Category Archives: Pulmonary and Critical Care Medicine

ZSFG Morning Report 6.12.2017 – High Flow Oxygen and PD-1 inhibitors

Thank you to the ICU team and Bennett Caughey for presenting the case of a middle-aged woman with advanced metastatic SCC of the lung, who presented with hypoxia and respiratory distress after esophageal stent placement.

Take Home Points

  • Escalating hi-flow oxygen needs should warrant ICU evaluation.
  • Differential for noninfectious causes of cavitary lung lesions includes neoplasm. SCC is the primary lung malignancy most likely to cavitate.
  • PD-1 inhibitor therapy can cause pneumonitis, but is a diagnosis of exclusion; infection and malignancy should be excluded. Median duration of treatment prior to development of pneumonitis is 2.8 months.

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High flow oxygen

  • What is it? Heated and humidified air that allows for comfortable delivery of higher flow oxygen
  • No specific threshold that absolutely warrants ICU level care (institution dependent) but an escalating requirement is worrisome and should prompt ICU evaluation
  • Liters per minute (LPM) and FiO2 are the two variables that can be manipulated, again this is institution dependent
  • High flow oxygen also provides a small amount of positive pressure. Also found to have decreased 90-day mortality in pts with nonhypercapnic acute hypoxemic respiratory failure.

What you need to know about PD-1 inhibitors:

  • PD1 stands for programmed cell death 1, and is involved in check point signaling pathway
  • PD1 inhibitors block normal inhibition response, and therefore boost immune response against cancer cells.
  • Nivolumab and pembrolizumab: currently being used in pts with advanced melanoma and non-small cell lung cancer.
  • The most common immune-related adverse events are typically transient, but can occasionally be severe or fatal. The most commonly implicated organ systems are dermatologic, diarrhea/colitis, hepatotoxicity, and endocrinopathies.
  • Overall incidence of PD-1 inhibitor related pneumonitis is ~5%
  • In general, mild symptoms can be observed and PD-1 therapy can be withheld. In more severe cases, checkpoint inhibitor therapy should be permanently discontinued, and consider use of steroids.

Moffitt Morning Report Pearls 6/2/17 – PEA + ARDS

Hello Moffitt!

Thanks for welcoming us to our first Morning Report! And a special thanks to Salman for presenting a great case of an older woman found down at home with asystole who developed shock and refractory hypoxemia.

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Top Pearls:

  1. Causes of PEA include both cardiac and non-cardiac etiologies. In women and non-whites, the non-cardiac etiologies, such as SAH and massive PE, are more common! (see more below)
  2. Some centers are using esophageal balloon catheters to estimate pleural pressures and guide PEEP therapy (see attached NEJM reference)!
  3. Therapeutic strategies with treating refractory hypoxemia include the 6 Ps:
  • Higher PEEP
  • lung Protective ventilation
  • Paralytics
  • Prostacylcins
  • Proning
  • P-ECMO (A-V)

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For those who want more info:

  1. Satvik Ramakrishna presented a fantastic R3 Talk on Thursday about redefining sudden cardiac death (SCD) using insights from the San Francisco POST SCD Study. Working with Dr. Zian Tseng, UCSF researchers used comprehensive autopsy data to determine the cause of death of nearly all out of hospital “sudden deaths” in San Francisco during a 3 year period. The group found that while under previous definitions, 80% of the nearly 5000 deaths would have been classified as SCD, including autopsy information reduced this proportion to 56%! They also found important disparities based on gender and race. Publication soon to come!
  2. Esophageal pressures to manage PEEP: NEJM RCT comparing MV directed by esophageal-pressure measurements with that according to ARDSNet recommendations. This study demonstrated the feasibility of using repeated measurements of esophageal pressures to determine the transpulmonary pressures and make timely adjustments to PEEP. Patients with ARDS in the esophageal pressure arm had improved oxygenation based on the P:F ratio and improved respiratory-system compliance. The researchers found that the 28 day mortality was lower among the patients with esophageal-pressure-guided MV, however, mortality at 180 days was the not different between the two groups.
  3. The supportive strategies that have shown mortality benefits for patients with ARDS include lung protective ventilation (pioneered here at UCSF!), early neuromuscular blockade and prone positioning. Prostacyclines, recruitment maneuvers, and ECMO are all used and can improve oxygenation, but a mortality benefit has not been shown. Each of the ground-breaking papers that showed mortality benefits for ARDS supportive therapies are below!

