SUBMITTED 30 MAY 22 1 REVISION REQ. 6 JUL 22; REVISION RECD. 1 AUG 22 2 ACCEPTED 31 AUG 22 3 ONLINE-FIRST: DECEMBER 2022 4 DOI: https://doi.org/10.18295/squmj.12.2022.71 5 6 Nil Intervention is at Times the Best Intervention 7 Benign emptying of pneumonectomy space 8 Pratap Upadhya,1 *Muniza Bai,2 Veeraraghavan Gunasekaran,3 Dharm P. 9 Dwivedi,1 Shahana M.P.1 10 11 1Department of Pulmonary Medicine, Jawaharlal Institute of Postgraduate Medical Education 12 and Research (JIPMER), Puducherry, India; 2Department of Pulmonary Medicine, Critical 13 Care and Sleep Medicine, All India Institute of Medical Sciences, New Delhi, India; 14 3Department of Radiodiagnosis, Jawaharlal Institute of Postgraduate Medical Education and 15 Research (JIPMER), Puducherry, India. 16 *Corresponding Author’s e-mail: muzuni123@gmail.com 17 18 Abstract 19 A sudden drop of air-fluid level in the pneumonectomy space in the absence of a 20 bronchopleural fistula and pleural infection is termed benign emptying of the post 21 pneumonectomy space (BEPS). We herein report a case of benign emptying of 22 pneumonectomy space, briefly review the literature and enumerate possible mechanisms for 23 the same. It is an extremely rare entity and follows a benign course. Patients with BEPS are 24 clinically stable, afebrile with no fluid expectoration, and have a normal white blood cell 25 count. Bronchoscopy reveals an intact bronchial stump and pleural fluid cultures are often 26 sterile. Close monitoring and early detection of a bronchopleural fistula is the management. 27 Clinicians should keep BEPS among the differential diagnosis in case of a drop in the air-28 fluid level of the post pneumonectomy space. Awareness of this entity is crucial as it helps 29 prevent unnecessary and morbid surgical interventions. 30 Keywords: Pneumonectomy; BEPS; Bronchopleural Fistula; India. 31 32 Introduction 33 Pneumonectomy, the surgical resection of an entire lung is associated with significant 34 perioperative morbidity and mortality. The understanding of the normal physiology and chest 35 radiography post pneumonectomy is imperative to pick up complications early. Immediately 36 following pneumonectomy, air fills the postpneumonectomy space. Within 24 hours, the 37 ipsilateral diaphragm becomes slightly elevated, mediastinum gets slightly shifted to the 38 contralateral side and fluid accumulation commences in the postpneumonectomy space. In the 39 early postoperative period, fluid accumulation occurs at the rate of one to two intercostal spaces 40 per day.1 Within 2 weeks, 80-90% of the space gets filled with fluid.1 A drop in the air-fluid 41 level should evoke the suspicion of a possible bronchopleural fistula.2 Similar radiologic 42 picture in the absence of bronchopleural fistula and associated infection points towards a lesser 43 known entity, benign emptying of pneumonectomy space.3 We herein report a case of benign 44 emptying of pneumonectomy space, briefly review the literature and enumerate possible 45 mechanisms for the same. 46 47 Case report 48 A 28-year young woman, a known case of type 1 diabetes mellitus was admitted in view of 49 diabetic ketoacidosis in the month of September 2020. She presented with complaints of 50 multiple episodes of vomiting. She had no history of cough with expectoration, breathlessness, 51 chest pain, or fever. The clinical diagnosis of DKA was made in view of elevated plasma 52 glucose, positive urinary ketones and acidosis in arterial blood gas analysis. 53 54 Her history revealed that she was diagnosed to have sputum smear-positive pulmonary 55 tuberculosis with left-sided secondary spontaneous pneumothorax in august 2017 (Figure1A). 56 Left-sided chest tube insertion was done at that time for the pneumothorax. She also received 57 category1 weight-based anti-tuberculosis treatment for 6 months and was declared cured. In 58 view of left lung persistent hydropneumothorax with pleural thickening (a trapped lung) in 59 spite of chest tube in situ (Figure1B) and tuberculosis drug treatment she underwent left-sided 60 pneumonectomy in July 2018 through posterolateral thoracotomy. She was discharged on the 61 fifth postoperative day without chest tube or any complications. A chest radiograph taken in 62 her follow up visit two weeks after discharge demonstrated the expected fluid increase in the 63 post pneumonectomy space (Figure 1C). 