Category Archives: Pulmonary and Critical Care Medicine

Moffitt Pearls – 11.13.17 – Pulmonary Report

Thank you to Dr. Wolters for joining us today and to Tyler for presenting the case of a man w/ hx of SCC on pembrolizumab p/w 2 months of DOE & 1 wk of cough not responsive to levofloxacin. We discussed the role of ABGs > VBGs and the ddx for organizing PNA. The patient ended up having pneumonitis 2/2 to his PD-1 inhibitor which was discontinued and he was then started on steroids.

Key Pearls

  1. There are several toxicities associated with PD-1 inhibitors. See here for prior pearls on these check point inhibitors!
  2. One needs to lose ~ 50% of their lung function to have SOB @ rest!!
  3. Try to obtain an ABG in a patient who is hypercarbic given the variability of a VBG and its estimation of pCO2. Per Dr. Wolter’s the pCO2 from a VBG can be wrong ~ 20% of the time.
  4. Reverse Halo Sign (RHS) on a CT Chest is a patch of normal lung surrounded by abnormal densities . There is a ddx and figure for RHS below!

ABG vs. VBG – Thank you Kenny for sharing!!

Pathophysiology:

  • Arterial: accurate O2 content; nl pH = 7.4 (7.35-7.45), CO2 = 40 (35-45)
  • Venous: carries excess CO2 to be ventilated off in the long. ~3-5 mmHg higher than arterial blood

EvidenceSystemic review and meta analysis

  • Arterial pH ~ 0.03 higher than venous
  • Venous and arterial pCO2 do NOT correlate that well (off in ~ 20% of gases)
  • Good negative predictive value of CO2 if low, but not as helpful if high

Practical application:

  • If you want O2 status, you can use SpO2 as a surrogate marker, but ABG is more accurate
  • If concerned for pH or CO2 status and ABG isn’t easy (ie painful and technically challenging); VBG as 1st pass -> understand limitations
  • If the VBG doesn’t make sense or you want to be totally sure, get an ABG

Organizing PNA

Defined as the lung’s response and subsequent repair to any insult. Often associated with the reverse halo sign (RHS) characterized by a central clearing surrounded by denser air-space consolidation (often ground glass) in the shape of ring/crescent. This happens because in the following situations the lung heals from the center outwards. Was initially described in cryptogenic organizing PNA, however is now part of a wider DDX that includes the following:

  • Autoimmune (Sarcoid, Wegener’s granulomatosis)
  • GVHD
  • Aspiration
  • Malignancy
  • Drug effect – PD-1 Inhibitors à 5% of patient’s will develop pneumonitis @ a mean of 7 months; 85% will respond to discontinuation & steroids.
  • Infectious – endemic fungal infections, PCP PNA,
  • Idiopathic – cryptogenic

Here is a great article and figure on the evaluation of Revere Halo Sign (RHS)RHS--g013

https://www.evernote.com/shard/s307/sh/553ffa9d-b57c-4946-a6ec-8d88fac245ad/9cf66d454abb647c86ed5696e6ee1a42

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Moffitt Pearls 11/7/17 – Cards Report – Vasopressors and PA Catheters

Thank you Matt H for your help with these PEARLS!!!

Thanks to Chloe for presenting a fascinating case of a 65 year old man with history of HOCM (w/o obstruction) who presented with acute onset shortness of breath, ultimately thought secondary to flash pulmonary edema from paroxysmal hypertension. We had a great discussion on vasopressors to use in different types of shock. Below is a summary of some of the more common vasopressors, as well as brief information on key considerations in their use. Finally, there is a bit of info on the ESCAPE trial that led to reductions in use of PA catheters in management of cardiogenic shock.

For more information, refer to the UCSF Hospitalist Handbook and the MGH CCU handbook.

Key Pearls

  • Dobutamine is considered a first line pressor in cardiogenic shock b/c it improves contractility and drops SVR (watch out for dropping BPs).
  • HOWEVER, never write for a MAP goal and titration parameters when using dobutamine as patients MAPs will sometimes drop with up titration (this is why we sometimes start this with norepinephrine).
  • The ESCAPE (2005) showed no improved 6 month mortality in patient with decompensated heart failure randomized to management with PA catheter monitoring vs. usual care. See indications for when to us a PA catheter below.

Vasoactive/Inotrope medications

Class Drug Dose Mechanism
Vasopressor Phenylephrine 0-200 mcg/min α-1 agonist
Vasopressin 0.04 units/min V-receptor agonist
Mixed Norepinephrine 1-20 mcg/min α-1, β-1 agonist
Epinephrine 1-20 mcg/min α-1, β-1, β-2 agonist
Dopamine 1-3 mcg/kg/min

2-10 mcg/kg/min

10-20 mcg/kg/min

D agonist

β-1, β-2 agonist

α-1 agonist

Inodilator Dobutamine 2-5 mcg/kg/min β-1 > β-2 agonist
Milrinone 0.375-0.75 mcg/kg/min PDE III inhibitor

 

Receptor Action
α-1 Vasoconstriction
β-1 Inotropy
β-2 Vasodilation, bronchodilation
D Splancnic vasodilation – increases renal blood flow
V Vasoconstriction

Quick info on selected vasoactive agents:

Norepinephrine: 1st line pressor for sepsis, cardiogenic shock, undifferentiated shock.

