Role of pleurodesis in the management of spontaneous pneumothorax Megan Cecchini R3 October 4, 2012 Role of pleurodesis in the management of spontaneous pneumothorax

Overview Review spontaneous pneumothorax Summarize initial management Discuss the role of pleurodesis Compare the efficacy of mechanical and chemical pleurodesis Discuss the safety of talc use in young patients based upon current literature

Definitions Simple pneumothorax – air within the pleural space Tension pneumothorax – air entering pleural space and unable to escape Primary – absence of underlying lung disease Secondary – presence of underlying lung disease Spontaneous – no antecedent traumatic or iatrogenic cause -Tension pneumothorax – air repeatedly entering the pleural space and unable to escape -> positive pressure develops in pleural space, lung collapse, mediastinal and heart shift away from side of pneumothorax -> respiratory and hemodynamic collapse (reduced venous return)

Epidemiology 7 to 18 cases per 100,000 people in men 1 to 6 cases per 100,000 people in women Most cases in tall, thin men < 30 Smoking increases risk by 22x in men and 9x in women Majority have subpleural bullae Most bullae are apical in location -Peak incidence between 16 and 24 years of age Pathogenesis -Two mechanisms to explain PSP -Acute increase in transpulmonary pressure -> alveolar distention -> rupture -Defects in visceral pleura -Occurrence during adolescence? -> growth during adolescence causes rapid increase in vertical dimension of thorax compared to horizontal dimension -> causes increase in negative pressure at lung apex -> formation of subpleural blebs

Presentation Chest pain Dyspnea Sharp, pleuritic, acute onset, radiation to ipsilateral shoulder Dyspnea Tachycardia and hypotension if tension pneumothorax PE – diminished breath sounds, decreased chest excursion, hyperresonance on percussion -Majority occur at rest, but can be precipitated by flying, weight lifting or Valsalva maneuver -Chest pain is the most common presenting symptom

Workup CXR – CT scan – Hyperlucent area with absent pulmonary markings Air in pleural space outlining visceral pleura Flattening or inversion of diaphragm Deep sulcus sign on supine film CT scan – Detection of apical blebs or underlying lung disease -CT scan – not routinely done

Few RCTs to develop evidence-based guidelines Guidelines based upon expert opinion -No standardized guidelines for management in children -> based upon adult literature -Delphi method – using anonymity, controlled feedback, and statistical group response; participants respond to questionnaires -> incorporate responses into new questionnaires -> consensus

Management Goals of management – 1) relieve ptx, 2) prevent recurrence, 3) minimize morbidity -If asymptomatic and small (<20% or <3 cm at apex) -> observation with repeat CXR (uncomplicated ptx reabsorbs at rate of 1% per day) -Methods to measure size have not been standardized in children -If moderate (20-40%) or large (>40%) -> needle aspiration, percutaneous small bore pigtail catheter placement or tube thoracostomy -Recurrence -> risk of 1st time recurrence is up to 50-60% in pediatric population with conservative management (recur w/ increasing frequency after each episode) -Tube thoracostomy – 5th intercostal space in the mid to anterior axillary line -Small bore catheter inserted using Seldinger technique -Needle aspiration using thoracentesis kit

Management

Indications for surgical intervention Recurrent pneumothorax Bilateral pneumothorax Complete pneumothorax High risk professions (pilots, scuba divers) Persistent air leak -Persistent air leak beyond 5 days based upon ACCP and BTS guidelines for adults

Surgical options Approach Technique Open thoracotomy Mini-thoracotomy Video-assisted thoracoscopic surgery (VATS) Technique Blebectomy Pleurectomy Mechanical abrasion Chemical pleurodesis -Recurrence rate < 5% w/ VATS -No approach has been shown to be superior, although higher morbidity with open thoracotomy approach

Pleurodesis Procedure to obliterate the pleural space to prevent recurrent pleural effusion or pneumothorax Chemical Talc Antibiotics Silver nitrate Bleomycin Mechanical Cautery scratch pad Partial pleura stripping

542 papers identified with 6 representing best evidence to answer clinical question Conclusion: similar outcome profile in comparison of mechanical and chemical pleurodesis -542 papers identified -> 6 represented best evidence to answer question of mechanical vs chemical pleurodesis to prevent recurrence? 1) Retrospective case series of 480 pts undergoing 550 VATS procedures -Recurrence rate: 1.4% of bullectomy + abrasion, 0.4% of bullectomy + chemical 2) Cohort study of 432 pts undergoing VATS for PSP (compared parietal pleurectomy w/ talc pleurodesis) -Recurrent rate: 9.15% in parietal pleurectomy group and 1.79% in talc pleurodesis group (p<0.00018) -However, most studies did not show statistical significance between groups -Conclusion – similar outcome profiles in comparison of mechanical and chemical pleurodesis with modest evidence suggesting lower rates of recurrence with chemical talc pleurodesis

