Evidence map›Paper›PMID 35716828›Full record

Observational studyChest2022

Bleeding Risk With Combination Intrapleural Fibrinolytic and Enzyme Therapy in Pleural Infection: An International, Multicenter, Retrospective Cohort Study.

Jason Akulian, Eihab O Bedawi, Hawazin Abbas, Christine Argento, David T Arnold, Akshu Balwan, Hitesh Batra, Juan Pablo Uribe Becerra, Adam Belanger, Kristin Berger and 42 more

Open access · hybridAbstract readObservational StudyMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Chest, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 2 pooled it
7.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 54 citations in OpenAlex.

  1. Outcomes of intrapleural fibrinolytic and deoxyribonuclease therapy in pleural infection: a systematic review and meta-analysis.European respiratory review : an official journal of the European Respiratory Society · 2026
    Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. Article
  7. Article
  8. Article
  9. Article
  10. WABIP/AABIP statement on therapeutic indications of medical thoracoscopy for benign pleural disease.European respiratory review : an official journal of the European Respiratory Society · 2026
    Review
  11. Article
  12. Review
  13. Local management of pleural infection: a narrative review.European journal of medical research · 2026
    Review
  14. What is new in pleural infections?Breathe (Sheffield, England) · 2026
    Review
  15. Article
  16. Article
  17. Surgical interventions for pleural infection.Breathe (Sheffield, England) · 2025
    Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

52 authors at 20 institutions in 2 countries.

Jason AkulianDivision of Pulmonary and Critical Care, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC; Carolina Center for Pleural Diseases, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC.
Eihab O BedawiOxford Pleural Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, England; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, England. Electronic address: eihab.bedawi@ouh.nhs.uk.
Hawazin AbbasDivision of Pulmonary, Critical Care and Sleep Medicine, University of Florida, Gainesville, FL.
Christine ArgentoDivision of Pulmonary and Critical Care, Johns Hopkins University School of Medicine, Baltimore, MD.
David T ArnoldDivision of Pulmonary and Critical Care, Duke University, Durham, NC.
Akshu BalwanDivision of Pulmonary, Critical Care and Sleep Medicine, University of New Mexico School of Medicine, Albuquerque, NM.
Hitesh BatraDivision of Pulmonary, Allergy, and Critical Care Medicine, The University of Alabama at Birmingham, Birmingham, AL.
Juan Pablo Uribe BecerraDivision of Thoracic Surgery and Interventional Pulmonology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Adam BelangerDivision of Pulmonary and Critical Care, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC.
Kristin BergerDivision of Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York, NY.
Allen Cole BurksDivision of Pulmonary and Critical Care, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC; Carolina Center for Pleural Diseases, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC.
Jiwoon ChangDivision of Pulmonary, Allergy, and Critical Care Medicine, Stanford University School of Medicine, Palo Alto, CA.
Ara A ChrissianDivision of Pulmonary, Critical Care, Hyperbaric, Allergy, and Sleep Medicine, Loma Linda University, Loma Linda, CA.
David M DiBardinoSection of Interventional Pulmonology, Division of Pulmonary, Allergy, and Critical Care Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Xavier Fonseca FuentesDivision of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN.
Yaron B GesthalterDivision of Pulmonary, Critical Care, Allergy and Sleep, The University of California San Francisco, San Francisco, CA.
Christopher R GilbertDivision of Thoracic Surgery and Interventional Pulmonology, Swedish Cancer Institute and Center for Lung Cancer Research in Honor of Wayne Gittinger, Seattle, WA.
Kristen GlisinskiDivision of Pulmonary and Critical Care, National Jewish Health, Denver, CO.
Mark GodfreyDivision of Pulmonary and Critical Care, Yale University School of Medicine, New Haven, CT.
Jed A GordenDivision of Thoracic Surgery and Interventional Pulmonology, Swedish Cancer Institute and Center for Lung Cancer Research in Honor of Wayne Gittinger, Seattle, WA.
Horiana GrosuDivision of Pulmonary and Critical Care, The University Texas MD Anderson Cancer Center, Houston, TX.
Mridul GuptaDivision of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi Medical Center, Jackson, MS.
Fayez KheirDivision of Thoracic Surgery and Interventional Pulmonology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Kevin C MaSection of Interventional Pulmonology, Division of Pulmonary, Allergy, and Critical Care Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Adnan MajidDivision of Thoracic Surgery and Interventional Pulmonology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Fabien MaldonadoDivision of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN.
Nick A MaskellAcademic Respiratory Unit, Bristol Medical School, University of Bristol, Bristol, England.
Hiren MehtaDivision of Pulmonary, Critical Care and Sleep Medicine, University of Florida, Gainesville, FL.
Joshua MercerDivision of Pulmonary and Critical Care, Johns Hopkins University School of Medicine, Baltimore, MD.
John MullonDivision of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN.
Darlene NelsonDivision of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN.
Elaine NguyenDivision of Pulmonary, Critical Care, Hyperbaric, Allergy, and Sleep Medicine, Loma Linda University, Loma Linda, CA.
Edward M PickeringDivision of Pulmonary and Critical Care, University of Maryland School of Medicine, Baltimore, MD.
Jonathan PuchalskiDivision of Pulmonary and Critical Care, Yale University School of Medicine, New Haven, CT.
Chakravarthy ReddyDivision of Pulmonary and Critical Care, University of Utah, Salt Lake City, UT.
Alberto E ReveloInterventional Pulmonology Section, Division of Pulmonary, Critical Care and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, OH.
Lance RollerDivision of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN.
Ashutosh SachdevaDivision of Pulmonary and Critical Care, University of Maryland School of Medicine, Baltimore, MD.
Trinidad SanchezDivision of Pulmonary and Critical Care, Virginia Commonwealth University, Richmond, VA.
Priya SathyanarayanDivision of Pulmonary and Critical Care, Johns Hopkins University School of Medicine, Baltimore, MD.
Roy SemaanDivision of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.
Michal SenitkoDivision of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi Medical Center, Jackson, MS.
Samira ShojaeeDivision of Pulmonary and Critical Care, Virginia Commonwealth University, Richmond, VA.
Ryan StoryInterventional Pulmonology Section, Division of Pulmonary, Critical Care and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, OH.
Jeffrey ThiboutotDivision of Pulmonary and Critical Care, Johns Hopkins University School of Medicine, Baltimore, MD.
Momen WahidiDivision of Pulmonary and Critical Care, Duke University, Durham, NC.
Candice L WilshireDivision of Thoracic Surgery and Interventional Pulmonology, Swedish Cancer Institute and Center for Lung Cancer Research in Honor of Wayne Gittinger, Seattle, WA.
Diana YuDivision of Pulmonary, Critical Care and Sleep Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Aline ZoukDivision of Pulmonary, Allergy, and Critical Care Medicine, The University of Alabama at Birmingham, Birmingham, AL.
Najib M RahmanOxford Pleural Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, England; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, England.
Lonny YarmusDivision of Pulmonary and Critical Care, Johns Hopkins University School of Medicine, Baltimore, MD.
Interventional Pulmonary Outcomes Group
Johns Hopkins University · USBeth Israel Deaconess Medical Center · USMayo Clinic · USSwedish Medical Center · USUniversity of North Carolina at Chapel Hill · USDuke University · USLoma Linda University Children's Hospital · USThe Ohio State University Wexner Medical Center · USUniversity of Alabama at Birmingham · USUniversity of Florida · USUniversity of Maryland, Baltimore · USUniversity of Mississippi Medical Center · USUniversity of Pennsylvania · USVanderbilt University Medical Center · USVirginia Commonwealth University · USYale University · USCornell University · USNational Jewish Health · USOxford Health NHS Foundation Trust · GBStanford University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Medical Research Council G1001128NCATS NIH HHS UL1 TR001863
6 · The paper itself

