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22
Pleural Sclerosis for the Management of Initial Pneumothorax
Richard W. Light
model to assess the factors associated with re currence of pneumothorax in 138 patients and found that recurrence was signifi cantly more frequent in patients with secondary spontan- eous pneumothorax, in taller patients, and in patients with lower weight. Other authors have also reported that the recurrence rates with secondary spontaneous pneumothorax without treatment are slightly higher than those for primary spontaneous pneumothorax without treatment.6,7
The main difference in the treatment of primary and secondary spontaneous pneumo- thoraces is that it is more important to prevent recurrences with secondary pneumothoraces because a recurrence of a secondary pneumotho- rax may be life threatening. In contrast, the recurrence of a primary pneumothorax is usually not life threatening.
22.1. Summary of Published Data
There are several ways by which one can try to prevent recurrence of a pneumothorax. These include the injection of various sclerosing agents such as a tetracycline derivative or talc suspended in saline (talc slurry) through a chest tube, medical thoracoscopy with the insuffl ation of talc, and video-assisted thoracic surgery (VATS) with the treatment of subpleural blebs and a concomitant procedure to produce a pleurodesis.
The pleurodesis can be produced by pleural abra- sion, partial parietal pleurectomy, talc insuffl a- tion, or the intrapleural instillation of another A pneumothorax occurs when there is air in the
pleural space. Pneumothoraces are classifi ed as spontaneous, which occur without preceding trauma or other obvious cause, or traumatic, which occur as a result of trauma to the chest.
Spontaneous pneumothoraces are subclassifi ed as primary or secondary. A primary spontaneous pneumothorax occurs in an otherwise healthy person without underlying lung disease. A sec- ondary spontaneous pneumothorax complicates an underlying lung disease, most commonly chronic obstructive pulmonary disease.
Because there is a high rate of recurrence after an initial primary spontaneous pneumothorax, consideration should be given to preventing a recurrence when the patient is initially seen.
Sadikot and associates1 followed 153 patients with primary spontaneous pneumothorax for a mean of 54 months and reported that the ipsilat- eral recurrence rate was 39% and most recurred within the fi rst year. In this same study, 15% of the 153 patients developed a pneumothorax on the contralateral side.1 Patients who are tall and those who continue to smoke are more likely to have a recurrence.1 However, there is no relation- ship between the number of blebs or the size of the blebs on computed tomography (CT)2 or the appearance of the lung at thoracotomy3 and the risk of recurrence. Once a patient has had one recurrence, the risk of another recurrence increases to more than 50%.4
The recurrence rates after secondary sponta- neous pneumothorax are higher than those after primary spontaneous pneumothorax. Guo and coworkers5 used the Cox proportional hazard
sclerosing agent such as tetracycline, silver nitrate, or iodopovidone.
Unfortunately, there are a very limited number of randomized, controlled studies, as outlined in Table 22.1, comparing the various methods for preventing a recurrent pneumothorax. In the dis- cussion that follows, the results from three ran- domized studies, eight uncontrolled studies, and two statements from thoracic societies are sum-
marized. There are many other studies on the prevention of recurrent pneumothorax that are uncontrolled, but the selected ones are most pertinent.
A large Veterans Administration (VA) cooper- ative study in the 1980s6 demonstrated that the intrapleural administration of 1500mg tetracy- cline when a patient had a chest tube for treat- ment of a pneumothorax decreased the overall
TABLE 22.1. Summary of published data on management of spontaneous pneumothorax.
No. of Level of Reference
First citation Summary patients Conclusion evidence no.
