National Institute of Health COVID treatment guidelines

Sorry that I am making you go through my website. I don’t earn any income for what I post on Instagram so think of this minor inconvenience as your way of contributing to the effort I put onto my page. Thanks!

-EJ

Link to NIH Guideline

Link to Aerosolization Article



Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Corticosteroids for COVID-19

Some legendary names came out to play for this article. Meduri is the author of the famous Meduri Protocol for methylprednisolone in ARDS and Villar is the author of the article I shared on February 13th (seems like forever ago, really) where they provided dexamethasone for ARDS and showed a mortality benefit amongst many others. I personally like looking into strategies such as corticosteroids as they are inexpensive and available worldwide. You can't really count on third world countries obtaining a -zumab drug. This paper is an opinion piece and is missing formal RCT data. I recommend you read the article yourself and don't trust me. This is not medical advice but I am carefully administering corticosteroids to my COVID patients based on certain clinical and laboratory criteria. It is a custom tailored approach so I can't say exactly what I'm doing. Every patients is different. I am trying to reach for dexamethasone to avoid my team having to go into the room numerous times a day to give a medication. 

Steroids for Cytokine Storm
The authors state that the cytokine storm is what kills COVID patients. I do not disagree with this. You watch the ferritin and CRP spike up and the patient get sicker (we don't have IL-6 at our shop). Their O2 requirement goes up, their renal function starts to worsen. Things get ugly and in a hurry. Some use the -zumab drugs which we have all have a certain allocation of and is expensive, but what if we can reach for plentiful and cheap steroids instead? We all know the adverse reactions to this. The authors cite how the WHO guidelines on steroids is misleading and potentially harmful. 

The Evidence for Steroids in ARDS
We do not have great studies in all this. We have harped on this enough. The authors acknowledge this and pull observational data from Wuhan where there was a decreased risk of death for giving methylprednisolone to the patients in ARDS. They acknowledge that randomized controlled trials are ongoing but that we should not withhold giving patients steroids in the ICU for ARDS in lieu of study results. I know I'm not allowing my patients to wait themselves. 

Simple yes or no question to you all: Are your teams providing steroids to your COVID patients?

-EJ

Villar, Jesús MD, PhD; Confalonieri, Marco MD; Pastores, Stephen M. MD, MACP, FCCP, FCCM; Meduri, G. Umberto MD. Rationale for Prolonged Corticosteroid Treatment in the Acute Respiratory Distress Syndrome Caused by Coronavirus Disease 2019, Critical Care Explorations: April 2020 - Volume 2 - Issue 4 - p e0111 doi: 10.1097/CCE.0000000000000111

Link to Article



Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

ECMO in Adults Training Courses for FREE from ELSO

ELSO, the Extracorporeal Life Support Organization, is now doing free training modules on ECMO (extracorporeal membranous oxygenation), both VV and VA in this COVID-19 time. Take advantage! You need to register, of course. It has been over two years since I did ECMO and this is a good refresher course for me. Check it out for yourself! It's free!

Shout out to Jamie Zink @jamiezink77 for sharing this with me. 

Link to ELSO

Link to Training Modules





Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

IDSA Guidelines on COVID-19

I typically appreciate guidelines. They do a pretty reasonable job to help us take care of our patients and standardize how we do things. That being said, with all due respect to the Infectious Disease Society of America, I do not like these guidelines. I'd rather they didn't say anything at all. In fact, they do not give any recommendations as to what to do. Seems like they're saying "don't do anything in the absence of a clinical trial". Sorry guys, the RCT days are at a halt. People are dying faster than we can wait for results for clinical trials. We can't just sit back and do nothing while these people get sicker on us. This is all my opinion and download the source material. Do not trust me. 
Here we go with the recs and my interpretation:

Recommendation 1
Hydroxychloroquine (hospitalized patients): give in the context of a clinical trial. What about all the other hospitals who are not in a clinical trial? We are learning that it is not so good in severe/ICU cases with better data but there is still a void and a large absence of adverse effects in this population when patients are carefully monitored (daily EKGs, telemetry). 

Recommendation 2
HCQ/Azithro combo: give in a clinical trial. I'm cool with this. Two QTc prolonging agents is a time bomb. 

Recommendation 3
Lopinavir/Ritonavir: give only in a clinical trial. We have learned via an NEJM article I posted that this doesn't work in severe patients but what about the mild/moderate camp? Remdesivir is hard to get a hold of these days. 

Recommendation 4
Steroids in patients without ARDS: recommendation against. I tend to agree with this.

Recommendation 5
Steroids in patients with ARDS: give in the context of a clinical trial. Yeah, sure. And what am I supposed to do for the cytokine storm if I'm not in a center that enrolls patients in a clinical trial? Can the IDSA then, since they're not helping, facilitate the PI contact info for these clinical trials?

