62. Sepsis Roundtable: Best Practices and Future Directions

We’re starting off 2024 with a bang!! Today we’re hosting another expert Roundtable discussion and we’re joined by internationally recognized experts in the field. We’ll tackle everything from teaching about sepsis, to how to incorporate guidelines into education and practice, to future research directions in the field. This is a can’t-miss discussion. Let us know what you think and other sepsis questions you have!

Meet Our Guests

Dr. Derek Angus is a Professor at the University of Pittsburgh where he holds the Mitchell P. Fink Endowed Chair in Critical Care Medicine and is the Chair of the Department of Critical Care Medicine. He is a world-renowned researcher in a range of critical care topics including sepsis, has hundreds of publications, and has led numerous NIH-funded studies.

Dr. Hallie Prescott is an Associate Professor in Pulmonary and Critical Care Medicine at the University of Michigan. She is the Co-Chair of the Surviving Sepsis Campaign Guidelines and is also an internationally recognized expert due to her research in improving sepsis outcomes. She has been recognized by both medical journals and professional societies for her outstanding contributions to the field.

Summary of Episode Discussion Topics

1. Sepsis Guidelines and Education

  • Surviving Sepsis Guidelines: Stressed as essential reading for professionals in pulmonary and critical care. They provide a structured approach to sepsis management.
  • Teaching Approaches: Transition from during-rounds teaching to focused, separate teaching sessions for trainees. Emphasizes the need to go beyond guidelines to include discussions on seminal articles, management strategies, and areas lacking robust data.

2. Clinical Skills and Decision Making in Sepsis Care

  • Early Recognition and Polypharmacy: Highlighted the need for timely sepsis identification and caution against excessive polypharmacy.
  • Mental Models in Care: Encourages building comprehensive mental models for understanding sepsis, stressing the importance of not just treating symptoms but understanding underlying causes.

3. Implementation of Sepsis Guidelines

  • Guideline Application in Bedside Care: Discusses the challenge of applying guidelines while considering patient-specific factors.
  • Fluid Resuscitation Practices: Identifies fluid resuscitation as a key area for improvement, with a shift towards more conservative approaches.
  • Overcoming Institutional Barriers: Addresses the fear of causing harm as a significant barrier to guideline implementation and emphasizes the need for balanced decision-making.

4. Advances in Sepsis Care and Prevention

  • Pre-Hospital Sepsis Management: Explores the role of early intervention in community settings and the potential of wearables for early detection.
  • Paramedic Role in Early Antibiotic Administration: Underlines the importance of starting antibiotics in the ambulance for suspected sepsis cases.

5. Recovery and Post-Discharge Care

  • Post-Discharge Initiatives: Focuses on improving handoffs from ICU to ward and from hospital to home. Highlights the importance of medication reconciliation and clear communication with primary care.
  • Challenges in Continuity of Care: Discusses the need for clear documentation and communication during patient transitions to ensure continuity of care.

6. Future Directions in Sepsis Treatment and Research

  • Phenotyping for Targeted Treatment: The potential of identifying patient subgroups through phenotyping for more effective, tailored treatments.
  • Adaptive Trial Designs: Advocates for large-scale adaptive platform trials that can test multiple interventions across diverse patient populations.

7. Personal Involvements and Perspectives

  • Experts’ Current Work: The panelists share their ongoing projects and research in sepsis care, reflecting a commitment to advancing the field through comprehensive and adaptive approaches.

