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.

 

Infographic

 

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)

 

79. RFJC 10 – ARDS Series – FACTT

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.

Infographic

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:

  • Randomized Controlled Trial: Conducted at 20 North American medical centers from 2000 to 2005.
  • Participants: Included intubated ARDS patients who required or were planned to receive a central venous catheter. Excluded patients with chronic diseases, recent MI, or irreversible conditions. Shock was not an exclusion criterion.
  • Interventions: Patients were randomly assigned to either a liberal or conservative fluid management strategy, and also received either a PA catheter or a central line.

Fluid Management Protocol:

  • Liberal Strategy: Aimed for higher filling pressures (CVP of 10-14 or wedge pressure of 14-18).
  • Conservative Strategy: Aimed for lower filling pressures (CVP less than 4 or wedge pressure under 14).
  • Fluid Balance: The liberal group had a net positive fluid balance of around 7 liters, while the conservative group had a net negative balance of about 130 cc.

    Results:

    • Mortality: No statistically significant difference in 60-day mortality between the liberal and conservative groups (25.5% vs. 28.4%, respectively).
    • Ventilator and ICU-Free Days: The conservative strategy resulted in more ventilator-free and ICU-free days.
    • Shock and Dialysis: There was no difference in shock rates, but the conservative group had a trend toward fewer dialysis requirements (10% vs. 14%, p=0.06).

    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.

      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.

      Infographic

      Correction:

      We mention a step-wise titration of tidal volume in the control group to achieve Pplats of 45-50. To clarify, there was no adjustment of Vt in the traditional Vt group unless Pplat > 50. If Vt had been decreased in the traditional Vt group because Pplat was > 50, it would not be subsequently increased back to 12 unless Pplat < 45 (to avoid a cycle of corrections and re-adjustments). Similarly in the lower Vt group, there was no adjustment (“titration”) of Vt unless Pplat > 30, and there was a similar protocol in place not to increase the Vt again unless the Pplat was < 25.

      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.

      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.

      32. VV-ECMO Roundtable

      For the first Pulm PEEPs episode of 2023, we are starting off with a bang and a Roundtable discussion about venovenous extracorporeal membrane oxygenation (VV-ECMO). VV-ECMO has been increasing in use in the intensive care unit for patients with severe respiratory failure, especially during the COVID-19 pandemic. We are joined by experts in the field, Cara Agerstrand, Eddy Fan, and Nida Qadir, to discuss the basics of how ECMO works, physiologic goals, when to use ECMO for patients with ARDS, and much more. Let us know your thoughts and stay tuned for more great content in 2023.

      Meet Our Guests

      Cara Agerstrand is an Associate Professor of Medicine at Columbia University Irving Medical Center / NewYork-Presbyterian Hospital, where she is also the Director of the Medical ECMO Program. She is an international renown ECMO expert and is the current Conference Chair for the Extracorporeal Life Support Organization (or ELSO). Finally, she is a lauded educator and has received the American College of Chest Physicians Distinguished Educator Award.

      Eddy Fan is an Associate Professor at the University of Toronto, and the University Health Network / Mount Sinai Hospital. He is also the Director of Critical Research and the Medical Director of the Extracorporeal Life Support Program. He has literally 100s of publications about ARDS, ECMO, and critical care, chairs the ELSO Research Committee, and spearheads multiple international collaborative studies.

      Nida Qadir is an Associate Professor at the University of California Los Angeles and is an Associate Director of the MICU, as well as the co-director of the Post-ICU Recovery Clinic. Nida is also on the Critical Care Editorial Board for CHEST and is a highly regarded pulmonary and critical care educator.

      Key Learning Points

      VV- ECMO Basic Components and Core Physiology

      Oxygenation Delivery on VV-ECMO

      Carbon Dioxide Removal on VV-ECMO

      Flows and Line Pressures on VV-ECMO

      ECMO for ARDS

      • Should be considered after conventional therapies have failed (including ventilator optimization and proning)
      • Allows for ultra-lung protective ventilation
      • Lung rest means settings that minimize ventilator-induced lung injury
      • EOLIA Trial (see below) shows that ECMO can be delivered safely, and likely has a benefit in severe ARDS, although the magnitude of that benefit remains uncertain. A Bayesian re-analysis showed a high likelihood of benefit even if skeptical of ECMO