References:

Talmor et al. Mechanical ventilation guided by esophageal pressure in acute lung injury. http://www.nejm.org/doi/full/10.1056/NEJMoa0708638#t=article

ARDS-net. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. http://www.nejm.org/doi/full/10.1056/NEJM200005043421801#t=abstract

Papazian L, et al. Neuromuscular blockers in early acute respiratory distress syndrome.

http://www.nejm.org/doi/full/10.1056/NEJMoa1005372

 

Guerin et al. Prone positioning in severe acute respiratory distress syndrome. http://www.nejm.org/doi/full/10.1056/NEJMoa1214103#t=article

Blog:

Evernote: https://www.evernote.com/shard/s462/sh/7b428e2c-0771-49cf-ab44-2a8262dee775/ce84685da30f0cc865557bc94ee80226

Have a great weekend!

Your super sweet Moffitt chiefs – DKA

VA ICU Report 5.26.17

Morning, some good neuro critical care action at the VA this week, thought we’d cover something today not yet covered on the blog: non-invasive estimations of elevated ICP, namely fundoscopy and ocular ultrasound

Dan Reiss correctly pointed out the acute finding in elevated ICP on an ocular ultrasound is the optic nerve sheath diameter, a handful of smaller studies (n in each about 40-60) have evaluated the correlation between nerve sheath diameter and MRI/CT findings of elevated CT, Sensitivity and Specificy depends on the cutoff chosen, in adults typically a ONSD of >4.5mm is considered too high, which yields a sens and spec of around 70-80% for the detection of elevated ICP. The challenge here, as with fundoscopy, is inter-observer variability presumably due to operator characteristics. Here is a review paper on non-invasive determination of ICP.

Other quick pearls

#generally opt for beta blockers and ccb in the acute treatment of hypertensive emergency due to the theoretical concern for cerebral vasodilation with nitro/hydral, nicardipine and esmolol are good options

#PRES, covered elswhere, stands for posterior reversible encephalopathy syndrome, though not always posterior or reversible. Remember, MRI is the diagnostic test for PRES.

 

MOFFITT MORNING REPORT PEARLS 5/5/17: Cavitary Lung Lesions and Castleman Disease!

Hey Everyone! Thanks to Braden for presenting a super interesting case of a middle-aged man with multicentric Castleman disease who was incidentally found to have a cavitary pulmonary nodule! We discussed an extensive differential for cavitary lung nodules and reviewed Castleman disease. Pearls below!

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Top Pearls:

  1. The ddx of cavitary lung lesions is broader than just TB/fungal/cancer! See below.
  2. Unicentric Castleman disease is usually curable while multicentric has a variable prognosis.
  3. Steroids predispose to infection with aspergillus, cryptococcus, nocardia, PCP, and legionella.

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For those who want more info:

Cavitary lung lesions:

Here’s the differential we discussed with Harry’s help!

  • Infection! TB, NTM, fungal (crypto, dimorphics, molds, rarely PCP), bacterial (staph, strep, nocardia, actinomyces, rhodococcus), strongyloides, rarely viral (CMV, VZV)
  • Malignancy! Primary lung cancer, metastases, lymphoma, rarely Kaposi sarcoma
  • Rheumatologic! Vasculitis (GPA, rarely MPA), sarcoidosis
  • Emboli! Bland or septic

 

Castleman disease:

Now a review of Castleman disease. Or maybe your first time learning about it. That’s ok too. 🙂

Castleman disease, aka angiofollicular lymph node hyperplasia! Obvi.

