106. Pulm PEEPs Pearls: ICI Pneumonitis

Posted on August 12, 2025 by Pulm PEEPs

We are so excited to be launching a new series here at Pulm PEEPs! We’ll be talking about high yield topics in 15 minutes or less. In this series, Furf and Monty will tackle core points and provide an overview, key points, and further reading. We’re starting with a key point review of Immune Checkpoint Inhibitor Pneumonitis. Let us know if there are other topics you want to hear about!

Key Learning Points

Epidemiology & Pathophysiology

- Increasingly common as immunotherapy use grows in oncology.
- Caused by immune activation from PD-1, PD-L1, or CTLA-4 inhibitors.
- Mechanisms:
  1. Overactive T cells
  2. Autoantibody production
  3. Cytokine-mediated inflammation (e.g., ↑IL-1, ↑IL-6)

Clinical Suspicion & Diagnosis

- Any new respiratory symptoms in a patient currently or previously on ICI → consider ICI pneumonitis.
- CT findings are variable: can mimic organizing pneumonia, NSIP, ARDS, or diffuse ground glass opacities. Imaging pattern does not determine severity grade.
- Diagnosis is of exclusion — infection and malignancy progression must be ruled out first.
- Workup:
  - Broad infectious evaluation (cultures, viral panel, fungal markers).
  - Early bronchoscopy with BAL if feasible — typically lymphocyte-predominant in ICI pneumonitis.
  - Screen for TB and hepatitis early (in case infliximab is needed).

Severity Grading (Symptom- & O₂-based, not imaging-based)

- Grade 1: Asymptomatic → monitor, may hold ICI.
- Grade 2: Symptomatic but not hypoxic → prednisone 1 mg/kg/day PO.
- Grade 3–4: Hypoxemia or ICU-level care → methylprednisolone 1–2 mg/kg/day IV. Usually hold or permanently stop ICI.

Steroid Management

- Typical taper: over 6 weeks for grade ≥3.
  - Week 1: 1–2 mg/kg/day
  - Gradual step-down to 0.25 mg/kg/day by week 5, then stop week 6.
- Chronic/recurrent cases may need slower tapers over months.
- Add GI prophylaxis and PJP prophylaxis during prolonged steroid use.

If Steroids Fail (no improvement after 48–72 hrs)

- Consider adding:
  - IVIG (2 g/kg over 5 days)
  - Infliximab (TNF-α inhibitor — requires TB/hepatitis screening)
  - Mycophenolate mofetil (1–1.5 g/day BID or TID, start at effective dose quickly)
- IVIG may have lower mortality in some series but comes with risks (volume overload, thrombosis, infusion reactions).

Emerging Therapies

- JAK inhibitors are under investigation as possible future options.

Multidisciplinary Care

- ICU management is a team sport — coordinate with oncology, critical care, infectious disease, and pharmacy.

Infographic

References and Further Reading

Podcast: Play in new window | Download

105. ICU Acquired Weakness

Posted on July 29, 2025 by Pulm PEEPs

Today we’re talking about a topic that is relevant for all critical care physicians but under-examined: ICU Acquired Weakness. We are joined by two excellent guests to walk through a case and discuss the diagnosis, pathophysiology, prevention, and treatment of ICU Acquired Weakness. Check out our associated infographics and key learning points below.

Meet Our Guests

Jim Devanney is a Physiatrist who just completed a neurocritical care fellowship at BIDMC. He is transitioning to a clinical associate position at University Health Network – University of Toronto where he will be working as a PM&R consultant within the ICU.

Kalaila Pais is a third year internal medicine resident at BIDMC, interested in pulmonary and critical care and medical education and is returning for her third Pulm PEEPs episode.