References and Further Reading

  1. Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Hylander Møller M, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021 Nov 1;49(11):e1063-e1143. doi: 10.1097/CCM.0000000000005337. PMID: 34605781.
  2. Rudd KE, Kissoon N, Limmathurotsakul D, Bory S, Mutahunga B, Seymour CW, Angus DC, West TE. The global burden of sepsis: barriers and potential solutions. Crit Care. 2018 Sep 23;22(1):232. doi: 10.1186/s13054-018-2157-z. PMID: 30243300; PMCID: PMC6151187.
  3. Talisa VB, Yende S, Seymour CW, Angus DC. Arguing for Adaptive Clinical Trials in Sepsis. Front Immunol. 2018 Jun 28;9:1502. doi: 10.3389/fimmu.2018.01502. PMID: 30002660; PMCID: PMC6031704.
  4. Prescott HC, Angus DC. Enhancing Recovery From Sepsis: A Review. JAMA. 2018 Jan 2;319(1):62-75. doi: 10.1001/jama.2017.17687. PMID: 29297082; PMCID: PMC5839473.
  5. https://mi-hms.org/quality-initiatives/sepsis-initiative
  6. Kowalkowski M, Chou SH, McWilliams A, Lashley C, Murphy S, Rossman W, Papali A, Heffner A, Russo M, Burke L, Gibbs M, Taylor SP; Atrium Health ACORN Investigators. Structured, proactive care coordination versus usual care for Improving Morbidity during Post-Acute Care Transitions for Sepsis (IMPACTS): a pragmatic, randomized controlled trial. Trials. 2019 Nov 29;20(1):660. doi: 10.1186/s13063-019-3792-7. PMID: 31783900; PMCID: PMC6884908.
  7. Schmidt K, Worrack S, Von Korff M, Davydow D, Brunkhorst F, Ehlert U, Pausch C, Mehlhorn J, Schneider N, Scherag A, Freytag A, Reinhart K, Wensing M, Gensichen J; SMOOTH Study Group. Effect of a Primary Care Management Intervention on Mental Health-Related Quality of Life Among Survivors of Sepsis: A Randomized Clinical Trial. JAMA. 2016 Jun 28;315(24):2703-11. doi: 10.1001/jama.2016.7207. PMID: 27367877; PMCID: PMC5122319.

40. Pulm PEEPs and ATS RCMB Assembly: Short Telomeres and Interstitial Lung Disease

This week on Pulm PEEPs we are thrilled to share a collaboration with the American Thoracic Society Assembly on Respiratory Cell & Molecular Biology. We are joined by two expert members of the ATS RCMB Assembly who have done basic and translational research in respiratory biology and lung disease. We explore the topic of Short Telomeres and their role in lung disease. With the annual ATS Conference just around the corner, this is a great intro episode for everyone from aspiring researchers and clinical pulmonologists.

Meet The Guests

Mark Snyder is an Assistant Professor of Medicine at the University of Pittsburgh Medical Center, and a member of the Graduate Program in Microbiology and Immunology there. He does research on the role of the adaptive immune system’s role in chronic rejection after lung transplantation and has received both a Parker B Francis Foundation award and an NIH K23 grant for this work.

Jonathan Alder is an Assistant Professor of Medicine at the University of Pittsburgh. His research focuses on telomeres and their role in human health and disease. He is an accomplished researcher, was a Parker B Francis fellow, and now has an NIH RO1 studying Telomere-mediated Lung disease.

Further Reading and References

Alder JK, Armanios M. Telomere-mediated lung disease. Physiol Rev. 2022 Oct 1;102(4):1703-1720. doi: 10.1152/physrev.00046.2021. Epub 2022 May 9. PMID: 35532056; PMCID: PMC9306791.

Alder JK, Chen JJ, Lancaster L, Danoff S, Su SC, Cogan JD, Vulto I, Xie M, Qi X, Tuder RM, Phillips JA 3rd, Lansdorp PM, Loyd JE, Armanios MY. Short telomeres are a risk factor for idiopathic pulmonary fibrosis. Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):13051-6. doi: 10.1073/pnas.0804280105. Epub 2008 Aug 27. PMID: 18753630; PMCID: PMC2529100.

Armanios MY, Chen JJ, Cogan JD, Alder JK, Ingersoll RG, Markin C, Lawson WE, Xie M, Vulto I, Phillips JA 3rd, Lansdorp PM, Greider CW, Loyd JE. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med. 2007 Mar 29;356(13):1317-26. doi: 10.1056/NEJMoa066157. PMID: 17392301.

