected, and first-line treat- ment with isoniazid, rifampicin, pyrazinamide, and ethambu- tol (HRZE) was commenced. Ethambutol was included because of the high prevalence of isoniazid resistance in our part of Spain [2,5], and because the primary cause was initially un- known. Cultures of the gastric aspirate collected on the sec- ond day of hospitalization and the specimens collected during the first bronchoscopy were negative. Mycobacterium tuber- Figure 6. Chest computed tomography (CT) imaging of a culosis was isolated in the cultures from surgical lymphade- 3-month-old infant with pulmonary tuberculosis and nopathy specimens. persistent air leak. Chest CT shows the collapse of the right lung and parenchymal infiltrates in the left lung. Because tuberculosis in children is often paucibacillary, Mycobacterium tuberculosis is isolated in only 20–40% of another drainage tube. These measures failed to achieve ade- cases and failure to identify the pathogen can result in de- quate oxygenation, with a PaFi (PaO2/FiO2) <150, and an oxy- layed treatment [1]. In this case, the diagnosis of tuberculo- genation index of 24. A persistent air leak excluded the use sis was confirmed by both cultures and histologic findings of conventional mechanical ventilation. The patient was then of the resected lymph nodes. In this patient, the most chal- managed with high-frequency oscillatory ventilation (HFOV) for lenging management issue was the persistent air leak. Most 48 hours, with the maximum parameters including a mean air- persistent air leaks resolve spontaneously, and the insertion way pressure (MAP) of 23 cmH2O, a frequency of 9 Hz, and an of chest tubes are the initial treatment of choice. However, amplitude of 50%, but no improvement was seen. the best approach to persistent air leaks that do not heal re- mains controversial [4,6,7]. During the first days of hospital- To enable the left lung to be ventilated while allowing the per- ization, severe airway obstruction due to enlarged mediastinal sistent air leak in the right lung to resolve and the pleura to lymph nodes caused significant parenchymal emphysema and heal, the left main bronchus was selectively intubated with an air leak that could not be controlled with drainage tubes. a 4 mm cuffed endotracheal tube. Volume-controlled venti- Some cases of tuberculosis can lead to atypical or paradoxical lation PEEP of up to 14 cmH2O and tidal volumes of 5 ml/kg findings when treatment is initiated, resulting in worse clini- achieved adequate oxygenation and ventilation. As the contra- cal or radiological findings [8,9]. Because conservative treat- lateral lung was atelectatic, no problems with lung secretions ment is recommended in air leak in children, chest tubes and occurred. Chest drains were kept in place, and PEEP was pro- medical treatment were maintained and there were no other gressively reduced. Nine days after selective left main bron- interventions. The patient was ventilated in both a volume- chus intubation, he was weaned off PEEP, and chest CT showed controlled mode and a volume support mode, with tidal vol- right lung collapse, left mediastinal displacement, and paren- umes ranging from 6 mL/kg to 7 mL/kg, peak pressures of chymal infiltrates in the left lung (Figure 6). Given his clinical around 20 cmH2O to 25 cmH2O, and plateau pressures around improvement, he was extubated 24 hours later but required 12 cmH2O to 18 cmH2O. Initially, PEEP was set at 5 cmH2O, but a nasal cannula for the next 13 days. On the 69th day of hos- it had to be increased to up to 8 cmH2O to avoid bronchial col- pitalization, the last chest tube was removed. The patient was lapse at end-expiration and to prevent the bronchial occlusion discharged home 13 days later with no respiratory support. At and secondary emphysema. Increasing the PEEP did not in- this time, the patient is now 15 months old, and no compli- crease the plateau pressures, which indicated that the risk of cations have been observed during follow-up. He has not re- pneumothorax did not increase. However, when no improve- quired respiratory support, and follow-up chest X-rays showed ment was seen, surgery was considered. Although mediastinal normal expansion of the right upper lobe. lymphadenopathy is common in pediatric patients with tuber- culosis, particularly in children <4-years-old, they rarely cause life-threatening airway compression, as they did in this case. This work is licensed under Creative Common Attribution- Indexed in: [PMC] [PubMed] [Emerging Sources Citation Index (ESCI)] NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) e920453-5 [Web of Science by Clarivate] Vargas-Pons L. Et al.: Management of persistent air leak in an infant with TB © Am J Case Rep, 2020; 21: e920453 Goussard et al. [10] reported the findings from a study of a se- from 24 hours to seven days, and all but one of the patients ries of 250 children treated for pulmonary tuberculosis with were ventilated with HFOV [14]. Emphysema resolved in seven life-threatening airway compression, where 86 required lymph cases, and in the other two cases, pneumothorax recurred but node decompression, with urgent procedures performed in was successfully managed conservatively [14]. Selective main 25 children. As in the present case, the lymph nodes adhered bronchus intubation is also used as an intermediary measure to the surrounding structures and were difficult to remove, for patients when ventilation of both lungs is very difficult. In so they were aspirated, and all patients were successfully ex- these cases, the patient remains under selective intubation tubated and discharged home without ventilatory support [10]. for hours or a few days until lobectomy or pneumonectomy Despite surgery, in the present case, the air leak persisted