Key Learning Points

Definition & Clinical Presentation

ICU-AW refers to new-onset, generalized muscle weakness that arises during critical illness, not explained by other causes.It typically presents as:

Symmetric, proximal > distal weaknessRespiratory muscle involvementPreserved cranial nerve functionNo sensory deficits in myopathy (sensory loss points toward neuropathy)

Differential Diagnosis Using Neuroanatomical ApproachAn anatomical approach (central → peripheral) helps localize the etiology weakness

CNS: trauma, stroke, encephalitis, seizuresAnterior horn cells: viral myelitis, motor neuron diseasePeripheral nerves: Guillain-Barré, vasculitis, critical illness polyneuropathy (CIP)Neuromuscular junction: myasthenia gravis, botulism, Lamber EatonMuscle: rhabdomyolysis, inflammatory or drug-induced myopathies, critical illness myopathy (CIM)

Subtypes of ICU-AW

Critical Illness Myopathy (CIM):

Muscle dysfunctionEarly onset (within 48 hrs)Sensation intactproximal > distal weakness

Critical Illness Polyneuropathy (CIP):

Nerve involvementDistal > proximal weakness, sensory deficits

Critical Illness Polyneuromyopathy (CIPNM): Combination of both

Diagnosis

Medical Research Council Score (MRC-SS):
- Score < 48: ICU-AW
- Score < 36: severe ICU-AW
Handgrip dynamometry: <11 kg (men), <7 kg (women)
Electrophysiology: EMG/NCS to distinguish CIM vs CIP
Muscle ultrasound: bedside monitoring
MRI/CT/Muscle biopsy: rarely used due to practical limitation

Risk Factors

Modifiable:

Hyper/hypoglycemia
Electrolyte derangement
Parenteral nutrition
Immobility
Medications (steroids, NM blockers, sedatives, aminoglycosides)

Non-modifiable:

Age, female sex, comorbidities
Severity of illness, prolonged ventilation
Sepsis, multi-organ failure

Management & Prevention

Prevention is key:
- Early treatment of sepsis and inflammation
- Glycemic control
- Early enteral nutrition
- Minimize sedation (A-F bundle)
- Early mobilization and physical therapy
NMES (neuromuscular electrical stimulation): emerging therapy, needs more evidence

Outcomes

Short-term: increased LOS, ventilation duration, mortality
Long-term: decreased function, discharge to rehab, prolonged recovery

Final Takeaways

Prevention is crucial — start interventions early.
Systematic approach to ICU weakness helps rule out dangerous mimics.
ICU-AW is common but often under-recognized — awareness and early rehab can significantly impact recovery.

Infographics

References and Further Reading

Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Devlin JW, Skrobik Y, Gélinas C, et al. Critical Care Medicine. 2018;46(9):e825-e873. doi:10.1097/CCM.0000000000003299.

The ABCDEF Bundle: Science and Philosophy of How ICU Liberation Serves Patients and Families. Ely EW. Critical Care Medicine. 2017;45(2):321-330. doi:10.1097/CCM.0000000000002175.

Caring for Critically Ill Patients With the ABCDEF Bundle: Results of the ICU Liberation Collaborative in Over 15,000 Adults. Pun BT, Balas MC, Barnes-Daly MA, et al. Critical Care Medicine. 2019;47(1):3-14. doi:10.1097/CCM.0000000000003482.

Delirium in Critical Illness: Clinical Manifestations, Outcomes, and Management. Stollings JL, Kotfis K, Chanques G, et al. Intensive Care Medicine. 2021;47(10):1089-1103. doi:10.1007/s00134-021-06503-1.

ICU-acquired Weakness. Vanhorebeek I, Latronico N, Van den Berghe G. Intensive Care Medicine. 2020;46(4):637-653. doi:10.1007/s00134-020-05944-4.

Clinical Review: Intensive Care Unit Acquired Weakness. Hermans G, Van den Berghe G. Critical Care (London, England). 2015;19:274. doi:10.1186/s13054-015-0993-7.

