Pleurodesis for malignant pleural effusions

 

Abstract

Background

Approximately half of all patients with metastatic cancer develop a malignant pleural effusion which is likely to lead to a significant reduction in quality of life secondary to symptoms such as dyspnoea and cough. The aim of pleurodesis in these patients is to prevent re-accumulation of the effusion and thereby of symptoms, and avoid the need for repeated hospitalization for thoracocentesis.

Objectives

To ascertain the optimal technique of pleurodesis in cases of malignant pleural effusion; to confirm the need for a sclerosant; and to clarify which, if any, of the sclerosants is the most effective.

Search methods

CENTRAL, MEDLINE and EMBASE databases were searched in June 2002.

Selection criteria

Randomised control trials (RCTs) of adult participants undergoing pleurodesis for pleural effusion in the context of metastatic malignancy (or a malignant process leading to pleural effusion) were included.

Data collection and analysis

Two review authors independently selected studies for inclusion in the review, and extracted data. Primary outcome measures sought were effectiveness of pleurodesis as defined by freedom from recurrence of effusions, and mortality after pleurodesis. Secondary outcomes were adverse events due to pleurodesis. Dichotomous data were meta-analysed using a fixed-effect model and expressed as relative risk (RR). The number-needed-to-treat-to-benefit (NNTB) was calculated for pleurodesis efficacy. In addition, for adverse events, the overall percentage of participants across studies exhibiting a particular adverse effect such as fever, pain, or gastrointestinal symptoms was calculated.

Main results

A total of 36 RCTs with 1499 participants were eligible for meta-analysis. The use of sclerosants (mitozantrone, talc and tetracycline combined) compared with control (instillation of isotonic saline or equivalent pH isotonic saline or tube drainage alone) was associated with an increased efficacy of pleurodesis. The RR of non-recurrence of an effusion is 1.20 (95% CI 1.04 to 1.38) in favour of the use of sclerosants based on five studies with a total 228 participants. Comparing different sclerosants, talc was found to be the most efficacious. The RR of effusion non-recurrence was 1.34 (95% CI 1.16 to 1.55) in favour of talc compared with bleomycin, tetracycline, mustine or tube drainage alone based on ten studies comprising 308 participants. This was not associated with increased mortality post pleurodesis. The RR of death was 1.19 (95% CI 0.08 to 1.77) for talc compared to bleomycin, tetracycline, mustine and tube drainage alone based on six studies of 186 participants. Death was not reported in all studies and, when reported, was attributed to underlying disease, only one death being reported as procedure-related.

In the comparison of thoracoscopic versus medical pleurodesis, thoracoscopic pleurodesis was found to be more effective. The RR of non-recurrence of effusion is 1.19 (95% CI 1.04 to 1.36) in favour of thoracoscopic pleurodesis compared with tube thoracostamy pleurodesis utilizing talc as sclerosant based on two studies with 112 participants. Comparing thoracoscopic versus bedside instillation (with different sized chest tubes) of various sclerosants (tetracycline, bleomycin, talc or mustine) the RR of non-recurrence of effusion is 1.68 (95% CI 1.35 to 2.10) based on five studies with a total of 145 participants.

Adverse events were not reported adequately to enable meta-analysis.

Authors' conclusions

The available evidence supports the need for chemical sclerosants for successful pleurodesis, the use of talc as the sclerosant of choice, and thoracoscopic pleurodesis as the preferred technique for pleurodesis based on efficacy. There was no evidence for an increase in mortality following talc pleurodesis.

 

Plain language summary

Pleurodesis surgery to remove the build-up of fluid between the lung and chest cavity

Approximately half of all patients with metastatic cancer develop a malignant pleural effusion - a collection of fluid in the space between the lung and chest wall. The fluid compresses the lung and causes breathing problems, and hospital treatment is usually necessary. Pleurodesis is the treatment used to prevent re-accumulation of the fluid. It involves draining the fluid either by thoracoscopy under general anaesthetic or sedation, or by inserting a chest drain by 'bedside' thoracostomy under local anaesthetic. After the fluid has been removed, chemicals called sclerosants are introduced into the cavity to prevent the fluid from accumulating again. This review examined the effectiveness of different chemicals and found that talc was more effective than other sclerosants. The available evidence also showed that thoracoscopic pleurodesis was a more effective technique. No significant differences between the studies were found with regard to mortality rates and adverse events, but this information was provided in only a small number of studies.