Light RW. JAMA Patients with CT randomized to 229 25% reccurrence in 1++ 6
1990;264:2224–2230. tetracycline or only CT; tetracycline group, <41%
multicenter recurence in controls
Almind M. Thorax Patients randomized to 96 13%, 8%, and 36% 1+ 8
1989;44:627–630. tetracycline, talc slurry, or CT recurrence after talc, tetracycline, and CT, respectively
Alfageme I. Chest Nonrandomized with 66 with 117 9% recurrence after 2− 9
1994;106:347–350. tetracycline and 51 with CT tetracycline and 35%
recurrence after CT
Guo Y. Respirology Nonrandomized with 45 138 33%, 26%, and 50% 2+ 5
2005;10:378–384. tetracycline, 23 gentamicin, recurrence after
and 70 CT tetracyline, gentamicin,
and CT
Tschopp JM. Thorax Uncontrolled talc pleurodesis via 89 7.4% recurrence in patients 3 10
1997;52:329–332. medical thoracoscopy that had follow-up
Tschopp JM. Eur Respir J Randomized talc pleurodesis via 108 5% recurrence after talc 11 2002;20:1003–1009. medical thoracoscopy vs. CT; and 34% recurrence 1+
multicenter after CT
Yim AP. Surg L Endosc Uncontrolled VATS with pleural 483 1.7% recurrence, all 3 12 1997;7:236–240. abrasion ± treatment of blebs received mechanical
pleurodesis
Cardillo G. Ann Thorac Uncontrolled VATS with talc 432 4.4% recurrence 1.79% 2+ 13 Surg 2000;69:357–361. poudrage or parietal with talc 9.15% with
pleurectomy parietal pleurectomy
Waller DA. Ann R Coll Uncontrolled VATS with stapling 173 6.9% recurrence, but 3 14
Surg Engl of blebs and parietal decreased with
1999;81:387–392. pleurecdtomy increasing experience
Margolis M. Ann Thorac Uncontrolled VATS with stapling 156 No recurrences All primary 3 15 Surg 2003;76:1661–1663. of blebs and pleural abrasion spontaneous
pneumothoraces
Lee P. Chest Uncontrolled talc via medical 41 3.4% recurrence 30-day 16
2004;125:1315–1320. thoracoscopy, mean age morality 10% 3
>70 years
Henry M. Thorax BTS guidelines for management NA Chemical pleurodesis with 4 18
2003;58(suppl 2): of spontantous pneumothorax tetracycline if patient is
II39–II52. not a surgical candidate
Baumann MH. Chest ACCP statement on management NA Thoracoscopy with bleb 4 17
2001;119:590–602. of spontaneous pneumothorax stapling and pleural abrasion for preventing recurrence.
Abbreviations: ACCP, American College of Chest aphysicians; BTS, British Thoracic Society; CT, chest tube; VATS, video-assisted thorascopic surgery.
recurrence rate for the pneumothorax from 41%
to 25% when the patients were followed for 30 months. The intrapleural administration of tet- racycline effected a reduction in the recurrence rates in patients with primary spontaneous pneu- mothorax from 32% to 10%, in patients with sec- ondary spontaneous pneumothorax from 43% to 28%, and in patients with recurrent pneumotho- rax from 50% to 21%.6
The randomized, controlled study by Almind and associates8 also demonstrated that the injec- tion of either talc slurry or tetracycline through a chest tube resulted in a signifi cant reduction in the recurrence rate after a fi rst spontaneous pneumothorax. In their study, 34 patients received simple drainage, 33 patients received in addition tetracycline 550mg in 20mL, and 29 patients received in addition 5g of talc suspended in 250mL saline. The recurrence rates during the follow-up period were as follows: simple drainage 36%, tetracycline 13%, and 8% in the talc group.
The patients in the talc group tended to have more pain and more temperature elevation than the patients in the tetracycline group.
A nonrandomized study by Alfageme and coworkers9 also suggested that the intrapleural injection of tetracycline reduced the recurrence rate in patients with spontaneous pneumothorax.
These authors injected tetracycline (either 20mg/kg or a total dose of 2g) in 150mL saline.
For one control group, they used 66 patients who had active pleural or pulmonary infections or refused surgery. A second control group con- sisted of 32 patients who were treated by observa- tion because the pneumothorax size was less than 20%. The recurrence rate in the tetracycline group (9%) was signifi cantly less than that in the chest tube group (35%) or the observation group (36%).
