Severe Sepsis and Septic Shock: Using SvO2 and ScvO2 to Guide Resuscitation

You've heard all these fancy terms, mixed venous blood gas, ScvO2, SvO2, thrown around the ICU all the time. Regardless of whether you're a nurse, respiratory therapist, medical student, resident, or even a fellow, these terms may sometimes be quite confusing as everyone talks about them like, "duh, you're supposed to know this".

You're here because you don't know this. Or perhaps you don't know that you don't know this. Or perhaps you need a refresher course. I am not going to get into the deep dive complexities of venous oxygen levels as that could be a complete chapter in a textbook but feel free to ask questions below and either I or our community will try to answer the questions. 

SvO2: 
- venous oxygen saturation 
- taken from a Swan Ganz catheter. without a PA catheter, you can't measure this 
- also called a mixed venous oxygen saturation. 
- this is a combination of venous oxygen from both the SVC and IVC

ScvO2
- stands for central venous oxygen saturation
- taken from a central line that terminates in the SVC or right atrium. Could be an internal jugular, subclavian, or axillary line.
- it's easy to confuse the two because the PA is more "central" but think about it as getting this value from the "central line"

Correlation
ScvO2 is generally 5-6% higher (sometimes more) as this blood comes from the brain and upper extremities which generally consume less O2 than the organs and lower extremities. This is more pronounced in shock states. 

I'll dig deeper into this in the near future. The article where these images were taken from is FREE! A hat tip to the authors. 

-EJ

Rivers EP, McIntyre L, Morro DC, Rivers KK. Early and innovative interventions for severe sepsis and septic shock: taking advantage of a window of opportunity. CMAJ. 2005;173(9):1054‐1065. doi:10.1503/cmaj.050632

Link to Website with Article

Link to FULL FREE Article



Link to Reinhart Paper

ABIM Board Certification Exam: How I passed my critical care medicine boards

Back in December 2017, I found out that I had passed my ABIM board certification exam for critical care medicine. I created this video on youtube for those who are interested in learning about the methodologies I pursued to be able to pass this challenging exam. Needless to say, it was the most challenging board exam I have taken. Below is the link to the YouTube video. Thanks for following along.

-EJ

Link to Video on YouTube

ABIM Board Certification Exam: How I Passed my Internal Medicine Boards

Several years ago, I took and passed my ABIM Board Certification exam for internal medicine. I made this video for YouTube when I was a younger whipper snapper and it has proven to have been quite helpful for some. In this video, I go over the different methods which I used to study for and ultimately, pass the exam. 

You can watch the video here or click the link at the bottom to watch it directly on youtube where you can have greater control of the video regarding speed and other parameters. Thanks for following along! 

Link to video on youtube

-EJ

Resuscitation and Fluid Responsiveness and Mean Arterial Pressure

We take care of sick patients. In doing so, we have various tools in our disposal including the physical exam, history, and hemodynamic parameters. We check the blood pressure on our patients and depending on that number, we do things for them (hopefully not to them). 
We place the blood pressure cuff on their extremity, hopefully the right size, and cycle it. We have learned about the limitations of the oscillometric devices as I have covered that extensively and we have learned to trust the mean arterial pressure (MAP). 

We all learned that the equation for MAP is:
MAP= [(2 x diastolic)+systolic]/3
We also learned that we should target a MAP of 65 based on the surviving sepsis guidelines and I generally agree with this. Sometimes I target a higher MAP, sometimes a lower MAP. Every patient is needs personalized care in my book. 

Here's the other equation that we should know but don't. 
MAP= (CO x SVR) + CVP
- CO= cardiac output, also HR x SV (and don't forget that the stroke volume is affected by preload, contractility, and afterload)  
- SVR= systemic vascular resistance
- CVP= central venous pressure (tends to be zero in a spontaneously breathing patient). This value tends to be ignored for the sake of simplicity. 

We all give IV fluids to increase the MAP, because that is what we see on the monitor, but that's the missing the point. 
Fluid responsiveness is defined as an increase in stroke volume or cardiac output/cardiac index after being provided with a bolus. 

