Tag Archives: Pleural effusion

97. Rapid Fire Journal Club – MIST 2

Posted on by

In this episode, we add another article to our Rapid Fire Journal Club. Luke Hedrick and Dave Furfaro discuss the MIST 2 trial published in NEJM in 2011 evaluating enzymatic therapy for complex parapneumonic effusions and empyemas.

 

Article and Reference

We are talking today about the MIST 2 trial evaluating the use of intrapleural tPa and DNase for intrapleural infections.

Rahman NM, Maskell NA, West A, Teoh R, Arnold A, Mackinlay C, Peckham D, Davies CW, Ali N, Kinnear W, Bentley A, Kahan BC, Wrightson JM, Davies HE, Hooper CE, Lee YC, Hedley EL, Crosthwaite N, Choo L, Helm EJ, Gleeson FV, Nunn AJ, Davies RJ. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med. 2011 Aug 11;365(6):518-26. doi: 10.1056/NEJMoa1012740. PMID: 21830966.

Key Learning Points

  •  
  •  
    • Background:
      • Infections in the pleural space are common and morbid, often requiring surgical intervention. Unfortunately, antibiotics and chest tube drainage often fail. The MIST1 trial (NEJM, 2005) of intrapleural streptokinase showed no benefit. MIST2 studied intrapleural tPA and DNase to ease drainage by breaking down septations and thinning pleural fluid.
    • Study Design (design, primary outcome, participants, etc)
      • Design:
        • Double-blind, double-dummy, 2×2 factorial RCT at 11 UK hospitals from 12/2005 to 11/2008
          • By double dummy, we mean that there was a sham placebo for each of the study drugs
      • Primary Outcome
        • Change in the percent of the hemithorax taken up by effusion on CXR at day 7 compared to day 1
        • Key secondary outcomes:
          • Referral for surgery
          • Hospital LOS
          • All cause 3 month and 12 month mortality
          • AEs
      • Participants
        • Inclusion:
          • Clinical evidence of infection (assessed by recruiting MD; EG, fever, CRP, WBC) and
          • Pleural fluid with any of:
            • Grossly purulent
            • Positive pleural fluid culture or gram stain
            • pH < 7.2
        • Exclusion: aiming to exclude patients with increased bleeding risk or who can’t re-expand the lung after drainage
          • Age < 18
          • Previous intrapleural fibrinolytics, DNase, or both for empyema
          • Allergy to tPA or DNase
          • Coincidental stroke (hemorrhage risk)
          • Major hemorrhage or trauma
          • Major surgery in the last 5 days
          • Previous pneumonectomy on the infected side
          • Pregnancy, lactation
          • Expected survival < 3 months from something other than what caused the pleural problem
        • Summary: Middle-aged, mostly male patients with complicated pleural effusion or empyema occupying 1/3 to 2/5 hemithorax with mostly small-bore CDs for mostly community-acquired infections

Small-bore here meant < 15 Fr

  • Intervention/Limitations
    • N = 210 (193 analyzed) randomized approximately 1:1 to one of the following 4 arms:
      1. tPA/Dnase (10mg and 5mg)
      2. tPA and placebo
      3. DNase and placebo
      4. Double placebo
      • Medications were given BID for 3 days with clamping of the CD for 1 hour after each dose (to keep the drug in the pleural space)
  • Outcomes/Safety
    • Power: with N = 210 (actual analysis = 193), 80% power to detect 1 in 5 more patients with a 50% reduction in pleural opacity on CXR
    • We’ll discuss the outcomes of tPA/DNase in combination because there was a highly significant interaction between the two (P = 0.002) for the primary outcome
    • Efficacy:
      • Primary (pleural effusion size reduction): -29.5% hemithorax vs baseline and -7.9% effusion size vs placebo (P = 0.005)
        • Neither drug worked on their own
      • Secondary:
        • Referral for surgery: 4% vs 16% (OR 0.17, P = 0.03)
        • Hospital LOS (excluding 391d outlier in placebo group): mean 11.8 vs 17 days (P = 0.006)
        • Mortality: no difference
    • Safety:
      • No difference in AE between groups
      • 6 serious events across all groups, mostly related to bleeding (intra-pleural, GI, hemoptysis); other AE were made up of pain with drug administration, transient AMS, rash
  • Takeaway
    • Combination intrapleural enzyme therapy (IET) with tPA and DNase improves drainage of infected pleural fluid, and reduces need for surgery and hospital LOS

Infographic

 

Podcast: Play in new window | Download

Subscribe: Apple Podcasts | Spotify | Amazon Music | Android | iHeartRadio | Podcast Index | RSS | More

71. Fellows’ Case Files: University of New Mexico

Posted on by

Today we’re visiting the University of New Mexico for another interesting entry in our Fellows’ Case Files.