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

19. Severe COPD and Lung Volume Reduction

We are extremely excited for the third and final installment in our Pulm PEEPs and ATS Clinical Problems Assembly collaborative series on COPD. Today, we are joined by Drs. Jessica Bon, Michael Lester, and Niru Putcha to discuss severe COPD management and the role of lung volume reduction procedures. If you missed the first two parts of our series, make sure to check out episode 1 on COPD diagnosis and initial management, and episode 2 on COPD exacerbations.

Meet our Guests

Jessica Bon is an Associate Professor of Medicine at the University of Pittsburgh School of Medicine where she is also the Program Director for the Pulmonary and Critical Care Medicine Fellowship. Her research and clinical interests focus on lung disease progression in COPD and she manages patients with difficult-to-treat and severe COPD and evaluates patients for lung volume reduction surgery. Jessica was the chair of the ATS Clinical Problems Assembly Programming Committee from 2021 – 2022.

Michael Lester is an Assistant Professor of Medicine at Vanderbilt University Medical Center. Michael’s interests span both pulmonary and critical care medicine. He specializes in patients with advanced COPD and evaluation for bronchoscopic lung volume reduction surgery.

Niru Putcha is an Associate Professor of Medicine at Johns Hopkins School of Medicine and is an integral member and mentor in the Obstructive Lung Disease Group. Her research and clinical interests focus on the role of comorbidities on clinical outcomes in individuals with COPD. She also manages patients with difficult-to-treat and severe COPD and evaluates patients for lung volume reduction surgery. Niru is also the new chair of the ATS  Clinical Problems Assembly Programming Committee.

Key Learning Points

Patients with advanced COPD should also be considered for lung transplantation. We will have an episode on lung transplant coming up soon!

References

  1. Criner GJ, Sternberg AL. A Clinician’s Guide to the Use of Lung Volume Reduction Surgery. Proc Am Thorac Soc. 2008;5(4):461-467. doi:10.1513/pats.200709-151ET
  2. A Randomized Trial Comparing Lung-Volume–Reduction Surgery with Medical Therapy for Severe Emphysema. New England Journal of Medicine. 2003;348(21):2059-2073. doi:10.1056/NEJMoa030287
  3. Valipour A, Slebos DJ, Herth F, et al. Endobronchial Valve Therapy in Patients with Homogeneous Emphysema. Results from the IMPACT Study. Am J Respir Crit Care Med. 2016;194(9):1073-1082. doi:10.1164/rccm.201607-1383OC
  4. Sciurba FC, Ernst A, Herth FJF, et al. A Randomized Study of Endobronchial Valves for Advanced Emphysema. New England Journal of Medicine. 2010;363(13):1233-1244. doi:10.1056/NEJMoa0900928
  5. Klooster K, Slebos DJ. Endobronchial Valves for the Treatment of Advanced Emphysema. Chest. 2021;159(5):1833-1842. doi:10.1016/j.chest.2020.12.007
  6. Choi M, Lee WS, Lee M, et al. Effectiveness of bronchoscopic lung volume reduction using unilateral endobronchial valve: a systematic review and meta-analysis. Int J Chron Obstruct Pulmon Dis. 2015;10:703-710. doi:10.2147/COPD.S75314

12. Undifferentiated Shock Roundtable

This week the Pulm PEEPs, David Furfaro and Kristina Montemayor, are joined by three outstanding critical care doctors and medical educators to discuss the evaluation of patients with undifferentiated shock. We cover everything from the basics about defining shock, to advanced POCUS techniques to clarify the etiology of shock. Listen today and let us know your favorite technique for evaluating shock in the ICU.

Meet Our Guests

Molly Hayes is an Assistant Professor of Medicine at Beth Israel Deaconess Medical Center and Harvard Medical School, the Director of the MICU at BIDMC, and the Director of External Education at the Carl J Shapiro Institute for Education and Research. She is also a course director for a yearly CME course on principles of critical care medicine run by BIDMC and HMS.