Best Practices for Conducting Interprofessional Team Rounds to Facilitate Performance of the ICU Liberation (ABCDEF) Bundle. Stollings JL, Devlin JW, Lin JC, et al. Critical Care Medicine. 2020;48(4):562-570. doi:10.1097/CCM.0000000000004197.

ABCDE and ABCDEF Care Bundles: A Systematic Review of the Implementation Process in Intensive Care Units. Moraes FDS, Marengo LL, Moura MDG, et al. Medicine. 2022;101(25):e29499. doi:10.1097/MD.0000000000029499.

Podcast: Play in new window | Download

103. Fellows’ Case Files: University of Virginia

Posted on July 1, 2025 by Pulm PEEPs

Today, we’re virtually visiting the University of Virginia for another Fellows’ Case Files. This is a fantastic case that covers ARDS, the infectious work up of an immunosuppressed patient, and the evaluation of undifferentiated shock. Please let us know what you think of the episode and always feel free to reach out with interesting cases!

Meet Our Guests

John Popovich completed his residency training and chief year at UVA and has stayed on there for his pulmonary and critical care fellowship.

Tim Scialla is an associate professor of medicine at UVA. He completed his residency and fellowship at Johns Hopkins Hospital where he was also an ACS. His clinical and research focuses are advanced airways disease. He is also the program director of the PCCM fellowship.

Matt Freedman completed his residency training at Virginia Commonwealth University and is currently a second year fellow at University of Virginia.

Case Presentation

Patient: 52-year-old male with psoriasis, HIV/AIDS (CD4 count: 71), presenting with progressive shortness of breath, fever, non-productive cough, and weight loss.

Vital signs: Febrile (103°F), tachycardic (HR 110), hypoxemic on 6L O₂ (SpO₂ 90–92%).

Exam: Diffuse crackles, ill-appearing.

Imaging: CXR and CT showed bilateral upper lobe infiltrates, ground-glass opacities, septal thickening, and peripheral cystic changes.

Infographics

POCUS algorithms for investigating shock

Shock physiology:

Key Learning Points

Diagnostic Reasoning in Immunocompromised Hosts

Framework: Anchor the differential based on type of immunosuppression.
- HIV/AIDS → T-cell dysfunction, affecting susceptibility to PCP, TB, CMV, fungi (e.g. histo/blasto), and common CAP organisms.
PCP considerations:
- PCP can occur despite prophylaxis (e.g. Bactrim), especially if adherence or resistance issues exist.
- Classic symptoms in AIDS: acute, febrile, hypoxemic respiratory failure.

Use of Serum Markers and Imaging

LDH: Elevated in PCP, but non-specific. High negative predictive value when normal.
1,3-β-D-glucan: Elevated in PCP and other fungal infections. Very sensitive for PCP (up to 95%).
Imaging: Ground-glass opacities with cystic changes support PCP diagnosis.

Role of Bronchoscopy and Diagnostic Yield

BAL studies to obtain:
- DFA for PCP (rapid, high specificity, lower sensitivity)
- PCR for PCP (higher sensitivity, slower turnaround)
- Cultures: bacterial, fungal, mycobacterial
- Cytology, galactomannan, histo/blasto urine antigens
Bronch Risk-Benefit:
- Can change management in 40–60% of cases.
- Complication rate: ~10–15%, most often hypoxemia.
- Heuristic for pre-bronch ABG on non-rebreather:
  - PaO₂ >150 → likely safe
  - 100–150 → ~25% risk of intubation
  - <100 → high risk of decompensation

Steroids in PCP and Severe CAP

Steroids indicated in PCP with significant hypoxemia (PaO₂ <70 mmHg).
With new CAP guidelines (Cape Cod trial), steroids may also be considered in severe bacterial CAP.

