METHODS

Between December 1998 and June 2000 all patients older than 17 years with an onset of pleural effusion not treated elsewhere were admitted for further evaluation. All patients received a needle pleural biopsy and diagnostic thoracentesis (less than 50 ml) on the first day of hospitalisation. Tuberculous pleurisy was confirmed in each patient by the presence of caseating granulomas, either with or without acid fast bacilli on histological examination. Other causes of granulomatous disease were excluded. Informed signed consent was obtained from all patients eligible to participate in the study.

Participating patients were randomised to one of two treatment regimens: standard anti-TB drug treatment combined with pigtail drainage or standard anti-TB drug treatment only. The standard anti-TB treatment included isoniazid (300 mg/day), rifampin (450 mg/day in patients <50 kg body weight; 600 mg/day in patients ⩾50 kg body weight), ethambutol (800 mg/day), and pyrazinamide (1500 mg/day). With the exception of pyrazinamide which was administered during the initial 2 months only, all anti-TB drugs were administered for a total of 6 months.

Standard posterior-anterior and lateral chest radiographs were taken of each patient on admission and on the fourth and seventh days following admission. Chest radiographs were taken on a monthly basis during outpatient follow up visits up to 1 month after completion of the full treatment course. At initial presentation the amount of pleural effusion was recorded as small (less than one third of one hemithorax), moderate (between one third and two thirds of one hemithorax), or large (more than two thirds of one hemithorax). The test further defined two degrees of pleural thickening—first RPT (pleural thickening in excess of 10 mm at maximum thickness point); second RPT (pleural thickening of 2–10 mm)—using the presence or absence of RPT.

Standard spirometric tests were performed during the first, fourth, and sixth months using a Vitalograph Spirotrac III (Vitalograph Inc, USA). Pulmonary function measurements were performed in accordance with American Thoracic Society guidelines.⁶ A visual analogue scale (VAS) was used to grade dyspnoea, cough, night sweating, fatigue, appetite, pleuritic chest pain, and general well being on a scale of 0–100.⁷ The effects of pigtail drainage were evaluated by: (1) the number of days fever and dyspnoea persisted after treatment initiation; (2) the degree of improvement in VAS score; (3) forced vital capacity (FVC) at the end of the treatment period; and (4) RPT 6 months after treatment.

Statistical analysis

Numerical data were presented as mean (SD) values. Median values with interquartile range (IQR; 25% and 75%) were calculated for the skewed data. Repeated measures analysis of variance was used to test the difference in VAS scores between subjects (within a group in weeks and between pigtail drainage). For between group comparisons the Mann-Whitney U test was used for two sample comparison of non-normally distributed numerical data. χ² tests were performed for two sample comparison of proportions. p values of <0.05 were considered statistically significant. Statistical analyses were performed using commercially available software (SPSS Version 10.0; SPSS Inc, Chicago, Illinois, USA and Stata Statistical Software; Release 7.0, College Station, TX, USA).

RESULTS

Sixty six patients were diagnosed with tuberculous pleurisy; five were excluded from the final analysis because of non-compliance with treatment requirements and loss to follow up (three in pigtail drainage group and two in control group). Of the 61 remaining patients, 30 received pigtail drainage in combination with standard anti-TB treatment and 31 received only the standard anti-TB treatment. The characteristics of these patients are shown in table 1. There were no significant differences between the two groups.

Table 2 shows the duration of fever and dyspnoea, pleural changes, and the FVC at the completion of treatment. Median (IQR) time for fever subsidence was 0 days (0–6) for those receiving both anti-TB drugs and pigtail treatment and 0 days (0–5) for those receiving anti-TB treatment only. The difference between the two groups was not significant. Dyspnoea improved more rapidly in the dual treatment group than in the single treatment group (median (IQR) 4 days (4–5) v 8 days (7–16); p<0.001). Improvement in the individual VAS scores and combined VAS index scores was significantly different after 1 week of treatment in both groups. However, the difference between the two groups was not statistically significant at any other follow up evaluation (table 3). On completion of treatment no significant difference was seen between the two groups in the incidence of RPT, either >2 mm or >10 mm. Lung function was also similar in the two groups following completion of treatment (median (IQR) 85.5% (69–94) in the dual treatment group and 88% (78–96) in the single treatment group.

After a 6 month postoperative course of anti-TB drugs, all patients were cured of TB based on clinical response and serial chest radiographs. No morbidity related to pigtail drainage occurred.

DISCUSSION

Large et al⁴ have suggested a so-called “active” form of treatment of TB pleural effusions with repeated aspiration of the pleural cavity targeted to reduce the incidence of RPT. The positive effect of this treatment was noted before the routine use of rifampin. Dutt et al⁸ reported on the efficacy of a 6 month regimen of rifampin and isoniazid for tuberculous pleurisy in 1992, and this regimen has been widely used ever since to avoid repeated aspiration. Wyser et al² reported a positive effect (improvement in symptom scores) following complete drainage in a prospective study of 70 patients with tuberculous pleural effusions. However, as these studies did not include controls, they were unable to determine whether early drainage was superior to no drainage over a long period of treatment.

Using a control group, our study has shown that the addition of pleural space drainage to anti-TB drug treatment had neither a beneficial effect on RPT development nor shortened the duration of fever or other clinical symptoms. The only positive effect found in the drainage group was a more rapid resolution of dyspnoea (median 4 v 8 days between the two treatment groups). The incidence of RPT in all patients was about 50%, which is similar to that found in previous studies.^1–3 The incidence of RPT was similar whether or not pigtail drains were used. No significant difference in VAS score improvement was seen between the two groups after 1 week of treatment or during any scheduled follow up examination. Thus, while the combination treatment with anti-TB drugs appears key to improvement, the addition of pigtail drainage does not appear to make a significant difference.

RPT levels >10 mm may have important clinical repercussions. In our study approximately 26% and 28% in the combined and single treatment groups, respectively, had RPT levels >10 mm. Similarly, Pablo et al³ reported RPT levels of >10 mm in about 19% of their patients with tuberculous pleurisy. Clinical and functional impairment induced by RPT is therefore not uncommon in these patients when treated with standard anti-TB drugs, whether or not the pleural effusion is drained. The results of our study indicate that, while RPT is clinically significant on initial presentation of tuberculous pleurisy, it may subside over time. Drainage of pleural effusions, even in the early stages (as in this study), does not prevent the development of RPT, but early diagnosis and early initiation of anti-TB drug treatment has been implicated in a decrease in the development of RPT in patients with tuberculous pleurisy.³

In conclusion, while early clearance of tuberculous pleural effusions by pigtail drainage improves dyspnoea, it does not appear significantly to decrease the incidence of RPT and other clinical symptoms following 1 week of treatment with anti-TB drugs. The development of RPT in itself may not be a serious clinical problem as it tends to subside over time, as long as the patient receives an adequate anti-TB treatment regimen.