Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Mechanical or chemical and mechanical pleurodesis for spontaneous pneumothorax: what is the most effective approach in preventing recurrence? A systematic review and meta-analysis

Mechanical or chemical and mechanical pleurodesis for spontaneous pneumothorax: what is the most... Abstract Open in new tabDownload slide Open in new tabDownload slide OBJECTIVES Surgical management of spontaneous pneumothorax typically involves wedge resection and mechanical pleurodesis. It is unclear whether combining mechanical and chemical pleurodesis can further reduce the recurrence rate. We have performed a meta-analysis of studies comparing the combined approach with mechanical pleurodesis alone. METHODS A comprehensive search of the existing literature was performed using PubMed, EMBASE and Web of Science for all types of studies that compared combined pleurodesis to a single approach. We used the Cochrane Risk of Bias Tool and Strengthening The Reporting of OBservational Studies in Epidemiology (STROBE) to assess the quality of the studies. Relative risk of pneumothorax recurrence was calculated, and the differences between the studies were examined. The primary outcome was the recurrence of pneumothorax. RESULTS Of 2301 eligible studies, 5 studies were included. Five hundred sixty-one patients who received combined pleurodesis were compared to 286 patients who received mechanical pleurodesis only. Patients treated with combined intervention had a 63% lower risk of developing a recurrent pneumothorax compared to single intervention [relative risk 0.37, 95% confidence interval (CI) 0.18–0.76; P = 0.006]. There were no statistically significant differences in the length of stay (standardized mean difference −0.17, 95% CI −0.39 to 0.05, P = 0.138), the duration of postoperative air leak (standardized mean difference 0.17, 95% CI −1.14 to 1.47, P = 0.804) or the duration of postoperative chest tube drainage (standardized mean difference −0.07, 95% CI −0.27 to 0.12, P = 0.471). CONCLUSIONS This meta-analysis demonstrated that combined intervention with mechanical and chemical pleurodesis for spontaneous pneumothorax may be more effective in preventing recurrence than mechanical pleurodesis alone. These findings will provide some guidance to surgeons in the decision-making process. Pneumothorax, Mechanical, Chemical, Pleurodesis INTRODUCTION Spontaneous pneumothorax (SP) is one of the most common clinical conditions that thoracic surgeons encounter. It is more commonly seen in men compared to women with an incidence rate of 7.4 and 1.2 per 100 000 annually in the USA, respectively [1]. Based on the presence or absence of a clinically recognized underlying lung disease, thoracic literature classifies SP into primary SP (PSP) or secondary SP (SSP). An overall estimated recurrence rate of 32% (29% at 1 year) was reported in a systematic review that included 29 studies and 13 548 patients with PSP who were managed with non-operatively (pleural aspiration or chest drainage) [2]. One of the challenges in managing patients with SP (PSP or SSP) is preventing recurrence, which can be as high as 54% in the first 12 months with non-operative management [3]. With intervention, however, recurrence rate varies in the literature and ranges from 8% to 56% with needle aspiration, intercostal drainage and surgical intervention [2]. Although there are multiple risk factors for the recurrence of pneumothorax such as female gender, smoking status, body weight and some radiographic characteristics, the recurrence rate largely depends on the type of pneumothorax (a higher rates occur with SSP) and the episode number (first episode or recurrent pneumothorax in the ipsilateral or contralateral chest) [4, 5]. Whether to intervene on SP and the type of intervention chosen are areas of controversy. The British Thoracic Society guidelines recommend non-operative management for those with first episode pneumothorax while the American College of Chest Physicians are in favour of more aggressive interventions to alleviate symptoms and to prevent recurrence [3, 6]. Several intervention approaches have been tried and described including needle aspiration, chest tube placement, chemical pleurodesis and mechanical pleurodesis. In 1 systematic review and meta-analysis that examined the efficacy of all available intervention strategies for PSP management, chemical pleurodesis was found to be superior in reducing the recurrence rate compared to aspiration or chest tube drainage [7]. Among patients with persistent or recurrent pneumothorax, the study also found that thoracotomy with mechanical pleurodesis has better results in preventing recurrence compared to video-assisted thoracoscopy (VATS) with or without pleurodesis [7]. A pooled estimate of the effect of chemical pleurodesis alone (talc, tetracycline, minocycline and autologous blood patch) on pneumothorax recurrence found a recurrence rate that had ranges of 2.5–10% (talc poudrage via medical thoracoscopy or VATS), 3–30% (tetracycline through chest drain) and 15.6–18.2% (blood patch through chest drain). Although it was not statistically significant, adding talc during VATS resulted in extremely low recurrence rate (0.0–3.2%) [8]. Mechanical pleurodesis alone in preventing recurrence (pleural abrasion or pleurectomy) was extensively examined with a recurrence rate that ranges from 2% to 3.6% [9, 10]. The combined approach, mechanical and chemical pleurodeses, has been shown to have a better outcome in preventing recurrence when compared in single intervention in some randomized control trials (RCTs) and observational studies [11–16]. However, to our knowledge, there has been no systematic review that compared both intervention approaches. Therefore, we hypothesize that combining mechanical and chemical pleurodeses would result in a better outcome in preventing pneumothorax recurrence. Our goal in this systematic review is to determine which approach, single intervention (mechanical) or a combined intervention (mechanical and chemical), is more effective in preventing pneumothorax recurrence. Furthermore, we sought to identify differences in clinical outcomes such as length of stay (LOS), postoperative air leak and duration of chest tube drainage between the 2 approaches that can guide healthcare providers in the decision-making process when treating patients with SP. PATIENTS AND METHODS Search strategy and study selection In collaboration with the University of California San Francisco Library, we conducted a comprehensive review of the existing literature using the following electronic search databases: PubMed, EMBASE and Web of Science until 31 May 2019. The following search terms were used in the PubMed search (‘Pneumothorax’ [Mesh] OR pneumothorax) AND (‘Pleurodesis’ [Mesh] OR ‘mechanical pleurodesis’ OR ‘mechanical abrasion’ OR ‘chemical pleurodesis’ OR talc pleurodesis OR tetracycline pleurodesis OR minocycline pleurodesis OR iodopovidone pleurodesis OR blood pleurodesis OR bleomycin pleurodesis OR doxycycline pleurodesis OR iodine pleurodesis). Titles, abstracts and sometimes published manuscripts were searched for these terms. We searched EMBASE and Web of Science using the same criteria. We also manually identified additional relevant articles by reviewing the references of all the included studies and any systematic reviews or meta-analyses. Only studies that were published in the English language were included with no race, gender or geographic restrictions applied. Duplicate studies were removed from the final list of studies reviewed using EndNote. Two independent reviewers (A.A. and S.S.R.) screened all identified titles, abstracts and full articles if needed. In case of any disagreement between the 2 reviewers, the senior author (B.W.) was consulted to resolve the discrepancy. This review was conducted in compliance with preferred reporting items for systematic reviews and meta-analyses statement recommendations. Eligibility criteria All study designs (RCTs, prospective and retrospective cohort studies, case–control studies and case series) with a sample size of 10 patients or more were considered eligible. We included all types of SP including PSP or SSP and first episode or recurrent episode. All approaches of mechanical pleurodesis, open thoracotomy or VATS were considered. Regarding chemical pleurodesis, any chemical agents that were used in the pleurodesis process such as ‘talc’, ‘tetracycline’, ‘minocycline’, ‘iodopovidone’, ‘blood’ or ‘dextrose’ were included regardless of the approach of installing the chemical agent (chest tube, drainage catheter or VATS). However, studies with insufficient data on the chemical agents were excluded. Only those studies that compare the effect of combined intervention (mechanical and chemical) to a single intervention (mechanical or chemical) were included. Studies with no comparison group or with combined intervention alone were excluded. Wedge resection and/or bullectomy in addition to any of the interventions were not considered an exclusion criterion. In addition, studies were excluded if they did not include human subjects, had a population that was younger than 18 years and had no data on long-term follow-up, or pleurodesis was done for pathologies other than SP such as pleural effusion or postoperative air leak. We did not give any consideration to chest tube size or type (straight or coiled end). Quality assessment Similar to search strategy and data extraction, the 2 reviewers (A.A. and S.S.R.) assessed each study quality and risk of bias. For RCTs, we used Cochrane Risk of Bias tool (RoB2 [17] that assesses 5 main domains for RCTs, randomization process, deviations from intended intervention, missing outcome data, measurement of the outcome and selection of the reported result). Based on the result of each domain, the final risk of bias for each RCT is either low, somehow concerning, or high. We used the STROBE system for observation studies, and each element of the STROBE system (22 elements) system was given a score of 1. The total score of each study was summarized in a quality table. Data abstraction We created a spreadsheet with extracted data by each reviewer. Two reviewers independently examined each article and extracted the following data: study setting, design, year of publication, leading author name, publication date and study geographic region. Moreover, data on study participants, number and type of pneumothorax (primary or secondary, first episode or recurrent) were collected when available. Type of mechanical pleurodesis (open versus VATS), type of chemical agents, as well as our primary outcome, recurrence of pneumothorax, time to recurrence, duration of follow-up (months), postoperative LOS (days) and chest tube drainage (days) were also collected. Furthermore, we collected data on postoperative complications (chest pain and perioperative bleeding) as well as side effects or complications of chemical agents. Our primary exposure of interest was combined mechanical and chemical pleurodesis compared to either mechanical or chemical pleurodesis alone. Any discrepancies between the 2 reviewers were resolved by consulting the senior author (B.W.). Statistical analysis To assess the effectiveness of combined intervention (mechanical and chemical pleurodesis) on the recurrence rate of pneumothorax, the study effect sizes were calculated in frequencies and percentage for the outcome of interest, rates of recurrence of pneumothorax. This was done across the studies for each treatment group. We used a random-effect model for crude data. Data were entered and analysed using Meta-analysis package (metan command) in a STATA 2015 TX version. To calculate the relative risk (RR) of pneumothorax recurrence, events and total sample size for each group within a study were converted to proportions with associated 95% confidence intervals (CIs). To examine the differences