91. Tylenol Toxicity and Acute Liver Failure

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.

 

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.

 

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).

 

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

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

 

90. Rapid Fire Journal Club: ANDROMEDA-SHOCK

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.

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

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.

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.

      78. PREOXI Trial

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

       

       

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

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

      Summarized Key Points


      • Significance of the Problem: Tracheal intubation in emergency and ICU settings is common, with significant risks such as hypoxemia (10-20% incidence) and cardiac arrest (2% incidence) associated with the procedure. This makes effective pre-oxygenation crucial.

      • Methods of Pre-oxygenation: Common methods include face mask oxygen (e.g., non-rebreather, bag-mask devices) and more advanced techniques like non-invasive ventilation (used in about 15% of cases globally). Each method has pros (e.g., simplicity, no risk of aspiration for face masks; 100% oxygen delivery, positive pressure for non-invasive ventilation) and cons (e.g., potential for gastric insufflation with non-invasive ventilation).

      • Study Design: The study discussed in the podcast is a pragmatic trial aiming to optimize pre-oxygenation strategies to prevent peri-intubation hypoxemia. Eligibility criteria were broad, encompassing most patients undergoing tracheal intubation in the ED or ICU, with exclusions mainly for safety reasons.

      • Primary Outcome: The primary outcome of the trial was hypoxemia, defined as oxygen saturation < 85%. This threshold was chosen because it signifies a critical point on the oxygen dissociation curve, where patients are at higher risk of further desaturation and adverse outcomes.

      • Secondary Outcomes: Secondary exploratory outcomes included more severe levels of hypoxemia (oxygen saturation < 80% and < 70%), aiming to capture varying degrees of oxygenation failure during intubation. Rates of cardiac arrest during intubation were an additional outcome.

      • Intervention Comparison:

        • The trial compared two methods of pre-oxygenation: non-invasive ventilation (NIV) and oxygen mask (face mask)

        • Both methods aimed to provide at least three minutes of pre-oxygenation before intubation.

        • NIV group specifics: Expiratory pressure of 5 cm H2O, Inspiratory pressure of 10 cm H2O, respiratory rate of 10 breaths per minute, and 100% oxygen delivery

        • Oxygen mask group specifics: Non-rebreather or bag mask device with at least 15 liters per minute oxygen flow.

        • Nasal cannulas and HFNC could be used in both groups.



      • Logistics and Equipment Use:

        • The trial allowed flexibility in using available equipment (invasive ventilator capable of NIPPV vs. dedicated BiPAP machine).

        • Sites were encouraged to use the same ventilator for both pre-oxygenation and subsequent ventilation to streamline workflow and reduce logistical challenges.



      • Primary and Secondary Outcomes:

        • Results showed a significant reduction in hypoxemia incidents in the NIV group compared to the oxygen mask group.

        • There was also a reduction in severe hypoxemia and a notable decrease in cardiac arrest incidents in the NIV group.



      • Aspiration Safety:

        • There was no statistical difference in aspiration-related outcomes between the NIV and oxygen mask groups, indicating that NIV did not increase the risk of aspiration.



      • Conclusions:

        • The trial concluded that NIV for pre-oxygenation significantly reduced the incidence of hypoxemia and possibly cardiac arrest during tracheal intubation.

        • It also dispelled concerns about increased aspiration risk with NIPPV as pre-oxygenation, suggesting it can be safely used in clinical practice.


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

      77. RFJC 9 – ARDS Series – ARMA

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

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

      Article and Reference

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

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

      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.

      76. Fellows’ Case Files: University of Rochester

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

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

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

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

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

      Lactic Acidosis: Type A, Type B and Type D

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


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

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

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

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

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

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

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

      73. PulmPEEPs and ATS Critical Care Assembly: Dying in the ICU

      Welcome to our second episode of ATS 2024 highlighting content featured through the ATS Critical Care Assembly. Today we are going to be talking about one of the Critical Care Assembly Symposiums entitled: “Care of Dying in the ICU: End of Life Care in 2024 and Beyond”

      Dr. Theodore “Jack: Iwashyna is a Bloomberg Distinguished Professor at Johns Hopkins School of Medicine and the Johns Hopkins Bloomberg School of Public Health. Jack is a critical care physician and has a broad focus on research that understands the broader context of critical illness, and the long term impact on patients’ lives. He is an enormously productive and successful researcher with numerous publications in the field of critical care, and is a pioneer in the field of ICU survivorship. He is a devoted mentor and has received accolades from numerous societies

      Dr. Molly Hayes is an Associate 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 additionally is a co-founder of the BIDMC Center for Humanizing the ICU. Molly has been extensively involved with ATS with leadership roles in the Critical Care Assembly, and the newly minted Steering Committee on the Advancement of Learning.