64 65 However, a routine chest radiograph taken during this admission revealed a drop in the air-fluid 66 level in the left hemithorax (Figure1D). This incidental finding raised the alarms of a possible 67 bronchopleural fistula. But surprisingly, she had no specific respiratory complaints. Her pulse 68 rate was 70 beats per minute, blood pressure 110/70 mmHg, room air oxygen saturation was 69 96%, and respiratory rate 18 breaths per minute. She was afebrile with benign physical 70 examination findings except for decreased air entry on the left side of chest. So, we elected to 71 work up and not hurry up with a chest tube insertion. Her total white blood cell count and 72 routine biochemistry were reported normal. In view of recurrent vomiting episodes, an 73 ultrasound abdomen was done and reported normal. Pleural fluid diagnostic aspirate was sent 74 for culture which was reported sterile.The patient did not receive any course of antibiotics as 75 she did not have any clinical features suggestive of infection. She was afebrile, no purulent 76 expectoration, normal total leucocyte count and sterile pleural fluid culture report. 77 78 Given the ongoing COVID pandemic, a virtual bronchoscopy reconstruction was done from 79 high resolution computed tomography of the thorax instead of diagnostic flexible 80 bronchoscopy to rule out BPF (Figure 2). It showed linear thin fenestrated membranes partially 81 occluding the lumen of the left main bronchus, beyond which soft density was seen, probably 82 collapsed lung parenchyma or scar tissue with suture material. No obvious bronchopleural 83 fistula was noted. 84 85 These favored a diagnosis of benign emptying of pneumonectomy space. She was 86 conservatively managed and duly discharged once plasma glucose levels were controlled. 87 Repeat chest radiograph after two weeks revealed reaccumulation of fluid in the 88 postpneumonectomy space, reinstating our diagnosis (Figure 1E). Informed written consent 89 was obtained from the patient and attenders to share patient information and radiology images. 90 91 Discussion 92 The possible pulmonary complications of pneumonectomy are pulmonary edema, 93 postpneumonectomy syndrome and intraoperative spillage. The extrapulmonary complications 94 include post pneumonectomy empyema, post pneumonectomy syndrome, esophagopleural 95 fistlula, chylothorax, acute hemothorax, contralateral pneumothorax and bronchopleural fistula 96 is one among these. A drop in the air-fluid level within the post pneumonectomy space in an 97 erect chest radiograph is often considered pathognomonic of bronchopleural fistula (BPF). It 98 is a lethal condition and warrants early intervention in the form of prompt and urgent drainage 99 by chest tube insertion. The reported incidence of BPF after pneumonectomy is 0-9% and the 100 associated mortality rate is 16-23%.3 Patients with BPF usually have clinical features of cough 101 with fluid expectoration, fever, and breathlessness. Some may present with new infiltrates in 102 the contralateral lung due to trans-bronchial spill. Other radiographic presentations include 103 persistent or increasing pneumothorax despite adequate drainage via chest tube, progressive 104 mediastinal or subcutaneous emphysema, or mediastinal shift to the contralateral side. A 105 decrease in the height of the fluid column by 1.5cm or more is suggestive of BPF.4A decrease 106 in the fluid level less than 1.5cm can be ignored unless there is an associated mediastinal shift 107 to the contralateral side or features of infection.5 108 109 The confirmation of BPF can be done using bronchoscopy and/or contrast enhanced chest 110 tomography(CECT). Other methods include contrast bronchography, intrapleural methylene 111 blue administration, and ventilation scintigraphy.6 Bronchoscopic examination of the bronchial 112 stump is the most commonly used method to confirm the diagnosis of BPF. To identify BPF, 113 bronchial stump immersed in saline is visualized under positive pressure ventilation or can be 114 done by visualization of continuous air bubbles on lavage. Once diagnosed, the fistula needs 115 to be repaired. CT chest with airway virtual reconstruction is an alternative and safer option to 116 confirm or rule out BPF as it is easier to perform, faster and also allows better visualization of 117 the fistula tract. 118 119 A similar drop in the air-fluid level of pneumonectomy space without the existence of BPF is 120 termed benign emptying of pneumonectomy space (BEPS). It is a rare condition which may be 121 misdiagnosed and mismanaged as a BPF. The calculated incidence of BEPS is reported as 0.65 122 of pneumonectomies.3 Such patients are often asymptomatic, clinically stable, and do not 123 require any urgent intervention. They are often afebrile with normal white blood cell count and 124 sterile pleural fluid culture. Bronchoscopy reveals an intact bronchial stump with no fistula. 