Chemical Pleurodesis for Spontaneous Pneumothorax

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provided by Elsevier - Publisher Connector Journal of the Formosan Medical Association (2013) 112, 749e755

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REVIEW ARTICLE Chemical pleurodesis for spontaneous pneumothorax

Cheng-Hung How, Hsao-Hsun Hsu, Jin-Shing Chen*

Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

Received 9 September 2013; received in revised form 16 October 2013; accepted 17 October 2013

KEYWORDS Pneumothorax is deﬁned as the presence of air in the pleural cavity. Spontaneous pneumo- air leakage; thorax, occurring without antecedent traumatic or iatrogenic cause, is sub-divided into pri- pleurodesis; mary and secondary. The severity of pneumothorax could be varied from asymptomatic to pneumothorax; hemodynamically compromised. Optimal management of this benign disease has been a mat- recurrence; ter of debate. In addition to evacuating air from the pleural space by simple aspiration or chest thoracoscopy tube drainage, the management of spontaneous pneumothorax also focused on ceasing air leakage and preventing recurrences by surgical intervention or chemical pleurodesis. Chemical pleurodesis is a procedure to achieve symphysis between the two layers of pleura by sclerosing agents. In the current practice guidelines, chemical pleurodesis is reserved for patients unable or unwilling to receive surgery. Recent researches have found that chemical pleurodesis is also safe and effective in preventing pneumothorax recurrence in patients with the ﬁrst episode of spontaneous pneumothorax or after thoracoscopic surgery and treating persistent air leakage after thoracoscopic surgery. In this article we aimed at exploring the role of chemical pleurodesis for spontaneous pneumothorax, including ceasing air leakage and preventing recurrence. The indications, choice of sclerosants, safety, effects, and possible side effects or complications of chemical pleurodesis are also reviewed here. Copyright ª 2013, Elsevier Taiwan LLC & Formosan Medical Association. All rights reserved.

Deﬁnition and classiﬁcation of spontaneous pneumothorax

* Corresponding author. Department of Surgery, National Taiwan Pneumothorax, a common pleural disease worldwide, is University Hospital and National Taiwan University College of deﬁned as the presence of air in the pleural cavity, resulting 1 Medicine, Number 7, Chung-Shan South Road, Taipei, Taiwan. in parenchymal collapse. Pneumothorax can impair E-mail address: [email protected] (J.-S. Chen). oxygenation and/or ventilation. If the pneumothorax is

0929-6646/$ - see front matter Copyright ª 2013, Elsevier Taiwan LLC & Formosan Medical Association. All rights reserved. http://dx.doi.org/10.1016/j.jfma.2013.10.016 750 C.-H. How et al. significant, it can cause a shift of the mediastinum and differentiate between pneumothorax and bullous lung dis- compromise hemodynamic stability. Clinically, pneumo- ease, when aberrant tube placement is suspected and when thorax is divided into spontaneous and traumatic. Sponta- the plain chest radiograph is difficult to read owing to the neous pneumothorax is sub-divided into primary and presence of subcutaneous emphysema.4 secondary, according to with or without precipitating underlying lung disease.2À4 Primary spontaneous pneumothorax (PSP), which is Treatment options for spontaneous defined as a pneumothorax without obvious underlying lung pneumothorax disease, most commonly occurs in young, tall, lean males.2,4 PSP occurs at a frequency of 7.4e18 cases per The management of pneumothorax focused on evacuating 100,000 population per year in men and in 1.2e6 cases per air from the pleural space, ceasing air leakage, and pre- 100,000 population per year in women.5,6 With regard to venting recurrences.4,19,21 Available therapeutic options the etiology of PSP, anatomical abnormalities are include observation, simple aspiration, intercostal drainage commonly demonstrated at the apex of the lung. with a pigtail catheter or chest tube, intercostal drainage Emphysema-like changes, including subpleural blebs and with chemical pleurodesis, medical thoracoscopy with bullae were found in 50e90% of PSP patients on high- chemical pleurodesis, or surgical intervention (VATS or resolution computed tomography (CT) scanning and in thoracotomy) with/without chemical pleurodesis. The se- 76e100% of PSP patients during video-assisted thoraco- lection of an approach depends on the size of the pneu- À scopic surgery (VATS) or thoracotomy.7 12 mothorax, the severity of symptoms, whether there is a Secondary spontaneous pneumothorax (SSP) usually oc- persistent air leakage, and whether the pneumothorax is curs in older people with underlying lung disease, such as primary or secondary.4,19,21 Generally, surgical intervention emphysema, chronic obstructive lung disease, catamenial is reserved for patients with recurrent or complicated pneumothorax, cystic fibrosis, pulmonary infection, or spontaneous pneumothorax, and chemical pleurodesis can e lymphangioleiomyomatosis.3,13 16 be used as an adjunct after drainage or surgery.

