Pneumothorax management: current state of practice in the UK.

BACKGROUND AND OBJECTIVE: Spontaneous pneumothorax is a common pathology but optimal initial treatment regime is not well defined. Treatment options including conservative management, needle aspiration (NA) or insertion of a small-bore chest drain. Recent large randomised controlled trials may change the treatment paradigm: comparing conservative and ambulatory management to standard care, but current guidelines need to be updated. The aim of this study was to assess the current "state of play" in the management of pneumothorax in the UK. METHODS: Physicians and respiratory healthcare staff were invited to complete an online survey on the initial and subsequent management of pneumothorax. RESULTS: This study is the first survey of pneumothorax practice across the UK, which highlights variation in practice: 50% would manage a large primary pneumothorax with minimal symptoms conservatively, compared to only 3% if there were significant symptoms; 64% use suction if the pneumothorax had not resolved after > 2 days, 15% always clamp the chest drain prior to removal; whereas 30% never do. NICE guidance recommends the use of digital suction but this has not translated into widespread usage: only 23% use digital suction to check for resolution of air leak). CONCLUSION: Whilst there has always been allowance for individual clinician preference in guidelines, there needs to be consensus on the optimum management strategy. The challenge the new guidelines face is to design a simple and pragmatic approach, using this new evidence base.

Randomized Controlled Trial of Urokinase versus Placebo for Nondraining Malignant Pleural Effusion.

RATIONALE: Patients with malignant pleural effusion experience breathlessness, which is treated by drainage and pleurodesis. Incomplete drainage results in residual dyspnea and pleurodesis failure. Intrapleural fibrinolytics lyse septations within pleural fluid, improving drainage. OBJECTIVES: To assess the effects of intrapleural urokinase on dyspnea and pleurodesis success in patients with nondraining malignant effusion. METHODS: We conducted a prospective, double-blind, randomized trial. Patients with nondraining effusion were randomly allocated in a 1:1 ratio to intrapleural urokinase (100,000 IU, three doses, 12-hourly) or matched placebo. MEASUREMENTS AND MAIN RESULTS: Co-primary outcome measures were dyspnea (average daily 100-mm visual analog scale scores over 28 d) and time to pleurodesis failure to 12 months. Secondary outcomes were survival, hospital length of stay, and radiographic change. A total of 71 subjects were randomized (36 received urokinase, 35 placebo) from 12 U.K. centers. The baseline characteristics were similar between the groups. There was no difference in mean dyspnea between groups (mean difference, 3.8 mm; 95% confidence interval [CI], -12 to 4.4 mm; P = 0.36). Pleurodesis failure rates were similar (urokinase, 13 of 35 [37%]; placebo, 11 of 34 [32%]; adjusted hazard ratio, 1.2; P = 0.65). Urokinase was associated with decreased effusion size visualized by chest radiography (adjusted relative improvement, -19%; 95% CI, -28 to -11%; P < 0.001), reduced hospital stay (1.6 d; 95% CI, 1.0 to 2.6; P = 0.049), and improved survival (69 vs. 48 d; P = 0.026). CONCLUSIONS: Use of intrapleural urokinase does not reduce dyspnea or improve pleurodesis success compared with placebo and cannot be recommended as an adjunct to pleurodesis. Other palliative treatments should be used. Improvements in hospital stay, radiographic appearance, and survival associated with urokinase require further evaluation. Clinical trial registered with ISRCTN (12852177) and EudraCT (2008-000586-26).

Effect of Opioids vs NSAIDs and Larger vs Smaller Chest Tube Size on Pain Control and Pleurodesis Efficacy Among Patients With Malignant Pleural Effusion: The TIME1 Randomized Clinical Trial.

