Modified regimen intrapleural alteplase with pulmozyme in pleural infection management: a tertiary teaching hospital experience

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Abstract

Background

Current management of poorly draining complex effusions favours less invasive image-guided placement of smaller tubes and adjunctive intrapleural fibrinolysis therapy (IPFT). In MIST-2 trial, intrapleural 10 mg alteplase (t-PA) with 5 mg of pulmozyme (DNase) twice daily for 72 h were used. We aimed to assess the effectiveness and safety of a modified regimen 16 mg t-PA with 5 mg of DNase administered over 24 h in the management of complex pleural infection.

Methods

This was a single centre, prospective study involving patients with poorly drained pleural infection. Primary outcome was the change of pleural opacity on chest radiograph at day 7 compared to baseline. Secondary outcomes include volume of fluid drained, inflammatory markers improvement, surgical referral, length of hospitalisation, and adverse events.

Results

Thirty patients were recruited. Majority, 27 (90%) patients were successfully treated. Improvement of pleural opacity on chest radiograph was observed from 36.9% [Interquartile range (IQR 21.8–54.9%)] to 18.1% (IQR 8.8–32.7%) of hemithorax ( P < 0.05). T-PA/DNase increased fluid drainage from median of 45 mls (IQR 0–100) 24 h prior to intrapleural treatment to 1442 mls (IQR 905–2360) after 72 h; ( P < 0.05) and reduction of C-reactive protein ( P < 0.05). Pain requiring escalation of analgesia affected 20% patients and 9.9% experienced major adverse events. None required surgical intervention.

Conclusion

This study suggests that a modified regimen 16 mg t-PA with 5 mg DNase can be safe and effective for patients with poorly drained complex pleural infection.

Trial registration The study was registered retrospectively on 07/06/2021 with ClinicalTrials number NCT04915586 ( https://clinicaltrials.gov/ct2/show/NCT04915586).

Supplementary Information

The online version contains supplementary material available at 10.1186/s12890-022-01995-z.

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Most cited references 25

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Management of pleural infection in adults: British Thoracic Society Pleural Disease Guideline 2010.

, Abigail H. Davies, Robert Davies (2010)

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U.K. Controlled trial of intrapleural streptokinase for pleural infection.

John F. Gleeson, T. Peto, Jeffrey Rees … (2005)

Intrapleural fibrinolytic agents are used in the drainage of infected pleural-fluid collections. This use is based on small trials that did not have the statistical power to evaluate accurately important clinical outcomes, including safety. We conducted a trial to clarify the therapeutic role of intrapleural streptokinase. In this double-blind trial, 454 patients with pleural infection (defined by the presence of purulent pleural fluid or pleural fluid with a pH below 7.2 with signs of infection or by proven bacterial invasion of the pleural space) were randomly assigned to receive either intrapleural streptokinase (250,000 IU twice daily for three days) or placebo. Patients received antibiotics and underwent chest-tube drainage, surgery, and other treatment as part of routine care. The number of patients in the two groups who had died or needed surgical drainage at three months was compared (the primary end point); secondary end points were the rates of death and of surgery (analyzed separately), the radiographic outcome, and the length of the hospital stay. The groups were well matched at baseline. Among the 427 patients who received streptokinase or placebo, there was no significant difference between the groups in the proportion of patients who died or needed surgery (with streptokinase: 64 of 206 patients [31 percent]; with placebo: 60 of 221 [27 percent]; relative risk, 1.14 [95 percent confidence interval, 0.85 to 1.54; P=0.43), a result that excluded a clinically significant benefit of streptokinase. There was no benefit to streptokinase in terms of mortality, rate of surgery, radiographic outcomes, or length of the hospital stay. Serious adverse events (chest pain, fever, or allergy) were more common with streptokinase (7 percent, vs. 3 percent with placebo; relative risk, 2.49 [95 percent confidence interval, 0.98 to 6.36]; P=0.08). The intrapleural administration of streptokinase does not improve mortality, the rate of surgery, or the length of the hospital stay among patients with pleural infection. Copyright 2005 Massachusetts Medical Society.

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Intrapleural use of tissue plasminogen activator and DNase in pleural infection.