Abstract

backgroundCombination intrapleural fibrinolytic and enzyme therapy (IET) has been established as a therapeutic option in pleural infection. Despite demonstrated efficacy, studies specifically designed and adequately powered to address complications are sparse. The safety profile, the effects of concurrent therapeutic anticoagulation, and the nature and extent of nonbleeding complications remain poorly defined. RESEARCH QUESTION: What is the bleeding complication risk associated with IET use in pleural infection? STUDY DESIGN AND

methodsThis was a multicenter, retrospective observational study conducted in 24 centers across the United States and the United Kingdom. Protocolized data collection for 1,851 patients treated with at least one dose of combination IET for pleural infection between January 2012 and May 2019 was undertaken. The primary outcome was the overall incidence of pleural bleeding defined using pre hoc criteria.

resultsOverall, pleural bleeding occurred in 76 of 1,833 patients (4.1%; 95% CI, 3.0%-5.0%). Using a half-dose regimen (tissue plasminogen activator, 5 mg) did not change this risk significantly (6/172 [3.5%]; P = .68). Therapeutic anticoagulation alongside IET was associated with increased bleeding rates (19/197 [9.6%]) compared with temporarily withholding anticoagulation before administration of IET (3/118 [2.6%]; P = .017). As well as systemic anticoagulation, increasing RAPID score, elevated serum urea, and platelets of < 100 × 10

interpretationIET use in pleural infection confers a low overall bleeding risk. Increased rates of pleural bleeding are associated with concurrent use of anticoagulation but can be mitigated by withholding anticoagulation before IET. Concomitant administration of IET and therapeutic anticoagulation should be avoided. Parameters related to higher IET-related bleeding have been identified that may lead to altered risk thresholds for treatment.

Indexed as

Communicable DiseasesEmpyema, PleuralPleural DiseasesPleural EffusionEnzyme TherapyFibrinolytic AgentsHemorrhageHumansRetrospective StudiesTissue Plasminogen ActivatorFibrinolytic AgentsTissue Plasminogen Activatorbleedingempyemafibrinolysisintrapleuralparapneumonic pleural effusion

Identifiers

PMID35716828
PMCPMC9773231
OpenAlexW4282974257

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.