125 126 The possible mechanism behind BEPS might be (1) the presence of an occult fistula that heals 127 spontaneously before seeding and the occurrence of infection, (2) the presence of a valve-like 128 fistula of a small caliber that allows the passage of only air and does not allow the fluid to enter 129 the airway or a large number of bacteria to enter the pleural cavity to fuel an infection.3 A 130 transient microscopic and spontaneously healing fistula is the most accepted mechanism. The 131 transit of air into the pleural space causes an increase in the intrapleural pressure forcing the 132 fluid out of the hemithorax into the surrounding cavities or tissues. Three potential routes for 133 the pleural fluid to break free from the pleural space are (1) congenital diaphragmatic 134 fenestrations in individuals with porous diaphragm syndrome (2) diaphragm and peritoneal 135 defects formed at the time of extra pleural pneumonectomy and diaphragm reconstruction (3) 136 failure to produce watertight chest wall closure helps pleural fluid to escape into the 137 surrounding soft tissues, often resulting in an entity called woody chest wall.8.9 (1) and (2) 138 allow the egress of pleural fluid into the abdomen. 139 140 In 2011, Merritt et al surveyed 28 leading thoracic surgeons across the United States to acquire 141 an estimate of the incidence and varied clinical presentations of BEPS. Based on their 142 observations, a strict clinical and laboratory criterion was described to confidently diagnose 143 BEPS.3 The criteria include absence of fever, normal white blood cell count, no fluid 144 expectoration, negative bronchoscopy, and negative pleural fluid cultures if performed.3 Our 145 patient met the afore-mentioned criteria. It is important to note that a diagnostic pleural tap 146 could have been avoided in this case as she did not have any clinical features suggestive of 147 infection. Interestingly, a higher incidence of BEPS was noted following right lung resections 148 compared to the left, unlike our case. Right-sided predisposition can be due to the shorter length 149 and lesser concealment of the right bronchial stump and greater chances of ischemia when 150 blood is supplied by a single bronchial artery. 151 152 BEPS is managed conservatively, and the pneumonectomy cavity quickly refills over time. 153 Watchful waiting is the right approach. Such patients should be followed up closely with repeat 154 chest radiographs every 1-2 weeks until pleural fluid reaccumulates.3 Patients should be 155 counseled of the red flag signs suggestive of BPF and concomitant infection of the 156 pneumonectomy space. Empirical oral antibiotics are not recommended in BEPS. 157 158 Conclusion 159 Clinicians should keep BEPS among the differential diagnosis in case of a drop in the air-fluid 160 level of the post pneumonectomy space. A drop in air fluid level of the post pneumonectomy 161 space is not always a pointer to bronchopleural fistula and does not warrant an intercostal drain 162 placement or a surgical intervention. It can just be a benign emptying of pneumonectomy space 163 which does not require any intervention. A right diagnosis of BEPS, when clinched early, will 164 avoid unnecessary, costly, and morbid surgical interventions. 165 166 167 Authors’ Contribution 168 PU and DPD provided care for the patient. VG and SMP collected the data. DPD supervised 169 the work. MB and PU drafted the manuscript. All authors critically reviewed the manuscript 170 while MB and SMP edited the manuscript. All authors approved the final version of the 171 manuscript. 172 173 Acknowledgements 174 We are grateful to Dr Sivaselvi and Dr Lakshmi S residents of the department of Pulmonary 175 Medicine, JIPMER for the help rendered in diagnosis, workup and patient care. 176 177 References 178 1. Paone G, Rose GD, Giudice GC, Cappelli S. Physiology of pleural space after pulmonary 179 resection. Journal of Xiangya Medicine. 2018 Mar 14;3(3). 180 2. Hollaus PH, Lax F, el-Nashef BB, Hauck HH, Lucciarini P, Pridun NS. Natural history of 181 bronchopleural fistula after pneumonectomy: a review of 96 cases. Ann ThoracSurg 182 1997;63:1391–1396. 183 3. Merritt RE, Reznik SI, DaSilva MC, Sugarbaker DJ, Whyte RI, Donahue DM, Hoang CD, 184 Smythe WR, Shrager JB. Benign emptying of the postpneumonectomy space. 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Efficacy of video-assisted thoracoscopic surgery with talc 198 pleurodesis for porous diaphragm syndrome in patients with refractory hepatic 199 hydrothorax. Ann Thorac Surg 2006;82:457–9. 200 201 202 Figure 1: Chest radiographs showing A - left side pneumothorax with tracheal and mediastinal 203 shift to the right, B – persistent left hydropneumothorax with left chest tube in place, C –totally 204 filled up post pneumonectomy space (July 2018), D – drop in the air fluid level in the 205 pneumonectomy space (September 2020), E – reaccumulation of fluid in the post 206 pneumonectomy space (2 weeks later). 207 208 209 Figure 2: Image of virtual bronchoscopy reconstruction showing linear thin fenestrated 210 membranes partially occluding the lumen of the left main bronchus and an intact left bronchial 211 stump with no evidence of bronchopleural fistula. 212