 

Meet Our Guests

Neel Vahil is a second-year internal medicine resident at the University of New Mexico. He completed medical school at New York Medical College and is planning on applying to pulmonary critical care fellowship programs.

Ishan Patel is a third year PCCM fellow at the University of New Mexico and will be pursuing a second fellowship in clinical informatics this year. He completed medical school and residency in Internal Medicine at Oregon Health & Science University. His fellowship research has focused on clinical outcomes of intensivist-led ECMO programs.

Dr. Lucie Griffin completed her internal medicine residency and PCCM fellowship at the University of New Mexico and is currently the Director of the Albuquerque VA medical intensive care unit.

 

Case Presentation

A 69 year old male veteran who presents with 6 weeks of weight loss, cough, and malaise. He has ongoing tobacco use, and history of rheumatoid arthritis on HCQ and weekly MTX with etanercept, which he had stopped taking in the three prior months. Vitals: Afebrile, mildly tachycardic to 101, BP of 93/59, saturating appropriately on room air without any signs of respiratory distress

 

Key Learning Points

References and Further Reading

Komarla A, Yu GH, Shahane A. Pleural effusion, pneumothorax, and lung entrapment in rheumatoid arthritis. J Clin Rheumatol. 2015;21(4):211-215.

Boddington MM, Spriggs AI, Morton JA, Mowat AG. Cytodiagnosis of rheumatoid pleural effusions. J Clin Pathol. 1971;24(2):95-106.

Balbir-Gurman A, Yigla M, Nahir AM, Braun-Moscovici Y. Rheumatoid pleural effusion. Semin Arthritis Rheum. 2006;35(6):368-378

Podcast: Play in new window | Download

Subscribe: Apple Podcasts | Spotify | Amazon Music | Android | iHeartRadio | Podcast Index | RSS | More

Radiology Rounds – 8/8/23

Posted on by

Time for another Radiology Round by our Associate Editor Tess Litchman!

We have an older-aged woman found to have gastric and duodenal ulcers requiring multiple abdominal surgeries and transhepatic biliary drainage presenting with respiratory distress

She underwent pleural fluid drainage with the following pleural fluid studies

She ultimately had a right chest tube placed with 1.6 liters of green pleural fluid was drained

Given concern for a bilothorax, a pleural and serum bilirubin test were added. Her pleural bilirubin level was 17.2 and her serum bilirubin level was 0.5. Her chest tube was maintained, IV antibiotics were started and multi-disciplinary meetings occurred to determine next steps.

49. Top Consults: Malignant Pleural Effusions

Posted on by

We’re diving back into some pleural fluid today (okay that is kind of gross to think about and we apologize). If you haven’t listened to our prior pleural effusion episodes and want to start from the top, then check out Episode 36 for a general approach to pleural effusions, and Episode 37 to hear about parapneumonic effusions. Malignant effusions are another common consult question and we’ll talk about everything from detection to monitoring, to definitive management.

Meet Our Guests

Dr. David DiBardino is an Assistant Professor of Medicine at the University of Pennsylvania Medicine and is the Associate Director for Clinical Research within the Section of Interventional Pulmonology. He is also the Program Director for the Interventional Pulmonary Fellowship there.

Dr. Jamie Bessich is an Assistant Professor of Medicine and Cardiothoracic Surgery at NYU Grossman School of Medicine. She is the Section Chief of Interventional Pulmonology and is the Director of Bronchoscopy at Tisch Hospital.

Dr. Van Holden is an Associate Professor of Medicine at the University of Maryland School of Medicine and is the Pulmonary and Critical Care Fellowship Program Director there. She was last on the show for our very first Fellows’ Case Files when we discussed a fascinating case of pulmonary alveolar proteinosis.

Case Presentation

The page: 72M smoker, new effusion, concern for malignancy, tap?