Shock Evaluation in ICU

Framework: Simplify into likely causes — distributive most common, but rule out cardiogenic, obstructive, hypovolemic.
Physical exam + POCUS essential early.
- POCUS: cardiac views, IVC, lung US, abdominal free fluid.
- Low EF doesn’t exclude distributive shock.
PA catheter (Swan) utility:
- Useful when physiology unclear or when tracking response to therapy is critical.
- Swan data in this patient: low CVP and wedge, high SVR → distributive shock, not cardiogenic despite low EF.

Podcast: Play in new window | Download

102. Journal Club with BMJ Thorax – Sleep and Non-Invasive Ventilation

Posted on June 17, 2025 by Pulm PEEPs

Today is our third episode in our collaborative series with BMJ Thorax. Our mission at Pulm PEEPs is to disseminate and promote pulmonary and critical care education, and we highly value the importance of peer reviewed journals in this endeavor. Each month in BMJ Thorax, a journal club is published looking at high yield and impactful publications in pulmonary medicine. We will be putting out quarterly episodes in association with Thorax to discuss a journal club publication and synthesize four valuable papers. This week’s episode covers four articles related to obstructive sleep apnea therapies, and the use of non-invasive ventilation and high flow nasal cannula for intubation and COPD exacerbations.

Meet Our Guests

Chris Turnbull is an Associate Editor for Education at Thorax. He is an Honorary Researcher and Respiratory Medicine Consultant at Oxford University Hospitals. In addition to his role as Associate Editor for Education at BMJ Thorax, he is also a prominent researcher in sleep-related breathing disorders.

Natalie McLeod is a resident in respiratory medicine and is currently doing a clinical fellowship in sleep and ventilation at Oxford University Hospitals.

Journal Club Papers

To submit a journal club article of your own to Thorax, you can contact Chris directly – christopher.turnbull@ouh.nhs.uk

To engage with Thorax, please use the social media channels (Twitter – @ThoraxBMJ; Facebook – Thorax.BMJ) and subscribe on your preferred platform, to get the latest episodes directly on your device each month.

Podcast: Play in new window | Download

100. ATS 2025 Critical Care Assembly: The Future of Mechanical Ventilation

Posted on May 18, 2025 by Pulm PEEPs

We are podcasting today directly from ATS 2025 in San Francisco! Every year, in collaboration with the ATS Critical Care Assembly, we highlight some of the scientific symposium programming from the conference. Today, Furf and Monty sit down with the three chairs of the scientific symposium entitled: Mechanical Ventilation of the Future: New Foundations For Ventilator Strategies.

Meet Our Guests

Juliana Ferreira is an Associate Professor at the University of Sao Paulo, Brazil where she is also co-director of the pulmonary and critical care fellowship program. She is an MD, PhD, and a physician scientist with specific interests in mechanical ventilation and medical education. Finally, she serves ATS as the ATS MECOR Latin America Director.

Bhakti Patel is an Assistant Professor Medicine at the University of Chicago. She is a dedicated researcher and educator. Her research focuses on non-invasive ventilator support.

Akram Khan is an Associate Professor of Medicine at Oregon Health and Science University. Akram is a pulmonary, critical care, and sleep provider with specific clinical interests in critical illness, pulmonary vascular disease and sleep apnea. Additionally, he is an accomplished translational science researcher.

Podcast: Play in new window | Download

99. Fellows’ Case Files: Rutgers – Robert Wood Johnson Medical School

Posted on May 6, 2025 by Pulm PEEPs

We’re back with another edition of Fellows’ Case Files! Today, we’re virtually visiting Rutgers University, Robert Wood Johnson Medical School to work through a fascinating pulmonary case. Enjoy, and let us know your thoughts.

Meet Our Guests

Khalil El Gharib completed his residency training at Northwell at Staten Island University Hospital Program and is currently a first year fellow at Rutgers Robert Wood Johnson Medical School.

Sabiha Hussain completed her residency training at Robert Wood Johnson Medical School and her fellowship training at Columbia Presbyterian Medical Center in New York. She is currently a Professor of Medicine and the fellowship Program Director.