Recommendation 6
Tocilizumab: only in the context of a clinical trial. Should I sit on my hands as I watch the inflammatory markers skyrocket? Sigh.

Recommendation 7
Convalescent plasma: in the context of a clinical trial. Well at least this is something you can ONLY get in a clinical trial so there's that.

I'd like to invite these fine folks to step out of the Ivory tower, and into the front lines with us in non-academic centers/community hospitals to practice some real world medicine. I trained in an Ivory tower institution myself. The vast majority of us are not in the Cleveland Clinic, Bringham and Women's, Vanderbilt, Mass Gen, Northwestern, Mayo Clinic, and Johns Hopkins. 

Link to Website

Link to Full FREE PDF

Plasma Exchange for COVID-19

Let's straighten out some nomenclature first. We all have questions about what is what and there is much confusion. I personally like the say all these words roll off the tongue. Makes you sound smart when you say it. There's more to it than what I am going to mention here, of course. 
Plasmapheresis is to remove, treat, and exchange blood plasma for other plasma or something else (i.e. albumin). I am going to focus on the exchange component called "plasma exchange" or even sexier: PLEX. This is typically used to treat various disorders of the immune system like TTP, Guillain-Barre, etc. 

Could this work for COVID? 
First of all, this is not a treatment for the virus itself. This will not be a viral load monitoring type therapy. This is intended to treat the cytokine storm and systemic response. What PLEX does is "remove inflammatory cytokines, stabilizing endothelial membranes, and resetting the hypercoagulable state".
The paper, which you should download and read for yourself, states that PLEX was used in a small number of patients during the H1N1 outbreak which had a full recovery. The authors are trialing this modality at the moment and have a paper that's cooking and is currently undergoing peer-review for publication. I tip my hat to the fact that they propensity matched their s/p PLEX patients to similar patients with similar illness who received standard of care. I wish the HCQ/azithro studies, remdesivir, and FFP studies to date would have done this but they didn't. Sigh.
Based on the experience of the group, they are using PLEX earlier in the disease course rather than later for better outcomes. They're working on a larger trial as well. Seems hopeful. 

Cons:
Adverse effects/Caveats/concerns: patients will need a dialysis catheter. More bleeding when placing the catheter versus a traditional line but given that most patients end up on renal replacement therapy anyway, this may not matter. These prothrombotic patients may potentially clot off this circuit.
This is also a big machine that needs to be placed in a patients room. Concerns exist for cleaning the machine.
Some patients also develop hypotension and transfusion reactions. 

As an aside, the Critical Care Medicine world is TINY! The author of the cited article trained at the same fellowship program I did and I interviewed at a place where he used to work. He's one brilliant dude. Everyone always loved working with him and sung his praises left and right. I picked up on his great energy myself immediately upon meeting him in person. 

Keith, P., Day, M., Perkins, L. et al. A novel treatment approach to the novel coronavirus: an argument for the use of therapeutic plasma exchange for fulminant COVID-19. Crit Care 24, 128 (2020). https://doi.org/10.1186/s13054-020-2836-4

This data is current as of 4/13/2020

Link to Article

Link to FREE PDF

Link to Pre-pub article

Hints on when to anticoagulate your COVID-19 patients

I have written and said this before but I am quite convinced that many of these patients need full anticoagulation. My opinion, not medical advice. This is due to what I have seen in my clinical practice, what others have anecdotally mentioned, and post-mortem data. We need more data to find out when to start it. Obtaining CT scans of the chest and having a radiology tech come in to scan everyone's extremities may not be realistic. This article was published yesterday and I learned about it from Josh Farkas (@pulmcrit). I'll read his take after I put this out. There's ultimately no randomized control trial for anticoagulation in these patients and this is pure clinical gestalt. Please strongly weight risks vs. benefits if you go down this route.

In my practice, I have been keeping track of numerous parameters to try my best to decide when to pull the trigger of when to start anticoagulation. It's a big mystery. As the authors of this paper mentioned, we don't know what is the prevalence of venous thromboembolism in patients with severe COVID-19 infections. They looked at checking d-dimers to predict VTE in these patients.

Retrospective study published on 4/9. They looked at 81 ICU patients in Wuhan, China. They did lower extremity ultrasounds. I am personally reporting that I’ve seen upper extremity VTE's so these could have been missed in the study. They also performed numerous other lab tests.

What they found
25% of patients (n=20) had lower extremity VTE. Again, they didn’t check the uppers.
8 of these 20 patients died.
VTE group: older patients, lower lymphocyte counts, longer PTT (all statistically significant)

What lab value did they find to be most helpful?
D-dimer greater than 1.5mcg/mL.
85% Sensitivity. 88.5% Specificity. 94.7% Negative predictive value.