Clinical presentation and diagnosis of Chemical pleurodesis spontaneous pneumothorax Pleurodesis is a procedure to achieve symphysis between Sudden onset of dyspnea and pleuritic chest pain were most the two layers of pleura to prevent recurrent pleural complained.17,18 The severity of the symptoms is primarily effusion or recurrent pneumothorax.4,26,27 Either instilling a related to the volume of air in the pleural space. Symptoms chemical irritant (chemical pleurodesis) or performing are greater in SSP, even if the pneumothorax is relatively mechanical abrasion (mechanical pleurodesis) that induced small in size.4 Owing to the additional presence of the pa- inflammation and fibrosis caused the symphysis between tient’s underlying lung disease, SSP is considered a poten- the two layers of pleura.8 Clinically, chemical pleurodesis tially life-threatening event, whereas PSP is virtually was widely applied for stopping air-leak or for preventing always a nuisance rather than a life-threatening pneumothorax recurrence. Chemical pleurodesis can be condition.19 applied through the intercostal drainage tube, medical Diagnosis of pneumothorax is confirmed by imaging thoracoscopy, or during the operation. In clinical practice, studies, primarily a plain chest film obtained during forced a variety of sclerosants have been used, including tetra- inspiration with the patient in a standing position.20,21 The cycline and derivatives (doxycycline or minocycline), talc, presence of a pneumothorax is established by demon- bleomycin, autologous blood patch, iodopovidone, piciba- À strating a white visceral pleural line on the chest radio- nil, silver nitrate, and quinacrine.27 31 In a survey from five graph. Inspiratory and expiratory films have equal English-speaking countries (United States, United Kingdom, sensitivity in detecting pneumothoraces; thus, a standard Canada, Australia, and New Zealand), the most commonly inspiratory chest radiograph is sufficient in most cases. used agent was talc followed by tetracycline derivatives The percentage of collapsed lung can be estimated using and bleomycin.32 a plain chest film by the measurement of the average diameter of the collapsed lung and the involved hemithorax (Light’s formula).22 Chemical pleurodesis for persistent air leakage Although chest CT scans can reveal the underlying after chest drainage pathophysiologic lesions that cause spontaneous pneumothorax and can be regarded as the “gold standard” in the Persistent air leakage is defined as air leakage more than detection of small pneumothoraces and in size estima- 5e7 days after intercostal drainage, which are more com- tion,23,24 the American Collage of Chest Physicians (ACCP) mon with secondary pneumothorax than with primary does not recommend the routine use of this imaging tech- pneumothorax.33À35 For patients with persistent air nique for patients with first-time primary or secondary leakage, physicians must consider surgical intervention to pneumothoraces.21 CT may, however, be useful for evalu- prevent prolonged hospitalization and the possibility of a ating patients with recurrent secondary pneumothorax, to recurrent pneumothorax.4,19,21 VATS has been advocated in determine the best treatment for persistent air leakage, or the management of patients with PSP and the selection of to plan a surgical intervention.25 The British Thoracic So- patients with SSP who suffer from persistent air ciety (BTS) recommends using CT when required to leakage.33,36À39 For patient has objective evidence of Chemical pleurodesis for pneumothorax 751 inoperable condition, chemical pleurodesis is a reasonable mentioned.35,53À55 Recently, How et al55 reported that option. chemical pleurodesis using OK-432 or minocycline were In 1994, Alfageme et al40 reported that the intrapleural effective to cease air leakage for patients of PSP with instillation of tetracycline has 60% of success rate among prolonged air leakage after thoracoscopic surgery. spontaneous pneumothorax patients with persistent air Furthermore, patients undergoing OK-432 pleurodesis leakage. Cagirici et al41 in 1998 conducted a prospective seems to be more effective by having shorter durations of randomized study to examine the efficacy of autologous post pleurodesis chest drainage and postoperative hospital blood patch pleurodesis when compared with tube thor- stay than those undergoing minocycline pleurodesis.55 acostomy alone. Air leakage resolution occurred in 84% of patients within 72 hours and was significantly reduced when Sclerosing agents for chemical pleurodesis compared with tube thoracostomy alone. Talc Chemical pleurodesis for preventing pneumothorax recurrence At the present time, talc is one of the agents most commonly used for chemical pleurodesis in patients with One of the most important issues of managing spontaneous either a spontaneous pneumothorax or a recurrent pleural pneumothorax is to prevent pneumothorax recurrence. The effusion, even though the occasional reports of severe side 32,56 1-year recurrence rate in PSP patients with the first episode effects. There are at least 32 cases of adult respiratory using chest tube drainage is around 30% (16e52%) and pro- failure syndrome (ARDS) following intrapleural talc admin- gressively increases after the second or third episode.19,42 istration in the literature, 17 following the use of talc 56e58 Although chemical pleurodesis effectively reduces the slurry, and the remaining 15 following talc insufflation. recurrence of spontaneous pneumothorax in surgical and The development of ARDS after talc pleurodesis was nonsurgical patients,22,43À45 published guidelines do not later found to be related to the size of the particles as well recommend it as the initial treatment for primary sponta- as the employed doses. In a multicentre prospective study 59 neous pneumothorax.4,19À21 conducted by Bridevaux et al, including 418 patients In a recent published clinical trial, Chen et al46 ran- diagnosed with spontaneous pneumothorax, neither ARDS domized patients with the first episode of PSP to simple nor pneumonitis cases were reported using low doses of talc m aspiration/drainage only (control, n Z 108) or simple (2 g) and medium-sized particles (31.5 m). aspiration/drainage and minocycline pleurodesis (n Z 106). Empyema is also reported after talc pleurodesis, which After a follow-up for at least 12 months, pneumothorax may be related to techniques used for the sterilization of 60,61 recurrence was lower in the minocycline group (29.2%) talc. The other concern regarding the potential effect compared with controls (49.1%), which led to fewer sub- of long-term pulmonary function by talc pleurodesis on sequent surgical interventions.46 Autologous blood patch young pneumothorax patients has been addressed. 28 pleurodesis maybe also effective to prevent pneumothorax Although Lange et al showed only a mild restrictive res- e recurrence. The pneumothorax recurrence rate following piratory impairment at a follow-up of 22 35 years, Dubois 53 autologous blood patch pleurodesis ranged from 0% to 29%, et al showed that thoracoscopic apical bullectomy and in comparison with tube thoracostomy alone 35e41%.47À49 talc poudrage would cause changes in pulmonary function Although surgical treatment is the most effective way in at 1 year. treating spontaneous pneumothorax, 5e15% of patients Another important concern in patients undergoing talc developed pneumothorax recurrence after thoracoscopic pleurodesis is the possibility of false positives in the inter- surgery, which is significantly higher compared with thora- pretation of fluorine 18 (18 F) flurorodeoxyglucose (FDG) due cotomy (0e1%).4,44,50,51 The possible explanations have to a high capitation of FDG in the acute and chronic phases of included inadequate exposure of chest cavity and pleural inflammation, leading to pleural symphysis or the decreased severity of pleural inflammation caused by appearance of pleural pseudotumoral granulomatous (tal- thoracoscopy than by thoracotomy.36,44 Loubani et al52 re- coma) or pseudosarcomatous reactions, similar to primary ported significant reduced rates of pneumothorax recur- malignant tumoral or metastatic lesions with increased rence in patients who underwent thoracoscopic staple metabolic activity as reported by the positron emission 62 bullectomy alone (20%) against those who received bul- tomography-computed tomography (PET-CT). lectomy and tetracycline pleurodesis (4%). Similar result was also reported by Chen et al43,44 that additional mino- Tetracycline and minocycline cycline pleurodesis after thoracoscopic surgery had lower pneumothorax recurrence compared with thoracoscopic Tetracycline, which was the most commonly used irritant,22 surgery alone. is no longer available. Minocycline, a derivative of tetracycline, is as effective as tetracycline in inducing pleural fibrosis in rabbits.63 No major complication or mortality was Chemical pleurodesis for postoperative air associated with chemical pleurodesis using minocycline. leakage after surgery for pneumothorax The main disadvantage of minocycline is immediate chest pain after instillation, which is relieved spontaneously Prolonged air leakage is the most common complication, within several hours and does not impair pulmonary func- range from 7% to 14%, following thoracoscopic treatment tion or increase the risk of residual chest pain 6 months for PSP, and the optimal management is rarely after the operation.43,44 752 C.-H. How et al.