Guo and associates5 performed multiple risk factor analysis on factors related to the recur- rence of pneumothorax in 138 patients who had a spontaneous pneumothorax. They reported that the most important characteristic associated with recurrence was increased height (p < 0.0045) followed by decreased weight (p < 0.0051), the presence of pre-existing lung disease (p < 0.0073), and the absence of a pleurodesis procedure (p < 0.017). The recurrence rate after 3 years in
the 68 patients who had pleurodesis was 27%
while the recurrence rate in the 70 patients who had only chest tubes was 50%. The recur- rence rates were similar for the 23 patients who received gentamicin 16mg as a sclerosing agent and the 45 patients who received tetracycline 1000mg.5
The effi cacy of pleurodesis induced by the insuffl ation of talc at the time of medical thora- coscopy was demonstrated by Tschopp and coworkers.10 In an uncontrolled study of 93 procedures in 89 patients, 3 to 5g of pure talc were insuffl ated into the pleural space at the time of medical thoracoscopy under local anesthesia.
In the immediate postoperative period, two patients required an additional surgical proce- dure because the lung did not expand, three patients had tetracycline instilled because of per- sistent bubbling, two patients had a third drain inserted, and two patients had a second medical thoracoscopy because of relapse or persistent bubbling. During the follow-up period for a mean of 5.1 years, 6 of 81 patients (7.4%) available for follow-up had a recurrence.10
The effectiveness of talc insuffl ation at medical thoracoscopy was compared to chest tube drainage in a prospective, randomized multi- center study of 108 patients with primary spon- taneous pneumothorax, the majority of which were recurrent.11 Patients with bullae more than 5cm in diameter were excluded. In this study, the recurrence rate was 5% in the group that received talc and 34% in the group that received chest tubes. However, it should be noted that 10 of the 16 recurrences in the chest-tube group occurred during the initial hospitalization while only 1 recurrence occurred in the talc group during hospitalization. The recurrence rates after the initial hospitalization were 5% in the talc group and 13% in the chest-tube group, although 10 of the 47 patients in the chest-tube group also got talc during their initial hospitalization. This study also concluded that medical thoracoscopy with the insuffl ation of talc was cost effective in comparison to chest tube alone in patients with primary spontaneous pneumothorax requiring a chest tube.11
Although there have been no randomized, controlled studies evaluating the effectiveness of
VATS in the prevention of recurrent pneumotho- rax, there have been many case series and some of the largest are summarized. Yim and Liu12 reported their experience with 518 VATS proce- dures in 483 patients with primary spontaneous pneumothorax. They treated the blebs in various ways including stapled bullectomy (196), endoloop ligation (261), argon beam coagulation (6), and endoscopic suturing (35). All patients received mechanical abrasion of their pleura. The overall recurrence rate with a mean follow-up of 20 months was 1.74%. Twenty of their patients received only mechanical pleurodesis and the recurrence rate was 25% in this subgroup.12
Cardillo and associates13 reviewed their expe- rience with VATS in 432 patients for primary spontaneous pneumothorax. They treated the blebs with stapling or ligation, and they attempted to induce pleurodesis via partial parietal pleurec- tomy or talc insuffl ation (2g). They reported that the overall recurrence rate with a mean follow-up of 38 months was 4.16%. The recurrence rates in patients who received ligation was 11 of 104 (10.6%), while the recurrence rates in patients who received stapling was 3 of 235, or 1.27%.
The recurrence rates in patients who received subtotal pleurectomy was 14 of 153 (9.15%), while the recurrence rates in patients who received t alc insuffl ation was 5 of 279 (1.79%). However, most of the difference in the recurrence rates between talc and subtotal pleurectomy was due to the fact that many more ligations were per- formed in the group that received the subtotal pleurectomy.13
In another uncontrolled study, Waller14 reported his experience with VATS in 173 patients for spontaneous pneumothorax, including 55 patients with secondary spontaneous pneumo- thoraces. He performed stapling of the bullae and an apical parietal pleurectomy on all patients.