IMPORTANCE: For treatment of malignant pleural effusion, nonsteroidal anti-inflammatory drugs (NSAIDs) are avoided because they may reduce pleurodesis efficacy. Smaller chest tubes may be less painful than larger tubes, but efficacy in pleurodesis has not been proven. OBJECTIVE: To assess the effect of chest tube size and analgesia (NSAIDs vs opiates) on pain and clinical efficacy related to pleurodesis in patients with malignant pleural effusion. DESIGN, SETTING, AND PARTICIPANTS: A 2×2 factorial phase 3 randomized clinical trial among 320 patients requiring pleurodesis in 16 UK hospitals from 2007 to 2013. INTERVENTIONS: Patients undergoing thoracoscopy (n = 206; clinical decision if biopsy was required) received a 24F chest tube and were randomized to receive opiates (n = 103) vs NSAIDs (n = 103), and those not undergoing thoracoscopy (n = 114) were randomized to 1 of 4 groups (24F chest tube and opioids [n = 28]; 24F chest tube and NSAIDs [n = 29]; 12F chest tube and opioids [n = 29]; or 12F chest tube and NSAIDs [n = 28]). MAIN OUTCOMES AND MEASURES: Pain while chest tube was in place (0- to 100-mm visual analog scale [VAS] 4 times/d; superiority comparison) and pleurodesis efficacy at 3 months (failure defined as need for further pleural intervention; noninferiority comparison; margin, 15%). RESULTS: Pain scores in the opiate group (n = 150) vs the NSAID group (n = 144) were not significantly different (mean VAS score, 23.8 mm vs 22.1 mm; adjusted difference, -1.5 mm; 95% CI, -5.0 to 2.0 mm; P = .40), but the NSAID group required more rescue analgesia (26.3% vs 38.1%; rate ratio, 2.1; 95% CI, 1.3-3.4; P = .003). Pleurodesis failure occurred in 30 patients (20%) in the opiate group and 33 (23%) in the NSAID group, meeting criteria for noninferiority (difference, -3%; 1-sided 95% CI, -10% to ∞; P = .004 for noninferiority). Pain scores were lower among patients in the 12F chest tube group (n = 54) vs the 24F group (n = 56) (mean VAS score, 22.0 mm vs 26.8 mm; adjusted difference, -6.0 mm; 95% CI, -11.7 to -0.2 mm; P = .04) and 12F chest tubes vs 24F chest tubes were associated with higher pleurodesis failure (30% vs 24%), failing to meet noninferiority criteria (difference, -6%; 1-sided 95% CI, -20% to ∞; P = .14 for noninferiority). Complications during chest tube insertion occurred more commonly with 12F tubes (14% vs 24%; odds ratio, 1.91; P = .20). CONCLUSIONS AND RELEVANCE: Use of NSAIDs vs opiates resulted in no significant difference in pain scores but was associated with more rescue medication. NSAID use resulted in noninferior rates of pleurodesis efficacy at 3 months. Placement of 12F chest tubes vs 24F chest tubes was associated with a statistically significant but clinically modest reduction in pain but failed to meet noninferiority criteria for pleurodesis efficacy. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN33288337.

Efficacy of sonographic and biological pleurodesis indicators of malignant pleural effusion (SIMPLE): protocol of a randomised controlled trial.

INTRODUCTION: Malignant pleural effusion (MPE) is common and currently in UK there are an estimated 50 000 new cases of MPE per year. Talc pleurodesis remains one of the most popular methods for fluid control. The value of thoracic ultrasound (TUS) imaging, before and after pleurodesis, in improving the quality and efficacy of care for patients with MPE remains unknown. Additionally, biomarkers of successful pleurodesis including measurement of pleural fluid proteins have not been validated in prospective studies.The SIMPLE trial is an appropriately powered, multicentre, randomised controlled trial designed to assess 'by the patient bedside' use of TUS imaging and pleural fluid analysis in improving management of MPE. METHODS AND ANALYSIS: 262 participants with a confirmed MPE requiring intervention will be recruited from hospitals in UK and The Netherlands. Participants will be randomised (1:1) to undergo either chest drain insertion followed by instillation of sterile talc, or medical thoracoscopy and simultaneous poudrage. The allocated procedure will be done while the patient is hospitalised, and within 3 days of randomisation. Following hospital discharge, participants will be followed up at 1, 3 and 12 months. The primary outcome measure is the length of hospital stay during initial hospitalisation. ETHICS AND DISSEMINATION: The trial has received ethical approval from the South Central-Oxford C Research Ethics Committee (Reference number 15/SC/0600). The Trial Steering Committee includes an independent chair and members, and a patient representative. The trial results will be published in a peer-reviewed journal and presented at international conferences. TRIAL REGISTRATION NUMBER: ISRCTN: 16441661.