between the studies (statistical heterogeneity), we used Cochran Q χ2 test. In addition, we conducted sensitivity analysis by removing the study/studies that had the highest influence on the meta-analysis. For secondary outcomes [continuous variables LOS, chest tube drainage (days) and air leak (>5 days)], we calculated the standardized mean difference (SMD) with 95% CI among studies. RESULTS Search result and study selection Our initial comprehensive search revealed a total of 3402 studies (PubMed 724, Web of Science 595 and EMBASE 2083), of which 2301 were included for the review of titles and abstracts after excluding the duplicates (1101) using EndNote (Fig. 1). No further studies were identified by manually searching the references of the included studies or available systematic reviews and meta-analyses. A total of 2301 studies seemed eligible for inclusion. Of those, 9 were selected for manuscript review. Figure 1 illustrates the excluded articles. From this group, 4 studies were excluded. One study did not report outcomes, and 3 included only a single intervention and did not have a comparative group (Fig. 1). Of the 5 studies that were included, all patients received combined pleurodesis (mechanical and chemical) and were compared to mechanical pleurodesis except for 1 study that had 3 groups, mechanical alone, mechanical combined with 1 chemical agent and single intervention with 2 chemical agents (Chung et al.) [14]. Figure 1: Open in new tabDownload slide Flow diagram of the included and excluded studies in this meta-analysis. Figure 1: Open in new tabDownload slide Flow diagram of the included and excluded studies in this meta-analysis. Study characteristics Of the 5 studies included, 3 were RCTs and 2 were retrospective cohort studies. The combined group, chemical and mechanical pleurodeses, had a total of 561 patients with per-study range 16–313, compared with 286 patients in the mechanical group and per-study range 6–99 (Table 1). In most of the studies, the VATS approach was utilized more frequently than open thoracotomy (Table 1). Pleural abrasion was performed with or without pleurectomy while in some studies, bleb resection was done in addition to the pleurodesis (Table 1). Chemical agents used in the combined intervention group included tetracycline, talc, minocycline and dextrose. Different doses and methods of applying the chemical agents into the chest were used. In all studies, although there were no major complications related to the chemical agents reported, a higher rates of chest pain and higher doses of narcotics were required by patients who received chemical pleurodesis (Table 2). Chung et al. reported an RCT that compared 3 types of interventions, blebectomy and abrasion, dextrose and pleural abrasion and dextrose plus talc chemical abrasion without any mechanical pleural abrasion [14]. From this study, only the first group (single intervention) and the second group (combined intervention) were included in this meta-analysis. We excluded the third group because of the combination of 2 chemical agents. None of the 5 studies had chemical agent as a single intervention and, therefore, in our final analysis, single intervention was mechanical pleurodesis. Regarding the type of pneumothorax, 4 studies included patients with PSP, 1 study included patients with SSP only and 1 study included patients with both PSP and SSP. In terms of first episode versus recurrence pneumothorax, only a few studies have reported the type of pneumothorax being treated (see Table 1. The mean follow-up postoperative time was 25 months with a range from 1 to 56 months (Table 2). Table 1: Studies characteristics and types of intervention, combined (mechanical and chemical) and the single intervention (mechanical intervention) Author . Year . Location . Design . Type of pneumothorax . First episode versus recurrence . Total patients . Combined intervention/ recurrence . Single intervention/ recurrence . Mechanical pleurodesis . Chemical agent . Jin-Shing Chen 2004 Taiwan Retrospective Primary First episode and recurrence 364 313 51 VATS pleurodesis + blebectomy Minocycline Arife Zeybek 2013 Iran Retrospective Primary and secondary 55, 1st episode and 24, 2nd and 3rd episode 22 16 6 VATS pleurodesis + blebectomy Tetracycline/talc Jin-Shing Chen 2012 Taiwan RCT Primary High recurrence risk 160 80 80 VATS pleurectomy or pleural abrasion Minocycline Won Jae Chung 2008 Korea RCT Primary Not reported 99 49 50 VATS pleurodesis and blebectomy 20% dextrose Jin-Shing Chen 2006 Taiwan RCT Primary First episode and recurrence 202 103 99 VATS pleurodesis and blebectomy Minocycline Author . Year . Location . Design . Type of pneumothorax . First episode versus recurrence . Total patients . Combined intervention/ recurrence . Single intervention/ recurrence . Mechanical pleurodesis . Chemical agent . Jin-Shing Chen 2004 Taiwan Retrospective Primary First episode and recurrence 364 313 51 VATS pleurodesis + blebectomy Minocycline Arife Zeybek 2013 Iran Retrospective Primary and secondary 55, 1st episode and 24, 2nd and 3rd episode 22 16 6 VATS pleurodesis + blebectomy Tetracycline/talc Jin-Shing Chen 2012 Taiwan RCT Primary High recurrence risk 160 80 80 VATS pleurectomy or pleural abrasion Minocycline Won Jae Chung 2008 Korea RCT Primary Not reported 99 49 50 VATS pleurodesis and blebectomy 20% dextrose Jin-Shing Chen 2006 Taiwan RCT Primary First episode and recurrence 202 103 99 VATS pleurodesis and blebectomy Minocycline RCT: randomized control trials, VATS: video-assisted thoracoscopy. Open in new tab Table 1: Studies characteristics and types of intervention, combined (mechanical and chemical) and the single intervention (mechanical intervention) Author . Year . Location . Design . Type of pneumothorax . First episode versus recurrence . Total patients . Combined intervention/ recurrence . Single intervention/ recurrence . Mechanical pleurodesis . Chemical agent . Jin-Shing Chen 2004 Taiwan Retrospective Primary First episode and recurrence 364 313 51 VATS pleurodesis + blebectomy Minocycline Arife Zeybek 2013 Iran Retrospective Primary and secondary 55, 1st episode and 24, 2nd and 3rd episode 22 16 6 VATS pleurodesis + blebectomy Tetracycline/talc Jin-Shing Chen 2012 Taiwan RCT Primary High recurrence risk 160 80 80 VATS pleurectomy or pleural abrasion Minocycline Won Jae Chung 2008 Korea RCT Primary Not reported 99 49 50 VATS pleurodesis and blebectomy 20% dextrose Jin-Shing Chen 2006 Taiwan RCT Primary First episode and recurrence 202 103 99 VATS pleurodesis and blebectomy Minocycline Author . Year . Location . Design . Type of pneumothorax . First episode versus recurrence . Total patients . Combined intervention/ recurrence . Single intervention/ recurrence . Mechanical pleurodesis . Chemical agent . Jin-Shing Chen 2004 Taiwan Retrospective Primary First episode and recurrence 364 313 51 VATS pleurodesis + blebectomy Minocycline Arife Zeybek 2013 Iran Retrospective Primary and secondary 55, 1st episode and 24, 2nd and 3rd episode 22 16 6 VATS pleurodesis + blebectomy Tetracycline/talc Jin-Shing Chen 2012 Taiwan RCT Primary High recurrence risk 160 80 80 VATS pleurectomy or pleural abrasion Minocycline Won Jae Chung 2008 Korea RCT Primary Not reported 99 49 50 VATS pleurodesis and blebectomy 20% dextrose Jin-Shing Chen 2006 Taiwan RCT Primary First episode and recurrence 202 103 99 VATS pleurodesis and blebectomy Minocycline RCT: randomized control trials, VATS: video-assisted thoracoscopy. Open in new tab Table 2: Shows the summary of studies primary outcomes, recurrence of pneumothorax and secondary outcomes of both types of intervention Author . Intervention . Total . Recurrence . Time to recurrence (month) . Follow-up in months (range/mean) . LOS (days) . Air leak (>5 days) . Chest drainage (days) . Pre/post bleeding . Other complications . Comments . Jin-Shing Chen 2004 Combined 313 9 17.7 mean 1–120/39 5.8 ± 3.7 22 ± 7 4.2 ± 2.9 2 No Single 51 5 6.4 mean 7.7 ± 3.2 9 ± 18 5.2 ± 2.6 0 Chest pain Arife Zeybek 2013 Combined 16 0 NA 12–36 (18) 8.4 ± 5.9 NR NR NR No One mortality Single 6 0 NA 8.4 ± 5.9 NR NR NR No Jin-Shing Chen 2012 Combined 80 3 9.5 (0.6–22) 12–50 (26.9) 3.6 ± 1.3 2 ± 2.5 2.6 ± 1.2 0 Chest pain requires more analgesia Single 80 3 8.5 (0.6–24) 12–51 (25.5) 3.6 ± 1.2 2 ± 2.5 2.5 ± 1.1 3 Won Jae Chung 2008 Combined 49 1 NR 23.65 ± 2.5 SD 4.49 ± 2.10 NR 2.95 ± 2.31 No Postoperative fever Single 50 3 NR 20.22 ± 9.7 SD 4.50 ± 1.85 NR 2.96 ± 1.56 No Jin-Shing Chen 2006 Combined 103 2 NR 14–47 (28 median) 4.0 ± 1.6 2 ± 1.9 3 ± ± 1.2 No Chest pain requires more analgesia Single 99 8 NR 12–47 (30 median) 4.3 ± 2.8 6 ± 6.1 3 ± 2.6 No Author . Intervention . Total . Recurrence . Time to recurrence (month) . Follow-up in months (range/mean) . LOS (days) . Air leak (>5 days) . Chest drainage (days) . Pre/post bleeding . Other complications . Comments . Jin-Shing Chen 2004 Combined 313 9 17.7 mean 1–120/39 5.8 ± 3.7 22 ± 7 4.2 ± 2.9 2 No Single 51 5 6.4 mean 7.7 ± 3.2 9 ± 18 5.2 ± 2.6 0 Chest pain Arife Zeybek 2013 Combined 16 0 NA 12–36 (18) 8.4 ± 5.9 NR NR NR No One mortality Single 6 0 NA 8.4 ± 5.9 NR NR NR No Jin-Shing Chen 2012 Combined 80 3 9.5 (0.6–22) 12–50 (26.9) 3.6 ± 1.3 2 ± 2.5 2.6 ± 1.2 0 Chest pain requires more analgesia Single 80 3 8.5 (0.6–24) 12–51 (25.5) 3.6 ± 1.2 2 ± 2.5 2.5 ± 1.1 3 Won Jae Chung 2008 Combined 49 1 NR 23.65 ± 2.5 SD 4.49 ± 2.10 NR 2.95 ± 2.31 No Postoperative fever Single 50 3 NR 20.22 ± 9.7 SD 4.50 ± 1.85 NR 2.96 ± 1.56 No Jin-Shing Chen 2006 Combined 103 2 NR 14–47 (28 median) 4.0 ± 1.6 2 ± 1.9 3 ± ± 1.2 No Chest pain requires more analgesia Single 99 8 NR 12–47 (30 median) 4.3 ± 2.8 6 ± 6.1 3 ± 2.6 No LOS: length of stay; NA: not applicable; NR: not reported. Open in new tab Table 2: Shows the summary of studies primary outcomes, recurrence of pneumothorax and secondary outcomes of both types of intervention Author . Intervention . Total . Recurrence . Time to recurrence (month) . Follow-up in months (range/mean) . LOS (days) . Air leak (>5 days) . Chest drainage (days) . Pre/post bleeding . Other complications . Comments . Jin-Shing Chen 2004 Combined 313 9 17.7 mean 1–120/39 5.8 ± 3.7 22 ± 7 4.2 ± 2.9 2 No Single 51 5 6.4 mean 7.7 ± 3.2 9 ± 18 5.2 ± 2.6 0 Chest pain Arife Zeybek 2013 Combined 16 0 NA 12–36 (18) 8.4 ± 5.9 NR NR NR No One mortality Single 6 0 NA 8.4 ± 5.9 NR NR NR No Jin-Shing Chen 2012 Combined 80 3 9.5 (0.6–22) 12–50 (26.9) 3.6 ± 1.3 2 ± 2.5 2.6 ± 1.2 0 Chest pain requires more analgesia Single 80 3 8.5 (0.6–24) 12–51 (25.5) 3.6 ± 1.2 2 ± 2.5 2.5 ± 1.1 3 Won Jae Chung 2008 Combined 49 1 NR 23.65 ± 2.5 SD 4.49 ± 2.10 NR 2.95 ± 2.31 No Postoperative fever Single 50 3 NR 20.22 ± 9.7 SD 4.50 ± 1.85 NR 2.96 ± 1.56 No Jin-Shing Chen 2006 Combined 103 2 NR 14–47 (28 median) 4.0 ± 1.6 2 ± 1.9 3 ± ± 1.2 No Chest pain requires more analgesia Single 99 8 NR 12–47 (30 median) 4.3 ± 2.8 6 ± 6.1 3 ± 2.6 No Author . Intervention . Total . Recurrence . Time to recurrence (month) . Follow-up in months (range/mean) . LOS (days) . Air leak (>5 days) . Chest drainage (days) . Pre/post bleeding . Other complications . Comments . Jin-Shing Chen 2004 Combined 313 9 17.7 mean 1–120/39 5.8 ± 3.7 22 ± 7 4.2 ± 2.9 2 No Single 51 5 6.4 mean 7.7 ± 3.2 9 ± 18 5.2 ± 2.6 0 Chest pain Arife Zeybek 2013 Combined 16 0 NA 12–36 (18) 8.4 ± 5.9 NR NR NR No One mortality Single 6 0 NA 8.4 ± 5.9 NR NR NR No Jin-Shing Chen 2012 Combined 80 3 9.5 (0.6–22) 12–50 (26.9) 3.6 ± 1.3 2 ± 2.5 2.6 ± 1.2 0 Chest pain requires more analgesia Single 80 3 8.5 (0.6–24) 12–51 (25.5) 3.6 ± 1.2 2 ± 2.5 2.5 ± 1.1 3 Won Jae Chung 2008 Combined 49 1 NR 23.65 ± 2.5 SD 4.49 ± 2.10 NR 2.95 ± 2.31 No Postoperative fever Single 50 3 NR 20.22 ± 9.7 SD 4.50 ± 1.85 NR 2.96 ± 1.56 No Jin-Shing Chen 2006 Combined 103 2 NR 14–47 (28 median) 4.0 ± 1.6 2 ± 1.9 3 ± ± 1.2 No Chest pain requires more analgesia Single 99 8 NR 12–47 (30 median) 4.3 ± 2.8 6 ± 6.1 3 ± 2.6 No LOS: length of stay; NA: not