Vasopressin: Often 2nd line pressor in sepsis. Use caution in patients with coronary or peripheral vascular ischemia. Not affected by acidosis (many other pressors are less effective in this situation)

Phenylephrine: Useful for pure vasodilatory hypotension (e.g. sedation-related hypotension). Generally avoid in cardiac patients as can cause reflex bradycardia with decreased cardiac output. HOWEVER, can be useful in unstable arrhythmias when beta agonism may be undesirable. Also useful in HOCM with dynamic outflow obstruction (‘stents’ open the obstruction) or fixed obstruction in AS as it increases SVR without changing afterload felt by the heart.

Epinephrine: Primary use is in ACLS, though can also be used as 3rd pressor in refractory hypotension. Adverse effects include tachycardia/tacchyarrythmias, peripheral vasoconstriction and end-organ damage

Dobutamine: Increases contractility while reducing SVR. Often decreases blood pressure, therefore should not be thought of as a vasopressor, should also not be titrated to MAP goals. Risk of arrhythmia with higher doses, also risk of myocardial ischemia from increased oxygen demand.

Milrinone: PDE-3 inhibitor, inhibits cAMP breakdown. Similar to dobutamine, results in both inotropy and decreased SVR (perhaps more reduction in afterload, but also more risk of hypotension, than dobutamine). Requires dose-reduction in renal impairment.

Indications for PA Catheters

ESCAPE trial (2005) – randomized patients with acute decompensated heart failure to therapy guided by PA catheter vs no PA catheter. No difference in 6 month mortality or days out of the hospital. Based on this trial and meta-analysis, PA catheters are no longer used routinely. They still have a role in shock of uncertain etiology or when initial management is unsuccessful.

AHA guidelines on PA catheters (2013):

  • Recommended in patients with respiratory distress or evidence of impaired perfusion when intracardiac filling pressures can’t be determined by clinical assessment (class I, level C)
  • Can be useful in heart failure with persistent symptoms despite standard therapy if any of the following are present: (class IIa, level C):
    • Uncertain volume status, perfusion, SVR, PVR
    • Persistent hypotension
    • Worsening renal function despite initial therapy
    • Need for vasoactive agents
    • Anticipated need for mechanical cardiac support
  • Routine use not recommended in normotensive patients with acute decompensated heart failure responding to diuresis and afterload reduction (class III, level B)

https://www.evernote.com/shard/s307/sh/c214c30c-a21c-46f6-a447-cd73bcbc2bc4/aafe54bf6c950077c1d6e738d608cced

Moffitt Pearls 8.23.2017 – Morning Report – ILD

Thank you to James for presenting a fascinating case of middle aged woman with a questionable history of ILD presenting with acute worsening of a chronic cough concerning for an ILD flare vs. undiagnosed infection.

KEY PEARLS

  1. In a patient presenting with an ILD ALWAYs rule out infection & look for an underlying cause.
  2. When BAL is negative x48h, then you can consider empiric steroids. Steroids are really only useful for acute idiopathic ILD (COP and AEP) and for some ILDs from known causes (see “approach to ILD” below)!
  3. Idiopathic pulmonary fibrosis (IPF) & nonspecific interstitial pneumonia (NSIP) p/w a restrictive PFT pattern, however hypersensitivity pneumonitis (HS) can present with air trapping and obstructive +/-restrictive PFTs
  4. Back to the Jen B rule – A patient is considered immunosuppressed if they take ~20 mg of Prednisone for 2-3 (remember PCP prophylaxis)

An Approach to ILD

Broken down into 4 categories

  1. Known Causes – drugs, RA or CTD,
  2. Idiopathic interstitial pneumonia
  3. Granulomatous disease (eg, Sarcoid)
  4. Other causes

And a few more pearls on ILD

  1. Try to find any underlying cause!
  2. Bronchial biopsy can be very useful if it can be obtained!
  3. Alphabet soup: What about UIP (usual interstitial pneumonia) This is pattern – that is characteristic of end-stage IPF (see chart below).
  4. Steroids are useful in acute idiopathic ILD and some forms of ILDs from known causes (eg connective tissue diseases). NOT useful in other forms. However, for critically ill patients in the ICU with respiratory failure from ILD flare, oftentimes our pulmonary experts will still recommend it

Table to better understand the alphabet soup!