Commonly associated with HIV and HHV-8 but not always! Our patient today was negative for both.

Divided into unicentric and multicentric Castleman disease, which have very different prognoses (hint, unicentric is more favorable…).

Unicentric (UCD):

  • Lymphoproliferative disorder of young adults
  • Usually asymptomatic, enlarged lymph node discovered incidentally on exam or imaging
  • Node/mass is most often in mediastinum or lung
  • Biopsy shows polyclonal expansion (ie. NOT a monoclonal disorder!)
  • PET/CT rules out involvement of other sites
  • Complete resection of the involved lymph node is curative with excellent prognosis
  • If resection not possible, systemic therapy as in MCD (see below)

Multicentric (MCD):

  • Lymphoproliferative disorder (usually plasma cells) presenting in 5th or 6th decade of life
  • Peripheral lymphadenopathy and systemic symptoms
  • Biopsy shows polyclonal expansion (ie. NOT a monoclonal disorder!)
  • PET/CT demonstrates involvement of multiple sites
  • Treatment depends on HIV/HHV-8 status and disease aggression
  • HIV/HHV-8 neg without organ failure: anti-IL-6 immunotherapy (siltuximab or tocilizumab)
  • HIV/HHV-8 neg with organ failure: etoposide + rituximab
  • HIV/HHV-8 pos: ARVs + ganciclovir + rituximab, with etoposide if aggressive disease
  • Prognosis is variable, worse with HIV infection in which a rapidly progressive form can lead to death within weeks!

There is a strong association between MCD and POEMS syndrome; 15-50% of patients with POEMS also have MCD. POEMS stands for polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes.

RCT showing efficacy of siltuximab in MCD leading to FDA approval. Side effects included pruritis, weight gain, rash, hyperuricemia, URI, fatigue, night sweats, and anemia. Serious adverse events included pneumonia, anaphylaxis, and sepsis. https://www.ncbi.nlm.nih.gov/pubmed/25042199

*Harry pearl: High dose steroids predispose to five infections in particular- aspergillus, cryptococcus, nocardia, PCP, and legionella!

 

Evernote: https://www.evernote.com/shard/s272/sh/c22fc556-a0e2-48db-9acb-1c4e4c1e9aad/19a8b86aeffd850429a8e38c0d6c64cd

Have a great day everyone!

SamMy

MOFFITT PULMONARY REPORT PEARLS 4/10/17: Aspergillosis and Rhinovirus!

Hey everyone! Thanks to Ashley for presenting the case of an elderly man with a history of malignancy and invasive fungal disease who developed cough and a new pulmonary nodule. Workup was still pending, but RVP returned with rhinovirus. Pearls below!

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Top Pearls:

  1. Aspergillosis can affect the GI tract! (the patient this morning also had GI symptoms)
  2. Rhinovirus is associated with CAP (direct causation controversial in immunocompetent adults)
  3. Rhinovirus can be deadly in immunocompromised and critically ill patients.

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For those who want more info:

Aspergillosis can manifest in MANY different ways.

 

  • Pulmonary aspergillosis
    • Bronchopneumonia
    • Angioinvasive aspergillosis
    • Tracheobronchitis
    • Subacute invasive aspergillosis (aka chronic necrotizing)
    • Chronic (>3 months): aspergilloma, nodules, chronic cavitation, chronic fibrosis
    • ABPA (asthma and CF patients)
  • Rhinosinusitis
  • Disseminated infection: skin, brain, eyes, liver, kidneys, endocarditis
  • GI: enterocolitis, appendicitis, colonic ulcers, abdominal pain, GI bleeding

 

Some info on Rhinovirus!