 

摘要

背景

以肋膜沾黏術治療惡性肋膜腔積液

大約有一半的轉移性癌症患者會產生惡性肋膜腔積液，進一步可能產生呼吸困難和咳嗽以致降低生活品質。肋膜沾黏術的目的是避免這些病人重複產生積液，從而減輕症狀，並避免需要反復住院行胸腔放液術。許多的臨床研究曾設法了解何謂最佳的肋膜沾黏術的方法，將這些研究整合分析有助於決定最適當的方式是處理惡性肋膜腔積液為何。

目標

本文獻回顧的目的在於確定治療惡性肋膜積液最佳肋膜沾黏術的技術，並確認沾黏硬化劑之必要性與哪一種沾黏硬化劑最為有效。

搜尋策略

我們使用關鍵字“肋膜沾黏術”搜尋了 Cochrane Central Register of Controlled Trials和MEDLINE (1980年 to June 2002年)以及EMBASE (1980年 to May 2002年)。搜尋的文獻沒有語言的限制。

選擇標準

納入以成人為試驗對象的隨機對照試驗，且在文中提及使用肋膜沾黏術處理因轉移性惡性腫瘤或與惡性腫瘤病程相關之肋膜積液皆被納入。

資料收集與分析

兩位獨立的評估者依據納入條件選定研究並使用標準的列表收集數據。主要評估的結果是積液不再復發率以及肋膜沾黏術後之死亡率。次要評估的結果是肋膜沾黏術後所產生之不良事件。資料分析使用固定效應模型(fixed effect model)，並以相對危險性(relative risk; RR)來表示結果。肋膜沾黏術之療效是以需益需沾數(numberneededtotreat; NNT)來計算。此外，對於各研究所報告之副作用，如發燒，疼痛，或胃腸道症狀也列入計算。

主要結論

共有36個RCT包含1499個案例進行統合分析。結果顯示使用硬化劑 (包括mitozantrone ，滑石粉和4環黴素)與對照組(灌輸生理鹽水或相同酸鹼值之鹽水或引流管引流)相比可以增加治療的效益。根據5個共有228個案例的研究贊成使用硬化劑，使用硬化劑導致積液不復發的相對危險率(RR)是1.20 (95 ％CI為1.04至1.38)比較不同硬化劑，的最有效的硬化劑是滑石粉。依據10個研究(包括308個案例)的結果發現滑石粉相較於博萊黴素、四環素、mustine或胸管引流管導致積液不復發的相對危險率是1.34 (95 ％CI為1.16至1.55)，且此項結果並不會合併較高之術後死亡率。依據6個研究(包括186個案例) ，滑石粉與博萊黴素，四環素，mustine和胸管引流術相比，肋膜固定術後死亡率的相對危險率是1.19 (95 ％CI為0.08至1.77)。並非所有的研究皆有報告死亡案例，且在報告的案例中，病人之死亡多是與其疾病相關，只有一案例死因與肋膜固定術有關。在2個利用滑石粉作為硬化劑的研究(包括112個案例) 中比較胸腔鏡與一般肋膜固定術，發現胸腔鏡輔助之肋膜固定術更為有效，積液不復發的RR是1.19 (95 ％ CI為1.04至1.36)。在5個研究(包括145個案例) 中比較胸腔鏡輔助相較於病床旁輸注(使用管徑不同大小的胸管)輔以各種不同硬化劑(四環素，博萊黴素，滑石粉或mustine)的積液不復發相對RR = 1.68 (95 ％CI為1.35至2.10) 。至於不良事件的分析因目前尚未有充分資料故無法進行統合分析。

作者結論

現有的證據支持使用化學硬化劑來遂行成功的肋膜沾黏術，首選的胸膜沾黏術是使用滑石粉作為沾黏劑，而以印效來說則是以胸腔鏡胸膜沾黏術為較被喜愛的技術之。目前沒有證據顯示使用滑石粉作肋膜沾黏術會增加術後死亡率。

翻譯人

本摘要由三軍總醫院吳宜穎翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

目前證據顯示治療惡性肋膜積液最有效的硬化劑是滑石粉，而胸腔鏡肋膜沾黏術為最佳的技術。大約有一半的轉移性癌症病患會產生惡性肋膜積液(意及在肺和胸壁之間積水)。這些液體會壓縮肺並造成呼吸困難，通常需要住院治療。肋膜沾黏術是用來防止重新累積胸水，通常藉由全身麻醉或鎮靜在胸腔鏡輔助下施行，或在局部麻醉下於床邊插入胸管。胸水引流後才注入化學硬化劑到胸腔，以防止胸水再形成。這篇文章檢討不同的化學品的成效，發現滑石粉是最有效的硬化劑。現有的證據更指出，胸腔鏡肋膜沾黏術能更加強成效。關於死亡率和不良反應事件各研究間無顯著的差異，但目前只有少數的研究提供此資訊。