Further history: 72 year old man with PMH of GOLD B COPD, tobacco use (55 pack years), HTN, HLD, and diabetes. He presented to the ED with progressive dyspnea and fatigue. He is on LAMA/LABA for his COPD, and he does not frequently have exacerbations. He has no increased sputum production or wheezing, but he has been feeling progressively fatigued and lethargic. H Over the past few weeks he has had more dyspnea on exertion, and now has it at rest too. It is a bit worse when he lies flat. He has had no weight gain or edema in his legs and has actually lost 10-15 pounds in the last 3 months. In the ED, he is newly requiring 3-4L NC, has decreased breath sounds on the right, and a CXR shows a large right-sided pleural effusion, as well as a large apical nodule with some spiculation, both of which are new from prior.

Key Learning Points

Causes of malignant pleural effusion

–Lung cancer is the most common in men

–Breast cancer is the most common cause in women

–Lung and breast cancer account for > 50% of all malignant pleural effusions

–Other less common causes are lymphoma, GU or GI tract cancer

–Remember to consider mesothelioma

Prognosis of MPE

–Malignant pleural effusion means the cancer is advanced and stage 4 by definition

–The average life expectancy after a diagnosis of MPE is 3-12 months, depending on the patient and the malignancy

Imaging and MPE

–Make sure to get a CT scan after drainage so no lesions are missed

–Ultrasound can be helpful to look for disruptions of the pleural line, loculated fluid, or pleural nodules

Pleural fluid analysis

–Make sure to send common labs (gram stain, culture, pH)

–Cell count is very important as most MPE are lymphocyte-predominant

–Triglycerides can be helpful as well (more on chylothorax in future episodes)

–Cytology is essential and makes the diagnosis. The sensitivity is 65 – 75 percent so repeat taps may be needed and you need to send at least 60 cc of fluid (often more)

–If you have high suspicion and no diagnosis after two taps, pleuroscopy and pleural biopsy is warranted

Management of MPE

–First you need to determine if the MPE is recurrent. This requires drainage and then monitoring

— The main options are repeat thoracenteses, pleurodesis, or indwelling pleural catheter. A combination can often be used, and shared decision making is essential to the determining the best option

–The three things to consider with recurrent malignant pleural effusion are:

  1. Did the patient feel better after drainage?
  2. Did the lung fully re-expand?
  3. What is the best option for this specific patient to optimize quality of life and time outside of the hospital?

–In AMPLE, pleural cetehters and talc pleurodesis were compared, and both are reasonable options with equivalent outcomes on quality of life; although pleural catehters had fewer hospital days overall.

References and Further Reading

  1. Thomas R, Fysh ETH, Smith NA, Lee P, Kwan BCH, Yap E, Horwood FC, Piccolo F, Lam DCL, Garske LA, Shrestha R, Kosky C, Read CA, Murray K, Lee YCG. Effect of an Indwelling Pleural Catheter vs Talc Pleurodesis on Hospitalization Days in Patients With Malignant Pleural Effusion: The AMPLE Randomized Clinical Trial. JAMA. 2017 Nov 21;318(19):1903-1912. doi: 10.1001/jama.2017.17426. PMID: 29164255; PMCID: PMC5820726.
  2. Iyer NP, Reddy CB, Wahidi MM, Lewis SZ, Diekemper RL, Feller-Kopman D, Gould MK, Balekian AA. Indwelling Pleural Catheter versus Pleurodesis for Malignant Pleural Effusions. A Systematic Review and Meta-Analysis. Ann Am Thorac Soc. 2019 Jan;16(1):124-131. doi: 10.1513/AnnalsATS.201807-495OC. PMID: 30272486.
  3. Wahidi MM, Reddy C, Yarmus L, Feller-Kopman D, Musani A, Shepherd RW, Lee H, Bechara R, Lamb C, Shofer S, Mahmood K, Michaud G, Puchalski J, Rafeq S, Cattaneo SM, Mullon J, Leh S, Mayse M, Thomas SM, Peterson B, Light RW. Randomized Trial of Pleural Fluid Drainage Frequency in Patients with Malignant Pleural Effusions. The ASAP Trial. Am J Respir Crit Care Med. 2017 Apr 15;195(8):1050-1057. doi: 10.1164/rccm.201607-1404OC. PMID: 27898215.
  4. Feller-Kopman DJ, Reddy CB, DeCamp MM, Diekemper RL, Gould MK, Henry T, Iyer NP, Lee YCG, Lewis SZ, Maskell NA, Rahman NM, Sterman DH, Wahidi MM, Balekian AA. Management of Malignant Pleural Effusions. An Official ATS/STS/STR Clinical Practice Guideline. Am J Respir Crit Care Med. 2018 Oct 1;198(7):839-849. doi: 10.1164/rccm.201807-1415ST. PMID: 30272503.