applicable; NR: not reported. Open in new tab Study quality assessment Table 3 demonstrates the STROBE results of the 2 retrospective studies. Of the 22 items recommended, an average score of 17 was observed with a range of 16.83–17.84. Items that were commonly missed or not fully reported in most of the studies were description of any efforts to address potential sources of bias, participants in the result section and addressing the external validity (generalizability) of the study findings (Table 3). One study did not disclose the funding source (Chen 2004) [12]. Overall, the majority of the key items were reported among the 2 retrospective studies (Table 3). For RCTs, using the newly revised Cochrane Risk of Bias tool (RoB2), only 1 study (Chung et al.) had a mark for final risk of bias judgement as some concern [14]. This was mostly due to some concern of risk of bias in the deviations from intended intervention and the randomization process (Fig. 2). The other 2 studies (Chen 2006 and Chen 2012) have low risk of bias in all 5 domains (Fig. 2) [15, 16]. Figure 2: Open in new tabDownload slide (A) Cochrane Risk of Bias Tool (RoB2). (B) Risk of bias summary and quality assessment of included randomized control trials. Figure 2: Open in new tabDownload slide (A) Cochrane Risk of Bias Tool (RoB2). (B) Risk of bias summary and quality assessment of included randomized control trials. Table 3: Quality assessment score for retrospective studies using the STROBE system Author . Year . TA . Ba . O . SD . S . P . V . DS . Bi . SS . QV . SM . P . DD . OD . MR . OA . KR . L . I . G . F . Total . Jin-Shing Chen 2004 1 1 1 1 1 1 0.5 1 0 1 1 1 0.67 1 1 0.67 1 1 1 1 0 0 17.84 Arife Zeybek 2013 1 0.5 1 1 0.5 1 1 0.5 0 0.5 1 1 1 1 1 0.33 0 1 1 1 0.5 1 16.83 Author . Year . TA . Ba . O . SD . S . P . V . DS . Bi . SS . QV . SM . P . DD . OD . MR . OA . KR . L . I . G . F . Total . Jin-Shing Chen 2004 1 1 1 1 1 1 0.5 1 0 1 1 1 0.67 1 1 0.67 1 1 1 1 0 0 17.84 Arife Zeybek 2013 1 0.5 1 1 0.5 1 1 0.5 0 0.5 1 1 1 1 1 0.33 0 1 1 1 0.5 1 16.83 Each element represent 1 point. Ba: background; Bi: bias; DD: descriptive data; DS: data sources; F: funding; G: generalizability; I: interpretation; KR: key results; L: limitation; MR: main results; O: objective; OA: other analysis; OD: outcome data; P: participants; QV: quantitative variables; S: setting; SD: study design; SM: statistical methods; SS: study size; TA: title and abstract; V: variables. Open in new tab Table 3: Quality assessment score for retrospective studies using the STROBE system Author . Year . TA . Ba . O . SD . S . P . V . DS . Bi . SS . QV . SM . P . DD . OD . MR . OA . KR . L . I . G . F . Total . Jin-Shing Chen 2004 1 1 1 1 1 1 0.5 1 0 1 1 1 0.67 1 1 0.67 1 1 1 1 0 0 17.84 Arife Zeybek 2013 1 0.5 1 1 0.5 1 1 0.5 0 0.5 1 1 1 1 1 0.33 0 1 1 1 0.5 1 16.83 Author . Year . TA . Ba . O . SD . S . P . V . DS . Bi . SS . QV . SM . P . DD . OD . MR . OA . KR . L . I . G . F . Total . Jin-Shing Chen 2004 1 1 1 1 1 1 0.5 1 0 1 1 1 0.67 1 1 0.67 1 1 1 1 0 0 17.84 Arife Zeybek 2013 1 0.5 1 1 0.5 1 1 0.5 0 0.5 1 1 1 1 1 0.33 0 1 1 1 0.5 1 16.83 Each element represent 1 point. Ba: background; Bi: bias; DD: descriptive data; DS: data sources; F: funding; G: generalizability; I: interpretation; KR: key results; L: limitation; MR: main results; O: objective; OA: other analysis; OD: outcome data; P: participants; QV: quantitative variables; S: setting; SD: study design; SM: statistical methods; SS: study size; TA: title and abstract; V: variables. Open in new tab Primary outcome: rate of pneumothorax recurrence All studies reported the recurrence rate of each group, combined and single intervention. Of the 5 studies included in this meta-analysis, the pooled RR estimate of recurrence using the random-effect model was 0.37 (95% CI 0.18–0.76, P = 0.006). Patients treated with combined intervention had a 63% lower risk of developing a recurrent pneumothorax compared to those treated with single intervention (mechanical pleurodesis) as shown in Fig. 3. Our results also showed no evidence of heterogeneity among the included studies with the test of heterogeneity of 2.0 and the P-value of 0.564. Only 1 study (Chen 2004) reported their recurrence rate in ˂12 months (Table 2) [12]. We were interested in reporting time to recurrence; however, only 2 studies reported time to recurrence (Chen 2004 and Chen 2012) among their combined and single intervention groups (Table 2) [12, 15]. A shorter time to recurrence was observed among patients treated with mechanical compared to combined pleurodesis: a median of 6.4 vs 17.7 months (Chen et al. 2004) and 8.5 vs 9.5 months (Chen et al. 2012) (Table 1). All studies reported bleb resection in both groups of patients; Chen et al. (2004) reported that the number of blebs was a significant predictor for pneumothorax recurrence [12]. Chen et al. (2004) was also the only study that reported the smoking status among the recurrence group; they did not find it to be a significant predictor for recurrence [12]. Figure 3: Open in new tabDownload slide Forrest plot. The estimated RR of recurrence of spontaneous pneumothorax in the combined versus single intervention using the weight of random model. CI: confidence interval; RR: relative risk. Figure 3: Open in new tabDownload slide Forrest plot. The estimated RR of recurrence of spontaneous pneumothorax in the combined versus single intervention using the weight of random model. CI: confidence interval; RR: relative risk. Sensitivity analysis Because the meta-analysis result showed that the Chen 2004 study has a weight of 37.8% of the total summary, we removed this study from the analysis [12]. The estimated summary of the combined intervention showed a reduction of recurrence risk of 55%. However, this did not reach a significant level (RR 0.45, 95% CI 0.16–1.08; P = 0.110). Secondary outcomes Patients who received mechanical and chemical pleurodeses (combined intervention) experienced more chest pain and required higher doses of narcotic pain medications compared to those who received only mechanical intervention. In terms of postoperative bleeding, in his 2004 publication, Chen et al [12]. reported 2 incidences of postoperative bleeding among the combined intervention versus 0 among the single and 0 (combined intervention) versus 2 (single intervention) in his 2012 publication (Table 2) [15]. There were no statistically significant differences between the combined intervention group and single intervention group in terms of length of hospital stay measured in days (LOS) (SMD −0.17, 95% CI −0.39 to 0.05, P = 0.138 and I = 45.8%) [Fig. 4A, duration of postoperative air leak (number of days after day 5) (SMD 0.17, 95% CI −1.14 to 1.47, P = 0. 804 and I = 98%)] (Fig. 4B), or duration of postoperative chest tube drainage (days) (SMD −0.07, 95% CI −0.27 to 0.12, P = 0.471 and I = 36%) (Fig. 4C). Figure 4: Open in new tabDownload slide (A) The estimated SMD of length of stay between the combined and single intervention. (B) The estimated SMD of air leak between the combined and single intervention. (C) The estimated SMD of chest tube duration/drainage between the combined and single intervention. CI: confidence interval; SD: standard deviation; SMD: standardized mean difference. Figure 4: Open in new tabDownload slide (A) The estimated SMD of length of stay between the combined and single intervention. (B) The estimated SMD of air leak between the combined and single intervention. (C) The estimated SMD of chest tube duration/drainage between the combined and single intervention. CI: confidence interval; SD: standard deviation; SMD: standardized mean difference. DISCUSSION In this systematic review, we summarized the evidence that compared mechanical pleurodesis to combined chemical and mechanical pleurodesis on the recurrence rate of SP. Our meta-analysis of the available RCTs and observational studies showed that adding chemical pleurodesis agents to mechanical pleurodesis resulted in a lower risk of pneumothorax recurrence and shorter length of hospital stay with no statistically significant difference between the 2 types of intervention in terms of air leak and chest tube drainage. However, our results also showed that adding a chemical agent to mechanical pleurodesis comes with an increased rate of postoperative pain, which is mainly attributed to the chemical agent instilled in the chest cavity. The goal of both chemical and mechanical pleurodeses is to achieve pleural symphysis between the visceral and parietal surfaces by irritating the pleural surface through either physical abrasion (mechanical pleurodesis) or chemical agent instillation (chemical pleurodesis), with resultant inflammation of the pleural space. Therefore, the lower risk of recurrence among those who had both types of pleurodesis may be due to the synergistic effect of dual methods used to irritate the pleural space and create a stronger and more lasting inflammatory process. However, this is associated with an increase in chest pain postoperatively. In the current era of advanced techniques in local and regional, anaesthesia, one could argue that postoperative chest pain is outweighed by the reduced risk of recurrence with associated costs for hospitalization and possible intervention. However, a discussion between healthcare providers and patients should occur with regard to the risks and benefits of both interventions. The findings of the current study are consistent with another systematic review by Sudduth et al. who found that a combination of wedge resection + chemical pleurodesis and wedge resection + pleural abrasion + chemical pleurodesis has the lowest recurrence rates of pneumothorax among patients with SP when they compared them to other interventions such as wedge resection alone, wedge resection with pleural abrasion/pleurectomy and other intervention [18]. In contrast to our findings, however, a systematic review by Ling et al. [5] showed no difference in the recurrence rate of pneumothorax (3.8%) between the minocycline pleurodesis combined with pleural abrasion group when compared with apical pleurectomy alone (3.8%). In addition, they found no difference in recurrence rate between pleural abrasion alone and abrasion plus minocycline pleurodesis [5]. In another study, adding talc during VATS procedures for bullectomy, bleb resection or electrocoagulation without pleural abrasion or pleurectomy is associated with extremely low recurrence rate (0.0–3.2%) [8]. Furthermore, in a review of the literature that looked at the difference in effectiveness between chemical and mechanical pleurodesis in terms of pneumothorax recurrence, of the 6 studies that were included, Sepehripour et al. [19] concluded that, although chemical and mechanical pleurodesis have similar outcomes, chemical pleurodesis with talc appears to have a lower rate of recurrence. In a more comprehensive review of all RCTs of any PSP treatment, Vuong et al. found that among patients with first episode of pneumothorax, VATS followed by chemical pleurodesis is the most effective in preventing recurrence. For patients with recurrence or persistent pneumothorax, thoracotomy with mechanical pleurodesis (abrasion or pleurectomy) provided the best results in preventing recurrence [7]. However, this review did not directly compare/comment on the effectiveness of the combined intervention (chemical and mechanical) [7]. In terms of postoperative chest pain, similar to our results, a higher rate of chest pain was observed among patients who received minocycline pleurodesis [5]. Moreover, a review article on chemical pleurodesis showed that almost all chemical agents may cause significant chest pain as an adverse effect, while some patients may even experience fever, pneumonia, effusion and haemothorax [20]. As far as guideline recommendations about SP management and recurrence prevention are concerned, the American College of Chest Physicians recommends intervention