83. RFJC 13 – ARDS Series – DEXA-ARDS

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

  • DEXA-ARDS; Lancet Respiratory Medicine, 2020
    • DOI:10.1016/S2213-2600(19)30417-5
    • Link: https://doi.org/10.1016/s2213-2600(19)30417-5
    • Background: ARDS is an intense inflammatory process without proven, specific pharmacotherapies. Previous work and a recent meta-analysis demonstrated improvements in inflammation, gas exchange, and ventilator and ICU liberation but did not adequately address mortality.
    • Study Design (design, primary outcome, participants, etc)
      • Design: investigator-initiated, multicenter, unblinded, randomized controlled trial in 17 academic ICUs in Spain, conducted from 3/2013 to 12/2018
      • Primary Outcome
        • VFD at 28d
        • Secondary:
          • 60d mortality
          • Actual duration of ventilation in ICU survivors
          • ICU acquired infections
      • Participants
        • Inclusion ARDS with P/F < 200 for < 24hr on LTVV
        • Exclusion:
          • Already receiving steroids or immunosuppression
          • CHF
          • Severe COPD
          • DNR
        • Summary: Middle aged, mostly male patients with < 24hr of moderate to severe ARDS receiving LPV without chronic heart or lung disease
          • Like many ARDS trials, just over 3/4 of patients’ ARDS was caused by PNA or sepsis. Mean P/F was ~140
    • Intervention/Limitations
      • N = 277, stratified by center and then randomized
      • Intervention: dexamethasone 20mg qd for 5d followed by 10mg qd for 5d
        • Stopped early for extubation before day 10
        • First dose given no more than 30 hours after P/F < 200
      • Control: no placebo, just SOC
      • All patients received LTVV
    • Outcomes/Safety
      • Power: with N = 314 (actual N = 277), 80% power to detect 2 additional VFD and 15% mortality reduction
        • As an aside, this seems to be a theme in ICU trials: massively ambitious proposed benefits during power calculations and then under-enrolling for that power calculation ultimately resulting with a point estimate that favors the intervention but is not statistically significant.
      • Efficacy:
        • 60d mortality: 21% vs 36%, P = 0.0047
          • NNT of just < 7!
        • VFD at 28d: 12.3 vs 7.5, P < 0.0001
        • Actual duration of ventilation in ICU survivors: 14.2d vs 19.5d (P = 0.0009)
      • Safety:
        • Hyperglycemia: 76% vs 70%, P = 0.33
          • Always interesting in steroid trials when no change in glucose control is seen. This isn’t the most EBM thing I’ll ever say, but frankly I disregard this and assume steroids will cause hyperglycemia regardless of the trial results.
        • ICU acquired infections: 24% vs 25%, P = 0.75
    • Takeaway
      • In a narrowly selected population of patients without chronic heart or severe lung disease and with early, moderate ARDS (mostly from sepsis or pneumonia), dexamethasone reduced mortality and duration of mechanical ventilation.
        • If time, insert soap-box about etiology of ARDS being very important (EG, flu, fungal, parasitic, mycobacterial infections)

 

78. PREOXI Trial

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.

 

 

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.


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.

77. RFJC 9 – ARDS Series – ARMA

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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55. The Autumn Ghost

We are excited to bring you a special episode where we are joined by author Dr. Hanna Wunsch and will discuss her book, “The Autumn Ghost: How the Battle Against a Polio Epidemic Revolutionized Modern Medical Care.

Meet our Guests

Dr. Hannah Wunsch a Professor of Anesthesiology and Critical Care Medicine at the University of Toronto and is an intensivist at Sunnybrook Hospital. Hannah completed her medical training at Washington University School of Medicine and  received a Master’s Degree in Epidemiology from the London School of Hygiene and Tropical Medicine. She completed her anesthesia residency and critical care fellowship at Columbia University in New York and was on faculty there for 6 years prior to moving to Toronto. The Autumn Ghost is her first book.

In The Autumn Ghost, Dr. Hannah Wunsch shares the story of the polio epidemic in the autumn of 1952 in Copenhagen. She masterfully tells the story of how specialties came together to advance mechanical ventilation and intensive care units, and connects history to modern day medicine.

39. Fellows’ Case Files: Indiana University

Join us as we head to Indiana University! Listen in as we discuss another great case and hear teaching points from our amazing guests.

Meet our Guests


Parth Savsani is currently an internal medicine resident at Indiana University School of Medicine. He received his undergraduate degree from the University of Wisconsin-Madison and his medical degree from the University of Illinois College of Medicine. He enjoys medical education and was selected to be the VA chief resident next year.