Podcast: Play in new window | Download

Subscribe: Apple Podcasts | Spotify | Amazon Music | Android | iHeartRadio | Podcast Index | RSS | More

Radiology Rounds – 4/25/2023

Posted on by

Today’s #RadiologyRounds is a reminder that pulmonary care extends beyond the lungs! Although we’ll have a CT chest too

A 70-year-old woman with a diagnosis of seronegative RA presents with progressive dyspnea. PFTs show a moderate restrictive defect and moderately reduced DLCO. Here is the CT scan:

The CT was interpreted as indeterminate for UIP / fibrosing NSIP. The basilar and subpleural fibrosis and honeycombing are consistent with UIP, but with reticular nodular infiltrates and pleural effusions that are less consistent. In reviewing her history: RF, CCP, and anti-SCL70 were all negative. On hand exam, she had MCP enlargement, some PIP synovitis, and slight R hand ulnar deviation. She did not have clear telangiectasias. She had a history of GERD. She denied Raynauds. She had significant skin thickening over her legs and limited ankle mobility. X-rays were obtained:

This showed severe dystrophic calcifications and no bony erosions. This degree of extensive dystrophic calcifications is consistent with scleroderma and the patient was felt to have limited scleroderma, and possibly an overlap syndrome

The patient was started on MMF as the initial agent based on the Scleroderma Lung Study II (SLSII): https://pubmed.ncbi.nlm.nih.gov/27469583/ Glucocorticoids were avoided given the risk of scleroderma renal crisis with steroids. An anti-fibrotic was also considered but not started as 1st line.

Radiology Rounds – 3/28/2023

Posted on by

It is Tuesday #RadiologyRounds time! We are in a pleural state of mind here at Pulm PEEPs. This is another great case authored by rockstar-associate editor @TessLitchman

A 65-year-old man with cirrhosis presents to the ED with progressive shortness of breath:

The CXR has a right lower opacity decreasing in density that is silhouetting the right hemi-diaphragm without signs of volume loss on the right concerning for pleural effusion. There is also associated atelectasis adjacent to the effusion

What is your next step for this patient?

This patient had a bedside POCUS revealing a simple pleural effusion and abdominal ascites. He also had a CT scan performed:

Based on his imaging and history, the most likely diagnosis on the differential was a hepatic hydrothorax. Here is some more information on hepatic hydrothoraces:

A transudative effusion was confirmed on thoracentesis, and no other clear etiologies were identified The treatment of hepatic hydrothorax should always start with medical management of volume overload in cirrhosis. Pleural procedures can be used for disease that is refractory

36. Top Consults Series: Approach to Pleural Effusions

Posted on by

Today the PulmPEEPs are joined by two amazing educators as we start off our Top Consult series on Pleural Disease. Join us today as we go through cases to learn a systematic approach for evaluation and management of pleural effusions.

Meet our Guests

Dr. Mira John received her medical degree from Tulane University School of Medicine in New Orleans and completed internal medicine residency at Icahn School of Medicine at Mount Sinai. She is currently a second-year pulmonary and critical fellow at the University of Washington.

Dr. Ylinne Lynch completed her fellowship training at the University of Washington and is currently a Clinical Instructor at the UW. She is a great medical educator and spends her clinical time on the pulmonary consult service as well as in the ICU. 

Learning Points

Podcast: Play in new window | Download

Subscribe: Apple Podcasts | Spotify | Amazon Music | Android | iHeartRadio | Podcast Index | RSS | More

Radiology Rounds – 2/14/23

Posted on by

What better way to celebrate Valentine’s Day than with a new #RadiologyRounds?! We think it is time for a Lung-centered holiday, but until then enjoy this case.

The patient’s pneumothorax was managed conservatively with observation and temporary 100% oxygen via a non-rebreather for nitrogen washout. The consolidations and effusion were concerning, so the patient had a CT chest performed.