Bleomycin most authors emphasized that no major complication was observed.49 Other possible complications of autologous Bleomycin was widely used for the treatment of malignant blood patch pleurodesis have included empyema and 41 pleural effusions because of its antineoplastic actions and pleural effusions. However, a reported case of tension because it appeared comparable in effectiveness to tetra- pneumothorax highlights the potential risk for an 68 cycline in the treatment of malignant pleural effusions.64,65 obstructing clot in the chest tube. In an animal study, Vargas et al64 revealed that the intrapleural injection of bleomycin was ineffective in creating OK-432 (Picibanil) pleural fibrosis, either grossly or microscopically. As bleomycin is expensive and relatively ineffective compared 31 OK-432 (Picibanil ), a lyophilized mixture of a low virulence with other sclerosing agents, it is not recommended be strain (Su) of Streptococcus pyogenes incubated with ben- used as a pleural sclerosant in patients with non-neoplastic zylpenicillin, has been used in sclerotherapy for neck lym- pleural disease, such as pneumothorax, congestive heart 64 phangioma, malignant pleural effusion, and intractable failure, or liver cirrhosis. pneumothorax with satisfactory results.69À71 No major complication of pleurodesis using picibanil was reported. Autologous blood patch The main side effects of the pleurodesis with picibanil were fever and chest pain, which were well controlled by nonsteroidal anti-inflammatory drugs.55,69 In contrast to other chemical irritants for pleurodesis such as talc or tetracycline, autologous blood patch does not cause systemic inflammatory reactions or severe pain. The Iodopovidone procedure of pleurodesis with autologous blood was as following: 50 mL of autologous blood without anticoagulant Iodopovidone is a topical antiseptic and has been shown to was obtained from each patient. As soon as the blood was be safe and effective in several studies.30,31,72 A solution drawn, it was immediately injected into the pleural space containing a mixture of 20-mL 10% iodopovidone and 80-mL through a chest tube.66 Although transient fever may normal saline was used to create pleurodesis. Iodopovidone develop following autologous blood patch pleurodesis,48,67 pleurodesis is generally safe. The most common side effect