Maria Srour is a Pulmonary and Critical Care Fellow at Indiana University School of Medicine. She completed her internal medicine residency at Saint Louis University where she was also a chief resident, and received her medical degree from IU. She works in global health to improve care for sepsis patients in low resources settings, and is currently pursuing her MPH.

Laura Hinkle is a Indiana University die hard and has been there from her since medical school through residency and fellowship, and is now an Assistant Professor of Clinical  Medicine and the Associate Program Director for the Pulmonary and Critical Care Medicine Fellowship. She will be taking over as the Program Director July 1, 2023. She is a dedicated educator and is the Key Clinical Educator for Pulmonary and Critical Care, and the Director of the Clinical Transitions Curriculum.  Additionally, she is working on a Master’s Degree in Education through the University of Cincinnati. 

Case Presentation

A male in her early 60s is transferred from a neighboring facility with a 1 week history of fatigue and lethargy. Three days prior to presentation he developed dyspnea and increased weakness with a near fall at home. HIs family also reported recent fevers, chills, dyspnea, and diarrhea. On his way to seek evaluation, he developed slurred speech without any other focal abnormalities.

Additional information is summarized as below:

Follow along our episode to hear the final diagnosis and key teaching points from the case!

Radiology Rounds – 4/11/2023

For “#RadiologyRounds” today, we won’t be looking at any imaging, but we’ll be looking at some vent wave forms and examining dysynchrony! This is a re-booted @david_furfaro Tweetorial. I hope you enjoy and this is an open invitation for all dysynchrony waveforms!

A 40s M is intubated for ARDS. In order to maintain lung protective ventilation, he was on high does of propofol, fentanyl and midazolam. His sedation is being weaned slightly now, and the RN calls for vent dysynchrony. His ventilator looks like this

Before delving into the type of dysynynchrony and management, based on these waveforms what is actually happening? Note: when we say “exhales” or “inhales” I am referring to the mechanical, vent-driven breaths

Let’s take a look at the waveforms and identify the phase of breathing. This is VC with a square flow waveform, so as a set volume is delivered, the flow is at a constant rate, and the pressure is measured. Expiration is about 2x as long as inspiration (determined by I time or flow rate)

With a passive patient (no dysynchrony) after inspiration, the volume curve should show a smooth decrease with exhalation, the pressure curve should flatten to the set PEEP, and the flow will be negative and gradually return to 0 as the patient exhales

In our case, you can see simultaneous dysynchrony in all three waveforms during exhalation (red arrows) vs normal (orange lines). There is a pressure negative deflection; the flow quickly rises to 0 before returning to negative; and the volume curve plateaus as exhalation pauses

Putting this together, it means that during expiration there is an inspiratory effort. The patient is trying to inhale, which causes a negative pressure deflection, and a pause in air flowing out of the lungs. If this effort triggered a breath, there could be breath stacking. Notice that the same pattern occurs after every breath, and clinically we said the patient was still heavily sedated. This combination of findings is a type of dysynchrony called REVERSE TRIGGERING or ENTRAINMENT.

You could consider whether this dysynchrony was an ineffective effort, but the trigger sensitivity was low, and the pattern and consistent timing after inspiration is more consistent with reverse triggering.

The change in pressure and flow of a ventilator-initiated, mandatory breath stimulates an inspiratory effort from the patient. Theories differ on if this is mediated by the diaphragm or central respiratory center. This can start during the ventilator-delivered breath, or afterwards in exhalation, as with our patient.

Reverse triggering often occurs in heavily sedated patients, and is defined by a stable, repetitive pattern (i.e. it is not voluntary, but reflex mediated). It can also occur in anoxic brain injury. Treating it involves breaking the pattern and avoiding harmful therapies. It can even be induced in healthy patients but this is much less clinically relevant, and is rare.

DO NOT just increase the trigger sensitivity of the vent. This can stop breath stacking but does not prevent dysynchrony and it can cause harmful changes in transpulmonary pressure. For this patient, sedation was lightened slightly, and the respiratory rate decreased and the pattern of reverse triggering ultimately broke without the need for paralysis.

35. The Future of ARDS Research Roundtable

We are extremely excited for another PulmPEEPs Roundtable table discussion today. We have spent multiple episodes talking about different aspects of ARDS and respiratory failure. Today, multiple expert guests return, as well as a new guest to the show, to discuss the future of ARDS research. This is a can’t miss discussion that is so jam-packed with pearls you’ll have to listen twice!

Meet Our Guests

Carolyn Calfee is a Professor of Medicine and Anesthesia at the University of California, San Francisco. She is a world-renowned ARDS researcher and has authored multiple landmark studies in the field. She previously joined us for a discussion on ARDS precision medicine and phenotypes.

