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Am J Respir Crit Care Med
Am J Respir Crit Care Med
ajrccm
American Journal of Respiratory and Critical Care Medicine
1073-449X
1535-4970
American Thoracic Society

202404-0755LE
10.1164/rccm.202404-0755LE
Correspondence
Reply to Ravaglia et al.: MIST-3 Is Well Worth an Echo!
https://orcid.org/0000-0001-9196-3934
Bedawi Eihab O. 1 2
Stavroulias Dionisios 3
Belcher Elizabeth 3
Rahman Najib M. 4 5 6
1 Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom;
2 Academic Directorate of Respiratory Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom;
3 Department of Cardiothoracic Surgery, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom;
4 Oxford Respiratory Trials Unit, Nuffield Department of Medicine,
5 NIHR Oxford Biomedical Research Centre, and
6 Chinese Academy of Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
Correspondence and requests for reprints should be addressed to Eihab O Bedawi, Ph.D., F.R.C.P., Department of Respiratory Medicine, Brearley Wing, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Herries Road, Sheffield S5 7AU, UK. Email: eombedawi1@sheffield.ac.uk.
11 7 2024
1 9 2024
11 7 2024
210 5 695696
Copyright © 2024 by the American Thoracic Society
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0. For commercial usage and reprints, please e-mail Diane Gern (dgern@thoracic.org).
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pmcFrom the Authors:

We thank Ravaglia and colleagues for their interest in MIST-3 (Third Multicenter Intrapleural Sepsis Trial) and their letter to the Journal about our recent article (1). In modern practice, the role of empyema staging in predicting failure of optimal image-guided drain placement remains unclear, given that most patients have mixed-stage disease and stage 3 empyema being a predictor of risk for conversion rather than a direct contraindication to video-assisted thoracoscopic surgery (2, 3). The point here is that, regardless of stage, an appropriately trained surgeon proceeding to video-assisted thoracoscopic surgery has the prerequisite training and expertise to proceed to decortication and convert to open thoracotomy as and when required in the safest environment with appropriate anesthetic support, including single-lung ventilation.

This is at odds with medical thoracoscopy (MT), which, by definition, is performed by physicians with no formal surgical training, in most cases with the patient under local anesthetic with awake sedation, as in the series referenced. MT has been proposed as “effective and safe” on the basis of a retrospective series equivalent to three patients per hospital per year, which questions the generalizability and applicability. These are the two largest multicenter series in the literature; however, the selection bias is a major limitation in the MT evidence base (4). To date, the only randomized controlled trial (RCT) addressing this question was underpowered (n = 32) and was methodologically flawed in its primary outcome (5).

Brutsche and colleagues reported that MT was “primarily successful in 91% of cases”; yet, half of these patients required postintervention fibrinolytics “for 3–5 days,” which, by virtue of this need for additional intervention, equates to a treatment failure rate of 49% (6). In the more recent cohort described by Ravaglia and colleagues (n = 131), treatment success, similar to the RCT by Kheir and colleagues (5), was reported at 75%. This is an improvement on the 66% success rate of chest tube and antibiotics (7) but still falls significantly short compared with surgery and combination intrapleural enzyme therapy (IET), both with success rates in excess of 85–90% (2). Moreover, MT has a considerable pooled complication rate relating to post-procedural surgical emphysema and persistent air leak that has been reported as high as 26.7% (4).

The authors suggested that stratification by RAPID (renal [urea], age, fluid purulence, infection source, dietary [albumin]) score (7), the only prospectively and externally validated prognostic tool in the literature, was inadequate because it did not consider ultrasound. The evidence linking sonographic parameters to clinical outcomes is limited to small retrospective case series (8).

We applaud Ravaglia and colleagues for their MT expertise and access, but their practice is based on what we perceive to be a very limited evidence base. A recent consensus statement suggested that physicians only occasionally consider MT in multiloculated pleural infection in elderly and frail patients considered to be at high surgical risk (2). We strongly encourage the authors to proceed with a well-designed, adequately powered, multicenter RCT to address this unmet need for a higher level of evidence in the literature.

Originally Published in Press as DOI: 10.1164/rccm.202404-0755LE on July 11, 2024

Author disclosures are available with the text of this letter at www.atsjournals.org.
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References

1. Bedawi EO Stavroulias D Hedley E Blyth KG Kirk A De Fonseka D et al. Early video-assisted thoracoscopic surgery or intrapleural enzyme therapy in pleural infection: a feasibility randomized controlled trial. The Third Multicenter Intrapleural Sepsis Trial—MIST-3 Am J Respir Crit Care Med 2023 208 1305 1315 37820359
2. Bedawi EO Ricciardi S Hassan M Gooseman MR Asciak R Castro-Anon O et al. ERS/ESTS statement on the management of pleural infection in adults Eur Respir J 2022 61 2201062
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6. Brutsche MH, Tassi GF, Györik S, Gökcimen M, Renard C, Marchetti GP, et al. Treatment of sonographically stratified multiloculated thoracic empyema by medical thoracoscopy. Chest 2005;128:3303–3309.
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