As detailed in Figure 1, the literature search identified 1,011 potentially eligible reports. After review of the title, abstract, or complete manuscript, 986 reports were excluded based on the inclusion and exclusion criteria. Only two studies8,9 that appeared to meet other criteria were excluded due to non-English language; the authors of one of these8 later published their experience in English, and this study is included.10 Of the remaining 25 eligible reports, 6 were excluded due to overlap with patients reported in other studies.11
The 19 included reports (Table 2) were all consecutive case series of patients with MPE who received a TIPC, except one randomized controlled trial of doxycycline pleurodesis versus TIPC; only the group receiving the TIPC is included in this analysis.6 Three meeting abstracts10,17,18 and one letter19 were eligible and presented sufficient data to be included in the analysis. Eight studies were conducted outside the USA. All except one study20 employed the Pleurx® tunneled pleural catheter system initially manufactured by Denver Biomedical (Golden, Colorado), a company that was acquired by Cardinal Health (Dublin, Ohio) in 2006. The oldest study, published in 1994, used a tube known as the Tenckhoff catheter, which is also a small-bore flexible catheter that was tunneled into the pleural space.20 One study employed a reusable plastic pump to drain pleural fluid instead of the standard vacuum drainage bottles designed for use with the Pleurx® catheter.21 Funding source was noted for only two reports, and in those cases the study was supported by the Pleurx® manufacturer.6,22 Quality of evidence, as rated using the GRADE system, was very low for all of the case series and moderate for the one randomized controlled trial.6
A total of 1,370 patients were included in the analysis, with an average age of 63.0 years and 50.5% women. Of the 1,370 patients, 1,348 patients had malignant pleural effusions; two studies included a minority of patients with pleural effusions of benign etiology, such as heart failure and hepatic hydrothorax.23,24 Because data were not reported separately for the patients with non-MPE, these 22 patients were included in the overall analysis, but are felt to contribute insignificantly. Most patients had recurrent effusions that had failed previous thoracentesis or other treatments; details of the individual patient populations are included in Table 2. In the 17 studies that reported distribution of cancer type among 1,236 participants, lung cancer, breast cancer, and mesothelioma together comprised approximately 70% of the included patients (33.5%, 25.9%, and 10.5%, respectively). A variety of other hematologic malignancies and solid tumors were represented in smaller numbers, as described in Table 2.
Survival and catheter permanence times were reported in 10 and 11 studies, respectively, either as a median or a mean, with or without a range. These times were defined starting from the day of TIPC placement. Survival varied from 3 to 1,240 days, with a combined mean of 87 and reported medians ranging from 59.5 to 144 days. Catheter permanence time varied from 2 to 434 days, with a combined mean of 51 and reported medians ranging from 44 to 60 days.
Studies differed significantly in how they reported outcomes, but results were pooled when possible, as described in the Methods section. Combined outcomes are presented in Figure 2. Note that denominators in this figure are different because not all studies reported all complications, and if an outcome was not recorded, the study was removed from both the numerator and denominator.
Of the reported complications, malfunction of the catheter (11/121, 9.1%), catheter clogging (33/895, 3.7%), and unspecified pain (8/142, 5.6%) were the most common. One study reported that mild procedure-related pain occurred in "most" patients,23 but pain that persisted beyond the immediate post-procedural period was documented formally in only 18/558 patients (3.2%) from five studies. Infectious complications such as empyema (33/1168, 2.8%), cellulitis (32/935, 3.4%), and unspecified infection (7/346, 2.0%) were similarly uncommon. The TIPC was removed before death because of a complication in 54/633 patients (8.5%). Tumor metastasis along the catheter tract, although initially a strong theoretical concern, was well documented in these studies and occurred in less than 1% of patients. One procedure-related death was reported in the earliest published study and was related to respiratory arrest following intravenous sedation in a patient who had previously requested no resuscitation.20 Ten studies reported that TIPC devices were used without any complication in a total of 517/591 patients (87.5%).
Symptomatic improvement was reported in a variety of ways. Some studies simply stated that patients experienced “symptomatic improvement” without further delineation.10,20,25 One study rated dyspnea improvement on a 3-point scale as complete, partial, or absent.26 The remaining studies reported symptomatic improvement as “relief of dyspnea,” “improvement in respiratory performance status,” “increased exercise tolerance,” “improvement of pain,” and “catheter was useful.” In sum, these studies showed that 95.6% of patients experienced symptomatic improvement after placement of the TIPC. Putnam et al.6 used Borg scores and the Guyatt Chronic Respiratory Questionnaire to assess symptomatic improvement and found similar improvements after treatment with both the TIPC and doxycycline pleurodesis; the number of patients with improvement was not reported and therefore could not be included in this combined outcome statistic. Quality of life assessments were infrequently included, but 46/46 patients from two studies cited improvement from the TIPC.27,28
Spontaneous pleurodesis was also defined in a variety of ways. In general, these studies used the term spontaneous pleurodesis to describe enduring or long-term achievement of pleural symphysis allowing for TIPC removal without recurrence of the pleural effusion, although some patients chose to keep the catheters in place despite achievement of pleurodesis. Spontaneous pleurodesis occurred in 430/943 patients, for an overall rate of 45.6%, with an average time to pleurodesis of 52 days. The catheter was removed due to pleurodesis in 381/808 patients (47.1%). Recurrence of effusion after initial control was reported in 50/651 patients (7.7%), and 33/652 patients (5.1%) required repeat placement of the catheter after it had been removed.