after the second episode of PSP with thoracoscopic with mechanical pleurodesis to be the preferred method, given the success rate of 95–100% [6, 21]. Although this guideline states that there is no role of talc poudrage in recurrence prevention of PSP, there was no direct recommendation or comment on the use of the combined, chemical and mechanical pleurodesis. For SSP, surgical intervention is recommended after the first episode, given the increased risk of recurrence compared to PSP [6]. Similarly, the British Thoracic Society recommended a conservative approach for the first episode of PSP with needle aspiration or chest drain based on patient clinical presentation, underlying lung disease and size of pneumothorax [3]. However, they recommend that patients with SSP should be referred to a chest physician or thoracic surgeon for evaluation. Again, surgical intervention is preferred over chemical pleurodesis alone by the British Thoracic Society unless the patient is unfit or unable to undergo surgical intervention [3]. Belgian Society of Pneumology guidelines recommended observation for small and minimally symptomatic PSP and simple aspiration/catheter placement for symptomatic/large PSP. They recommend a more invasive approach (thoracotomy or VATS with pleurectomy, mechanical abrasion or talc poudrage) for persistent air leak, incomplete lung expansion or recurrent pneumothorax (PSP or SSP) [22]. In agreement with the previous 2 guidelines, strong evidence showed that open thoracotomy with total pleurectomy provides the most effective approach in preventing recurrence. However, less invasive procedures such as partial pleurectomy, pleural abrasion and talc poudrage are preferred [22]. The findings of this review and the ability to make a definitive conclusion from the results of this study are limited by several factors. First, although we have used the STROBE system in assessing the quality of the observational studies, this system acts as a check list and does not account for any risk of bias adjustment. Therefore, there is a potential risk of bias in these studies in terms of patient selection, surgeon preference and institutional experience and practice. Second, due to the limited number of studies that met our inclusion criterion, and to synthesize a summary of our result, we have combined observational studies and RCTs. By comparing only RCTs or observational studies, we would have not been able to synthesize such a summary. Third, our analysis included a mixed group of patients with mixed type and number of episodes of pneumothorax and could not evaluate the relative effectiveness of various methods used to perform mechanical pleurodesis (apical pleurectomy, partial or complete parietal pleural abrasion). Nonetheless, this does not change our final conclusion that, if mechanical pleurodesis is chosen, adding a chemical agent may lead to a decreased likelihood of recurrence. Fourth, in our analysis, we considered both pleurectomy and/or pleural abrasion as mechanical pleurodeses. This assumption was based on a meta-analysis review showing that there was no difference in the RR of reoccurrence between the 2 methods of mechanical pleurodesis [23]. Lastly, time to recurrence is another important measure for the effectiveness of an intervention. Unfortunately, from the current data, we were not able to synthesize a statistical summary for 12-month recurrence rate and ˃12 months. However, a recently published (2018) review showed that most recurrence occurs in the first year with 32% of patients with PSP experiencing recurrence [2]. CONCLUSION In this review, our summary showed that combined intervention with mechanical and chemical pleurodesis for SP is more effective in preventing recurrence and is also associated with a shorter hospital stay than mechanical pleurodesis alone. Our results also showed that this combined intervention is associated with higher rates of postoperative chest pain. When managing patients with pneumothorax, there are multiple factors that need to be considered including patients’ preference, age, gender, clinical condition and risk stratification, as well as healthcare provider preference and expertise, institution cultures and local guidelines. Despite this complexity in approaching patients with pneumothorax, we believe that the findings of this review will provide some useful guidance to healthcare providers in the decision-making process. ACKNOWLEDGEMENTS This study is a part of graduation requirements for a master’s degree in Clinical and Translational Research at the University of California San Francisco. We would like to acknowledge and thank the committee members from the University of California San Francisco for providing some insight and feedback on the project design, statistical analysis and manuscript development. The authors thank Quan-Yang Duh, professor, endocrine surgeon and chief of endocrine surgery section; Anne Schafer, associate professor, endocrinologist and epidemiologist; and Peter Bacchetti, professor, epidemiology and biostatistics. Conflict of interest: none declared. Author contributions Ammar Asban: Conceptualization; Data curation; Formal analysis; Writing—original draft. Syed Sikandar Raza: Conceptualization; Data curation. Chandler McLeod: Formal analysis. James Donahue: Writing—review & editing. Benjamin Wei: Writing—review & editing. REFERENCES 1 Light RW. Pleural Diseases . Philadelphia : Lippincott, Williams and Wilkins , 2013 . Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC 2 Walker SP , Bibby AC, Halford P, Stadon L, White P, Maskell NA. Recurrence rates in primary spontaneous pneumothorax: a systematic review and meta-analysis . Eur Respir J 2018 ; 52 : 1800864 . Google Scholar Crossref Search ADS PubMed WorldCat 3 MacDuff A , Arnold A, Harvey J; on behalf of the BTS Pleural Disease Guideline Group. Management of spontaneous pneumothorax: British Thoracic Society Pleural Disease Guideline 2010 . Thorax 2010 ; 65 : ii18 – 31 . Google Scholar Crossref Search ADS PubMed WorldCat 4 Tschopp JM , Bintcliffe O, Astoul P, Canalis E, Driesen P, Janssen J et al. ERS task force statement: diagnosis and treatment of primary spontaneous pneumothorax . Eur Respir J 2015 ; 46 : 321 – 35 . Google Scholar Crossref Search ADS PubMed WorldCat 5 Ling ZG , Wu YB, Ming MY, Cai SQ, Chen YQ. The effect of pleural abrasion on the treatment of primary spontaneous pneumothorax: a systematic review of randomized controlled trials . PLoS One 2015 ; 10 : e0127857 . Google Scholar Crossref Search ADS PubMed WorldCat 6 Baumann MH , Strange C, Heffner JE, Light R, Kirby TJ, Klein J et al. Management of spontaneous pneumothorax—an American College of Chest Physicians Delphi Consensus Statement . Chest 2001 ; 119 : 590 – 602 . Google Scholar Crossref Search ADS PubMed WorldCat 7 Vuong NL , Elshafay A, Thao LP, Abdalla AR, Mohyeldin IA, Elsabaa K et al. Efficacy of treatments in primary spontaneous pneumothorax: a systematic review and network meta-analysis of randomized clinical trials . Respir Med 2018 ; 137 : 152 – 66 . Google Scholar Crossref Search ADS PubMed WorldCat 8 Hallifax RJ , Yousuf A, Jones HE, Corcoran JP, Psallidas I, Rahman NM. Effectiveness of chemical pleurodesis in spontaneous pneumothorax recurrence prevention: a systematic review . Thorax 2017 ; 72 : 1121 – 31 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Gossot D , Galetta D, Stern JB, Debrosse D, Caliandro R, Girard P et al. Results of thoracoscopic pleural abrasion for primary spontaneous pneumothorax . Surg Endosc 2004 ; 18 : 466 – 71 . Google Scholar Crossref Search ADS PubMed WorldCat 10 Lang-Lazdunski L , Chapuis O, Bonnet PM, Pons F, Jancovici R. Videothoracoscopic bleb excision and pleural abrasion for the treatment of primary spontaneous pneumothorax: long-term results . Ann Thorac Surg 2003 ; 75 : 960 – 5 . Google Scholar Crossref Search ADS PubMed WorldCat 11 Tsukioka T , Inoue K, Oka H, Mizuguchi S, Morita R, Nishiyama N. Intraoperative mechanical and chemical pleurodesis with 50% glucose solution for secondary spontaneous pneumothorax in patients with pulmonary emphysema . Surg Today 2013 ; 43 : 889 – 93 . Google Scholar Crossref Search ADS PubMed WorldCat 12 Chen JS , Hsu HH, Kuo SW, Tsai PR, Chen RJ, Lee JM et al. Effects of additional minocycline pleurodesis after thoracoscopic procedures for primary spontaneous pneumothorax . Chest 2004 ; 125 : 50 – 5 . Google Scholar Crossref Search ADS PubMed WorldCat 13 Zeybek A , Kalemci S, Gürünlü Alma Ö, Süzen A, Akgül M, Koç K. The effect of additional pleural procedures onto recurrence rates on the spontaneous pneumothorax surgery . Iran Red Crescent Med J 2013 ; 15 : 136 – 41 . Google Scholar Crossref Search ADS PubMed WorldCat 14 Won JC , Jo WM, Sung HL, Ho SS, Kwang TK. Effects of additional pleurodesis with dextrose and talc-dextrose solution after video assisted thoracoscopic procedures for primary spontaneous pneumothorax . J Korean Med Sci 2008 ; 23 : 284 – 7 . Google Scholar Crossref Search ADS PubMed WorldCat 15 Chen J-S , Hsu H-H, Huang P-M, Kuo S-W, Lin M-W, Chang C-C et al. Thoracoscopic pleurodesis for primary spontaneous pneumothorax with high recurrence risk a prospective randomized trial . Ann Surg 2012 ; 255 : 440 – 5 . Google Scholar Crossref Search ADS PubMed WorldCat 16 Chen JS , Hsu HH, Chen RJ, Kuo SW, Huang PM, Tsai PR et al. Additional minocycline pleurodesis after thoracoscopic surgery for primary spontaneous pneumothorax . Am J Respir Crit Care Med 2006 ; 173 : 548 – 54 . Google Scholar Crossref Search ADS PubMed WorldCat 17 Sterne JAC , Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I et al. RoB 2: a revised tool for assessing risk of bias in randomised trials . BMJ 2019 ; 366 : l4898 . Google Scholar Crossref Search ADS PubMed WorldCat 18 Sudduth CL , Shinnick JK, Geng Z, McCracken CE, Clifton MS, Raval MV. Optimal surgical technique in spontaneous pneumothorax: a systematic review and meta-analysis . J Surg Res 2017 ; 210 : 32 – 46 . Google Scholar Crossref Search ADS PubMed WorldCat 19 Sepehripour AH , Nasir A, Shah R. Does mechanical pleurodesis result in better outcomes than chemical pleurodesis for recurrent primary spontaneous pneumothorax? . Interact CardioVasc Thorac Surg 2012 ; 14 : 307 – 11 . Google Scholar Crossref Search ADS PubMed WorldCat 20 How CH , Hsu HH, Chen JS. Chemical pleurodesis for spontaneous pneumothorax . J Formos Med Assoc 2013 ; 112 : 749 – 55 . Google Scholar Crossref Search ADS PubMed WorldCat 21 Baumann MH , Strange C. Treatment of spontaneous pneumothorax - A more aggressive approach? Chest 1997 ; 112 : 789 – 804 . Google Scholar Crossref Search ADS PubMed WorldCat 22 De Leyn P , Lismonde M, Ninane V, Noppen M, Slabbynck H, Van Meerhaeghe A et al. ; Guidelines Belgian Society of Pneumology. Guidelines on the management of spontaneous pneumothorax . Acta Chir Belg 2005 ; 105 : 265 – 7 . Google Scholar Crossref Search ADS PubMed WorldCat 23 Bille A , Barker A, Maratos EC, Edmonds L, Lim E. Surgical access rather than method of pleurodesis (pleurectomy or pleural abrasion) influences recurrence rates for pneumothorax surgery: systematic review and meta-analysis . Gen Thorac Cardiovasc Surg 2012 ; 60 : 321 – 5 . Google Scholar Crossref Search ADS PubMed WorldCat Abbreviations CI Confidence interval LOS Length of stay PSP Primary spontaneous pneumothorax RCT Randomized control trial RR Relative risk SSP Secondary spontaneous pneumothorax SP Spontaneous pneumothorax VATS Video-assisted thoracoscopy Author notes Accepted for presentation at the General Thoracic Surgical Club 33rd Annual Meeting, Tucson, AZ, USA, 12-15 March 2020. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Cardio-Thoracic Surgery Oxford University Press

Mechanical or chemical and mechanical pleurodesis for spontaneous pneumothorax: what is the most effective approach in preventing recurrence? A systematic review and meta-analysis

Download PDF
10 pages

Loading next page...