  • Most common “cold” virus but can also infect lower respiratory tract!
  • Causes greater morbidity than previously thought
  • Frequent cause of asthma exacerbations
  • Children are the major reservoir J
  • About half of rhinovirus infections in immunocompetent adults are asymptomatic
  • Typical illness is nasal discharge, cough, sore throat. Fever is rare in immunocompetent adults.
  • Controversial whether rhinovirus directly contributes to CAP since most specimens in which it is identified are from the upper airway. What is clear is that rhinovirus is strongly associated with CAP. The direct association is stronger in transplant patients (see below).
  • *Pearl: Rhinovirus is dangerous in immunocompromised and critically ill patients.
    • Recent studies show comparable rhinovirus morbidity and mortality in hospitalized elderly and immunocompromised patients to that of influenza (Hung Int J Mol Sci 2017, Kraft J Clin Microbiol 2012)
    • Particularly high mortality when rhinovirus infects the lower resp tract of bone marrow transplant patients (Seo Haematologica 2017, Jacobs Transpl Infect Dis 2013)
    • Our pulmonary experts taught us that rhinovirus is a cause of lung transplant rejection!
  • Treatment: None currently, but there is a drug in the pipeline, vapendavir, that binds to rhinovirus capsid protein and prevents viral RNA release.

 

Evernote: https://www.evernote.com/shard/s272/sh/14d87383-a10f-416c-9d20-7a01421e6907/421f3f77b69828162ec4fc55b6acd974

 

Have a great day everyone!

SamMy

MOFFITT PULMONARY REPORT PEARLS 3/13/17: Hypersensitivity Pneumonitis and CMV!

Thanks to Jesse for presenting the case of a middle-aged man with chronic hypersensitivity pneumonitis who developed fever and cough progressing to critical illness and hypoxemic respiratory failure, found to have positive blood and respiratory PCR for CMV concerning (but not diagnostic) for CMV pneumonitis! Pearls below:

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Top Pearls:

  1. Hypersensitivity pneumonitis (HP) is categorized as acute, subacute, or chronic.
  2. Diagnosis of chronic HP usually requires bronchoscopy and open or VATS lung biopsy.
  3. CMV pneumonitis is difficult to distinguish from asymptomatic viral shedding!

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For those who want more info:

Hypersensitivity pneumonitis (HP) is divided into acute, subacute, and chronic progressive forms. These depend on the frequency, length, and intensity of antigen exposure as well as the duration of the subsequent illness.

Acute HP has abrupt onset (hours) of fever, chills, cough, and dyspnea. Removal from antigen exposure leads to improvement within hours to days and resolution within weeks.

Subacute HP has gradual onset of symptoms, and the degree of respiratory impairment is more pronounced than acute HP with more extensive radiographic findings. Symptoms resolve more slowly after antigen removal.

Chronic HP may not be preceded by a history of acute episodes, and symptom onset is insidious. It can be difficult to distinguish from IPF. PFTs show a moderate to severe restrictive defect, but mixed and isolated obstructive defects can also be seen. Diffusing capacity is invariably reduced, and both resting and exertional hypoxemia are common. HRCT shows ground glass, nodules, and possibly honeycombing and/or emphysema.

Etiology: There are a ton of etiologies to consider, including mold, animals (especially birds), humidifiers, hot tubs, grains, wood/dust, chemicals, textiles, and many more.

*Pearl: Cigarette smoking is actually associated with a decreased risk of HP! But once the disease is established, smoking does not attenuate severity and instead may predispose to a more chronic and severe course.

Diagnosis of chronic HP usually requires bronchoscopy, and open or VATS lung biopsy is often necessary (in addition to thorough exposure history!!).

Treatment: Remove antigen exposure! Steroids reserved for severely symptomatic patients. Lung transplant may be necessary for severe cases.

Prognosis: Most have near-total recovery of lung function which may take several years after cessation of antigen exposure, but fibrosis on biopsy portends worse prognosis.

 

CMV Pneumonitis:

CMV is a major pathogen for immunocompromised patients. The range of disease is broad and includes febrile syndromes, hepatitis, pneumonitis, retinitis, encephalitis, esophagitis, and colitis.

