Category Archives: Grand Rounds

Updates to severe CAP recommendations and the microbiome

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Thanks to Dr. Szabo and Dr. Pickens for a fantastic grand rounds covering the new updated recommendations to severe CAP! [https://link.springer.com/article/10.1007/s00134-023-07033-8]

1) Suggest adding multiplex PCR to lower respiratory sample (very low evidence)

ResPOC trial [https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(17)30120-0/fulltext] – 720 patients presenting to ED with resp symptoms ran multiplex PCR and given information to clinical team -> slightly less abx (one dose vs 48hrs) and shorter LOS and good identification of viruses -> results 48-72hrs earlier than cultures, can quickly de-escalate or target resistance

Sputum biofires more often positive than BAL biofire (72% vs 49% and more likely polymicrobial, and also common discrepancy with cultures)

2) Consider HFNC instead of regular oxygen

RCT of standard oxygen facemask, HFNC, NIV [Frat NEJM 2015 https://pubmed.ncbi.nlm.nih.gov/25981908/] -> mortality benefit in those who got HFNC [though NIV might’ve been confounded because they targeted high tidal volumes]

3) Steroids? Based on their own meta-analysis, recommended if shock is concurrently present.

Didn’t include CAPE COD study, and driven by Meduri VA study [?confounded by gender]

Interesting thoughts on environmental ecology – examining the microbe in its true environment interacting with other bugs rather than taking it out and isolating it on a plate!

First, identify all microbes present [Human Microbiome Project – https://hmpdacc.org/]; there’s been a lot of interest recently!

The upper respiratory tract is different from the lower respiratory tract when you’re sick. Some features like bacterial burden or composition/diversity are associated with different outcomes!

Thanks, Dr. Szabo and Dr. Pickens!

Slides: 2023.05.10 grand rounds – ERS sCAP guidelines

CAPE-COD: steroids in severe CAP

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Thanks to Jose for presenting this today! CAPE-COD (paper here)

  • 800 patients with severe CAP randomized (excluded those who were on pressors, influenza, aspiration)
  • Balanced baseline groups
  • Hydrocortisone infusion 200mg/day, duration could be extended based on criteria + taper vs placebo with same protocol; median duration 5 days
  • Fewer death by day 28 in those given hydrocortisone 6.2% vs 11.9%
  • Fewer intubation by day 28 19.5% vs 27.7%
  • More insulin in steroid group
  • Especially helpful in women and age>65 by subgroup analysis
  • strengths included fast onset to medication dosage ~15 hours, and high adherence to protocol, reasonable 21% VAP rate (compared to many studies with low rates)
  • limitations: surprisingly low mortality, unstandardized microbiology (45% without identified pathogen)

Discussion points brought up included the variety of pathogens and heterogeneous groups and the syndrome of CAP, unclear exactly which subpopulation would be most benefitted (compared with COVID, where things were more clear and homogeneous), unusual population where a large number of patients had high CRP (based on a prior Spanish study that showed benefit in this population that took years to enroll a certain number of patients); steroids are a blunt instrument, choice of specific steroid (hydrocortisone vs dexametahsone). Of note – immediate meta-analysis incorporating this data – slight benefit?

Recent VA study showing no benefit (mostly men so maybe one explanation for the difference): https://link.springer.com/article/10.1007/s00134-022-06684-3

Of note – new guidelines for severe CAP including our very own Dr. Wunderink: https://link.springer.com/article/10.1007/s00134-023-07033-8

Future thoughts: designing trials better phenotyping to target specific pathways!

Grand Rounds: COLDSTER trial

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Thanks to Scott for summarizing this trial today! COLDSTER

Cold Weather Health Risks: A Detailed Guide | Everyday Health

In patients who had COVID 3-8 weeks ago, who have dyspnea or hypoxia and >20% abnormalities on CT, do high vs low dose steroids help and is one dose better than the other?

290 patients -> 160 excluded (82 too mild lung abnormalities)

130 randomized 1:1 -> high dose (40 x1 w then 30mg x1w then 20mgx2w then 10mg x2w) vs low dose (10mg x6w) treatment

Baseline tests, 2, 4 weeks in telephone checkin for adherence, adverse effects, final 6 week checkin – lost 4 in one arm and 5 in another arm

57yo, only 32% female, 73% had at least one comorbidity, all had required hospitalization for acute COVID, 98% having WHO severe disease, 43% received mech vent, 91% had organizing pneumonia patterns on CT

Scored images by lobe and averaged and primary outcome was >90% radiological improvement and they also had numerous subgroups.

There were low rates of ‘complete radiological response’ in both groups 25%-19%. Both groups had improvements in FVC, 6MWT, symptom scores, and overall CT scores.

Both groups had adverse effects including hyperglycemia (though only 30%), hypertension (23-21%), cushinoid habitus (20%). No deaths in either groups, 3 infections in high dose and 1 in low dose group, all treated.