For some background, an elevated d-dimer is a sign of "excess coagulation activation and hyperfibrinolysis". Once you start anticoagulation, the d-dimer should start coming down. I am seeing this in my practice. I haven't decided where to pull the trigger, though. Anecdotal evidence. Poo poo evidence.

Cui, S., Chen, S., Li, X., Liu, S. and Wang, F. (2020), Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost. Accepted Author Manuscript. doi:10.1111/jth.14830

- EJ

Link to Website with Article

Link to Article



Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Remdesivir in Severe COVID-19

Let's be quite clear here, there's no miracle drug for all this. I personally have zero experience with remdesivir at this point in time. Hopefully you all can comment on whether you anecdotally think it works or not. This study was published earlier today in the NEJM and is free for you to download and read for yourself. Do not trust me. This is not medical advice. This is industry sponsored but someone had to pay for the medication. 

We've all been hearing about compassionate use but what does it mean? Well, it means that we can give an unapproved (by the FDA in the US) medication has the potential benefit to justify the risks of treatment. In this case, remdesivir has been pulled from the shelf to allow us to try to treat COVID-19 due to its in vitro activity against SARS-CoV-2. It also has numerous other applications that you can check out on your own. 

n=53 (originally 61 but some couldn't be analyzed) 75% were dudes. 57% on vent. 8% on ECMO. 
Patients: sats < 94% on RA or need for O2. Also needed to have kidneys and a liver (that all worked). Symptoms started a median 12 days prior to starting treatment. 
Dose: 200mg IV on day 1, 100mg IV on days 2-10.

What did they do? 
They monitored the patients for at least 28 days and quantified events. No specified end points. It was a "let's see what happens" study. Compassionate use, indeed. Patients were obviously not randomized. No control arm. Sigh. 

What did they find?
68% had an improvement in their O2 support. 15% worsened. It's not 100% but nothing is except death and taxes. Was this because of the medication? We do not know.
Pts on RA or low flow: 100% got better. either they were going to get better on their own or the medication helped. 
NIV or HFNC: 71% got better. Again, either they were going to get better on their own or the medication helped.  

13% of all patients died. 18% of the patients on vents died. 5% of the patients on NIV died. Are these numbers about what we're seeing for patients who end up in our hospitals? 

Did they cause harm?
60% had adverse effects but if you honestly look at these, I can't say they're necessarily the fault of the study drug. 23% had pyrexia (fever) well, duh. And we are seeing renal impairment, AKI, MODS, DVT, ARDS all because of cytokine release syndrome. Can't blame this necessarily on remdesivir. Also, two patients had pneumothoraces. That's definitely not the study drug. 

The limitations are endless and listed thoroughly by the authors. I honestly don't know what to do with this data. It's not like the results are too good to be true. They're just meh. 

-EJ

Link to Article

Link to PDF

FDA definition of "compassionate use"



Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Summer heat may help us with COVID-19! (Hopefully!!)

Summer, my favorite season. It can't get here soon enough. Will it help us with the coronavirus and help terminate this thing sooner rather than later? 

This study was published on April 2nd out of Hong Kong in Lancet Microbe. I believe it may be some good news or I may be too optimistic. This paper is also an exercise in why you need to look up the supplementary material because a lot of goodies live in there. Download it for yourself!

They measured the stability of SARS-CoV-2 at different temperatures. I'm going to break it down in Fahrenheit so that you don't have to ask Siri to convert Celsius to Fahrenheit numerous times like I did. I am completely open to be wrong regarding the following interpretations as looking at virus titers is not something I've honestly ever done. These following numbers do not necessarily mean that they are infective at those titers either. 

At 39.2 degrees Fahrenheit, the virus is extremely stable. It seems to hang around just fine for two weeks, unfortunately. When it starts heating up, however, things become a bit more favorable for us. The temps in NY in Feb/March were 30-50 degrees. 

At 71.6 degrees Fahrenheit, this stability gets cut in half to where it's barely around at one week. 

At 98.6 degrees Fahrenheit, the virus is even more unstable living about just a day. 

I tried to find how this correlates to other viruses such as influenza but this was a wild goose chase with apples to oranges comparisons. Not worth confusing you all (nor myself) with that data.

How this translates to planning for spread in different climates and curve modeling, I don't know. I also don't know how different surfaces will affect this outside of irresponsible extrapolation on my part. I'll leave that up to the epidemiologists. I just know that the virus living in my car that's sitting in the hot Florida sun will be routinely knocked out as I contaminate it with my dirty scrubs daily and my laundry sits in my hot garage.

The paper also discusses the stability on paper, tissue paper, wood, cloth, glass, money, stainless steel, plastic, and masks. Hope you all have a good amount of sterilizing wipes around!

A hat tip to the authors and to my wife who sent me this paper. 