Table 1 Indications, effects, and complications of chemical pleurodesis for spontaneous pneumothorax. Sclerosing agent Indications Effect Side effects and complications Talc28,30,45,53,58e61,74,75 Initial treatment for PSP Decreased pneumothorax Chest pain (7e15.6%), fever and SSP recurrence to 0e9% (1.6e63.2%), dyspnea (57.9%), pleural effusion (1.2%), pneumonia (0.5e0.9%), hemothorax (0.9%), and ARDS (0e9%) Autologous blood Initial treatment for PSP Ceasing air leakage in Empyema (5e9.4%), pleural patch29,34,41,47e49,66e68 and SSP 75e93% effusion (5e15.6%), and fever Decreased pneumothorax (10e12.5%) recurrence to 0e29% after VATS Tetracycline22,27,40,76 Initial treatment for PSP Decreased pneumothorax Chest pain (33e90%), fever and SSP recurrence to 9e25% (9e81%), dyspnea (36%), and elevated liver enzyme (45%) Minocycline55 Prolonged air leakage for Ceasing air leakage in 63% Chest pain, fever (1%), and PSP after VATS loculated effusion (1.7%) Minocycline11,46 Initial treatment for PSP Decreased pneumothorax Chest pain (67%) recurrence to 13e29% Minocycline43,44,77 Adjuvant treatment for Decreased pneumothorax Chest pain (44.6e83.5%), fever PSP after VATS recurrence to 2e4% (4.1%), and hemothorax (0.6%) Povidone-iodine30,72,73 Initial treatment for PSP Decreased pneumothorax Chest pain (13%), fever and SSP recurrence to 0e6% (6.1e33%), empyema, and wound infection (2.4%) Picibanil55,69 Adjuvant treatment for Ceasing air leakage in 95% Chest pain and fever (21%) PSP after VATS and decreased and initial treatment for pneumothorax recurrence SSP to 5% after VATS

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