Nick Mark is a Pulmonologist and Intensivist at Swedish Medical Center in Seattle, Washington. He is also the founder of ICU One Pager, which produces high yield critical care education one-page guides that have been downloaded by thousands of learners.

Matt Siuba is an Assistant Professor of Medicine and intensivist at the Cleveland Clinic, where he is the associate program director for the Critical Care Medicine fellowship. He founded and runs the website Zentensivist.com, has his own associated podcast, and is a senior editor at CriticalCareNow.com.

Key Learning Points

Key graphics

Courtesy of Nick Mark and ICU One Pager
Courtesy of Matt Siuba
Courtesy of Nick Mark and ICU One Pager

Definition of shock

– Shock is defined as inadequate oxygen delivery to meet the body’s needs. Decreased perfusion and oxygen delivery leads to cell injury and death

– If you define just as hypotension, you will miss people who have cryptic shock, and categorize some people with shock who don’t have it

– Cryptic shock = a patient with normal blood pressure (MAP > 65), but who still has shock based on inadequate O2 delivery

– O2 delivery is broken down in to cardiac output and arterial oxygen content

Causes of shock

Shock can be divided into three large categories:

1) A pump problem – low cardiac output. This includes cardiogenic and obstructive shock. Make sure to remember to look for tamponade and valvulopathies.

2) A pipe problem – low systemic vascular resistance. This includes distributive shock. Distributive shock is most often due to sepsis but can be due to anaphylaxis, endocrinopathies, cirrhosis, or spinal shock.

3) A tank problem – low preload. This includes hypovolemic and hemorrhagic shock. Make sure to remember about high intrathoracic pressure, which can decrease effective preload.

Examining a patient with undifferentiated shock

– See if the patient is on the “Shock BUS” by examining their brain (mental status), urine output, and skin

– Feel if their skin is warm vs cold and if it is mottled

– Feel the patient’s pulses to see if they are bounding, normal, or thready

Point of Care Ultrasound

– “Ultrasound is the new stethoscope”

– The first step is to always look at the heart and look for chamber size and function. You can then look for pericardial effusion

– Point of care ultrasound then includes looking at the lungs for signs of fluid overload, consolidation, or pneumothorax

– A complete ultrasound also involves looking at the abdomen and at the extremities for DVT

– More specific ultrasound techniques include looking at:

1) IVC exam to estimate right atrial pressure. This test is often misused. It is most helpful in states when the patient has low stroke volume and trying to figure out if they have cardiac limitation to stroke volume vs if they are hypovolemic.

2) Velocity time index as a measure of cardiac output to trend with interventions

References and links for further reading

  1. Vincent JL, De Backer D. Circulatory shock. N Engl J Med. 2013;369(18):1726-1734. doi:10.1056/NEJMra1208943
  2. Seymour CW, Liu VX, Iwashyna TJ, et al. Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):762-774. doi:10.1001/jama.2016.0288
  3. Chukwulebe SB, Gaieski DF, Bhardwaj A, Mulugeta-Gordon L, Shofer FS, Dean AJ. Early hemodynamic assessment using NICOM in patients at risk of developing Sepsis immediately after emergency department triage. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 2021;29(1):23. doi:10.1186/s13049-021-00833-1
  4. Hernández G, Ospina-Tascón GA, Damiani LP, et al. Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial. JAMA. 2019;321(7):654-664. doi:10.1001/jama.2019.0071
  5. Wang J, Zhou D, Gao Y, Wu Z, Wang X, Lv C. Effect of VTILVOT variation rate on the assessment of fluid responsiveness in septic shock patients. Medicine (Baltimore). 2020;99(47):e22702. doi:10.1097/MD.0000000000022702
  6. Sweeney DA, Wiley BM. Integrated Multiorgan Bedside Ultrasound for the Diagnosis and Management of Sepsis and Septic Shock. Semin Respir Crit Care Med. 2021;42(5):641-649. doi:10.1055/s-0041-1733896
  7. Yuan S, He H, Long Y. Interpretation of venous-to-arterial carbon dioxide difference in the resuscitation of septic shock patients. J Thorac Dis. 2019;11(Suppl 11):S1538-S1543. doi:10.21037/jtd.2019.02.79
  8. Volpicelli G, Lamorte A, Tullio M, et al. Point-of-care multiorgan ultrasonography for the evaluation of undifferentiated hypotension in the emergency department. Intensive Care Med. 2013;39(7):1290-1298. doi:10.1007/s00134-013-2919-7
  9. Perera P, Mailhot T, Riley D, Mandavia D. The RUSH exam: Rapid Ultrasound in SHock in the evaluation of the critically lll. Emerg Med Clin North Am. 2010;28(1):29-56, vii. doi:10.1016/j.emc.2009.09.010