Overall, the recurrence rate with a mean follow- up of 2 years was 6.6%. Most of the recurrences occurred in patients who were operated upon early in the experience. The late recurrence rate was lower for the secondary spontaneous pneu- mothorax than it was for the primary spontane- ous pneumothorax.14
The best results with VATS were reported by Margolis and associates,15 who treated 156 young
adults with primary spontaneous pneumothorax via VATS with stapling of blebs and pleural abra- sion. In this uncontrolled study there were no postoperative air leaks and the mean hospital stay was only 2.4 days. During the median follow- up 62 months, there were no recurrences.
In an uncontrolled study, Lee and coworkers16 evaluated the effectiveness of medical thoracos- copy with the insuffl ation of talc in the treatment of secondary spontaneous pneumothorax in patients with advanced chronic obstructive pul- monary disease (COPD). They insuffl ated 3g of talc in 41 patients with a mean age of 70.7 years and a mean forced expiratory volume in 1s (FEV1) of 0.88L. The 30-day mortality in this group of patients was 10% and all the patients that died had an FEV1 between 0.5L and 0.7L. The recurrence rate in the survivors was 2 of 37 (5.4%).
The American College of Chest Physicians (ACCP) and the British Thoracic Society (BTS) have both published guidelines for the manage- ment of spontaneous pneumothorax in the past few years. The ACCP guidelines were generated by pulmonologists, thoracic surgeons, emergency room physicians, and interventional radiologists and used the Delphi process.17 The consensus of these physicians was that procedures to prevent the recurrence of primary spontaneous pneumo- thorax should be reserved for the second pneu- mothorax occurrence. This guideline felt that thoracoscopy was the preferred intervention for primary spontaneous pneumothorax and that patients with apical bullae should undergo intra- operative bullectomy. They also recommended that parietal pleural abrasion should be per- formed in most patients to induce a pleurodesis.
They felt that instillation of sclerosing agents through a chest tube was an acceptable approach for pneumothorax prevention in patients who decline surgery or who have an increased surgi- cal risk. The ACCP guidelines for patients with secondary spontaneous pneumothorax recom- mended an intervention to prevent pneumotho- rax recurrence after the fi rst occurrence because of the potential lethality of secondary pneumo- thoraces.17 Otherwise, the recommendations for primary and secondary pneumothorax were very similar.
The British Thoracic Society concluded that chemical pleurodesis is best achieved with the insuffl ation of 5g sterile talc.18 They also con- cluded that chemical pleurodesis can prevent recurrent pneumothorax, but that is should be performed only if the patient is unwilling or unable to undergo surgery. The BTS gave the fol- lowing indications for operative intervention: (1) second ipsilateral pneumothorax, (2) fi rst contra- lateral pneumothorax, (3) bilateral spontaneous pneumothorax, (4) persistent air leak (>5–7 days of tube drainage; (5) air leak or failure to com- pletely re-expand), (6) professions at risk (e.g., pilots, divers).
22.2. How Should Published Data Impact on Clinical Practice
The data summarized in the above section and in the table demonstrate the paucity of randomized studies comparing the different methods for pleurodesis. Nevertheless, several conclusions can be made. First, the instillation of a tetracy- cline derivative or talc suspended in saline through a chest tube will decrease the risk of recurrent pneumothorax from ~50% to ~20%
(recommendation grade A). Second, no agent has been shown to have clear-cut superiority in inducing a pleurodesis when injected through a chest tube (recommendation grade A). Third, medical thoracoscopy with the insuffl ation of talc will decrease the risk of recurrence of primary spontaneous pneumothorax to less than 10%
(recommendation grade B) and this procedure was also effective in preventing recurrences in one small study of patients with secondary spon- taneous pneumothorax (recommendation grade C). Fourth, VATS with the stapling of blebs and the application of some procedure to create a pleurodesis will decrease the risk of recurrence to less than 5% (recommendation grade A). There are no randomized, controlled studies compar- ing the effectiveness of medical thoracoscopy with VATS for the prevention of recurrent pneu- mothorax. Likewise there are no randomized studies comparing medical thoracoscopy with VATS in the management of patients with pneumothorax.
