Intrapleural Fibrinolysis for the Treatment of Indwelling Pleural Catheter-Related Symptomatic Loculations: A Multicenter Observational Study

Our plain-English summary of Intrapleural Fibrinolysis for the Treatment of Indwelling Pleural Catheter-Related Symptomatic Loculations: A Multicenter Observational Study, by R. Thomas, F. Piccolo, D. Miller, et al (Chest, 2015).

The study

• Authors: R. Thomas, F. Piccolo, D. Miller, P.R. MacEachern, A.C. Chee, T. Huseini, L. Yarmus, R. Bhatnagar, H.J. Lee, D. Feller-Kopman, N.A. Maskell, A. Tremblay, Y.C.G. Lee
• Journal: Chest
• Published: 2015;148(3):746-751
• Cited by: 59 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Indwelling pleural catheters (IPCs) are an effective option in the management of malignant pleural effusion. Up to 14% of patients with IPCs develop symptomatic pleural loculations causing ineffective fluid drainage and breathlessness. To our knowledge, this is the first study to describe intrapleural fibrinolytic therapy for IPC-related symptomatic loculations.

Methods: All patients who received intrapleural fibrinolytic therapy for symptomatic loculations between January 1, 2002, and June 30, 2014, in four established IPC centers were retrospectively included. Patient outcomes, treatment effectiveness, and adverse events were recorded.

Results: Sixty-six patients (mean age, 64.7 ± 14.2 years; 52% women) were included. Lung cancer (31.3%) and malignant pleural mesothelioma (20.3%) were the most common malignancies. Fibrinolytic instillation was performed in outpatient (61%) and inpatient settings. Tissue-plasminogen activator (n = 52), urokinase (n = 12), and streptokinase (n = 2) were used. The majority (69.7%) received only one fibrinolytic dose (range, one to six). Pleural fluid drainage increased in 93% of patients, and dyspnea improved in 83% following therapy. The median cumulative pleural fluid volume drained at 24 h posttreatment was 500 mL (interquartile range 300-1,034 mL). The area of opacity caused by pleural effusion on chest radiograph decreased from (mean, SD) 52% (14%) to 31% (21%) of the hemithorax (n = 13; P = .001). There were two cases of nonfatal pleural bleed (3%).

Conclusions: Intrapleural fibrinolytic therapy can improve pleural fluid drainage and symptoms in selected patients with IPC and symptomatic loculation, but it carries a small risk of pleural bleeding. There is significant heterogeneity in its use currently, and further studies are needed to determine patient selection and optimal dosing regimen and to define its safety profile.