Chin A W H, Chu J T S, Perera M R A, et al. Stability of SARS-CoV-2 in different environmental conditions. Lancet Microbe 2020; published online April 2. https://doi.org/10.1016/S2666-5247(20)30003-3.

Link to Full Text

Link to FREE PDF

Link to Supplementary Materials



Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Two phenotypes for Respiratory Failure

Conventional ARDS treatment is not cool anymore, or is it? Gattinoni, one of the authors of this paper, has really made a name for himself during this pandemic as we have learned much from his experience and that of his team. They start off by pointing out that the Surviving Sepsis Campaign guidelines need adjusting. Shots fired! Kidding... ish... Please download the paper for yourself and don't trust me.

In this editorial which has yet to be published in the Intensive Care Medicine journal discusses two phenotypes: L and H. There could be a transition from L to H, by the way. The virus can't make this too easy for us. The type could be identified via CT scan but also looking at the respiratory system elastance and recruitability. The rationales as to why someone would fit into one category or another is dependent on many factors (gray area yet to be determined).

Type L (more than 50% of patients, what they come in with)

- Low elastance (i.e. high compliance)

- Low ventilation to perfusion ratio (loss of regulation of perfusion and loss of hypoxic vasoconstriction/vasoplegia) *I have mixed feelings about this one. 

- Low lung weight (not much generalized infiltrate nor edema)

- Low recruitability (since there's not much infiltrate nor edema)

Tx: Reverse hypoxemia. Try non-invasive options. Try higher tidal volumes (8-9cc/kg) if hypercapnic and intubated. Keep PEEP from 8-10. Prone positioning doesn't really work.

This is where we see the tachypnic patients before they crash. They may improve on their own or worsen. They describe patient-self inflicted lung injury (P-SILI). Perhaps decreasing their work of breathing could buy the patient time to recover before transitioning to type H.

Type H (20-30% of patients)

High elastance (lots of edema in there)

High right-to-left-shunt

High lung weight

High recruitability

Tx: treat like severe ARDS, high PEEP, prone positioning, ECMO if needed.

My take is that this paper is missing some components on the microthrombi and leading to some of the shunt physiology we are seeing leading to the refractory hypoxia. I feel that rather than vasoplegia we are seeing the effects of micro thrombi creating shunts. I could be totally wrong.

Gattinoni L. et al. COVID-19 pneumonia: different respiratory treatment for different phenotypes? (2020) Intensive Care Medicine; DOI: 10.1007/s00134-020-06033-2

Link to PDF

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Anticoagulation in COVID-19

Should we anticoagulate COVID patients? Simple question, not so simple answer.

Autopsies have found occlusion and microthrombosis formation in the small vessels of the lungs. We all know that people have just decided to drop dead for one reason or another after looking fine. Could this also be happening in the heart and kidneys? Can we at least band-aid this by anticoagulating somewhere in the course?

75% of the COVID ICU patients I've personally cared for have developed DVT's of some sort during their hospital course and are currently on full anticoagulation. But could we have predicted this was going to occur and have been proactive when it comes to all this micro and macro thrombi we are seeing? By the way, I have reached out to some hematologists I know and trust for their opinions and no one really knows. Even though I started writing this post yesterday, Josh Farkas beat me to the punch today.

Let's look at the data.

The paper I’m covering today was published on March 27th and came out of China. I'm late to the game. It is a retrospective study. They described "sepsis-induced coagulopathy" based on PT, platelets, and SOFA score.

They found that if the the SIC score was greater than or equal to 4 and the patients had received heparin, there was a decrease in their 28 day mortality from 64.2% to 40%. The number needed to treat with all its limitations was just 4.1 If the SIC score wasn't elevated, it really didn't make a difference. The D-dimer also held its own if it was greater than 6. When this is the case, patients who received heparin had a mortality of 32.8% versus 54.8% without it (NNT=5.1). This isn't the best data in the world and has numerous limitations that you can look at yourself to help you better interpret the study, but I know I will personally be formulating some anticoagulation strategies for these patients in the absence of a large clinical trial. Potential benefit has to be greater than the risks, of course.

It is important to note that the dosing utilized in this paper is comparable to our DVT prophylaxis doing. My curiosity ultimately stems from the utility of full dose anticoagulation. Could that hypothetically lead to even fewer deaths? I don't know.

Has anyone seen any data where patients who are chronically anticoagulated have less severe COVID? I'm curious.

A question for someone smarter than me:

Would there be a difference between using heparin, enoxaparin, or moving straight to the DOACs? I would like to limit the exposure of my nurses in titrating heparin drips.

- EJ

Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy [published online ahead of print, 2020 Mar 27]. J Thromb Haemost. 2020;10.1111/jth.14817. doi:10.1111/jth.14817

Link to Abstract

Link to FREE PDF


Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.