      The American Thoracic Society Critical Care Assembly is the largest Assembly in the American Thoracic Society. Their members include a diverse group of intensivists and care providers for both adult and pediatric critically ill patients. The primary goal of the Critical Care Assembly is to “improve the care of the critically ill through education, research, and professional development.”

      70. Bronchoscopy Emergencies with Critical Care Time

      We’re super excited to have a joint episode this week with Dr. Cyrus Askin and Dr. Nick Mark from Critical Care Time! We discuss all the ways that bronchoscopy can be your best friend in the ICU and how to be prepared for the unexpected scary situations that arise in the ICU. This ranges from airway bleeds, difficult intubations, lobar collapse, and trach emergencies. Don’t miss this great discussion!

      Utility of bronchoscopy in people with critical illness

      • Bronchoscopy can be both diagnostic and therapeutic; both are potentially lifesaving. 
      • General situations where bronchoscopy is useful in the ICU:
        • Placing (or confirming placement of) an endotracheal tube or tracheostomy tube
        • Removing a foreign body or mucous plugs from the lungs
        • Localizing the source of pulmonary hemorrhage or performing interventions to stop/contain the bleed
        • Diagnosing certain rare conditions, particularly those where the diagnosis can substantially change management (e.g. DAH, AEP, rare infections, etc).
      • Proficiency with bronchoscopy is important to realize the benefits. Simply “having the equipment” is insufficient, regular practice/simulation is essential
        • Anesthesiologists, emergency physicians, and other specialists may have limited experience with bronchoscopy in training. Even experienced pulmonologists, who may be good at diagnostic bronchoscopy often have limited experience deploying bronchial blockers, using retrieval baskets, etc.
        • Remember: “People don’t rise to the occasion, they sink to the level of their training.”
        • If you haven’t regularly practiced with a bronchoscope, you are not going to be able to use it effectively under stress when performing high acuity low occurrence (HALO) procedures such as in emergent airways, deploying bronchial blockers, retrieving foreign bodies, etc.

      Practice practice practice: High fidelity bronchoscopy simulators are available. Low cost bronchoscopy simulators (e.g. 3D printed DIY) are available.

      Difficult Airways

      • Two broad situations where a bronchoscope is generally used:
        • Awake intubation in the anticipated difficult airway (e.g. someone with abnormal anatomy, airway tumor, etc)
        • Rescue method in the unanticipated difficult airway (e.g. very anterior cords, difficulty with Bougie, etc)
      • Nasal vs Oral approach:
        • Oral approach is usually used in an unanticipated difficult airway
        • Nasal approach: More common if performing an awake intubation. Nasal is often better tolerated however epistaxis can make a difficult airway almost impossible.
      • Sedation strategy:
        • Full topicalization: lidocaine vs cocaine (equally effective and lidocaine is normally preferred, however the vasoconstriction action of cocaine may be helpful in preventing epistaxis).
          • Which types of topicalization work best?
            • Spray as you go w/ or w/o and atomizer 
            • Nebulization (maybe better? maybe)
            • Gurgling (Nick: from personal experience lidocaine is super gross)
          • Remember total dose of lidocaine: < 8 mg/kg
        • Ketamine
          • Ideal because it’s dissociative and analgesic, maintains respiratory drive and (maybe) airway reflexes
          • Consider scopolamine patch to reduce oral secretions
        • Dexmedetomidine
          • Great adjunct
      • One vs two operator
        • Especially in unanticipated difficult airways; the second operator can use VL/DL to facilitate visualization of the vocal cords.
        • Second operator can also be preparing for a surgical airway.
      • Equipment considerations:
        • Preload the endotracheal tube onto the bronchoscope. Use the bronchoscope as a bougie to guide the ETT through the vocal cords.
        • Suction! You want two – one connected to the bronch and one connected to a yankuer.
        • Disposable vs “good” scope
        • Remember to load the tube first!
        • Also remember to lube the tube!