Case Presentation

Patient: 28-year-old male with Asperger’s syndrome and IgA nephropathy.
Symptoms: 3-month history of progressive dry cough and dyspnea on exertion; later developed mild hemoptysis.
Notable exposure: Questionable black mold in the patient’s apartment.

Initial Workup and Diagnostic Reasoning

Vital signs: Hypoxemia (SpO₂ 91% on room air).
Exam: Inspiratory crackles.
ABG findings: Elevated A–a gradient (~50), indicating a gas exchange problem.
Chest X-ray: Bilateral, patchy infiltrates without specific lobar preference.
Initial management: Discharged with empiric antibiotics for presumed multifocal pneumonia.

Re-Presentation and Further Testing

Symptoms worsened; now with blood-tinged sputum.
Chest CT: Showed diffuse ground-glass opacities (GGOs) without fibrosis, consolidation, or lymphadenopathy.

Imaging and Pathology

Pathology images a courtesy to Dr Isago Jerrett, pathology resident at RWJMS

Key Learning Points

Diagnostic Framework for Hypersensitivity Pneumonitis (HP)

New classification: Based on fibrotic vs. non-fibrotic phenotype (not acute/chronic).
CT features of HP:
- GGOs with lobular air trapping.
- “Three-density sign” (normal lung, low-density air-trapping, and ground-glass opacities).
BAL: Typically shows lymphocytic predominance in chronic HP, neutrophilic in early stages.
Serum IgG testing: Helps identify antigen exposure but doesn’t confirm disease alone.
Lung biopsy (VATS): Revealed poorly formed granulomas and airway-centered inflammation—consistent with HP.

Differential Diagnosis of Granulomatous Disease

Infectious: TB, fungal (must rule out with stains/cultures).
Non-infectious: Sarcoidosis, HP, granulomatosis with polyangiitis.
Key pathology clues for HP: Loosely formed granulomas, airway inflammation, giant cells.

Management and Outcome

Primary treatment: Antigen avoidance (patient moved out of mold-exposed apartment).
Adjunct therapy: Oral prednisone with a slow taper.
Outcome: Symptomatic and radiographic improvement over six months.

Teaching Pearls

Always take a detailed environmental and occupational exposure history.
Hypoxemia with an elevated A–a gradient in a young adult should trigger concern for interstitial/parenchymal lung disease.
CT and history are often enough to diagnose HP—biopsy is reserved for uncertain cases.
Remember evolving terminology: think fibrotic vs. non-fibrotic HP, not acute/chronic.

Podcast: Play in new window | Download

91. Tylenol Toxicity and Acute Liver Failure

Posted on December 10, 2024 by Pulm PEEPs

This week we’re talking about a case as a lens for discussing Tylenol toxicity and Acute Liver Failure. These relatively common critical care presentations are essential knowledge for anyone practicing in the ICU. Listen in for some key discussion both about toxicology and the diagnosis and management of acute livery injury and failure.

Meet Our Guests

Kalaila Pais received her MD from Howard University College of Medicine and is currently a second year internal medicine resident at BIDMC. She is interested in pulmonary and critical care, as well as medical education. She also had the idea for this episode and was essential in its writing and production.

Hima Veeramachaneni received her MD from University of Missouri-Kansas City School of Medicine, and her residency at Emory where she was also a Chief Resident at Grady Memorial Hospital. She is a gastroenterologist and completed her GI and transplant hepatology training at Emory. She is also now doing a critical care medicine fellowship year.

Case Presentation

Presentation: Patient found down, surrounded by liquor bottles, with coffee-ground emesis, hemodynamic instability, scleral icterus, and metabolic derangements.

Key Lab Findings:

Severe transaminitis (AST >10,000, ALT ~3,000).
Elevated bilirubin (5.8), lactate (16), and INR (>2).
Metabolic acidosis with a pH of 7.04.
Tylenol level: 41 (slightly elevated but inconclusive without ingestion timing).