Ewan Goligher is an Assistant Professor at the University of Toronto and University Health Network. He has published many practice-changing papers in ARDS. These have included prospective studies and some fantastic retrospective analyses that have fundamentally shaped our interpretation of trial results.  He previously came on the show discussing lung and diaphragm protection.

Sarina Sahetya is an Assistant Professor of Medicine at Johns Hopkins. She is a funded researcher in ARDS and respiratory physiology and has published multiple studies on lung protection and ARDS. She last helped us understand how to titrate PEEP in ARDS.

Matthew Semler is an Assistant Professor of Medicine and Biomedical Informatics at Vanderbilt University Medical Center, where he is also the Associate MICU Director and the co-director of the Inpatient Division of the Learning Healthcare System at Vanderbilt. Through his role as Chair of the Steering Committee for the Pragmatic Critical Care Research Group, he has helped lead more than two dozen randomized trials leading to multiple high-impact publications.

Radiology Rounds – 1/31/23

For today’s #RadiologyRounds we have a combined Radiology and Ventilator imaging rounds! You’re in the ICU caring for a young patient on a ventilator when you are called to the bedside for a desaturation.

You perform an inspiratory hold and see that the PIP, plateau, and difference between peak and plateau have all increased. On exam you hear bilateral mechanical breath sounds anteriorly. You order a CXR and the student asks a question about the waveforms

There are pressure deviations corresponding to the flow deviations.

There is no clear patient effort The fact that the PIP and plat have changed makes water in the tubing or cardiac oscillations less likely.

You think this is mucus, with a plug ball-valving in a bronchus

The CXR arrives and shows right lower lobe collapse.

A bedside bronchoscopy is performed with large mucus plugs suctioned out of the RLL and RML. Afterward, the patient’s oxygenation is improved, the flow deviations resolve, and the plateau pressure drops to 19

33. Lung and Diaphragm Protective Ventilation Roundtable

Today the PulmPEEPs are discussing Lung and Diaphragm Protective Ventilation with two experts in the field. We are joined by Dr. Jose Dianti and Dr. Ewan Goligher.

Meet Our Guests

Dr. Jose Dianti is a clinical and research fellow at the University of Toronto and University Health Network. He completed his residency in Critical Care and worked as a critical care attending previously at the Hospital Italiano in Buenos Aires, Argentina. He is particularly interested in ventilator induced lung injury and personalized ventilation strategies. Dr. Ewan Goligher is an Assistant Professor at the University of Toronto and University Health Network, and is a world renowned researcher in the mechanisms of ventilator induced lung and diaphragm injury.

7. Top Consults: Severe Asthma Exacerbation

We are excited to bring you another episode in our Pulm PEEPs Top Consults series! Kristina Montemayor and David Furfaro, are joined by Sandy Zaeh to discuss the assessment and management of a patient with a severe asthma exacerbation. We’ll follow a consult patient from the emergency department to the ICU, and cover everything from the physiology of pulsus paradoxus in asthma to how to manage the ventilator in status asthmaticus. Listen today and please send any questions our way on Twitter @pulmPEEPS.

Meet Our Guests

Sandy Zaeh is an Instructor of Medicine and Pulmonary & Critical Care Medicine physician at Yale School of Medicine.

Key Learning Points

References and links for further reading

  1. Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. European Respiratory Journal. 2014;43(2):343-373. doi:10.1183/09031936.00202013
  2. Rodrigo GJ, Rodrigo C, Hall JB. Acute asthma in adults: a review. Chest. 2004;125(3):1081-1102. doi:10.1378/chest.125.3.1081
  3. Godwin HT, Fix ML, Baker O, Madsen T, Walls RM, Brown CA. Emergency Department Airway Management for Status Asthmaticus With Respiratory Failure. Respir Care. 2020;65(12):1904-1907. doi:10.4187/respcare.07723
  4. Althoff MD, Holguin F, Yang F, et al. Noninvasive Ventilation Use in Critically Ill Patients with Acute Asthma Exacerbations. Am J Respir Crit Care Med. 2020;202(11):1520-1530. doi:10.1164/rccm.201910-2021OC
  5. Brenner B, Corbridge T, Kazzi A. Intubation and Mechanical Ventilation of the Asthmatic Patient in Respiratory Failure. Proc Am Thorac Soc. 2009;6(4):371-379. doi:10.1513/pats.P09ST4
  6. Laher AE, Buchanan SK. Mechanically Ventilating the Severe Asthmatic. J Intensive Care Med. 2018;33(9):491-501. doi:10.1177/0885066617740079
  7. Leatherman J. Mechanical ventilation for severe asthma. Chest. 2015;147(6):1671-1680. doi:10.1378/chest.14-1733