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/

2. Cystic Fibrosis Roundtable

The Pulm PEEPs (Kristina Montemayor and Dave Furfaro) host a panel of Cystic Fibrosis (CF) providers to discuss the current state of the disease, recent advances in cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies, and the evolving faces and voices of Cystic Fibrosis.

Cystic Fibrosis is an autosomal recessive disorder caused by mutations in the CFTR gene that affects over 30,000 individuals in the United States and 70,000 people worldwide. Absence or dysfunction of the CFTR protein leads to abnormal secretion of mucus, sweat, and digestive fluids, which impacts the lungs, digestive tract, and reproductive system.

From the first formal publication on Cystic Fibrosis in 1938 by Dorothy Hansine Andersen, to the discovery of the delta F508 mutation and CFTR gene in 1988 -1989 by Lap-Chee Tsui, Francis Collins, and John R. Riordan, to the approval of the first CFTR modulator therapy, Ivacaftor, in 2012, our knowledge about Cystic FIbrosis has been advancing in leaps and bounds. As therapies have improved, they have dramatically impacted the lives of patients with Cystic Fibrosis. Join us today as we explore what this evolution in care has looked like from the perspective of Cystic Fibrosis providers, and hear about the new questions and challenges on the horizon.


Meet our guests

Emily DiMango is a Professor of Medicine at Columbia University Medical Center and the Director of the John Edsall-John Wood Asthma Center and the Gunnar Esiason Adult Cystic Fibrosis Program

Terri Laguna is an Associate Professor of Pediatrics at Northwestern Medicine / Feinberg School of Medicine and the Chief of Pulmonary and Sleep Medicine in the Department of Pediatrics

Patrick Sosnay is a Senior Medical Director at Vertex Pharmaceuticals and specializes in Cystic Fibrosis

Natalie West is an Assistant Professor of Medicine at Johns Hopkins Hospital and specializes in Cystic Fibrosis.


References and links for further reading

  1. Cystic Fibrosis Foundation
  2. Shteinberg M, Haq IJ, Polineni D, Davies JC. Cystic fibrosis. The Lancet. 2021;397(10290):2195-2211. doi:10.1016/S0140-6736(20)32542-3
  3. Rowe SM, Miller S, Sorscher EJ. Cystic Fibrosis. New England Journal of Medicine. 2005;352(19):1992-2001. doi:10.1056/NEJMra043184
  4. Davis PB. Cystic Fibrosis Since 1938. Am J Respir Crit Care Med. 2006;173(5):475-482. doi:10.1164/rccm.200505-840OE
  5. Barry PJ, Mall MA, Álvarez A, et al. Triple Therapy for Cystic Fibrosis Phe508del–Gating and –Residual Function Genotypes. New England Journal of Medicine. 2021;385(9):815-825. doi:10.1056/NEJMoa2100665
  6. Middleton PG, Mall MA, Dřevínek P, et al. Elexacaftor–Tezacaftor–Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. New England Journal of Medicine. Published online October 31, 2019. doi:10.1056/NEJMoa1908639