and of the affected lung is performed. was critically aggravated by ventilator-associated pneumonia and ARDS in the contralateral lung. At this point, it was im- Another widely used treatment option for persistent air leak possible to achieve adequate oxygenation with conventional is pleurodesis. Chemical agents, including talc, doxycycline, or mechanical ventilation, but as there was a persistent air leak, bleomycin, can be used to induce an inflammatory response the ventilation strategy was changed to high-frequency oscil- to seal the pleural space [15], but this aggressive technique latory ventilation (HFOV). Although HFVO has drawbacks, it is should be avoided in children. More recently, autologous blood used as rescue therapy in cases of pulmonary air leak, pul- patches have been used to induce pleurodesis for the treat- monary interstitial emphysema, and pneumothorax because it ment of persistent air leak [16–18]. In the patient described achieves adequate gas exchange without exposing the patient in this report, selective left main bronchus intubation was to changing pressures that can worsen the air leak. Poor man- used to allow the air leak to heal and the contralateral lung agement after the initiation of HFVO can lead to gas trapping, (affected by ARDS) to be ventilated. The use of selective main but PaCO2 levels in this patient remained normal. bronchus intubation can have several challenges. Because very few cases have been reported in the literature and it was un- In this case, because HFOV had failed, more aggressive man- clear whether the bronchopleural fistula would close in this agement was considered, with the main treatment options case, it was difficult to determine when to extubate the pa- being selective left main bronchus intubation or occlusion of tient. However, the remaining intubated lung was known to the main bronchus of the affected lung to prevent air from es- be at a high risk of tension pneumothorax. Also, high doses caping through the bronchopleural fistula [4,6]. Several tech- of multiple sedatives were required when the patient was se- niques have been used to occlude the bronchi, but none have lectively intubated. For example, the maximum doses of sed- been widely studied. Bronchial occlusion can have complica- ative drugs included midazolam (6 mcg/kg/min), propofol tions, such as necrosis, erosion of the bronchial wall or bron- (4 mcg/kg/min), fentanyl (2 mcg/kg/h), ketamine (4 mcg/kg/h), chial stenosis, airway perforation, and distal infection [11]. and morphine (150 mcg/kg/h). The patient developed drug Lewis et al. [12] reported one of the first cases of selective withdrawal that required treatment with methadone (maxi- bronchial occlusion in a 26-week preterm infant with hyaline mum, 0.4 mg/kg/6 h), diazepam (maximum, 0.3 mg/kg/6 h), membrane disease with a persistent air leak that was success- and clonidine (maximum, 5 mcg/kg/8 h). fully treated using a Swan-Ganz catheter. There have been few previously reported cases of selective intubation of the main A further difficulty, in this case, was the unavailability of a bronchus for persistent air leak. Hathorn et al. [11] evaluated digital pleural drainage system, which required the use of a six cases, including two cases with bronchopulmonary fistula, conventional chest drainage system until the air leak healed. and four cases with intrapulmonary air leaks treated with en- Digital systems reduce interobserver variability and enable dobronchial balloons. In this previous study, no complications more continuous pressure than conventional devices [19], and occurred, and the treatment was successful in four cases [11]. using this technology throughout the period when chest tubes were in place might have improved the management of the Selective intubation of the main bronchus of the healthy lung air leak. This patient recovered completely. Currently, no com- is an option that has been widely reported in preterm in- plications have found at 12-month follow-up. However, close fants with bronchopulmonary dysplasia that resulted in lung follow-up remains necessary to confirm the clinical outcome hyperinflation and tension pneumothorax. The technique of and to assess possible future complications. selective main bronchus intubation was first described by Brooks et al. [13], who reported selective intubation of the main right bronchus in four preterm infants with pulmonary Conclusions emphysema. Jakob et al. [14] published a case series of nine preterm infants with emphysema with failed conservative This report presented a rare case of persistent air leak in therapy, including lateral decubitus positioning and HFOV for a 3-month-old infant with pulmonary tuberculosis that three days. Selective bronchial intubation was maintained was managed by selective left main bronchus intubation. This work is licensed under Creative Common Attribution- Indexed in: [PMC] [PubMed] [Emerging Sources Citation Index (ESCI)] NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) e920453-6 [Web of Science by Clarivate] Vargas-Pons L. Et al.: Management of persistent air leak in an infant with TB © Am J Case Rep, 2020; 21: e920453 The management of this patient required a multidisciplinary Conflict of interest approach to a potentially life-threatening condition and resulted in a successful outcome. This case highlights that when medi- None. cal management of persistent air leak associated tuberculosis is not effective, surgery, active ventilation, and selective main bronchus intubation should be considered. References: 1. Moreno-Pérez D, Andrés Martín A, Altet Gómez N et al: [Diagnosis of tu- 10. Goussard P, Gie RP, Janson JT et al: Decompression of enlarged mediasti- berculosis in pediatrics. 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