It seems that in these post-acute COVID patients, low steroid dose with 10mg prednisolone performs similarly to high dose steroids to improve symptoms and imaging.

Limitations include the small size and lack of blinding. There haven’t yet been a placebo trial either, so that could be a next step. Also, was this done too soon, as patients may still have been recovering from the original infection? Multi-center would be nice as well, and blinding where able (for example, reviewers of the CT).

Thanks, Dr. Laurenzo!

Grand Rounds – 9/30/22 – Pulmonary Hypertension Updates

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Last week in Grand Rounds, 3rd year fellow Romy Lawrence treated us an update on the latest advances in Pulmonary Hypertension.

The graphic below provides a helpful organizer for the three physiologic categories of PH: pre-capillary (Pre-PH), combined pre-and-post capillary (Cpc-PH), and isolated post-capillary (Ipc-PH)

Another common characterization for PH is WHO category. As a reminder of categories:

  • 1: PAH
  • 2: 2/2 left heart disease
  • 3: 2/2 lung disease
  • 4: CTEPH
  • 5: Other/misc

 

I. Updates in PH definitions

First, how did the 2022 ESC/ERS update change from the 2018 WSPH Guidelines?

The PVR cutoff was changed to 2! This was decided as it was roughly the cutpoint above which an increased hazard ratio for mortality was observed in the CART cohort. An important point here – these do not yet translate to therapeutic recommendations, as efficacy of PH therapy between mPAP 21-24 and 2-3 WU remains unknown. 

So if the new cutoffs haven’t resulted in updates in therapeutic recommendations, what do we do with them??

 

The entity of exercise PH, defined as a mPAP/CO slope between rest and exercise >3 Hg/L/min, was also defined.

A really important point here – symposia have been exclusively held in affluent countries, despite the fact that most of the global PH burden is in low and middle income countries. What implications does this have for focus of therapeutics, imaging, advocacy?

 

 

II. Pulmonary hypertension therapeutics:

Here’s a broad overview by WHO group:

Romy reminded us that the mainstay of PAH therapy is to target one of three pathways known to be implicated in the pathogenesis of PAH: (1) excessive endothelin-1 production, (2) deficient prostacyclin, and (3) low nitric oxide production.

After vasoreactivity testing and CCB trial if applicable, the most important determinant of treatment is risk assessment (REVEAL score or ESC/ERS risk stratification). An algorithmic approach from there:

The risk calculator is linked below if you’d like to learn more!

 

 

III. PAH in pregnancy

PAH in the pregnant woman – an uncommon situation with extremely high (30-50%) mortality. The WHO recommends against pregnancy in PAH. We also discussed the following:

  • Patients should be counseled around risk and provided contraceptive advice
  • Referral to a PH center if patient considering becoming pregnant and/or if pregnant and considering termination for maternal safety
  • ERAs (macitentan, bosentan, ambrisentan) are teratogenic

 

IV. Chronic thromboembolic pulmonary hypertension (CTEPH)

3 criteria for CTEPH:

  • mPAP >20
  • PCWP <15
  • Evidence of chronic perfusion defects after 3 mo anticoagulation

What is the relationship between acute PE and onset of CTEPH?

Important to know that certain factors increase the likelihood of CTEPH. These include some unsurprising conditions, such as prior PE (OR 19) especially unprovoked (OR 5.7).

Less intuitive – splenectomy (OR 18), ventriculo-atrial shunt or infected pacemaker (OR 76!!)

Finally, an overview of CTEPH treatment pathways:

Balloon pulmonary angioplasty (BPA) is used in distal or surgically inaccessible disease, and/or in patients for whom comorbidities preclude surgery. This is done in series of 4-6 sessions separated in time by several weeks.

Riociguat is approved for use in medical management of inoperable CTEPH based off of the CHEST trials.

The role of medical therapy as a bridge to surgery or BPA is less certain, given that it may delay appropriate referral and expedited treatment.

 

 

A few take home points from the discussion.

Thanks for an outstanding Grand Rounds, Romy!

Sources

  • Humbert et. al. ESC/ERS Guidelines 2022
  • Maron et. al Lancet 2021
  • Auger et al. Clin Chest Med 31 (2010) 741–758
  • Bonderman D et al. Thromb Haemost 2005;93:512-516
  • Humbert M.  Eur Respir Rev 2010; 19: 115, 59–63
  • Pengo V et al. New Engl J Med 2004;350:2257-2264
  • Ghofrani, HA. D’Armini, AM., et. al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med 2013.
  • Jais, X., D’Armini, AM., et. al. Bosentan for treatment of inoperable chronic thromboembolic pulmonary hypertension” BENEFiT. J Am Coll Cardiol . 2008.
  • Ghofrani, HA, Simonneau, G., et. al. Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension. (MERIT-1): Lancet Respir Med 2017.
  • https://pahriskcalculatorre.com/