      ECMO For Bridge to Lung Transplant

      • Allows for patients to maintain gas exchange while awaiting transplant
      • Ideally done with patient extubated
      • Can allow for patients to maintain nutrition and mobility while awaiting transplant

      References and Further Reading

      1. Brodie D, Bacchetta M. Extracorporeal Membrane Oxygenation for ARDS in Adults. N Engl J Med. 2011;365(20):1905-1914. doi:10.1056/NEJMct1103720
      2. Munshi L, Brodie D, Fan E. Extracorporeal Support for Acute Respiratory Distress Syndrome in Adults. NEJM Evidence. 2022;1(10):EVIDra2200128. doi:10.1056/EVIDra2200128
      3. Combes A, Hajage D, Capellier G, et al. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome. New England Journal of Medicine. 2018;378(21):1965-1975. doi:10.1056/NEJMoa1800385
      4. Goligher EC, Tomlinson G, Hajage D, et al. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome and Posterior Probability of Mortality Benefit in a Post Hoc Bayesian Analysis of a Randomized Clinical Trial. JAMA. 2018;320(21):2251-2259. doi:10.1001/jama.2018.14276
      5. Erdeneochir E, Strunina S. Analysis of blood flow in extracorporeal membrane oxygenation circuit. Published online 2017.
      6. Schmidt M, Pham T, Arcadipane A, et al. Mechanical Ventilation Management during Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome. An International Multicenter Prospective Cohort. Am J Respir Crit Care Med. 2019;200(8):1002-1012. doi:10.1164/rccm.201806-1094OC
      7. Tonna JE, Abrams D, Brodie D, et al. Management of Adult Patients Supported with Venovenous Extracorporeal Membrane Oxygenation (VV ECMO): Guideline from the Extracorporeal Life Support Organization (ELSO). ASAIO Journal. 2021;67(6):601-610. doi:10.1097/MAT.0000000000001432
      8. Hayanga JWA, Hayanga HK, Holmes SD, et al. Mechanical ventilation and extracorporeal membrane oxygenation as a bridge to lung transplantation: Closing the gap. J Heart Lung Transplant. 2019;38(10):1104-1111. doi:10.1016/j.healun.2019.06.026

      25. ARDS Precision Medicine & Phenotypes Roundtable

      We’re very excited this week on Pulm PEEPs to be resuming our Roundtable series. We are joined by two outstanding critical care doctors to discuss precision medicine in the ICU, specifically ARDS phenotypes. This is a topic of increasing clinical and research interest, and personalized medicine in the ICU will certainly change the landscape of how care is delivered in the coming years and decades. We are honing in on ARDS today and how phenotyping can influence future research and clinical care.

      Meet Our Guests

      Carolyn Calfee is a Professor of Medicine and Anesthesia at the University of California, San Francisco. She is a leader in the field of ARDS research and a pioneer in the field of ARDS phenotyping research. She has received numerous NIH grants and has literally 100s of publications on ARDS and other topics. She is also a previous ATS CC Assembly chair, and in 2022 received the ATS Recognition Award for Scientific Accomplishments.

      Annette Esper is an Associate Professor of Medicine at Emory University School of Medicine. She works clinically in critical care and is the Medical Director of the stepdown Intensive Care Unit at Grady Memorial Hospital. In addition to her clinical activities, Annette does both clinical and translational research in ARDS, and was the Assembly Chair for the ATS Critical Care Assembly from 2021 – 2022.

      Key Learning Points

      Berlin Criteria of ARDS:

      — Acute symptoms developing within 7 days of a known insult

      — Bilateral airspace opacites on chest imaging

      — Hypoxemia not fully explained by cardiogenic pulmonary edema

      — P:F ratio < 300 on a PEEP of 5

      Heterogeneity in ARDS

      — ARDS has a broad definition so it is comprised of people with a wide range of disease characteristics and severity

      — There is heterogeneity in clinical characteristics, but also underlying biological drivers of disease

      — Heterogeneity stymies research efforts to identify effective therapies in ARDS

      Phenotyping in ARDS

      — There are many ways of phenotyping for critical illness and ARDS

      1. Etiology. Examples: COVID vs non-COVID, pulmonary vs non-pulmonary, bacterial vs viral

      2. Physiologic phenotypes: Severity (Berlin criteria P:F ratio); Compliance, Ventilatory ratio

      3. Biological phenotypes: Different underlying drivers of disease

      — The motivation for phenotyping is to find treatment-responsive subgroups within the broader heterogeneous subgroups

      — Phenotyping embodies more than risk factors, because it includes information about the host response, not just predictors of outcome

      Biomarkers in ARDS

      — There is probably a role for biomarkers in ARDS clinically and in research

      > Prognostication

      > Identify who will be responsive to specific therapies

      > May not be one biomarker, will likely be a panel

      — What is the perfect ARDS biomarker?