In plain English

This retrospective study from four specialist centers in Australia, Canada, the UK and the USA reviewed 66 patients, treated between 2002 and 2014, whose indwelling pleural catheters (long-term chest drainage tubes) stopped draining well because fluid became trapped in pockets (loculations), causing breathlessness. All received clot-dissolving drugs through the catheter: tissue-plasminogen activator (52 patients), urokinase (12) or streptokinase (2). Most had fluid caused by cancer; 13 had malignant pleural mesothelioma, but results were not reported separately for them. Drainage increased in 56 of 60 patients, and breathlessness improved in 40 of 48 with a recorded response. In 13 patients with before-and-after X-rays, the fluid shadow fell from a mean 52% to 31% of that side of the chest. Two patients (3%) had serious but non-fatal bleeding into the chest. Loculations returned in 27 patients (40.9%). The authors concluded the treatment can improve drainage and symptoms in selected patients but carries a small bleeding risk. They noted the study was retrospective and may have missed cases.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: multi-center retrospective observational study (case series) from four centers
• Who was studied: 66 patients with an indwelling pleural catheter (IPC) who developed symptomatic loculation and received at least one dose of a fibrinolytic agent, at Sir Charles Gairdner Hospital (Perth, Australia), University of Calgary (Canada), Southmead Hospital (Bristol, UK) and Johns Hopkins Hospital (Baltimore, USA), between January 1, 2002 and June 30, 2014; 52% female, mean age 64.7 years; 64 had a malignant pleural effusion, including 13 (20.3%) from malignant pleural mesothelioma and 20 (31%) from lung carcinoma
• Exposure: Not an asbestos exposure study. The treatment studied was fibrinolytic drugs instilled through the IPC: tissue-plasminogen activator at 4 to 10 mg (52 patients), urokinase 100,000 IU (12 patients) and streptokinase 250,000 IU (2 patients); 69.7% received a single dose (range 1 to 6 doses)
• Main results:
  • Among the 64 patients with malignant pleural effusion, 13 (20.3%) had malignant pleural mesothelioma and 20 (31%) had lung carcinoma; outcomes were not reported separately by cancer type
  • Pleural fluid drainage increased after fibrinolytic treatment in 56 of 60 patients (93.3%)
  • Cumulative fluid drained rose from a median of 0 mL at baseline to 500 mL at 24 hours (56 patients; p less than 0.001) and to 900 mL at 72 hours (44 patients)
  • Breathlessness improved in 40 of the 48 patients (83%) who had a recorded symptomatic response; no patient reported worse breathlessness
  • In the 13 patients with chest X-rays before and after treatment, the area of opacity from effusion fell from a mean 52% (SD 14) to 31% (SD 21) of the hemithorax within 72 hours, p=0.001
  • Two patients (3%) had significant but non-fatal pleural bleeding requiring red blood cell transfusions; neither needed invasive radiological or surgical intervention; there was no extra-thoracic bleeding
  • Symptomatic loculations recurred in 27 patients (40.9%) at a median of 13 days (range 2 to 69) after treatment
  • Mortality was 20% at 30 days and 54.5% at 90 days after treatment; all deaths were attributed to progression of the underlying cancer and none directly to fibrinolytic therapy
  • 40 patients (61%) were treated as outpatients at two centers; inpatients had a median hospital stay of 2 days from the first dose
• The authors' conclusion: The authors concluded that intrapleural fibrinolytic therapy can improve drainage and symptoms in selected patients with an IPC and symptomatic loculation but carries a small risk of pleural bleeding, that its use currently varies widely, and that further studies are needed on patient selection, dosing and safety.
• Limitations the authors state:
  • Only about 4% of IPC patients (66 of an estimated 1690) received fibrinolytics, which is below the reported incidence of loculation; this may reflect under-reporting because the study was retrospective and/or selection bias
  • Risk factors for developing loculation and predictors of response to treatment could not be evaluated
  • All four centers were experienced in pleural medicine, so whether the findings apply to other centers requires validation
  • Centers used different agents, doses, instillation frequencies and settings, without consistent pre-defined patient selection criteria

Topics

Medical terms in this study, explained in our Lexicon: Indwelling Pleural Catheter, Pleural Effusion, Lung Cancer, Pleural Mesothelioma, Dyspnea, Chest X-Ray, Hemithorax.

Related studies

• Protocol of the Australasian Malignant Pleural Effusion-2 (AMPLE-2) trial: a multicentre randomised study of aggressive versus symptom-guided drainage via indwelling pleural catheters — M. Azzopardi, R. Thomas, et al. (2016)
• Catheter tract metastasis associated with indwelling pleural catheters — R. Thomas, C.A. Budgeon, et al. (2014)
• Aggressive versus symptom-guided drainage of malignant pleural effusion via indwelling pleural catheters (AMPLE-2): an open-label randomised trial — S. Muruganandan, M. Azzopardi, et al. (2018)
• Histopathology of removed indwelling pleural catheters from patients with malignant pleural diseases — C.L. Tobin, R. Thomas, et al. (2016)
• Catheter Tract Metastasis in Mesothelioma Patients with Indwelling Pleural Catheters: A Retrospective Cohort Study — M.A. Mitchell, P. Li, et al. (2019)
• The use of indwelling pleural catheters for the management of malignant pleural effusion--direct costs in a Dutch hospital — R.C. Boshuizen, S. Onderwater, et al. (2013)

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