Key Learning Points

Infographic:

Acute Liver Injury vs. Acute Liver Failure

Acute Liver Injury (ALI): Elevated liver enzymes without encephalopathy or significant synthetic dysfunction.
Acute Liver Failure (ALF): Defined by:
- Presence of encephalopathy.
- Coagulopathy (elevated INR).
- Rapid onset (<26 weeks) in patients without pre-existing liver disease.
ALF often leads to complications such as cerebral edema, which necessitates aggressive management.

Tylenol Toxicity and Interpretation

Pathophysiology:
- Tylenol overdose overwhelms liver glutathione, leading to accumulation of NAPQI, which causes hepatocyte necrosis.
Interpretation of Tylenol Levels:
- Timing of ingestion is critical to interpreting levels.
- The Rumack-Matthew Nomogram is used for acute ingestions but requires a known ingestion time.
Management:
- N-acetylcysteine (NAC): Standard of care; acts as a glutathione precursor and mitigates liver damage.
- Early use is recommended in suspected cases of Tylenol toxicity, even if ingestion timing is unclear.

Critical Management Principles

Stabilization: Focus on airway, hemodynamics, and perfusion.
- Monitor for signs of cerebral edema (e.g., pupillary changes, seizures).
- In select patients, use hypertonic saline to maintain sodium levels (145–150 mmol/L) to mitigate cerebral edema risks.
CRRT and Plasma Exchange:
- Continuous renal replacement therapy (CRRT) for hyperammonemia and acidosis.
- Plasma exchange (PLEX) may stabilize cytokine storms and improve survival.
Organ-Specific Considerations:
- Renal failure: Common due to hepatorenal syndrome; requires CRRT.
- Coagulopathy: Managed with blood products as needed but indicates worsening liver synthetic dysfunction.

Prognosis and Transplant Considerations

King’s College Criteria: Guides transplant listing for ALF patients.
- Factors: Encephalopathy severity, INR, lactate, bilirubin trends.
Ethical considerations for liver transplant in patients with substance use or overdose:
- Emphasis on assessing social support and addressing psychiatric needs.
- Efforts are made to ensure equitable access to transplant when warranted.

Takeaways for Clinical Practice

Broad Differential Diagnosis: Keep a wide perspective for acute liver presentations, considering toxins, infections, and systemic conditions.
Early Use of NAC: Err on the side of initiating NAC when Tylenol toxicity is suspected.
CNS Focus in ALF: Monitor and manage cerebral edema aggressively.
CRRT & PLEX: Advanced liver support techniques are critical in select cases.
Interdisciplinary Collaboration: Psychiatrists, neurocritical care, and hepatologists play pivotal roles in management.

Podcast: Play in new window | Download

90. Rapid Fire Journal Club: ANDROMEDA-SHOCK

Posted on November 27, 2024 by Pulm PEEPs

We are excited to be back with a Rapid Fire Journal Club. Today’s episode is hosted by PulmPEEPs Associate Editor, Luke Hedrick, and will delve into the ANDROMEDA-SHOCK trial published in JAMA in 2019.

Meet our Guests

Jose Meade Aguilar is a second year Internal Medicine resident at Boston University Medical Campus (BUMC).

Article and Reference

Today the discussion highlights the ANDROMEDA-SHOCK trial (JAMA, 2019) which evaluated whether resuscitation guided by capillary refill time (CRT) is superior to lactate-guided resuscitation in reducing mortality in patients with septic shock.