22.3. My View of the Data
My personal view of the clinical data presented above and my recommendations based on this data are as follows: When one is dealing with a patient with a pneumothorax who has a chest tube in place, consideration should be given to doing something to prevent a recurrence because a recurrence can be expected in approximately 50% of patients. The simplest and least expensive procedure is to inject a sclerosant through the chest tube that will reduce the recurrence rate to less than 25%. The two agents that have been used most commonly are talc slurry and doxycy- cline. I prefer doxycycline because the intrapleu- ral administration of talc has been associated with the development of the acute respiratory distress syndrome (ARDS).19,20 If parenteral dox- ycycline is not available, then the contents of doxycycline tablets or capsules can be injected after they are dissolved in saline and passed through a fi lter.21 I recommend this procedure for patients with their fi rst primary spontaneous pneumothorax and for patients who refuse or are thought not to be candidates for medical thora-
The instillation of a tetracycline derivative or talc suspended in saline through a chest tube will decrease the risk of recurrent pneumo- thorax from ~50% to ~20% (level of evidence 1; recommendation grade A).
No agent has been shown to have clear-cut superiority in inducing a pleurodesis when injected through a chest tube (level of evi- dence 1; recommendation grade A).
Thoracoscopy with insuffl ation of talc decreases the risk of recurrence of primary spontaneous pneumothorax to less than 10%
(level of evidence 2 to 3; recommendation grade B).
Thoracoscopy with insuffl ation of talc decreases the risk of recurrence of secondary spontaneous pneumothorax (level of evidence 3; recommendation grade C).
Video-assisted thorascopic surgery with the stapling of blebs and pleurodesis will decrease the risk of recurrence to less than 5% (level of evidence 1; recommendation grade A).
coscopy or VATS. If a tetracycline derivative is used as a pleurodesing agent, conscious sedation should be administered as the intrapleural injec- tion of a tetracycline derivative can be very painful.6
Patients with a recurrent primary spontaneous pneumothorax or a secondary spontaneous pneumothorax should be considered for a more aggressive procedure, which could be medical thoracoscopy with the insuffl ation of talc or a VATS procedure. In general, if everything else is equal, I prefer a VATS procedure. The two main reasons that I prefer the VATS procedure are the following: (1) I worry about the possibility of ARDS after the insuffl ation of talc intrapleurally, and (2) from a purely theoretical viewpoint, it makes more sense to me to treat the blebs that are responsible for the pneumothorax as well as to try to create a pleurodesis. At the time of VATS, the blebs should be stapled and a procedure done to crea te a pleurodesis, such as mechanical pleural abrasion or partial parietal pleurectomy. There are other factors that can affect whether to perform medical thoracoscopy or a VATS procedure. Cer- tainly, medical thoracoscopy with the insuffl ation of talc is less expensive than a VATS procedure.
Stapling of the blebs is very expensive.22 The avail- ability of individuals capable of performing medical thoracoscopy or VATS at a given institu- tion also affects the choice of procedure.
22.4. Future Studies
There are several clinical studies that could be performed that would be important aids in deci- sion making in the future. The effectiveness of transforming growth factor β, the agent that is most effective in producing pleurodesis in animals,23 should be compared to doxycycline or talc slurry injected through chest tubes for reduc- ing recurrence rates. The effectiveness (and the cost) of medical thoracoscopy should be com- pared with VATS in patients with both primary and secondary spontaneous pneumothoraces.
The effectiveness of mechanical pleural abrasion should be compared to that of partial parietal pleurectomy and other procedures advocated by some to produce a pleurodesis at the time of VATS.
Lastly, the cost effectiveness of medical thoracos-
copy compared with tube thoracostomy with the instillation of a sclerosing agent at the time that a patient has an initial primary or secondary spon- taneous pneumothorax should be compared.
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