Histological Pattern Clinical Syndrome Associated Diseases
Usual interstitial pneumonia Idiopathic pulmonary fibrosis (IPF) Connective tissue disease (CTD), drugs, asbestosis
Nonspecific interstitial pneumonia (NSIP) Idiopathic NSIP CTD, drugs, HP
Desquamative intestinal pneumonia (DIP) Idiopathic DIP Smoking, CTD, drugs, toxic inhalation
Organizing Pneumonia Cryptogenic OP  
Diffuse Alveolar Damage (DAD) Aute interstitial pneumonia Infection, aspiration, trauma, sepsis, pancreatitis

 

Moffitt Pearls 7.10.17 – PD-1 Inhibitors & PCP Pneumonia

Pulmonary Report 7.10.17

Thank you to Ugo for presenting the case of an elderly male with widely metastatic melanoma refractory to PD1 inhibitors presenting with 1-2 weeks of fatigue, FTT, DOE found to have PCP pneumonia!

Top Pearls:

  • PD1 inhibitors are considered first-line therapy for metastatic melanoma.
  • Common toxicities of immune check point inhibitors include immune-mediated inflammation of virtually any organ system. See below for more details on PD1 inhibitors.
  • The risk for opportunistic infections w/ checkpoint inhibitors is related to the steroids that are generally given to treat the checkpoint inhibitor toxicities. A case report & paper (https://www.ncbi.nlm.nih.gov/pubmed/27501841) illustrating this risk.
  • Remember! For patients on steroids if > 20 mg/day of prednisone for > 2 weeks –> give PCP prophylaxis. (per expert opinion -> the rule of Dr. Jen B!)

Which patient that are immunocompromised get PCP?

  • HIV-positive patients (CD4 < 200)
  • Cancer, solid organ transplant, BMT – related to type & chemo intensity
  • Rheumatologic (GPA has intrinsic risk)
  • Chronic steroids (see Jen rule above)

Steroids for Rx of PCP in HIV-Negative patients??

  • Not well studied in HIV-negative patients, only a few retrospective studies
  • No mortality benefit, but may expidite recovery
  • Steroids are recommended in the AJT guidelines
  • 40-60 mg Prednisone BID x 5-7 days with 7-14 day taper

 

Table Comparing PCP in HIV Positive and Negative Patients (thanks Jen!)

table PCP

 

PD-1 Inhibitors (blast from the past)

pd1

Emerging data show that 20% of patients with melanoma treated with ipilimumab achieve long-term survival! See this associated review.

PD-1 (programmed cell death 1) and its association with the ligand (PD-L1) is a necessary step in stimulating apoptosis of T-cells, serving as an immune checkpoint. PD-L1 is generally expressed by native cells, signaling to the T-cell “I’m one of you! Don’t hurt me”.  Some tumors have been found to also express PD-L1, enabling them to evade destruction by T-cells.  In order to treat these malignancies, PD-1 inhibitors (pembrolizumab, nivolumab) serve to block the interaction between PD-1 and PD-L1, enabling T-cells to stay “programmed on”, and thus enable immune-mediated destruction of tumor.

Because of this mechanism of action, a common consequence is the upregulation of cell-mediated immunity and, unfortunately, inhibition of native tissues to turn off T-cells. As a result, we commonly see autoimmune-mediated inflammation manifested as new rash, diabetes, thyroid disease, pneumonitis, hepatitis, colitis, etc.

Common Immune-Mediated Toxicities Seen with Check-point Inhibition:

Organ System Manifestation Management
Skin & Mucosa Pruritic rash (most common!)

Alopecia

Vitiligo

Mucositis

Topical corticosteroids

Oral antipruritics

Consider oral steroids

GI Tract Diarrhea/colitis – presents ~6wks into treatment R/O infxn

Anti-motility agents

Steroids if severe

Liver Hepatitis (rate <5%, severe toxicity very rare) Stop therapy if moderate-severe.

Steroids + mycophenolate given rarely.

Lung Pneumonitis – (rate <5%, but occasionally fatal) Steroids common. Infliximab, cyclophosphamide also used, though patients requiring therapy beyond steroids have nearly 100% mortality.
Endocrine Hypophysitis

Autoimmune thyroid disease

Adrenal Insufficiency T1 DM

Hormonal replacement

Steroids

Less commonly reported immune-mediated adverse events include the following: acute renal injury, pancreatitis, neurotoxicity (GBS, myasthenia gravis, PRES, aseptic meningitis, autoimmune encephalitis), cardiotoxicity (myocarditis), hematologic (cytopenias), and ocular inflammation.

Many of the adverse events described above can be managed with continued use of PD-1 inhibitors if mild. However, for severe adverse reactions, PD-1 inhibitors are withheld and potential discontinued permanently.

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.

……………………………………………………………

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.