      > Specific: identify a group of patients that are at risk, or respond to therapies differently

      > Easily measurable at the bedside

      > Reliable

      > Reproducible

      — Challengers in identifying useful biomarkers

      > Heterogeneity of disease

      > Real world applicability. For example, can you get IL-6 back in real-time? Can you apply it consistently when labs have different testing techniques and scales?

      > Temporal stability – how do biomarkers change over the time course of ARDS?

      — Biomarkers of interest

      > Inflammatory markers (IL-6, IL-8, TNF)

      > sRAGE – Soluble receptor for advanced glycation end products

      > Highest levels on type 1 alveolar epithelial cells

      > Seems to be a marker of alveolar epithelial injuries

      > Meta-genomic sequencing of patients in a real-time environment

      Latent class analysis

      — Clustering technique that, agnostic to outcomes, looks for existing groups within the data

      — Ideally, identifies biologically distinct phenotypes that may have different prognoses or response to therapy

      Omics in ARDS

      — Existing risk scores are quite limited, so using biological data to distinguish patients seems promising.

      — Unbiased approach to identifying subgroups to identify patients that behave similarly biologically

      — Omics is really thinking about endotyping patients and identifying the biological processes that are driving phenotypes

      Hypo and hyperinflammatory phenotypes in ARDS

      — Described by LCA incorporating demographics, clinical data, labs, vital signs, 6-8 plasma protein biomarkers

      — Importantly, the groups were identified agnostically to outcomes.

      — Distinguished by:

      > Inflammatory biomarkers (IL-6, IL-8, TNF 1)

      > Acidosis

      > Shock, vasopressor requirement, and multi-system organ failure

      — Consistently across 8 different data sets

      — Both RCTs and observational cohorts

      — Hyperinflammatory phenotype has dramatically worse clinically outcomes (higher mortality, fewer VFD)

      — The different phenotypes respond differently to therapies retrospectively in RCTs

      — The phenotypes did respond differently to PEEP, fluids conservative therapy, and simvastatin.

      — This was not seen universally (rosuvastatin did not have differential treatment response)

      — Note: We don’t really know that inflammation is at the heart of the pathogenesis of what distinguishes these two groups. The “hypoinflammatory” phenotype still has elevated levels of inflammatory biomarkers compared to controls.

      What is next?

      — This is all just subgroup analysis.

      — These hypotheses still need to be tested prospectively

      — Need to be able to easily identify the phenotypes quickly and easily

      — Working on biomarker-based and non-biomarker-based clinical classifications

      Key Quote:

      Dr. Calfee “My takeaway point would be, there is no one best or one right way to phenotype these patients. I think there are numerous different approaches that we’re probably going to be using over the years. But I would say that what we want to focus on is what has the potential to change outcomes for our patients and to really identify individual patients or groups of patients that respond differently to therapies. And I think if we can keep that goal in mind and start testing some of these hypotheses prospectively we’re going to make progress.”

      References and links for further reading

      1. Sinha P, Calfee CS. Phenotypes in ARDS: Moving Towards Precision Medicine. Curr Opin Crit Care. 2019;25(1):12-20. doi:10.1097/MCC.0000000000000571
      2. Calfee CS, Delucchi KL, Sinha P, et al. Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial. Lancet Respir Med. 2018;6(9):691-698. doi:10.1016/S2213-2600(18)30177-2
      3. Matthay MA, Arabi YM, Siegel ER, et al. Phenotypes and personalized medicine in the acute respiratory distress syndrome. Intensive Care Med. 2020;46(12):2136-2152. doi:10.1007/s00134-020-06296-9
      4. Wilson JG, Calfee CS. ARDS Subphenotypes: Understanding a Heterogeneous Syndrome. Crit Care. 2020;24(1):102. doi:10.1186/s13054-020-2778-x
      5. Yang P, Esper AM, Martin GS. The Future of ARDS Biomarkers: Where Are the Gaps in Implementation of Precision Medicine? In: Vincent JL, ed. Annual Update in Intensive Care and Emergency Medicine 2020. Annual Update in Intensive Care and Emergency Medicine. Springer International Publishing; 2020:91-100. doi:10.1007/978-3-030-37323-8_7

      21. Post Intensive Care Syndrome (PICS)

      Today on Pulm PEEPs, we are joined by two pioneers in the field of post-intensive care outcomes and delirium research. Drs. Dale Needham and Wes Ely talk to us all about the Post Intensive Care Syndrome (PICS) and cover everything from how it was first recognized, to the impact it has, and, most importantly, what we can do to prevent it. This is a huge topic in the field of critical care and we’re thrilled to be delving into it with such knowledgeable guides.