 
/lp/oxford-university-press/mechanical-or-chemical-and-mechanical-pleurodesis-for-spontaneous-HoE2ABZWzY

References (24)

Publisher
Oxford University Press
Copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
ISSN
1010-7940
eISSN
1873-734X
DOI
10.1093/ejcts/ezaa130
Publisher site
See Article on Publisher Site

Abstract

Abstract Open in new tabDownload slide Open in new tabDownload slide OBJECTIVES Surgical management of spontaneous pneumothorax typically involves wedge resection and mechanical pleurodesis. It is unclear whether combining mechanical and chemical pleurodesis can further reduce the recurrence rate. We have performed a meta-analysis of studies comparing the combined approach with mechanical pleurodesis alone. METHODS A comprehensive search of the existing literature was performed using PubMed, EMBASE and Web of Science for all types of studies that compared combined pleurodesis to a single approach. We used the Cochrane Risk of Bias Tool and Strengthening The Reporting of OBservational Studies in Epidemiology (STROBE) to assess the quality of the studies. Relative risk of pneumothorax recurrence was calculated, and the differences between the studies were examined. The primary outcome was the recurrence of pneumothorax. RESULTS Of 2301 eligible studies, 5 studies were included. Five hundred sixty-one patients who received combined pleurodesis were compared to 286 patients who received mechanical pleurodesis only. Patients treated with combined intervention had a 63% lower risk of developing a recurrent pneumothorax compared to single intervention [relative risk 0.37, 95% confidence interval (CI) 0.18–0.76; P = 0.006]. There were no statistically significant differences in the length of stay (standardized mean difference −0.17, 95% CI −0.39 to 0.05, P = 0.138), the duration of postoperative air leak (standardized mean difference 0.17, 95% CI −1.14 to 1.47, P = 0.804) or the duration of postoperative chest tube drainage (standardized mean difference −0.07, 95% CI −0.27 to 0.12, P = 0.471). CONCLUSIONS This meta-analysis demonstrated that combined intervention with mechanical and chemical pleurodesis for spontaneous pneumothorax may be more effective in preventing recurrence than mechanical pleurodesis alone. These findings will provide some guidance to surgeons in the decision-making process. Pneumothorax, Mechanical, Chemical, Pleurodesis INTRODUCTION Spontaneous pneumothorax (SP) is one of the most common clinical conditions that thoracic surgeons encounter. It is more commonly seen in men compared to women with an incidence rate of 7.4 and 1.2 per 100 000 annually in the USA, respectively [1]. Based on the presence or absence of a clinically recognized underlying lung disease, thoracic literature classifies SP into primary SP (PSP) or secondary SP (SSP). An overall estimated recurrence rate of 32% (29% at 1 year) was reported in a systematic review that included 29 studies and 13 548 patients with PSP who were managed with non-operatively (pleural aspiration or chest drainage) [2]. One of the challenges in managing patients with SP (PSP or SSP) is preventing recurrence, which can be as high as 54% in the first 12 months with non-operative management [3]. With intervention, however, recurrence rate varies in the literature and ranges from 8% to 56% with needle aspiration, intercostal drainage and surgical intervention [2]. Although there are multiple risk factors for the recurrence of pneumothorax such as female gender, smoking status, body weight and some radiographic characteristics, the recurrence rate largely depends on the type of pneumothorax (a higher rates occur with SSP) and the episode number (first episode or recurrent pneumothorax in the ipsilateral or contralateral chest) [4, 5]. Whether to intervene on SP and the type of intervention chosen are areas of controversy. The British Thoracic Society guidelines recommend non-operative management for those with first episode pneumothorax while the American College of Chest Physicians are in favour of more aggressive interventions to alleviate symptoms and to prevent recurrence [3, 6]. Several intervention approaches have been tried and described including needle aspiration, chest tube placement, chemical pleurodesis and mechanical pleurodesis. In 1 systematic review and meta-analysis that examined the efficacy of all available intervention strategies for PSP management, chemical pleurodesis was found to be superior in reducing the recurrence rate compared to aspiration or chest tube drainage [7]. Among patients with persistent or recurrent pneumothorax, the study also found that thoracotomy with mechanical pleurodesis has better results in preventing recurrence compared to video-assisted thoracoscopy (VATS) with or without pleurodesis [7]. A pooled estimate of the effect of chemical pleurodesis alone (talc, tetracycline, minocycline and autologous blood patch) on pneumothorax recurrence found a recurrence rate that had ranges of 2.5–10% (talc poudrage via medical thoracoscopy or VATS), 3–30% (tetracycline through chest drain) and 15.6–18.2% (blood patch through chest drain). Although it was not statistically significant, adding talc during VATS resulted in extremely low recurrence rate (0.0–3.2%) [8]. Mechanical pleurodesis alone in preventing recurrence (pleural abrasion or pleurectomy) was extensively examined with a recurrence rate that ranges from 2% to 3.6% [9, 10]. The combined approach, mechanical and chemical pleurodeses, has been shown to have a better outcome in preventing recurrence when compared in single intervention in some randomized control trials (RCTs) and observational studies [11–16]. However, to our knowledge, there has been no systematic review that compared both intervention approaches. Therefore, we hypothesize that combining mechanical and chemical pleurodeses would result in a better outcome in preventing pneumothorax recurrence. Our goal in this systematic review is to determine which approach, single intervention (mechanical) or a combined intervention (mechanical and chemical), is more effective in preventing pneumothorax recurrence. Furthermore, we sought to identify differences in clinical outcomes such as length of stay (LOS), postoperative air leak and duration of chest tube drainage between the 2 approaches that can guide healthcare providers in the decision-making process when treating patients with SP. PATIENTS AND METHODS Search strategy and study selection In collaboration with the University of California San Francisco Library, we conducted a comprehensive review of the existing literature using the following electronic search databases: PubMed, EMBASE and Web of Science until 31 May 2019. The following search terms were used in the PubMed search (‘Pneumothorax’ [Mesh] OR pneumothorax) AND (‘Pleurodesis’ [Mesh] OR ‘mechanical pleurodesis’ OR ‘mechanical abrasion’ OR ‘chemical pleurodesis’ OR talc pleurodesis OR tetracycline pleurodesis OR minocycline pleurodesis OR iodopovidone pleurodesis OR blood pleurodesis OR bleomycin pleurodesis OR doxycycline pleurodesis OR iodine pleurodesis). Titles, abstracts and sometimes published manuscripts were searched for these terms. We searched EMBASE and Web of Science using the same criteria. We also manually identified additional relevant articles by reviewing the references of all the included studies and any systematic reviews or meta-analyses. Only studies that were published in the English language were included with no race, gender or geographic restrictions applied. Duplicate studies were removed from the final list of studies reviewed using EndNote. Two independent reviewers (A.A. and S.S.R.) screened all identified titles, abstracts and full articles if needed. In case of any disagreement between the 2 reviewers, the senior author (B.W.) was consulted to resolve the discrepancy. This review was conducted in compliance with preferred reporting items for systematic reviews and meta-analyses statement recommendations. Eligibility criteria All study designs (RCTs, prospective and retrospective cohort studies, case–control studies and case series) with a sample size of 10 patients or more were considered eligible. We included all types of SP including PSP or SSP and first episode or recurrent episode. All approaches of mechanical pleurodesis, open thoracotomy or VATS were considered. Regarding chemical pleurodesis, any chemical agents that were used in the pleurodesis process such as ‘talc’, ‘tetracycline’, ‘minocycline’, ‘iodopovidone’, ‘blood’ or ‘dextrose’ were included regardless of the approach of installing the chemical agent (chest tube, drainage catheter or VATS). However, studies with insufficient data on the chemical agents were excluded. Only those studies that compare the effect of combined intervention (mechanical and chemical) to a single intervention (mechanical or chemical) were included. Studies with no comparison group or with combined intervention alone were excluded. Wedge resection and/or bullectomy in addition to any of the interventions were not considered an exclusion criterion. In addition, studies were excluded if they did not include human subjects, had a population that was younger than 18 years and had no data on long-term follow-up, or pleurodesis was done for pathologies other than SP such as pleural effusion or postoperative air leak. We did not give any consideration to chest tube size or type (straight or coiled end). Quality assessment Similar to search strategy and data extraction, the 2 reviewers (A.A. and S.S.R.) assessed each study quality and risk of bias. For RCTs, we used Cochrane Risk of Bias tool (RoB2 [17] that assesses 5 main domains for RCTs, randomization process, deviations from intended intervention, missing outcome data, measurement of the outcome and selection of the reported result). Based on the result of each domain, the final risk of bias for each RCT is either low, somehow concerning, or high. We used the STROBE system for observation studies, and each element of the STROBE system (22 elements) system was given a score of 1. The total score of each study was summarized in a quality table. Data abstraction We created a spreadsheet with extracted data by each reviewer. Two reviewers independently examined each article and extracted the following data: study setting, design, year of publication, leading author name, publication date and study geographic region. Moreover, data on study participants, number and type of pneumothorax (primary or secondary, first episode or recurrent) were collected when available. Type of mechanical pleurodesis (open versus VATS), type of chemical agents, as well as our primary outcome, recurrence of pneumothorax, time to recurrence, duration of follow-up (months), postoperative LOS (days) and chest tube drainage (days) were also collected. Furthermore, we collected data on postoperative complications (chest pain and perioperative bleeding) as well as side effects or complications of chemical agents. Our primary exposure of interest was combined mechanical and chemical pleurodesis compared to either mechanical or chemical pleurodesis alone. Any discrepancies between the 2 reviewers were resolved by consulting the senior author (B.W.). Statistical analysis To assess the effectiveness of combined intervention (mechanical and chemical pleurodesis) on the recurrence rate of pneumothorax, the study effect sizes were calculated in frequencies and percentage for the outcome of interest, rates of recurrence of pneumothorax. This was done across the studies for each treatment group. We used a random-effect model for crude data. Data were entered and analysed using Meta-analysis package (metan command) in a STATA 2015 TX version. To calculate the relative risk (RR) of pneumothorax recurrence, events and total sample size for each group within a study were converted to proportions with associated 95% confidence intervals (CIs). To