       

      Tracheostomy troubleshooting 

      • Similarly to intubation, bronchoscopy can be very useful to confirm placement
      • Mechanics are similar to above
      • Goal is to avoid inadvertent placement of the tracheostomy tube into the soft tissues of the neck and to avoid putting air into those tissues (false lumen).
      • Advanced trick for exchanging tubes: You can use a disposable bronchoscope to exchange tubes: you can get it in, confirm placement, then cut it with trauma shears! Now you can slide the old tube out and put a new one in. (Don’t try this on a $40,000 fiberoptic bronchoscope!)
      • Ideally you should load the ETT onto the bronchoscope in advance (red arrow). If necessary however, you can cut the ETT and turn the disposable bronchoscope into a improvised exchange catheter. This technique is very useful for exchanging tracheostomy tubes.

       

      Foreign Body Removal from airways

      • Bronchoscopy is invaluable for both diagnosis and treatment of foreign body aspirations. 
      • Most commonly these aspirations are food (nuts, seeds, etc), teeth, pills, etc
      • Great overview of the procedure.
      • Intubated vs awake
        • Intubated is harder in many cases: no cough to help, hard to get foreign body out of the ETT.
      • Flexible vs rigid
        • Most objects can be retrieved using flexible bronchoscope; however 15-20% require rigid bronchoscopy 
        • Flexible can reach smaller foreign bodies that are lodged more distally.
        • Rigid bronchoscopy is usually done if flexible bronchoscopy fails; an interventional pulmonologist wielding a rigid is superior but more invasive (requires GA)
      • Many different retrieval devices; technique depends on what equipment is available.
        • Forceps
          • Many types: shark tooth, rat tooth, alligator are most common
        • Basket
        • Grasper
        • Snare
        • Net (GI device repurposed)
        • Cryoprobe can be especially useful for frangible materials (e.g. food)

       

      Mucous Plugs & Lobar collapse

      • Presentation can be subtle or dramatic.
      • Bronchoscopy can remove mucous plugs and help re-expand collapsed lung areas, which is potentially life saving.
      • Additionally, bronchoscopy can permit diagnosis of tracheal bronchus (bronchus sui)
        • Pig bronchus – 1-3% of people – have a RUL bronchus that comes off the trachea. 
        • Often presents with RUL collapse in an intubated person.
      • Suction considerations and bronchoscope size
        • Remember that suctioning force is highly dependent (i.e. radius raised to the fourth power!) upon the working channel size. Use the largest size bronchoscopy possible when suctioning.
      • Remember that other interventions: regular inline suctioning, chest PT, adequate hydration, mucolytics are also important to prevent recurrent mucous plugging.

       

      Localization & Isolation of Pulmonary Hemorrhage

      • Pre-bronch interventions
        • Stabilization
        • Nebulized TXA
        • Bad side down → counter-intuitive because shifting blood flow, but also the goal is to protect the non-bleeding lung.
        • etc
      • Bronch can localize the bleeding site. Bronch can also perform interventions such as:
        • Cold saline
        • Epinephrine 1:100,000
        • Bronchial blockers – comparison of types
          • CRE balloon
          • Fogarty
        • Cryo probe – great for removing clots
        • Delivering ETT to contralateral side → single lung ventilation

       