      Meet Our Guests

      Wes Ely is the Grant W. Liddle Chair in Medicine and a Professor of Medicine at Vanderbilt University Medical Center. He is also the Associate Director of Aging Research at the VA Tennessee Valley Geriatric Research and Education Clinical Center and the co-director of the Critical, Illness, Brain Dysfunction and Survivorship Center. He has published 100s of manuscripts on critical illness survivorship and delirium. He also published a book called “Every Deep-Drawn Breath” about his and his patients’ experiences in the ICU and about the ramifications of critical illness. All net proceeds for the book are going to the CIBS Center Endowment for Survivorship

      Dale Needham is a Professor of Medicine at Johns Hopkins, where he is also the Medical Director of the Critical Care Physical Medicine and Rehabilitation Program and the Director of the Outcomes After Critical Illness and Surgery Group. He is the author of 100s of publications focusing on post-ICU outcomes and has received numerous research grants from the NIH and other organizations.

      Key Learning Points

      Visit our website www.pulmpeeps.com to see the key learning points from this episode summarized in two infographics.

      References and links for further reading

      1. Devlin JW, Skrobik Y, Gélinas C, et al. Executive Summary: Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Critical Care Medicine. 2018;46(9):1532-1548. doi:10.1097/CCM.0000000000003259
      2. Ely EW. The ABCDEF Bundle: Science and Philosophy of How ICU Liberation Serves Patients and Families. Crit Care Med. 2017;45(2):321-330. doi:10.1097/CCM.0000000000002175
      3. Mikkelsen ME, Still M, Anderson BJ, et al. Society of Critical Care Medicine’s International Consensus Conference on Prediction and Identification of Long-Term Impairments After Critical Illness. Crit Care Med. 2020;48(11):1670-1679. doi:10.1097/CCM.0000000000004586
      4. Needham DM, Sepulveda KA, Dinglas VD, et al. Core Outcome Measures for Clinical Research in Acute Respiratory Failure Survivors. An International Modified Delphi Consensus Study. Am J Respir Crit Care Med. 2017;196(9):1122-1130. doi:10.1164/rccm.201702-0372OC
      5. Needham DM, Wozniak AW, Hough CL, et al. Risk Factors for Physical Impairment after Acute Lung Injury in a National, Multicenter Study. Am J Respir Crit Care Med. 2014;189(10):1214-1224. doi:10.1164/rccm.201401-0158OC
      6. Semler MW, Bernard GR, Aaron SD, et al. Identifying Clinical Research Priorities in Adult Pulmonary and Critical Care. NHLBI Working Group Report. Am J Respir Crit Care Med. 2020;202(4):511-523. doi:10.1164/rccm.201908-1595WS
      7. Spruit MA, Holland AE, Singh SJ, Tonia T, Wilson KC, Troosters T. COVID-19: Interim Guidance on Rehabilitation in the Hospital and Post-Hospital Phase from a European Respiratory Society and American Thoracic Society-coordinated International Task Force. Eur Respir J. Published online August 13, 2020:2002197. doi:10.1183/13993003.02197-2020
      8. Turnbull AE, Sepulveda KA, Dinglas VD, Chessare CM, Bingham CO, Needham DM. Core Domains for Clinical Research in Acute Respiratory Failure Survivors: An International Modified Delphi Consensus Study. Crit Care Med. 2017;45(6):1001-1010. doi:10.1097/CCM.0000000000002435
      9. Ward DS, Absalom AR, Aitken LM, et al. Design of Clinical Trials Evaluating Sedation in Critically Ill Adults Undergoing Mechanical Ventilation: Recommendations From Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) Recommendation III. Crit Care Med. 2021;49(10):1684-1693. doi:10.1097/CCM.0000000000005049
      10. Ozga D, Krupa S, Witt P, Mędrzycka-Dąbrowska W. Nursing Interventions to Prevent Delirium in Critically Ill Patients in the Intensive Care Unit during the COVID19 Pandemic—Narrative Overview. Healthcare. 2020;8:578. doi:10.3390/healthcare8040578