examine the differences between the studies (statistical heterogeneity), we used Cochran Q χ2 test. In addition, we conducted sensitivity analysis by removing the study/studies that had the highest influence on the meta-analysis. For secondary outcomes [continuous variables LOS, chest tube drainage (days) and air leak (>5 days)], we calculated the standardized mean difference (SMD) with 95% CI among studies. RESULTS Search result and study selection Our initial comprehensive search revealed a total of 3402 studies (PubMed 724, Web of Science 595 and EMBASE 2083), of which 2301 were included for the review of titles and abstracts after excluding the duplicates (1101) using EndNote (Fig. 1). No further studies were identified by manually searching the references of the included studies or available systematic reviews and meta-analyses. A total of 2301 studies seemed eligible for inclusion. Of those, 9 were selected for manuscript review. Figure 1 illustrates the excluded articles. From this group, 4 studies were excluded. One study did not report outcomes, and 3 included only a single intervention and did not have a comparative group (Fig. 1). Of the 5 studies that were included, all patients received combined pleurodesis (mechanical and chemical) and were compared to mechanical pleurodesis except for 1 study that had 3 groups, mechanical alone, mechanical combined with 1 chemical agent and single intervention with 2 chemical agents (Chung et al.) [14]. Figure 1: Open in new tabDownload slide Flow diagram of the included and excluded studies in this meta-analysis. Figure 1: Open in new tabDownload slide Flow diagram of the included and excluded studies in this meta-analysis. Study characteristics Of the 5 studies included, 3 were RCTs and 2 were retrospective cohort studies. The combined group, chemical and mechanical pleurodeses, had a total of 561 patients with per-study range 16–313, compared with 286 patients in the mechanical group and per-study range 6–99 (Table 1). In most of the studies, the VATS approach was utilized more frequently than open thoracotomy (Table 1). Pleural abrasion was performed with or without pleurectomy while in some studies, bleb resection was done in addition to the pleurodesis (Table 1). Chemical agents used in the combined intervention group included tetracycline, talc, minocycline and dextrose. Different doses and methods of applying the chemical agents into the chest were used. In all studies, although there were no major complications related to the chemical agents reported, a higher rates of chest pain and higher doses of narcotics were required by patients who received chemical pleurodesis (Table 2). Chung et al. reported an RCT that compared 3 types of interventions, blebectomy and abrasion, dextrose and pleural abrasion and dextrose plus talc chemical abrasion without any mechanical pleural abrasion [14]. From this study, only the first group (single intervention) and the second group (combined intervention) were included in this meta-analysis. We excluded the third group because of the combination of 2 chemical agents. None of the 5 studies had chemical agent as a single intervention and, therefore, in our final analysis, single intervention was mechanical pleurodesis. Regarding the type of pneumothorax, 4 studies included patients with PSP, 1 study included patients with SSP only and 1 study included patients with both PSP and SSP. In terms of first episode versus recurrence pneumothorax, only a few studies have reported the type of pneumothorax being treated (see Table 1. The mean follow-up postoperative time was 25 months with a range from 1 to 56 months (Table 2). Table 1: Studies characteristics and types of intervention, combined (mechanical and chemical) and the single intervention (mechanical intervention) Author . Year . Location . Design . Type of pneumothorax . First episode versus recurrence . Total patients . Combined intervention/ recurrence . Single intervention/ recurrence . Mechanical pleurodesis . Chemical agent . Jin-Shing Chen 2004 Taiwan Retrospective Primary First episode and recurrence 364 313 51 VATS pleurodesis + blebectomy Minocycline Arife Zeybek 2013 Iran Retrospective Primary and secondary 55, 1st episode and 24, 2nd and 3rd episode 22 16 6 VATS pleurodesis + blebectomy Tetracycline/talc Jin-Shing Chen 2012 Taiwan RCT Primary High recurrence risk 160 80 80 VATS pleurectomy or pleural abrasion Minocycline Won Jae Chung 2008 Korea RCT Primary Not reported 99 49 50 VATS pleurodesis and blebectomy 20% dextrose Jin-Shing Chen 2006 Taiwan RCT Primary First episode and recurrence 202 103 99 VATS pleurodesis and blebectomy Minocycline Author . Year . Location . Design . Type of pneumothorax . First episode versus recurrence . Total patients . Combined intervention/ recurrence . Single intervention/ recurrence . Mechanical pleurodesis . Chemical agent . Jin-Shing Chen 2004 Taiwan Retrospective Primary First episode and recurrence 364 313 51 VATS pleurodesis + blebectomy Minocycline Arife Zeybek 2013 Iran Retrospective Primary and secondary 55, 1st episode and 24, 2nd and 3rd episode 22 16 6 VATS pleurodesis + blebectomy Tetracycline/talc Jin-Shing Chen 2012 Taiwan RCT Primary High recurrence risk 160 80 80 VATS pleurectomy or pleural abrasion Minocycline Won Jae Chung 2008 Korea RCT Primary Not reported 99 49 50 VATS pleurodesis and blebectomy 20% dextrose Jin-Shing Chen 2006 Taiwan RCT Primary First episode and recurrence 202 103 99 VATS pleurodesis and blebectomy Minocycline RCT: randomized control trials, VATS: video-assisted thoracoscopy. Open in new tab Table 1: Studies characteristics and types of intervention, combined (mechanical and chemical) and the single intervention (mechanical intervention) Author . Year . Location . Design . Type of pneumothorax . First episode versus recurrence . Total patients . Combined intervention/ recurrence . Single intervention/ recurrence . Mechanical pleurodesis . Chemical agent . Jin-Shing Chen 2004 Taiwan Retrospective Primary First episode and recurrence 364 313 51 VATS pleurodesis + blebectomy Minocycline Arife Zeybek 2013 Iran Retrospective Primary and secondary 55, 1st episode and 24, 2nd and 3rd episode 22 16 6 VATS pleurodesis + blebectomy Tetracycline/talc Jin-Shing Chen 2012 Taiwan RCT Primary High recurrence risk 160 80 80 VATS pleurectomy or pleural abrasion Minocycline Won Jae Chung 2008 Korea RCT Primary Not reported 99 49 50 VATS pleurodesis and blebectomy 20% dextrose Jin-Shing Chen 2006 Taiwan RCT Primary First episode and recurrence 202 103 99 VATS pleurodesis and blebectomy Minocycline Author . Year . Location . Design . Type of pneumothorax . First episode versus recurrence . Total patients . Combined intervention/ recurrence . Single intervention/ recurrence . Mechanical pleurodesis . Chemical agent . Jin-Shing Chen 2004 Taiwan Retrospective Primary First episode and recurrence 364 313 51 VATS pleurodesis + blebectomy Minocycline Arife Zeybek 2013 Iran Retrospective Primary and secondary 55, 1st episode and 24, 2nd and 3rd episode 22 16 6 VATS pleurodesis + blebectomy Tetracycline/talc Jin-Shing Chen 2012 Taiwan RCT Primary High recurrence risk 160 80 80 VATS pleurectomy or pleural abrasion Minocycline Won Jae Chung 2008 Korea RCT Primary Not reported 99 49 50 VATS pleurodesis and blebectomy 20% dextrose Jin-Shing Chen 2006 Taiwan RCT Primary First episode and recurrence 202 103 99 VATS pleurodesis and blebectomy Minocycline RCT: randomized control trials, VATS: video-assisted thoracoscopy. Open in new tab Table 2: Shows the summary of studies primary outcomes, recurrence of pneumothorax and secondary outcomes of both types of intervention Author . Intervention . Total . Recurrence . Time to recurrence (month) . Follow-up in months (range/mean) . LOS (days) . Air leak (>5 days) . Chest drainage (days) . Pre/post bleeding . Other complications . Comments . Jin-Shing Chen 2004 Combined 313 9 17.7 mean 1–120/39 5.8 ± 3.7 22 ± 7 4.2 ± 2.9 2 No Single 51 5 6.4 mean 7.7 ± 3.2 9 ± 18 5.2 ± 2.6 0 Chest pain Arife Zeybek 2013 Combined 16 0 NA 12–36 (18) 8.4 ± 5.9 NR NR NR No One mortality Single 6 0 NA 8.4 ± 5.9 NR NR NR No Jin-Shing Chen 2012 Combined 80 3 9.5 (0.6–22) 12–50 (26.9) 3.6 ± 1.3 2 ± 2.5 2.6 ± 1.2 0 Chest pain requires more analgesia Single 80 3 8.5 (0.6–24) 12–51 (25.5) 3.6 ± 1.2 2 ± 2.5 2.5 ± 1.1 3 Won Jae Chung 2008 Combined 49 1 NR 23.65 ± 2.5 SD 4.49 ± 2.10 NR 2.95 ± 2.31 No Postoperative fever Single 50 3 NR 20.22 ± 9.7 SD 4.50 ± 1.85 NR 2.96 ± 1.56 No Jin-Shing Chen 2006 Combined 103 2 NR 14–47 (28 median) 4.0 ± 1.6 2 ± 1.9 3 ± ± 1.2 No Chest pain requires more analgesia Single 99 8 NR 12–47 (30 median) 4.3 ± 2.8 6 ± 6.1 3 ± 2.6 No Author . Intervention . Total . Recurrence . Time to recurrence (month) . Follow-up in months (range/mean) . LOS (days) . Air leak (>5 days) . Chest drainage (days) . Pre/post bleeding . Other complications . Comments . Jin-Shing Chen 2004 Combined 313 9 17.7 mean 1–120/39 5.8 ± 3.7 22 ± 7 4.2 ± 2.9 2 No Single 51 5 6.4 mean 7.7 ± 3.2 9 ± 18 5.2 ± 2.6 0 Chest pain Arife Zeybek 2013 Combined 16 0 NA 12–36 (18) 8.4 ± 5.9 NR NR NR No One mortality Single 6 0 NA 8.4 ± 5.9 NR NR NR No Jin-Shing Chen 2012 Combined 80 3 9.5 (0.6–22) 12–50 (26.9) 3.6 ± 1.3 2 ± 2.5 2.6 ± 1.2 0 Chest pain requires more analgesia Single 80 3 8.5 (0.6–24) 12–51 (25.5) 3.6 ± 1.2 2 ± 2.5 2.5 ± 1.1 3 Won Jae Chung 2008 Combined 49 1 NR 23.65 ± 2.5 SD 4.49 ± 2.10 NR 2.95 ± 2.31 No Postoperative fever Single 50 3 NR 20.22 ± 9.7 SD 4.50 ± 1.85 NR 2.96 ± 1.56 No Jin-Shing Chen 2006 Combined 103 2 NR 14–47 (28 median) 4.0 ± 1.6 2 ± 1.9 3 ± ± 1.2 No Chest pain requires more analgesia Single 99 8 NR 12–47 (30 median) 4.3 ± 2.8 6 ± 6.1 3 ± 2.6 No LOS: length of stay; NA: not applicable; NR: not reported. Open in new tab Table 2: Shows the summary of studies primary outcomes, recurrence of pneumothorax and secondary outcomes of both types of intervention Author . Intervention . Total . Recurrence . Time to recurrence (month) . Follow-up in months (range/mean) . LOS (days) . Air leak (>5 days) . Chest drainage (days) . Pre/post bleeding . Other complications . Comments . Jin-Shing Chen 2004 Combined 313 9 17.7 mean 1–120/39 5.8 ± 3.7 22 ± 7 4.2 ± 2.9 2 No Single 51 5 6.4 mean 7.7 ± 3.2 9 ± 18 5.2 ± 2.6 0 Chest pain Arife Zeybek 2013 Combined 16 0 NA 12–36 (18) 8.4 ± 5.9 NR NR NR No One mortality Single 6 0 NA 8.4 ± 5.9 NR NR NR No Jin-Shing Chen 2012 Combined 80 3 9.5 (0.6–22) 12–50 (26.9) 3.6 ± 1.3 2 ± 2.5 2.6 ± 1.2 0 Chest pain requires more analgesia Single 80 3 8.5 (0.6–24) 12–51 (25.5) 3.6 ± 1.2 2 ± 2.5 2.5 ± 1.1 3 Won Jae Chung 2008 Combined 49 1 NR 23.65 ± 2.5 SD 4.49 ± 2.10 NR 2.95 ± 2.31 No Postoperative fever Single 50 3 NR 20.22 ± 9.7 SD 4.50 ± 1.85 NR 2.96 ± 1.56 No Jin-Shing Chen 2006 Combined 103 2 NR 14–47 (28 median) 4.0 ± 1.6 2 ± 1.9 3 ± ± 1.2 No Chest pain requires more analgesia Single 99 8 NR 12–47 (30 median) 4.3 ± 2.8 6 ± 6.1 3 ± 2.6 No Author . Intervention . Total . Recurrence . Time to recurrence (month) . Follow-up in months (range/mean) . LOS (days) . Air leak (>5 days) . Chest drainage (days) . Pre/post bleeding . Other complications . Comments . Jin-Shing Chen 2004 Combined 313 9 17.7 mean 1–120/39 5.8 ± 3.7 22 ± 7 4.2 ± 2.9 2 No Single 51 5 6.4 mean 7.7 ± 3.2 9 ± 18 5.2 ± 2.6 0 Chest pain Arife Zeybek 2013 Combined 16 0 NA 12–36 (18) 8.4 ± 5.9 NR NR NR No One mortality Single 6 0 NA 8.4 ± 5.9 NR NR NR No Jin-Shing Chen 2012 Combined 80 3 9.5 (0.6–22) 12–50 (26.9) 3.6 ± 1.3 2 ± 2.5 2.6 ± 1.2 0 Chest pain requires more analgesia Single 80 3 8.5 (0.6–24) 12–51 (25.5) 3.6 ± 1.2 2 ± 2.5 2.5 ± 1.1 3 Won Jae Chung 2008 Combined 49 1 NR 23.65 ± 2.5 SD 4.49 ± 2.10 NR 2.95 ± 2.31 No Postoperative fever Single 50 3 NR 20.22 ± 9.7 SD 4.50 ± 1.85 NR 2.96 ± 1.56 No Jin-Shing Chen 2006 Combined 103 2 NR 14–47 (28 median) 4.0 ± 1.6 2 ± 1.9 3 ± ± 1.2 No Chest pain requires more analgesia Single 99 8 NR 12–47 (30 median) 4.3 ± 2.8 6 ± 6.1 3 ± 2.6 No LOS: length of stay; NA: not applicable; NR: not reported. Open in new tab Study quality assessment Table 3 demonstrates the STROBE results of the 2 retrospective studies. Of the 22 items recommended, an average score of 17 was observed with a range of 16.83–17.84. Items that were commonly missed or not fully reported in most of the studies were description of any efforts to address potential sources of bias, participants in the result section and addressing the external validity (generalizability) of the study findings (Table 3). One study did not disclose the funding source (Chen 2004) [12]. Overall, the majority of the key items were reported among the 2 retrospective studies (Table 3). For RCTs, using the newly revised Cochrane Risk of Bias tool (RoB2), only 1 study (Chung et al.) had a mark for final risk of bias judgement as some concern [14]. This was mostly due to some concern of risk of bias in the deviations from intended intervention and the randomization process (Fig. 2). The other 2 studies (Chen 2006 and Chen 2012) have low risk of bias in all 5 domains (Fig. 2) [15, 16]. Figure 2: Open in new tabDownload slide (A) Cochrane Risk of Bias Tool (RoB2). (B) Risk of bias summary and quality assessment of included randomized control trials. Figure 2: Open in new tabDownload slide (A) Cochrane Risk of Bias Tool (RoB2). (B) Risk of bias summary and quality assessment of included randomized control trials. Table 3: Quality assessment score for retrospective studies using the STROBE system Author . Year . TA . Ba . O . SD . S . P . V . DS . Bi . SS . QV . SM . P . DD . OD . MR . OA . KR . L . I . G . F . Total . Jin-Shing Chen 2004 1 1 1 1 1 1 0.5 1 0 1 1 1 0.67 1 1 0.67 1 1 1 1 0 0 17.84 Arife Zeybek 2013 1 0.5 1 1 0.5 1 1 0.5 0 0.5 1 1 1 1 1 0.33 0 1 1 1 0.5 1 16.83 Author . Year . TA . Ba . O . SD . S . P . V . DS . Bi . SS . QV . SM . P . DD . OD . MR . OA . KR . L . I . G . F . Total . Jin-Shing Chen 2004 1 1 1 1 1 1 0.5 1 0 1 1 1 0.67 1 1 0.67 1 1 1 1 0 0 17.84 Arife Zeybek 2013 1 0.5 1 1 0.5 1 1 0.5 0 0.5 1 1 1 1 1 0.33 0 1 1 1 0.5 1 16.83 Each element represent 1 point. Ba: background; Bi: bias; DD: descriptive data; DS: data sources; F: funding; G: generalizability; I: interpretation; KR: key results; L: limitation; MR: main results; O: objective; OA: other analysis; OD: outcome data; P: participants; QV: quantitative variables; S: setting; SD: study design; SM: statistical methods; SS: study size; TA: title and abstract; V: variables. Open in new tab Table 3: Quality assessment score for retrospective studies using the STROBE system Author . Year . TA . Ba . O . SD . S . P . V . DS . Bi . SS . QV . SM . P . DD . OD . MR . OA . KR . L . I . G . F . Total . Jin-Shing Chen 2004 1 1 1 1 1 1 0.5 1 0 1 1 1 0.67 1 1 0.67 1 1 1 1 0 0 17.84 Arife Zeybek 2013 1 0.5 1 1 0.5 1 1 0.5 0 0.5 1 1 1 1 1 0.33 0 1 1 1 0.5 1 16.83 Author . Year . TA . Ba . O . SD . S . P . V . DS . Bi . SS . QV . SM . P . DD . OD . MR . OA . KR . L . I . G . F . Total . Jin-Shing Chen 2004 1 1 1 1 1 1 0.5 1 0 1 1 1 0.67 1 1 0.67 1 1 1 1 0 0 17.84 Arife Zeybek 2013 1 0.5 1 1 0.5 1 1 0.5 0 0.5 1 1 1 1 1 0.33 0 1 1 1 0.5 1 16.83 Each element represent 1 point. Ba: background; Bi: bias; DD: descriptive data; DS: data sources; F: funding; G: generalizability; I: interpretation; KR: key results; L: limitation; MR: main results; O: objective; OA: other analysis; OD: outcome data; P: participants; QV: quantitative variables; S: setting; SD: study design; SM: statistical methods; SS: study size; TA: title and abstract; V: variables. Open in new tab Primary outcome: rate of pneumothorax recurrence All studies reported the recurrence rate of each group, combined and single intervention. Of the 5 studies included in this meta-analysis, the pooled RR estimate of recurrence using the random-effect model was 0.37 (95% CI 0.18–0.76, P = 0.006). Patients treated with combined intervention had a 63% lower risk of developing a recurrent pneumothorax compared to those treated with single intervention (mechanical pleurodesis) as shown in Fig. 3. Our results also showed no evidence of heterogeneity among the included studies with the test of heterogeneity of 2.0 and the P-value of 0.564. Only 1 study (Chen 2004) reported their recurrence rate in ˂12 months (Table 2) [12]. We were interested in reporting time to recurrence; however, only 2 studies reported time to recurrence (Chen 2004 and Chen 2012) among their combined and single intervention groups (Table 2) [12, 15]. A shorter time to recurrence was observed among patients treated with mechanical compared to combined pleurodesis: a median of 6.4 vs 17.7 months (Chen et al. 2004) and 8.5 vs 9.5 months (Chen et al. 2012) (Table 1). All studies reported bleb resection in both groups of patients; Chen et al. (2004) reported that the number of blebs was a significant predictor for pneumothorax recurrence [12]. Chen et al. (2004) was also the only study that reported the smoking status among the recurrence group; they did not find it to be a significant predictor for recurrence [12]. Figure 3: Open in new tabDownload slide Forrest plot. The estimated RR of recurrence of spontaneous pneumothorax in the combined versus single intervention using the weight of random model. CI: confidence interval; RR: relative risk. Figure 3: Open in new tabDownload slide Forrest plot. The estimated RR of recurrence of spontaneous pneumothorax in the combined versus single intervention using the weight of random model. CI: confidence interval; RR: relative risk. Sensitivity analysis Because the meta-analysis result showed that the Chen 2004 study has a weight of 37.8% of the total summary, we removed this study from the analysis [12]. The estimated summary of the combined intervention showed a reduction of recurrence risk of 55%. However, this did not reach a significant level (RR 0.45, 95% CI 0.16–1.08; P = 0.110). Secondary outcomes Patients who received mechanical and chemical pleurodeses (combined intervention) experienced more chest pain and required higher doses of narcotic pain medications compared to those who received only mechanical intervention. In terms of postoperative bleeding, in his 2004 publication, Chen et al [12]. reported 2 incidences of postoperative bleeding among the combined intervention versus 0 among the single and 0 (combined intervention) versus 2 (single intervention) in his 2012 publication (Table 2) [15]. There were no statistically significant differences between the combined intervention group and single intervention group in terms of length of hospital stay measured in days (LOS) (SMD −0.17, 95% CI −0.39 to 0.05, P = 0.138 and I = 45.8%) [Fig. 4A, duration of postoperative air leak (number of days after day 5) (SMD 0.17, 95% CI −1.14 to 1.47, P = 0. 804 and I = 98%)] (Fig. 4B), or duration of postoperative chest tube drainage (days) (SMD −0.07, 95% CI −0.27 to 0.12, P = 0.471 and I = 36%) (Fig. 4C). Figure 4: Open in new tabDownload slide (A) The estimated SMD of length of stay between the combined and single intervention. (B) The estimated SMD of air leak between the combined and single intervention. (C) The estimated SMD of chest tube duration/drainage between the combined and single intervention. CI: confidence interval; SD: standard deviation; SMD: standardized mean difference. Figure 4: Open in new tabDownload slide (A) The estimated SMD of length of stay between the combined and single intervention. (B) The estimated SMD of air leak between the combined and single intervention. (C) The estimated SMD of chest tube duration/drainage between the combined and single intervention. CI: confidence interval; SD: standard deviation; SMD: standardized mean difference. DISCUSSION In this systematic review, we summarized the evidence that compared mechanical pleurodesis to combined chemical and mechanical pleurodesis on the recurrence rate of SP. Our meta-analysis of the available RCTs and observational studies showed that adding chemical pleurodesis agents to mechanical pleurodesis resulted in a lower risk of pneumothorax recurrence and shorter length of hospital stay with no statistically significant difference between the 2 types of intervention in terms of air leak and chest tube drainage. However, our results also showed that adding a chemical agent to mechanical pleurodesis comes with an increased rate of postoperative pain, which is mainly attributed to the chemical agent instilled in the chest cavity. The goal of both chemical and mechanical pleurodeses is to achieve pleural symphysis between the visceral and parietal surfaces by irritating the pleural surface through either physical abrasion (mechanical pleurodesis) or chemical agent instillation (chemical pleurodesis), with resultant inflammation of the pleural space. Therefore, the lower risk of recurrence among those who had both types of pleurodesis may be due to the synergistic effect of dual methods used to irritate the pleural space and create a stronger and more lasting inflammatory process. However, this is associated with an increase in chest pain postoperatively. In the current era of advanced techniques in local and regional, anaesthesia, one could argue that postoperative chest pain is outweighed by the reduced risk of recurrence with associated costs for hospitalization and possible intervention. However, a discussion between healthcare providers and patients should occur with regard to the risks and benefits of both interventions. The findings of the current study are consistent with another systematic review by Sudduth et al. who found that a combination of wedge resection + chemical pleurodesis and wedge resection + pleural abrasion + chemical pleurodesis has the lowest recurrence rates of pneumothorax among patients with SP when they compared them to other interventions such as wedge resection alone, wedge resection with pleural abrasion/pleurectomy and other intervention [18]. In contrast to our findings, however, a systematic review by Ling et al. [5] showed no difference in the recurrence rate of pneumothorax (3.8%) between the minocycline pleurodesis combined with pleural abrasion group when compared with apical pleurectomy alone (3.8%). In addition, they found no difference in recurrence rate between pleural abrasion alone and abrasion plus minocycline pleurodesis [5]. In another study, adding talc during VATS procedures for bullectomy, bleb resection or electrocoagulation without pleural abrasion or pleurectomy is associated with extremely low recurrence rate (0.0–3.2%) [8]. Furthermore, in a review of the literature that looked at the difference in effectiveness between chemical and mechanical pleurodesis in terms of pneumothorax recurrence, of the 6 studies that were included, Sepehripour et al. [19] concluded that, although chemical and mechanical pleurodesis have similar outcomes, chemical pleurodesis with talc appears to have a lower rate of recurrence. In a more comprehensive review of all RCTs of any PSP treatment, Vuong et al. found that among patients with first episode of pneumothorax, VATS followed by chemical pleurodesis is the most effective in preventing recurrence. For patients with recurrence or persistent pneumothorax, thoracotomy with mechanical pleurodesis (abrasion or pleurectomy) provided the best results in preventing recurrence [7]. However, this review did not directly compare/comment on the effectiveness of the combined intervention (chemical and mechanical) [7]. In terms of postoperative chest pain, similar to our results, a higher rate of chest pain was observed among patients who received minocycline pleurodesis [5]. Moreover, a review article on chemical pleurodesis showed that almost all chemical agents may cause significant chest pain as an adverse effect, while some patients may even experience fever, pneumonia, effusion and haemothorax [20]. As far as guideline recommendations about SP management and recurrence