PulmPEEPs

In the penultimate episode in our ARDS Rapid Fire Journal Club Summer Series we are talking about the DEXA-ARDS trial (published in Lancet Respiratory Medicine in 2020). This trial evaluated the impact of dexamethasone in the treatment of ARDS.

Article and Reference

Today we’re discussing the DEXA-ARDS trial published in Lancet Respiratory Medicine in 2020. This trial evaluated the impact of dexamethasone on mortality and duration of mechanical ventilation for patients with ARDS.

Villar J, Ferrando C, Martínez D, Ambrós A, Muñoz T, Soler JA, Aguilar G, Alba F, González-Higueras E, Conesa LA, Martín-Rodríguez C, Díaz-Domínguez FJ, Serna-Grande P, Rivas R, Ferreres J, Belda J, Capilla L, Tallet A, Añón JM, Fernández RL, González-Martín JM; dexamethasone in ARDS network. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med. 2020 Mar;8(3):267-276. doi: 10.1016/S2213-2600(19)30417-5. Epub 2020 Feb 7. PMID: 32043986.

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Article Notes

We have another great case in our Fellows’ Case Files coming today from UMass Chan. Listen in for a great discussion about a fascinating case with interesting physical exam and radiographic findings.

Meet Our Guests

Dr. Jen Kodela completed her residency training at UMass Memorial Medical Center and is currently a third year PCCM fellow at UMass Chan.

Dr. Ariel McKenna completed her residency training at Maine Medical Center and is also currently a third year PCCM fellow at UMass Chan.

Dr. Will Wong is an Assistant Professor of Medicine and is the Program Director of the PCCM fellowship at UMass Chan

Case Presentation

A 75 y/o F presenting with acute on chronic SOB, cough, L sided chest pain and rash. She has had ~7 months of progressive dyspnea, now a/w 2 months of productive cough, and several weeks of L sided chest pain and rash. She has been seen multiple times in the past two months for these sxs. During that time she received multiple antibiotic courses (urgent care, outpatient providers), including augmentin, azithromycin and levaquin, and asthma directed therapy (no steroids). Imaging throughout that time (CXRs, CTPE) show progression from a LLL infiltrate to bibasilar infiltrates. Despite these interventions, sxs continue to worsen. One month prior she was admitted to an OSH w/ continued worsening, vitals stable, exam nonfocal, mild leukocytosis but infectious w/u bland. Received broad spectrum abx. Bronch w/ BAL offers negative cultures, cytology, cell count w/ 66% neutrophils, 14% eosinophils. Discharged w/ dx of PNA on a 10 day course of levaquin and new exertional oxygen requirement of 2L. She then presents to Umass ~1 month later w/ continued progression of sxs

Key Learning Points

1. Formulate a differential diagnosis for non-resolving pneumonia

2. Evaluate the utility of transbronchial biopsy in the workup of undifferentiated ILD

3. Describe the clinical manifestations of antisynthetase syndrome and identify the differences in presentation associated with PL-12 positivity

References and Further Reading

1. Kuru T, Lynch JP 3rd. Nonresolving or slowly resolving pneumonia. Clin Chest Med. 1999 Sep;20(3):623-51. doi: 10.1016/s0272-5231(05)70241-0. PMID: 10516909.

2. Troy LK, Grainge C, Corte TJ, Williamson JP, Vallely MP, Cooper WA, Mahar A, Myers JL, Lai S, Mulyadi E, Torzillo PJ, Phillips MJ, Jo HE, Webster SE, Lin QT, Rhodes JE, Salamonsen M, Wrobel JP, Harris B, Don G, Wu PJC, Ng BJ, Oldmeadow C, Raghu G, Lau EMT; Cryobiopsy versus Open Lung biopsy in the Diagnosis of Interstitial lung disease alliance (COLDICE) Investigators. Diagnostic accuracy of transbronchial lung cryobiopsy for interstitial lung disease diagnosis (COLDICE): a prospective, comparative study. Lancet Respir Med. 2020 Feb;8(2):171-181. doi: 10.1016/S2213-2600(19)30342-X. Epub 2019 Sep 29. PMID: 31578168.

3. Hallowell RW, Danoff SK. Diagnosis and Management of Myositis-Associated Lung Disease. Chest. 2023 Jun;163(6):1476-1491. doi: 10.1016/j.chest.2023.01.031. Epub 2023 Feb 9. PMID: 36764512.