Hernández G, Ospina-Tascón GA, Damiani LP, Estenssoro E, Dubin A, Hurtado J, Friedman G, Castro R, Alegría L, Teboul JL, Cecconi M, Ferri G, Jibaja M, Pairumani R, Fernández P, Barahona D, Granda-Luna V, Cavalcanti AB, Bakker J; The ANDROMEDA SHOCK Investigators and the Latin America Intensive Care Network (LIVEN); Hernández G, Ospina-Tascón G, Petri Damiani L, Estenssoro E, Dubin A, Hurtado J, Friedman G, Castro R, Alegría L, Teboul JL, Cecconi M, Cecconi M, Ferri G, Jibaja M, Pairumani R, Fernández P, Barahona D, Cavalcanti AB, Bakker J, Hernández G, Alegría L, Ferri G, Rodriguez N, Holger P, Soto N, Pozo M, Bakker J, Cook D, Vincent JL, Rhodes A, Kavanagh BP, Dellinger P, Rietdijk W, Carpio D, Pavéz N, Henriquez E, Bravo S, Valenzuela ED, Vera M, Dreyse J, Oviedo V, Cid MA, Larroulet M, Petruska E, Sarabia C, Gallardo D, Sanchez JE, González H, Arancibia JM, Muñoz A, Ramirez G, Aravena F, Aquevedo A, Zambrano F, Bozinovic M, Valle F, Ramirez M, Rossel V, Muñoz P, Ceballos C, Esveile C, Carmona C, Candia E, Mendoza D, Sanchez A, Ponce D, Ponce D, Lastra J, Nahuelpán B, Fasce F, Luengo C, Medel N, Cortés C, Campassi L, Rubatto P, Horna N, Furche M, Pendino JC, Bettini L, Lovesio C, González MC, Rodruguez J, Canales H, Caminos F, Galletti C, Minoldo E, Aramburu MJ, Olmos D, Nin N, Tenzi J, Quiroga C, Lacuesta P, Gaudín A, Pais R, Silvestre A, Olivera G, Rieppi G, Berrutti D, Ochoa M, Cobos P, Vintimilla F, Ramirez V, Tobar M, García F, Picoita F, Remache N, Granda V, Paredes F, Barzallo E, Garcés P, Guerrero F, Salazar S, Torres G, Tana C, Calahorrano J, Solis F, Torres P, Herrera L, Ornes A, Peréz V, Delgado G, López A, Espinosa E, Moreira J, Salcedo B, Villacres I, Suing J, Lopez M, Gomez L, Toctaquiza G, Cadena Zapata M, Orazabal MA, Pardo Espejo R, Jimenez J, Calderón A, Paredes G, Barberán JL, Moya T, Atehortua H, Sabogal R, Ortiz G, Lara A, Sanchez F, Hernán Portilla A, Dávila H, Mora JA, Calderón LE, Alvarez I, Escobar E, Bejarano A, Bustamante LA, Aldana JL. 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 Feb 19;321(7):654-664. doi: 10.1001/jama.2019.0071. PMID: 30772908; PMCID: PMC6439620.

Infographic

Podcast: Play in new window | Download

83. RFJC 13 – ARDS Series – DEXA-ARDS

Posted on August 27, 2024 by Pulm PEEPs

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)

Podcast: Play in new window | Download

79. RFJC 10 – ARDS Series – FACTT

Posted on August 2, 2024 by Pulm PEEPs

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.

Podcast: Play in new window | Download

PulmPEEPs

Pulmonary and Critical Care content for learners and practitioners of all levels

Tag Archives: Critical Care

106. Pulm PEEPs Pearls: ICI Pneumonitis

105. ICU Acquired Weakness

103. Fellows’ Case Files: University of Virginia

102. Journal Club with BMJ Thorax – Sleep and Non-Invasive Ventilation

100. ATS 2025 Critical Care Assembly: The Future of Mechanical Ventilation

99. Fellows’ Case Files: Rutgers – Robert Wood Johnson Medical School

91. Tylenol Toxicity and Acute Liver Failure

90. Rapid Fire Journal Club: ANDROMEDA-SHOCK

83. RFJC 13 – ARDS Series – DEXA-ARDS

79. RFJC 10 – ARDS Series – FACTT