      6. PEEP in ARDS Roundtable

      This week on Pulm PEEPs, Dave Furfaro and Kristina Montemayor are joined by experts in the field of critical care medicine and ARDS to discuss all things PEEP! Drs. Roy Brower, Sarina Sahetya, Todd Rice, and Elias Baedorf-Kassis discuss everything ranging from PEEP basics to their approach to optimizing PEEP in patients with ARDS.

      Meet Our Guests

      Roy Brower is a Professor of Medicine at Johns Hopkins where he served as the MICU director for over 33 years, and he has been one of the pioneers for lung-protective ventilation for patients with ARDS.

      Elias Baedorf-Kassis is an Assistant Professor of Medicine at Beth Israel Deaconess Medical Center and Harvard Medical School. He is the Medical Director of Respiratory Care at BIDMC, and helps lead the VV-ECMO program.

      Todd Rice is an Associate Profess of Medicine in the Division of Allergy, Pulmonary, and Critical Care Medicine at Vanderbilt University and Vice President for Clinical Trial Innovation and Operations in the Vanderbilt Institute for Clinical and Translational Research.

      Sarina Sahetya is an Assistant Professor of Medicine at Johns Hopkins Hospital and does research in the diagnosis and treatment of ARDS.


      Key Learning Points

      Driving Pressure figure from Amato et al. 2015. Stress index figure from Hess 2014.
      • The plateau pressure can be measured on the ventilator with an inspiratory hold maneuver
      • Extrinsic PEEP is applied by the ventiilator, while intrinsic PEEP, or auto-PEEP, occurs when there is incomplete emptying of the lungs due to inadequate time for exhalation. This often happens with obstructive lung disease. Intrinsic PEEP can be measured on the ventilator with an end-expiratory hold maneuver
      • We utilize PEEP in all intubated patients to minimize atelectasis. When patients are supine, the heart moves back 2 cm and the diaphragm raises by 2 cm, so often the left lower lobe of the lung is compressed and there is atelectasis there. This is often seen on CXR:

      References, Image Sources, and Further Reading

      1. Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome. New England Journal of Medicine. 2004;351(4):327-336. doi:10.1056/NEJMoa032193
      2. Amato MBP, Meade MO, Slutsky AS, et al. Driving Pressure and Survival in the Acute Respiratory Distress Syndrome. New England Journal of Medicine. 2015;372(8):747-755. doi:10.1056/NEJMsa1410639
      3. Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators. Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA. 2017;318(14):1335-1345. doi:10.1001/jama.2017.14171
      4. Beitler JR, Sarge T, Banner-Goodspeed VM, et al. Effect of Titrating Positive End-Expiratory Pressure (PEEP) With an Esophageal Pressure-Guided Strategy vs an Empirical High PEEP-Fio2 Strategy on Death and Days Free From Mechanical Ventilation Among Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA. 2019;321(9):846-857. doi:10.1001/jama.2019.0555
      5. LaFollette R, Hojnowski K, Norton J, DiRocco J, Carney D, Nieman G. Using pressure–volume curves to set proper PEEP in acute lung injury. Nursing in Critical Care. 2007;12(5):231-241. doi:10.1111/j.1478-5153.2007.00224.x
      6. Hess DR. Respiratory mechanics in mechanically ventilated patients. Respir Care. 2014;59(11):1773-1794. doi:10.4187/respcare.03410
      7. Sahetya SK, Hager DN, Stephens RS, Needham DM, Brower RG. PEEP Titration to Minimize Driving Pressure in Subjects With ARDS: A Prospective Physiological Study. Respir Care. 2020;65(5):583-589. doi:10.4187/respcare.07102
      8. Umbrello M, Chiumello D. Interpretation of the transpulmonary pressure in the critically ill patient. Ann Transl Med. 2018;6(19):383. doi:10.21037/atm.2018.05.31
      9. Kenny JES. ICU Physiology in 1000 Words: Driving Pressure & Stress Index. PulmCCM. Published February 13, 2016. Accessed January 1, 2022. https://pulmccm.org/review-articles/icu-physiology-in-1000-words-driving-pressure-stress-index/