Importantly, serologic testing (CMV antibodies) has no role in diagnosing CMV disease in immunocompromised patients. Diagnosis requires quantitative PCR testing or antigen testing. The diagnosis of tissue invasive disease (e.g. pneumonitis) usually requires biopsy with immunostaining.

By contrast, in immunocompetent patients, a positive CMV IgM or fourfold rise in CMV IgG can provide a presumptive diagnosis.

Overall, it is difficult to distinguish invasive CMV pneumonitis from asymptomatic infection with viral shedding. The presence of CMV in BAL fluid, positive blood CMV viral load or antigen testing, and tissue histology are the best tests for invasive disease.

*Pearl: CMV infection occurs in up to 35% of immunocompetent adults with critical illness due to reactivation of latent infection, which in some studies is associated with prolonged ICU stay, prolonged mechanical ventilation, and possibly increased mortality. Other studies have not shown these associations.

Treatment: IV ganciclovir. Foscarnet is reserved for ganciclovir-resistant strains.

 

Evernote: https://www.evernote.com/shard/s272/sh/11b20731-bd7b-499a-a0a5-8fd8cd247c30/96f89e2bf66d134c7d2a5cf668c73734

 

Have a great day everyone!

SamMy

 

 

Eosinophilic Lung Disease

Today we discussed the case of a middle-aged man with chronic cough, who presented with worsening dyspnea and peripheral eosinophilia. He was ultimately diagnosed with likely EGPA (eosinophilic granulomatosis polyangiitis).  We discussed our approach to eosinophilic lung diseases.

TOP PEARLS

  • Eosinophilic lung diseases (or pulmonary eosinophilia) are a group of diffuse parenchymal lung diseases characterized by infiltration of lung interstitium and the alveolar spaces by eosinophils.
  • Multi-system involvement is quite common in EGPA, and this feature differentiates this entity from ABPA (another cause of pulmonary eosinophilia)

Eosinophilic Lung Diseases

  • Heterogeneous group of disorders that manifest with “pulmonary eosinophilia.”
  • How to diagnose pulmonary eosinophilia?
    • Peripheral blood eosinophilia + abnormalities on pulmonary imaging studies
    • Lung tissue eosinophilia from transbronchial or open lung biopsies
    • Increased eosinophils in bronchoalveolar lavage (BAL) fluid

CAUSES OF PULMONARY EOSINOPHILIA

  • Helminth infections
    • Loffler syndrome: 3 types of helminths (Ascaris, hookworms, and Strongyloides) have life cycles in which infecting larvae reach the lungs via bloodstream à penetrate into alveoli à mature à ascend the airways à descend the alimentary tract into the small bowel
    • Parenchymal invasion: lung flukes and cestodes can directly invade the pulmonary parenchyma
    • Hematogenous seeding: seeding of helminth larvae or eggs can lead to lung deposition & eosinophilic response. Think, hookworms, Trichinellosis, Schistosomiasis, and Strongyloides!
  • Nonhelminthic infections
    • Cocci
    • Pulmonary TB
  • Medications/Toxins
    • NSAIDs & antibiotics are most common classes of drugs associated with pulmonary eosinophilia
    • Toxins: aluminum, heroin, crack cocaine, dust or smoke, scorpion stings
  • Eosinophilic Pneumonia
  • EGPA (Eosinophilic Granulomatosis with Polyangiitis/ formerly Churg-Strauss)
    • Small vessel vasculitis characterized by sinusitis, asthma, and peripheral eosinophilia
    • Multisystem involvement is common (lungs, skin, CV, GI, renal, and neuro)
    • Finding of a positive p-ANCA strongly favors the diagnosis

 

  • ABPA (Allergic Bronchopulmonary Aspergillosis)
    • Hypersensitivity reaction that occurs in patients with asthma or cystic fibrosis with airway colonization by Apergillus
  • Other Causes
    • Hypereosinophilic syndrome
    • Idiopathic lung diseases: IPF, sarcoidosis, hypersensitivity pneumonitis, etc
    • Neoplasms: lymphoma, eosinophilic leukemia, metastatic ca to the lung