prevention are concerned, the American College of Chest Physicians recommends intervention after the second episode of PSP with thoracoscopic with mechanical pleurodesis to be the preferred method, given the success rate of 95–100% [6, 21]. Although this guideline states that there is no role of talc poudrage in recurrence prevention of PSP, there was no direct recommendation or comment on the use of the combined, chemical and mechanical pleurodesis. For SSP, surgical intervention is recommended after the first episode, given the increased risk of recurrence compared to PSP [6]. Similarly, the British Thoracic Society recommended a conservative approach for the first episode of PSP with needle aspiration or chest drain based on patient clinical presentation, underlying lung disease and size of pneumothorax [3]. However, they recommend that patients with SSP should be referred to a chest physician or thoracic surgeon for evaluation. Again, surgical intervention is preferred over chemical pleurodesis alone by the British Thoracic Society unless the patient is unfit or unable to undergo surgical intervention [3]. Belgian Society of Pneumology guidelines recommended observation for small and minimally symptomatic PSP and simple aspiration/catheter placement for symptomatic/large PSP. They recommend a more invasive approach (thoracotomy or VATS with pleurectomy, mechanical abrasion or talc poudrage) for persistent air leak, incomplete lung expansion or recurrent pneumothorax (PSP or SSP) [22]. In agreement with the previous 2 guidelines, strong evidence showed that open thoracotomy with total pleurectomy provides the most effective approach in preventing recurrence. However, less invasive procedures such as partial pleurectomy, pleural abrasion and talc poudrage are preferred [22]. The findings of this review and the ability to make a definitive conclusion from the results of this study are limited by several factors. First, although we have used the STROBE system in assessing the quality of the observational studies, this system acts as a check list and does not account for any risk of bias adjustment. Therefore, there is a potential risk of bias in these studies in terms of patient selection, surgeon preference and institutional experience and practice. Second, due to the limited number of studies that met our inclusion criterion, and to synthesize a summary of our result, we have combined observational studies and RCTs. By comparing only RCTs or observational studies, we would have not been able to synthesize such a summary. Third, our analysis included a mixed group of patients with mixed type and number of episodes of pneumothorax and could not evaluate the relative effectiveness of various methods used to perform mechanical pleurodesis (apical pleurectomy, partial or complete parietal pleural abrasion). Nonetheless, this does not change our final conclusion that, if mechanical pleurodesis is chosen, adding a chemical agent may lead to a decreased likelihood of recurrence. Fourth, in our analysis, we considered both pleurectomy and/or pleural abrasion as mechanical pleurodeses. This assumption was based on a meta-analysis review showing that there was no difference in the RR of reoccurrence between the 2 methods of mechanical pleurodesis [23]. Lastly, time to recurrence is another important measure for the effectiveness of an intervention. Unfortunately, from the current data, we were not able to synthesize a statistical summary for 12-month recurrence rate and ˃12 months. However, a recently published (2018) review showed that most recurrence occurs in the first year with 32% of patients with PSP experiencing recurrence [2]. CONCLUSION In this review, our summary showed that combined intervention with mechanical and chemical pleurodesis for SP is more effective in preventing recurrence and is also associated with a shorter hospital stay than mechanical pleurodesis alone. Our results also showed that this combined intervention is associated with higher rates of postoperative chest pain. When managing patients with pneumothorax, there are multiple factors that need to be considered including patients’ preference, age, gender, clinical condition and risk stratification, as well as healthcare provider preference and expertise, institution cultures and local guidelines. Despite this complexity in approaching patients with pneumothorax, we believe that the findings of this review will provide some useful guidance to healthcare providers in the decision-making process. ACKNOWLEDGEMENTS This study is a part of graduation requirements for a master’s degree in Clinical and Translational Research at the University of California San Francisco. We would like to acknowledge and thank the committee members from the University of California San Francisco for providing some insight and feedback on the project design, statistical analysis and manuscript development. The authors thank Quan-Yang Duh, professor, endocrine surgeon and chief of endocrine surgery section; Anne Schafer, associate professor, endocrinologist and epidemiologist; and Peter Bacchetti, professor, epidemiology and biostatistics. Conflict of interest: none declared. Author contributions Ammar Asban: Conceptualization; Data curation; Formal analysis; Writing—original draft. Syed Sikandar Raza: Conceptualization; Data curation. Chandler McLeod: Formal analysis. James Donahue: Writing—review & editing. Benjamin Wei: Writing—review & editing. REFERENCES 1 Light RW. Pleural Diseases . Philadelphia : Lippincott, Williams and Wilkins , 2013 . Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC 2 Walker SP , Bibby AC, Halford P, Stadon L, White P, Maskell NA. Recurrence rates in primary spontaneous pneumothorax: a systematic review and meta-analysis . Eur Respir J 2018 ; 52 : 1800864 . Google Scholar Crossref Search ADS PubMed WorldCat 3 MacDuff A , Arnold A, Harvey J; on behalf of the BTS Pleural Disease Guideline Group. Management of spontaneous pneumothorax: British Thoracic Society Pleural Disease Guideline 2010 . Thorax 2010 ; 65 : ii18 – 31 . Google Scholar Crossref Search ADS PubMed WorldCat 4 Tschopp JM , Bintcliffe O, Astoul P, Canalis E, Driesen P, Janssen J et al. ERS task force statement: diagnosis and treatment of primary spontaneous pneumothorax . Eur Respir J 2015 ; 46 : 321 – 35 . Google Scholar Crossref Search ADS PubMed WorldCat 5 Ling ZG , Wu YB, Ming MY, Cai SQ, Chen YQ. The effect of pleural abrasion on the treatment of primary spontaneous pneumothorax: a systematic review of randomized controlled trials . PLoS One 2015 ; 10 : e0127857 . Google Scholar Crossref Search ADS PubMed WorldCat 6 Baumann MH , Strange C, Heffner JE, Light R, Kirby TJ, Klein J et al. Management of spontaneous pneumothorax—an American College of Chest Physicians Delphi Consensus Statement . Chest 2001 ; 119 : 590 – 602 . Google Scholar Crossref Search ADS PubMed WorldCat 7 Vuong NL , Elshafay A, Thao LP, Abdalla AR, Mohyeldin IA, Elsabaa K et al. Efficacy of treatments in primary spontaneous pneumothorax: a systematic review and network meta-analysis of randomized clinical trials . Respir Med 2018 ; 137 : 152 – 66 . Google Scholar Crossref Search ADS PubMed WorldCat 8 Hallifax RJ , Yousuf A, Jones HE, Corcoran JP, Psallidas I, Rahman NM. Effectiveness of chemical pleurodesis in spontaneous pneumothorax recurrence prevention: a systematic review . Thorax 2017 ; 72 : 1121 – 31 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Gossot D , Galetta D, Stern JB, Debrosse D, Caliandro R, Girard P et al. Results of thoracoscopic pleural abrasion for primary spontaneous pneumothorax . Surg Endosc 2004 ; 18 : 466 – 71 . Google Scholar Crossref Search ADS PubMed WorldCat 10 Lang-Lazdunski L , Chapuis O, Bonnet PM, Pons F, Jancovici R. Videothoracoscopic bleb excision and pleural abrasion for the treatment of primary spontaneous pneumothorax: long-term results . Ann Thorac Surg 2003 ; 75 : 960 – 5 . Google Scholar Crossref Search ADS PubMed WorldCat 11 Tsukioka T , Inoue K, Oka H, Mizuguchi S, Morita R, Nishiyama N. Intraoperative mechanical and chemical pleurodesis with 50% glucose solution for secondary spontaneous pneumothorax in patients with pulmonary emphysema . Surg Today 2013 ; 43 : 889 – 93 . Google Scholar Crossref Search ADS PubMed WorldCat 12 Chen JS , Hsu HH, Kuo SW, Tsai PR, Chen RJ, Lee JM et al. Effects of additional minocycline pleurodesis after thoracoscopic procedures for primary spontaneous pneumothorax . Chest 2004 ; 125 : 50 – 5 . Google Scholar Crossref Search ADS PubMed WorldCat 13 Zeybek A , Kalemci S, Gürünlü Alma Ö, Süzen A, Akgül M, Koç K. The effect of additional pleural procedures onto recurrence rates on the spontaneous pneumothorax surgery . Iran Red Crescent Med J 2013 ; 15 : 136 – 41 . Google Scholar Crossref Search ADS PubMed WorldCat 14 Won JC , Jo WM, Sung HL, Ho SS, Kwang TK. Effects of additional pleurodesis with dextrose and talc-dextrose solution after video assisted thoracoscopic procedures for primary spontaneous pneumothorax . J Korean Med Sci 2008 ; 23 : 284 – 7 . Google Scholar Crossref Search ADS PubMed WorldCat 15 Chen J-S , Hsu H-H, Huang P-M, Kuo S-W, Lin M-W, Chang C-C et al. Thoracoscopic pleurodesis for primary spontaneous pneumothorax with high recurrence risk a prospective randomized trial . Ann Surg 2012 ; 255 : 440 – 5 . Google Scholar Crossref Search ADS PubMed WorldCat 16 Chen JS , Hsu HH, Chen RJ, Kuo SW, Huang PM, Tsai PR et al. Additional minocycline pleurodesis after thoracoscopic surgery for primary spontaneous pneumothorax . Am J Respir Crit Care Med 2006 ; 173 : 548 – 54 . Google Scholar Crossref Search ADS PubMed WorldCat 17 Sterne JAC , Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I et al. RoB 2: a revised tool for assessing risk of bias in randomised trials . BMJ 2019 ; 366 : l4898 . Google Scholar Crossref Search ADS PubMed WorldCat 18 Sudduth CL , Shinnick JK, Geng Z, McCracken CE, Clifton MS, Raval MV. Optimal surgical technique in spontaneous pneumothorax: a systematic review and meta-analysis . J Surg Res 2017 ; 210 : 32 – 46 . Google Scholar Crossref Search ADS PubMed WorldCat 19 Sepehripour AH , Nasir A, Shah R. Does mechanical pleurodesis result in better outcomes than chemical pleurodesis for recurrent primary spontaneous pneumothorax? . Interact CardioVasc Thorac Surg 2012 ; 14 : 307 – 11 . Google Scholar Crossref Search ADS PubMed WorldCat 20 How CH , Hsu HH, Chen JS. Chemical pleurodesis for spontaneous pneumothorax . J Formos Med Assoc 2013 ; 112 : 749 – 55 . Google Scholar Crossref Search ADS PubMed WorldCat 21 Baumann MH , Strange C. Treatment of spontaneous pneumothorax - A more aggressive approach? Chest 1997 ; 112 : 789 – 804 . Google Scholar Crossref Search ADS PubMed WorldCat 22 De Leyn P , Lismonde M, Ninane V, Noppen M, Slabbynck H, Van Meerhaeghe A et al. ; Guidelines Belgian Society of Pneumology. Guidelines on the management of spontaneous pneumothorax . Acta Chir Belg 2005 ; 105 : 265 – 7 . Google Scholar Crossref Search ADS PubMed WorldCat 23 Bille A , Barker A, Maratos EC, Edmonds L, Lim E. Surgical access rather than method of pleurodesis (pleurectomy or pleural abrasion) influences recurrence rates for pneumothorax surgery: systematic review and meta-analysis . Gen Thorac Cardiovasc Surg 2012 ; 60 : 321 – 5 . Google Scholar Crossref Search ADS PubMed WorldCat Abbreviations CI Confidence interval LOS Length of stay PSP Primary spontaneous pneumothorax RCT Randomized control trial RR Relative risk SSP Secondary spontaneous pneumothorax SP Spontaneous pneumothorax VATS Video-assisted thoracoscopy Author notes Accepted for presentation at the General Thoracic Surgical Club 33rd Annual Meeting, Tucson, AZ, USA, 12-15 March 2020. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Journal

European Journal of Cardio-Thoracic Surgery – Oxford University Press

Published: Oct 1, 2020

There are no references for this article.