4. Hallowell RW, Paik JJ. Myositis-associated interstitial lung disease: a comprehensive approach to diagnosis and management. Clin Exp Rheumatol. 2022 Feb;40(2):373-383. doi: 10.55563/clinexprheumatol/brvl1v. Epub 2021 Mar 25. PMID: 33769263; PMCID: PMC8855729.

5. Marie I, Josse S, Decaux O, Dominique S, Diot E, Landron C, Roblot P, Jouneau S, Hatron PY, Tiev KP, Vittecoq O, Noel D, Mouthon L, Menard JF, Jouen F. Comparison of long-term outcome between anti-Jo1- and anti-PL7/PL12 positive patients with antisynthetase syndrome. Autoimmun Rev. 2012 Aug;11(10):739-45. doi: 10.1016/j.autrev.2012.01.006. Epub 2012 Feb 3. PMID: 22326685.

In this podcast episode, we continue our summer series reviewing landmark ARDS studies. Today, Dave and Luke discuss the PROSEVA trial (published in NEJM in 2013) which evaluated the impact of early, prolonged proning in patients with severe ARDS.

Article and Reference

We are talking about the PROSEVA trial today which evaluated the patients with severe ARDS (P/F < 150) to undergo prone-positioning sessions of at least 16 hours or to be left in the supine position.

Guérin C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T, Mercier E, Badet M, Mercat A, Baudin O, Clavel M, Chatellier D, Jaber S, Rosselli S, Mancebo J, Sirodot M, Hilbert G, Bengler C, Richecoeur J, Gainnier M, Bayle F, Bourdin G, Leray V, Girard R, Baboi L, Ayzac L; PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013 Jun 6;368(23):2159-68. doi: 10.1056/NEJMoa1214103. Epub 2013 May 20. PMID: 23688302.

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In this podcast episode, we continue our summer series reviewing landmark ARDS studies. Today, Dave and Luke discuss the ROSE trial (published in NEJM in 2019) which investigated use of continuous neuromuscular blockade in moderate to severe ARDS.

Article and Reference

We are talking about the ROSE trial today which was a comparison of early continuous neuromuscular blockade in patients with ARDS who were receiving mechanical ventilation.

Reference: National Heart, Lung, and Blood Institute PETAL Clinical Trials Network; Moss M, Huang DT, Brower RG, Ferguson ND, Ginde AA, Gong MN, Grissom CK, Gundel S, Hayden D, Hite RD, Hou PC, Hough CL, Iwashyna TJ, Khan A, Liu KD, Talmor D, Thompson BT, Ulysse CA, Yealy DM, Angus DC. Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome. N Engl J Med. 2019 May 23;380(21):1997-2008. doi: 10.1056/NEJMoa1901686. Epub 2019 May 19. PMID: 31112383; PMCID: PMC6741345.

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In this podcast episode, we continue our summer series reviewing landmark ARDS studies. Today, Dave and Luke discuss the FACTT trial, which investigated fluid management strategies in ARDS. This was published in the NEJM in 2006.

Article and Reference

We’re talking about the FACTT trial today which was a “Comparison of Two Fluid-Management Strategies in Acute Lung Injury”

Reference: National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006 Jun 15;354(24):2564-75. doi: 10.1056/NEJMoa062200. Epub 2006 May 21. PMID: 16714767.

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Summary of discussion:

Background: The FACT trial aimed to address fluid balance in ARDS, given the complexity of managing pulmonary edema and systemic organ failure. The challenge has been finding the right balance between managing fluid to optimize cardiac function and avoiding exacerbation of pulmonary edema.

Study Design:

Fluid Management Protocol:

Results:

Conclusion: The trial indicated that a conservative fluid management strategy in ARDS patients can reduce ventilator dependence and ICU length of stay without worsening shock or end-organ function. It underscores the benefit of managing fluid conservatively to protect lung function, even though it didn’t significantly reduce mortality.

Overall, the FACT trial supports the practice of conservative fluid management in ARDS, advocating that “dry lungs are happy lungs” for improving patient outcomes.