Conclusion: both are acceptable approaches Retrospective review comparing VATS techniques in a pediatric population Results: Blebectomy + mechanical pleurodesis – shorter length of hospital stay and need for chest tube drainage Blebectomy + chemical pleurodesis – lower recurrence rates Conclusion: both are acceptable approaches -Largest pediatric series of VATS for PSP to date -Inclusion criteria: patients w/ PSP or recurrent PSP confirmed by CXR -VATS performed for: 1) persistent air leak following CT placement, 2) recurrent ipsilateral pneumothorax, 3) contralateral pneumothorax -CTs removed postop when air leak resolved and no ptx on CXR -41 VATS on 32 children -Mean follow up 46 months -Apical blebs identified in 26/32 (81%) -Blebectomy + mechanical pleurodesis – 2 recurrences requiring repeat VATS and 5 small recurrences treated nonop -> 23% recurrence rate -Blebectomy + chemical pleurodesis - 0 recurrences

Talc Hydrated magnesium silicate First used for pleurodesis in 1935 Provided in two forms approved by FDA 1) Sterile talc powder 2) Talc aerosol canister w/ 2 delivery tubes -Talc slurry via chest tube vs talc insufflation

Talc Mechanism of action: Production of cytokines, adhesion molecules, and other mediators of inflammation (IL-8, VEGF, TGF-beta) to produce an intense intrapleural inflammatory response

Important considerations Successful pleurodesis requires physical contact between visceral and parietal pleura Discontinue glucocorticoids and NSAIDs several days prior as they can decrease the effectiveness -Pleurodesis will fail if lung expansion is incomplete

Short term adverse events Fever (10-17%) Pain GI symptoms Less common – arrhythmia, dyspnea, respiratory failure, SIRS, empyema, talc dissemination -Higher risk with small particle sized talc

Long term effects? 8 papers presented best evidence to answer clinical question Conclusion: talc pleurodesis in young patients with primary spontaneous pneumothorax appears to have minimal long-term adverse effects -Goal: does talc used for pleurodesis in young pts with spontaneous ptx have any long-term adverse effects? -181 papers were identified -> 8 papers presented the best evidence to answer the question -Major concerns – risk for cancer or restrictive lung pathology in future? -Concerns about carcinogenic effect of talc likely came from early reports in miners exposed to impurities in talc dust leading to malignant tumors of lungs and pleura (possibly due to asbestos-like contaminants in the talc being used) -2 papers evaluated long-term evidence of respiratory compromise after use of talc 1) Lange: evaluated lung function 20-35 yrs after talc pleurodesis -> TLC 89% predicted in talc pts and 96% predicted in simple chest drainage -No significant long term effects on lung function 2) Viskum: re-examined 99 pts 22-35 yrs after talc pleurodesis for PSP -> no complications, recurrence rate 2.5% -Cardillo: large series of 861 pts who underwent VATS w/ talc pleurodesis -> 98% success rate at 50 months, no deterioration in lung function at 5 years -Conclusion – no cases of pulmonary fibrosis or lung cancer -> talc pleurodesis in young pts w/ PSP appears to have minimal long-term adverse effects

Recommendations Use size-calibrated talc with less than 10 percent small particles (5 to 10 microns) Use no more than 5 grams of talc Avoid simultaneous bilateral pleurodesis Avoid talc administration following extensive pleural abrasion -Likelihood for more systemic absorption of talc w/ larger percentage of small particles -Unfortunately, particle size distribution for FDA approved talc has not been disclosed by manufacturer -Wide variation in composition and particle size of various talc preparations used worldwide

Questions for discussion When would you use pleurodesis vs blebectomy alone? Thoughts about the use of talc in the pediatric population?

References Baumann MH, Strange C, Heffner JE, et al. Management of spontaneous pneumothorax: an American College of Chest Physicians Delphi consensus statement. Chest 2001; 119:590. Bialas RC, Weiner TM, Phillips JD. Video-assisted thoracic surgery for primary spontaneous pneumothorax in children: is there an optimal technique? J Pediatr Surg 2008; 43:2151. Hunt I, Barber B, Southon R, Treasure T. Is talc pleurodesis safe for young patients following primary spontaneous pneumothorax? Interact Cardiovasc Thorac Surg 2007; 6:117. Janahi IA. Spontaneous pneumothorax in children. UpToDate. 08/2012. Sepehripour AH, Abdul N, Shah R. Does mechanical pleurodesis result in better outcomes than chemical pleurodesis for recurrent primary spontaneous pneumothorax? Interact Cardiovasc Thorac Surg 2011; 14:307.