Najib M Rahman, Nicholas Maskell, Alex West … (2011)

More than 30% of patients with pleural infection either die or require surgery. Drainage of infected fluid is key to successful treatment, but intrapleural fibrinolytic therapy did not improve outcomes in an earlier, large, randomized trial. We conducted a blinded, 2-by-2 factorial trial in which 210 patients with pleural infection were randomly assigned to receive one of four study treatments for 3 days: double placebo, intrapleural tissue plasminogen activator (t-PA) and DNase, t-PA and placebo, or DNase and placebo. The primary outcome was the change in pleural opacity, measured as the percentage of the hemithorax occupied by effusion, on chest radiography on day 7 as compared with day 1. Secondary outcomes included referral for surgery, duration of hospital stay, and adverse events. The mean (±SD) change in pleural opacity was greater in the t-PA-DNase group than in the placebo group (-29.5±23.3% vs. -17.2±19.6%; difference, -7.9%; 95% confidence interval [CI], -13.4 to -2.4; P=0.005); the change observed with t-PA alone and with DNase alone (-17.2±24.3 and -14.7±16.4%, respectively) was not significantly different from that observed with placebo. The frequency of surgical referral at 3 months was lower in the t-PA-DNase group than in the placebo group (2 of 48 patients [4%] vs. 8 of 51 patients [16%]; odds ratio for surgical referral, 0.17; 95% CI, 0.03 to 0.87; P=0.03) but was greater in the DNase group (18 of 46 patients [39%]) than in the placebo group (odds ratio, 3.56; 95% CI, 1.30 to 9.75; P=0.01). Combined t-PA-DNase therapy was associated with a reduction in the hospital stay, as compared with placebo (difference, -6.7 days; 95% CI, -12.0 to -1.9; P=0.006); the hospital stay with either agent alone was not significantly different from that with placebo. The frequency of adverse events did not differ significantly among the groups. Intrapleural t-PA-DNase therapy improved fluid drainage in patients with pleural infection and reduced the frequency of surgical referral and the duration of the hospital stay. Treatment with DNase alone or t-PA alone was ineffective. (Funded by an unrestricted educational grant to the University of Oxford from Roche UK and by others; Current Controlled Trials number, ISRCTN57454527.).

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Author and article information

Contributors

Mohamed Faisal Abdul Hamid: faisal.hamid@ppukm.ukm.edu.my

Journal

Journal ID (nlm-ta): BMC Pulm Med

Journal ID (iso-abbrev): BMC Pulm Med

Title: BMC Pulmonary Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2466

Publication date (Electronic): 17 May 2022

Publication date PMC-release: 17 May 2022

Publication date Collection: 2022

Volume: 22

Electronic Location Identifier: 199

Affiliations

[1 ]GRID grid.240541.6, ISNI 0000 0004 0627 933X, Respiratory Unit, Department of Medicine, , Universiti Kebangsaan Malaysia Medical Centre, ; Jalan Yaacob Latif, Bandar Tun Razak, 56000 Kuala Lumpur, Malaysia

[2 ]GRID grid.240541.6, ISNI 0000 0004 0627 933X, Department of Radiology, , Universiti Kebangsaan Malaysia Medical Centre, ; Kuala Lumpur, Malaysia

[3 ]GRID grid.240541.6, ISNI 0000 0004 0627 933X, Department of Paediatrics, , Universiti Kebangsaan Malaysia Medical Centre, ; Kuala Lumpur, Malaysia

[4 ]GRID grid.240541.6, ISNI 0000 0004 0627 933X, Department of Pharmacy, , Universiti Kebangsaan Malaysia Medical Centre, ; Kuala Lumpur, Malaysia

Article

Publisher ID: 1995

DOI: 10.1186/s12890-022-01995-z

PMC ID: 9115979

PubMed ID: 35581627

SO-VID: ebb3e6de-f265-4a00-b945-4da04b3d27dd

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 19 February 2022

Date accepted : 3 May 2022

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100004515, Universiti Kebangsaan Malaysia;

Award ID: FF-2020-008

Award Recipient : Mohamed Faisal Abdul Hamid

Custom metadata

ScienceOpen disciplines: Respiratory medicine

Keywords: intrapleural fibrinolysis,pleural infection,empyema,alteplase,dnase

Data availability:

ScienceOpen disciplines: Respiratory medicine

Keywords: intrapleural fibrinolysis, pleural infection, empyema, alteplase, dnase

Modified regimen intrapleural alteplase with pulmozyme in pleural infection management: a tertiary teaching hospital experience

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Abstract

Background

Methods

Results

Conclusion

Supplementary Information

Related collections

Inflamed lung in vitro co-culture models

Most cited references 25

Management of pleural infection in adults: British Thoracic Society Pleural Disease Guideline 2010.

U.K. Controlled trial of intrapleural streptokinase for pleural infection.

Intrapleural use of tissue plasminogen activator and DNase in pleural infection.

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