Today, we’re going to be talking about pre-oxygenation methods for endotracheal intubation and the PREOXI Trial which is hot off the presses in the New England Journal of Medicine in June of 2024. This trial has potentially widespread, practice changing results and we’re lucky enough to be joined by two of the authors to discuss.

Meet Our Guests

Dr. Kevin Gibbs is an Associate Professor of Medicine at Wake Forest University School of Medicine. He obtained his MD at George Washington University School of Medicine, and completed his residency and fellowship training at Johns Hopkins. He is an active researcher in critical care, ARDS, mechanical ventilation, and pragmatic trial design.

Dr. Jon Casey is an Assistant Professor of Medicine for the Division of Allergy, Pulmonary, and Critical Care Medicine at Vanderbilt University Medical Center. He obtained his MD from the University of Louisville School of Medicine, and completed his residency training at Brigham and Women’s Hospital before going to Vanderbilt for fellowship training. He is a physician scientist and also has his Masters of Science in Clinical Investigation. His research is focused on comparative effectiveness of ICU treatments and he also has a focus on pragmatic trials. He is supported with NIH funding and is active in the American Thoracic Society Critical Care Assembly.

Summarized Key Points

• Significance of the Problem: Tracheal intubation in emergency and ICU settings is common, with significant risks such as hypoxemia (10-20% incidence) and cardiac arrest (2% incidence) associated with the procedure. This makes effective pre-oxygenation crucial.
• Methods of Pre-oxygenation: Common methods include face mask oxygen (e.g., non-rebreather, bag-mask devices) and more advanced techniques like non-invasive ventilation (used in about 15% of cases globally). Each method has pros (e.g., simplicity, no risk of aspiration for face masks; 100% oxygen delivery, positive pressure for non-invasive ventilation) and cons (e.g., potential for gastric insufflation with non-invasive ventilation).
• Study Design: The study discussed in the podcast is a pragmatic trial aiming to optimize pre-oxygenation strategies to prevent peri-intubation hypoxemia. Eligibility criteria were broad, encompassing most patients undergoing tracheal intubation in the ED or ICU, with exclusions mainly for safety reasons.
• Primary Outcome: The primary outcome of the trial was hypoxemia, defined as oxygen saturation < 85%. This threshold was chosen because it signifies a critical point on the oxygen dissociation curve, where patients are at higher risk of further desaturation and adverse outcomes.
• Secondary Outcomes: Secondary exploratory outcomes included more severe levels of hypoxemia (oxygen saturation < 80% and < 70%), aiming to capture varying degrees of oxygenation failure during intubation. Rates of cardiac arrest during intubation were an additional outcome.
• Intervention Comparison:
  • The trial compared two methods of pre-oxygenation: non-invasive ventilation (NIV) and oxygen mask (face mask)
  • Both methods aimed to provide at least three minutes of pre-oxygenation before intubation.
  • NIV group specifics: Expiratory pressure of 5 cm H2O, Inspiratory pressure of 10 cm H2O, respiratory rate of 10 breaths per minute, and 100% oxygen delivery
  • Oxygen mask group specifics: Non-rebreather or bag mask device with at least 15 liters per minute oxygen flow.
  • Nasal cannulas and HFNC could be used in both groups.
• Logistics and Equipment Use:
  • The trial allowed flexibility in using available equipment (invasive ventilator capable of NIPPV vs. dedicated BiPAP machine).
  • Sites were encouraged to use the same ventilator for both pre-oxygenation and subsequent ventilation to streamline workflow and reduce logistical challenges.
• Primary and Secondary Outcomes:
  • Results showed a significant reduction in hypoxemia incidents in the NIV group compared to the oxygen mask group.
  • There was also a reduction in severe hypoxemia and a notable decrease in cardiac arrest incidents in the NIV group.
• Aspiration Safety:
  • There was no statistical difference in aspiration-related outcomes between the NIV and oxygen mask groups, indicating that NIV did not increase the risk of aspiration.
• Conclusions:
  • The trial concluded that NIV for pre-oxygenation significantly reduced the incidence of hypoxemia and possibly cardiac arrest during tracheal intubation.
  • It also dispelled concerns about increased aspiration risk with NIPPV as pre-oxygenation, suggesting it can be safely used in clinical practice.