      Making “bronchoscopy only” diagnoses

      • Diffuse Alveolar Hemorrhage (DAH)
        • Finding: Increasingly bloody returns on serial lavages
      • Infections not covered by empiric therapies:
        • Invasive fungal infection (e.g. mucor), azole resistant fungi (C glabrata)
        • Rare/unusual infections (PJP, histoplasmosis, etc)
      • Infection mimics:
        • Acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP)
          • Finding: eosinophils > 20%
        • E-Cigarette Vaping Associated Lung Injury (EVALI)
          • Foamy lymphocytes
        • Organizing Pneumonia
        • Others
      • Remember to always send a cell count on a BAL! And cytology!
      • How often does bronchoscopy change management? Surprisingly often!
        • A study of how often bronchoscopy changes management in an oncology population. 500+ patients with AML or high grade myeloid neoplasms who underwent bronchoscopy at one center over 5+ years.
        • 1) an unexpected diagnosis was made and followed by a management change (as the most rigorous estimate of utility)
          • 13% of the time a diagnosis was only made because of bronchoscopy which changed management 
        •  2) the post-bronchoscopy diagnosis was discordant from the leading diagnosis considered before this procedure and was followed by a management change
          • 48% of the time pre and post procedure leading diagnoses were different
          • 26% of the time the change in leading diagnosis led to a change in therapy
        • 3) a change in management was made following bronchoscopy regardless of whether the diagnosis was expected or considered.
          • 32% escalation of antibiotics
          • 30% de-escalation of antibiotics
          • 9% addition of steroids
          • 2% mold → surgery
      • Remember that in critically ill patients whose symptoms are unexplained or failing to resolve with therapy, diagnostic flexible bronchscopy can provide useful insights.

       

       

       

       

       

      64. Fellows’ Case Files: Emory University School of Medicine

      Hi everyone, we’re here with another Fellows’ Case Files. Today, we’re going virtually to Emory University School of Medicine. We’re joined by Associated Editor Luke Hedrick to dive into a critical care case. Listen in and let us know if you have any additional thoughts or questions!

      Meet Our Guests

      Luke Hedrick is a first-year pulmonary and critical care fellow at Emory University. He did his internal medicine residency at BIDMC in Boston. He is also one of our amazing Associate Editors here at Pulm PEEPs

      Shirine Allam is an Associate Professor of Medicine at the Emory University School of Medicine where she is the Program Director of both the Pulmonary and Critical Care Medicine fellowship as well as the Critical Care Medicine fellowship. She completed her PCCM training at the Mayo Clinic in Rochester, followed by a Sleep Medicine fellowship at Stanford. She has received multiple teaching awards throughout her career

      Case Presentation

      A 32-year-old male is brought in by his coworkers unresponsive. He is a construction worker and was his usual self in the morning at the start of the day, but when they broke for lunch they noticed he was acting different—his arms were drooping, and while he initially was able to answer yes/no, he soon started babbling, then grunting, then vomited and became unresponsive. They laid him flat, threw cold water on him because it was 110 degrees and humid outside that day, and brought him to the ED.

      When they arrive in the ED, he is unresponsive and warm to the touch. His vitals are notable for an oral temperature of 105, HR in the 160s, BP 76/34, a RR in the high 30s, and an SpO2 100% RA. His exam is relatively unremarkable other than for significant diaphoresis and both bowel and bladder incontinence.

      Key Learning Points

      1. Definition and recognition of heat stroke: Heat stroke is characterized by hyperthermia (>104°F or 40°C) accompanied by CNS dysfunction, primarily caused by exertion or exposure. Encephalitis without significant heat load does not constitute heat stroke.
      2. Management priorities: Rapid cooling is paramount to minimize long-term complications and organ failure. Cooling should be initiated as soon as possible, even before transportation to a hospital, particularly in cases of exertional heat stroke.
      3. Cooling methods: Surface cooling, such as immersion in ice water, is the most effective way to cool heat-stroke patients. Alternative methods include the TACO method and evaporative cooling, although they are less efficient. Refrigerated IV fluids can be used as an adjunct, but they do not replace the need for surface cooling.
      4. Monitoring and goals: Shivering during cooling should be monitored to prevent excessive heat generation. The goal is to reach a normal core body temperature (~38°C or 100.4°F). Traditional antipyretics like aspirin and acetaminophen should be avoided due to ineffectiveness and potential toxicity.
      5. Approach to endotracheal tube (ETT) exchange: ETT exchange requires preparation for potential complications. This includes ensuring the availability of airway equipment, sedation of the patient, and having additional personnel for assistance. Direct visualization using a video laryngoscope is recommended, along with measuring and marking the exchange catheter for proper insertion depth.

      The following infographic can be downloaded from our website:

      References and Further Reading

      1.Epstein Y, Yanovich R. Heatstroke. New England Journal of Medicine. 2019;380(25):2449-2459. doi:10.1056/NEJMra1810762

      2. Sorensen C, Hess J. Treatment and Prevention of Heat-Related Illness. New England Journal of Medicine. 2022;387(15):1404-1413. doi:10.1056/NEJMcp2210623