Category Archives: Cathy’s Crit Care Corner

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!

ISICEM and steroids in severe pneumonia

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ISICEM has begun – lots of interesting papers being presented, can follow on Twitter with #ISICEM23 [https://twitter.com/hashtag/ISICEM23?src=hashtag_click].

Some studies of high interest: anticoagulation for COVID, ravulizumab for COVID, feeding in shock, and more:  https://twitter.com/tscquizzato/status/1638128616713101313

And of special interest – CAPE COD – are steroids back in for severe pneumonia? Out in NEJM today: https://www.nejm.org/doi/full/10.1056/NEJMoa2215145?query=featured_home

TL;DR – 800 patients with severe pneumonia admitted to the ICU randomized to 200mg daily hydrocortisone vs placebo; reduced mortality (6.2% vs 11.9%), higher ICU discharge, less intubation (18% vs 29.5%)! Note those with septic shock were excluded (probably because they would receive hydrocort 50q6 anyway?).

Especially beneficial in subgroup with high CRP (makes sense)

Farkas already has his take up here: https://emcrit.org/pulmcrit/cape-cod/

Bilateral pneumonectomies and ECMO support

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I read with fascination these case reports about bilateral pneumonectomies with ECMO support – came up during Lung Rescue discussion.

From Cypel et al

https://www.sciencedirect.com/science/article/pii/S0022522316316233 – Cypel et al, a CF patient who had shock from Pseudomonas bacteremia who had this done to get source control, after pneumonectomies, she had dramatic improvement. Had this configuration:

https://www.sciencedirect.com/science/article/pii/S1053249819316298?via%3Dihub – Barac et al, another young CF patient with Bulkholderia, with bilateral pneumonectomies to clear his infection prior to transplant. With this layout:

Figure 1

Really interesting to read about these cases. A more recent case: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8780122/ – severe COVID respiratory failure on ECMO with persistent COVID and Stenotrophomonas, interestingly had a PFO that was used for shunting to offload the left ventricle (they suggest atrial septostomy could be performed in those who don’t have a PFO).

Proning practices before and after COVID

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  • Before COVID, proning was clearly underused
  • Recommendation for proning by official ARDS guidelines are strong that severe ARDS should receive proning>12hr/day
  • Anecdotally have seen more proning during COVID
  • Full team is more comfortable and familiar with it – it’s less new, RT and nursing are used to it and ask about it, etc
  • But what do the numbers show?

Comparing Prone Positioning Use in COVID-19 Versus Historic Acute Respiratory Distress Syndrome, CCE, May 2022

  • Retrospective review of proning during COVID 2020-2021 or pre-COVID ARDS 2018-2019 at academic and community hospitals
  • Proning initiated faster and more in COVID vs historic ARDS (58%!!! vs 9%)
  • Practice sustained throughout the pandemic
  • Time will show if things will change over time if COVID numbers continue to stay low

Hand-washing and C.diff contact precautions

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I tried to find data on alcohol based hand rubs in C.diff but all I found is that hand washing is recommended – see this small study of volunteers who had C.diff spores spread on their hands then either soap or alcohol, then shook hands with other volunteers – hand washing was better at removing spore counts – https://pubmed.ncbi.nlm.nih.gov/20429659

Surprisingly, the IDSA guidelines – https://www.idsociety.org/practice-guideline/clostridium-difficile/– say okay to do alcohol based cleaning if gloves are worn in routine and non-endemic settings, though acknowledges that handwashing with soap and water is superior to alcohol based hand hygiene

My practice will be to continue hand-washing after C.diff rooms, time-consuming as it is, because don’t want to bring it home to your cat or dog (happened to one of my residents; https://www.hcplive.com/view/potential-transfer-of-clostridium-difficile-from-dog-cat-to-household-owners)

Blood biofire?

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I read a little more about the blood culture biofire that we’ve started seeing – BCID2 – 43 PCR results including organisms and resistance – https://www.biofiredx.com/products/the-filmarray-panels/filmarraybcid/ and some evidence – Banerjee et al randomized 617 patients with positive blood cultures to usual care (takes about two days to get results from micro lab cultures) vs BCID +- stewardship team – showed shorter time to organism identification and appropriate abx changes – no difference in mortality, LOS, or cost 

Comparison of time to organism identification, availability of phenotypic antimicrobial susceptibility results, and first appropriate modification of antimicrobial therapy for the subset of study subjects with organisms represented on the rapid multiplex polymerase chain reaction (rmPCR) panel (n = 481). Time 0 is when the positive Gram stain result was reported. Median time in hours (interquartile range [IQR]) to organism identification: control 22.3 (17–28), both rmPCR and rmPCR + stewardship 1.3 (0.9–1.6); de-escalation: control 39 (19–56), rmPCR 36 (22–61), rmPCR + stewardship 20 (6–36); escalation: control 18 (2–63), rmPCR 4 (1.5–24), rmPCR + stewardship 4 (1.8–9). *P < .05 vs control; †P < .05 vs control and rmPCR groups.https://academic.oup.com/cid/article/61/7/1071/289120 They also have a small number of discrepancies (11 cases) in their Table 2 – but pretty reasonable and only 3 true cases of organism identification discrepancy

I’m excited to see this and look forward to using it clinically!

Iron and the ICU

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Iron is needed by bacteria

Higher iron associated with higher mortality in ICU patients – https://www.nature.com/articles/s41598-018-29353-2

figure 2

Animal sepsis models – giving iron in septic animals leads to increased mortality – https://pubmed.ncbi.nlm.nih.gov/15190970/

Giving IV iron to stable outpatients doesn’t necessarily increase infections – https://pubmed.ncbi.nlm.nih.gov/31485910/

But wouldn’t give it to septic patients (though note the data for this are sparse – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3226152/)

Cefiderocol: A Siderophore Cephalosporin with Activity Against Carbapenem-Resistant and Multidrug-Resistant Gram-Negative Bacilli | SpringerLinkIn fact, check out Cefiderocol – trojan horse antibiotic – two cephalosporins (ceftaz, cefepime) and catechol-type siderophore ~iron – gets taken up by bacteria but then attacked by antimicrobial! – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054475/ – just recently approved

Cefiderocol

Activity of cefiderocol against high-risk clones of multidrug-resistant Enterobacterales, Acinetobacter baumannii, Pseudomonas aeruginosa and Stenotrophomonas maltophilia | Journal of Antimicrobial Chemotherapy | Oxford Academic (oup.com) –

DEXA-ARDS – steroids for ARDS?

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DEXA-ARDS study – Villar et al. in Lancet Resp –

https://www.thelancet.com/pdfs/journals/lanres/PIIS2213-2600(19)30417-5.pdf

https://www.thelancet.com/pdfs/journals/lanres/PIIS2213-2600(19)30417-5.pdf

RCT of 277 patients with ARDS P/F<200 todexa 20 daily x 5d then down to 10mg x5d or extubation; improved outcomes vent-free days, mortality (21% vs 36% at 60 days)! Rich says every few years steroids for ARDS come back into vogue but then another study shows no benefit or harm and the cyclerepeats though.

Pulmcrit has a nice summary of the previous studies too of steroids in ARDS – https://emcrit.org/pulmcrit/dexa-ards/