Reference

Gibbs KW, Semler MW, Driver BE, Seitz KP, Stempek SB, Taylor C, Resnick-Ault D, White HD, Gandotra S, Doerschug KC, Mohamed A, Prekker ME, Khan A, Gaillard JP, Andrea L, Aggarwal NR, Brainard JC, Barnett LH, Halliday SJ, Blinder V, Dagan A, Whitson MR, Schauer SG, Walker JE Jr, Barker AB, Palakshappa JA, Muhs A, Wozniak JM, Kramer PJ, Withers C, Ghamande SA, Russell DW, Schwartz A, Moskowitz A, Hansen SJ, Allada G, Goranson JK, Fein DG, Sottile PD, Kelly N, Alwood SM, Long MT, Malhotra R, Shapiro NI, Page DB, Long BJ, Thomas CB, Trent SA, Janz DR, Rice TW, Self WH, Bebarta VS, Lloyd BD, Rhoads J, Womack K, Imhoff B, Ginde AA, Casey JD; PREOXI Investigators and the Pragmatic Critical Care Research Group. Noninvasive Ventilation for Preoxygenation during Emergency Intubation. N Engl J Med. 2024 Jun 20;390(23):2165-2177. doi: 10.1056/NEJMoa2313680. Epub 2024 Jun 13. PMID: 38869091.

This episode is launching our 2024 Rapid Fire Journal Club summer series on ARDS! This summer we will be talking about landmark ARDS trials that have defined the literature and shaped patient care. Journal clubs often focus on new trials, and so learners may have a less thorough understanding of the baseline literature that defines many of our ICU practices. The goal of this series is to provide a quick, but in-depth look at these papers so that learners understand the modern landscape of ARDS.

Today, we’re kicking this initiative off by looking at the ARMA or ARDSNet Trial published in the NEJM in 2000. Enjoy!

Article and Reference

We’re talking about the ARMA trial today which examined “Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome.”

Reference: Acute Respiratory Distress Syndrome Network; Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801. PMID: 10793162.

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Today we’re back with another stop on our Fellows’ Case Files journey and making our way to the University of Rochester. Tune in to hear about this fascinating case and learn some key teaching points along the way.

Meet Our Guests

Dr. Shiv Patel completed his IM residency and a Chief year at the California Pacific Medical Center- Van Ness Campus and is currently a second-year PCCM fellow at the University of Rochester.

Dr. Mary Anne Morgan is an Associate Professor of Medicine and the Fellowship Program Director for the PCCM Fellowship at the University of Rochester. Her clinical interests range from the care of critically ill patients in the ICU to the diagnosis and management of rare lung disease in her role as Director of the University of Rochester LAM Clinic. She loves unwrapping clinical reasoning with trainees, exploring issues around communication and teamwork in the ICU, and is excited about curriculum revitalization in the growing URMC PCCM fellowship program.

Case Presentation

 A 75 y.o. female with a history of Hypertension, Hyperlipidemia, and Type 2 Diabetes presented for evaluation of hypoglycemia and generalized fatigue. She had felt poorly for about a week with symptoms of back pain, generalized weakness, and dyspnea, all of which acutely worsened on the day of presentation. 

She was found to be hypoglycemic with a blood glucose level in the to 40’s. Initial vital signs included a heart rate of 56, blood pressure of 70/40, respiratory rate of 30, and temperature of 28.5 degrees Celsius.

Key Learning Points

Lactic Acidosis: Type A, Type B and Type D

Type A: Typically secondary to conditions that impair oxygen delivery (respiratory failure, PE) to tissues or decrease tissue perfusion (severe anemia, shock). Patients typically present with hypotension, tachycardia, tachypnea, altered mental status, and signs of organ dysfunction.

Type B: Typically secondary to conditions that directly affect cellular metabolism or lactate clearance and characterized by the presence of hyperlactatemia without evidence of tissue hypoperfusion or hypoxia. Conditions associated include liver dysfunction (e.g., liver failure, cirrhosis), malignancies (especially hematological malignancies), medications/toxins (e.g., metformin, cyanide poisoning), inborn errors of metabolism, and mitochondrial disorders.

Type D: Less common presentation and can be seen in patients with short gut syndrome.

References

1.Blough B, Moreland A, Mora A Jr. Metformin-induced lactic acidosis with emphasis on the anion gap. Proc (Bayl Univ Med Cent). 2015 Jan;28(1):31-3. doi: 10.1080/08998280.2015.11929178. PMID: 25552792; PMCID: PMC4264704.

2.Callelo et al. Extracorporeal Treatment for Metformin Poisoning: Systematic Review and Recommendations From the Extracorporeal Treatments in Poisoning Workgroup. DOI: 10.1097/CCM.0000000000001002

3.Friesecke, S., Abel, P., Roser, M. et al. Outcome of severe lactic acidosis associated with metformin accumulation. Crit Care 14, R226 (2010). https://doi.org/10.1186/cc9376

4.Madias NE. Lactic acidosis. Kidney Int. 1986 Mar;29(3):752-74. doi: 10.1038/ki.1986.62. PMID: 3702227.

5. Stiller RH, Luks AM, Çoruh B. All That Raises Lactate Is Not Sepsis. ATS Sch. 2023 Jun 12;4(3):385-386. doi: 10.34197/ats-scholar.2023-0032OT.

We’re back with our Rapid Fire Journal Club, and talking about the NEJM 2023 STELLAR Trial of Sotatercept in Pulmonary Arterial Hypertension. This is a landmark trial that is actively changing the face of PAH treatment today. Listen to hear the details of the trial and how its findings can be utilized to help patients.

Article and Reference

We’re looking at the STELLAR Trial today which is a Phase 3 trial of Sotatercept in Pulmonary Arterial Hypertension.

Reference: Hoeper MM, Badesch DB, Ghofrani HA, Gibbs JSR, Gomberg-Maitland M, McLaughlin VV, Preston IR, Souza R, Waxman AB, Grünig E, Kopeć G, Meyer G, Olsson KM, Rosenkranz S, Xu Y, Miller B, Fowler M, Butler J, Koglin J, de Oliveira Pena J, Humbert M; STELLAR Trial Investigators. Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2023 Apr 20;388(16):1478-1490. doi: 10.1056/NEJMoa2213558. Epub 2023 Mar 6. PMID: 36877098.

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We have had a number of episodes on Acute Respiratory Distress Syndrome or ARDS. These episodes have ranged from how to titrate PEEP, subphenotypes in ARDS, and the future of ARDS research. Today, we are talking about how we all think about and define ARDS, and work that has highlighted a newer global definition of ARDS. 

Dr. Elisabeth Riviello is an Assistant Professor of Medicine at Harvard Medical School, and a PCCM physician at Beth Israeal Deconess Medical Center. She is also an Affiliate of the HMS Department of Global Health and Social Medicine and an honorary Associate Professor of Emergency Medicine and Critical Care at the University of Rwanda. She is passionate about improving critical care delivery in resource limited settings and has served on Committees for the World Health Organization. She is the Principal Investigator of BREATHE or the (Building Respiratory Support in East Africa Through High flow versus standard flow oxygen Evaluation); a RCT looking at HFNC in five sites in Kenya, Malawi, and Rwanda.

Dr. Theogen Twagirumugabe is an Anesthesiologist and Intensivist at the College of Medicine and Health Sciences, and a Professor at the University of Rwanda. In addition to clinical work, he has his PhD in Medical Sciences. He is a widely succesful researcher with over 70 publications in critical care and anesthesia delivery and is also a lead investigator in the BREATHE initiative.

References

Matthay MA, Arabi Y, Arroliga AC, Bernard G, Bersten AD, Brochard LJ, Calfee CS, Combes A, Daniel BM, Ferguson ND, Gong MN, Gotts JE, Herridge MS, Laffey JG, Liu KD, Machado FR, Martin TR, McAuley DF, Mercat A, Moss M, Mularski RA, Pesenti A, Qiu H, Ramakrishnan N, Ranieri VM, Riviello ED, Rubin E, Slutsky AS, Thompson BT, Twagirumugabe T, Ware LB, Wick KD. A New Global Definition of Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2024 Jan 1;209(1):37-47. doi: 10.1164/rccm.202303-0558WS. PMID: 37487152; PMCID: PMC10870872.

Riviello ED, Buregeya E, Twagirumugabe T. Diagnosing acute respiratory distress syndrome in resource limited settings: the Kigali modification of the Berlin definition. Curr Opin Crit Care. 2017 Feb;23(1):18-23. doi: 10.1097/MCC.0000000000000372. PMID: 27875408.

ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669. PMID: 22797452.