Studies have shown us that only 50% of patients who are septic actually respond to fluid resuscitation. The other 50% who we blast with fluids, well, they just get overloaded and have complications secondary to that. 

The point of this post is for us to think a bit more outside the box when we have a patient who is hypotensive. We can't just look at the blood pressure after being given a liter of fluid and call the patient fluid responsive. 

The FENICE study looked at 2213 patients and 42.7% of the time, the clinicians gave IVF without looking at any hemodynamic parameters. Even when the patient had a "negative response" to the fluid bolus, 49.4% of the time, the clinician gave an additional bolus after that! I think you can call that insanity per the Einstein definition of it. 

The clinicians were looking at primarily an increase of BP followed by urine output, decrease in HR, decrease in lactate rather than changes in CO or SV. Let's just say that we have all been guilty of this in the past but need to get better on the matter. 

Here are some examples on where that thinking can lead us astray:
If the MAP is low but their CO or SV is looking great but their SVR is on the floor, they may need earlier vasopressors and nuanced fluid challenges. In the case of cardiogenic shock, you may find that the CO is on the floor and their SVR is in the clouds, those patients may benefit from some careful peripheral vasodilators with some inotropes. That undefined patient who is hypotensive and we give a liter of fluids to indiscriminately is quite dangerous at the end of the day. People come to the hospital to be helped, in those cases, we may actually be causing harm. 

If we are going to call ourselves the best, we need to practice that way. Understanding hemodynamics are crucially important to saving lives. 

-EJ

Cecconi M, Hofer C, Teboul JL, et al. Fluid challenges in intensive care: the FENICE study: A global inception cohort study [published correction appears in Intensive Care Med. 2015 Sep;41(9):1737-8. multiple investigator names added]. Intensive Care Med. 2015;41(9):1529‐1537. doi:10.1007/s00134-015-3850-x

FENICE Link

Ivermectin in COVID-19: Taking another look

Ivermectin in COVID, this is the second time I cover this medication during this pandemic. 

This paper has NOT been peer reviewed. I will try to peer review it myself. Ultimately, I recommend you not trust me and read the paper for yourself. A healthy dose of skepticism is needed for peer-reviewed papers these days, much more for these non-peer reviewed. 

Observational trial with all the limitation that come with it. This is not a randomized controlled trial. At least the authors went through the trouble of propensity matching some controls to help out with the outcomes. This was also international and multicenter. I'm a fan of ivermectin as it is widely available and inexpensive (ahem, tocilizumab, remdesivir).

n=1408, 704 got the study drug
Drug: 150mcg/kg x 1 dose

Primary outcome: mortality
If on mechanical ventilation: Mortality 7.3% vs 21.3% (NNT=7.1)
Overall death rates: 1.4% vs. 8.5% (NNT=14.1)<0 .0001="" font="">

Issues: no comment on PF ratio of these patients, their underlying organ dysfunction, adverse effects of the study drug. We also don't know where in the course of the illness did they get the study drug. We also don't know if they were getting other therapies outside of them being matched in the two groups. 

The patients in the Ivermectin group seems sicker at baseline: more CAD (p=0.03), more COPD/asthma, black race (which seems to be harder hit), more immunocompromised (these are not statistically significant, but there is a trend). 

Ivermectin was associated with a higher likelihood of survival. The authors claim a shorter length of stay but this is not reported anywhere in the paper. The authors recommend an RCT, I agree. 

Credit to Dr Tim Connelly who was one of my mentors during training for sharing this paper with me. 

Link to Article

Remdesivir: NOT a Game Changer

How I wish that this was a positive study. We’re in need of a helpful tool. I’ve thrown every possible treatment including tPA at patients to try to save them and nothing is 100% at this point. I took apart the first Remdesivir study several weeks ago and was not impressed. History is repeating itself.

This study was published to much fanfare and media attention yesterday. It was so good that the Lancet hid it behind the paywall when they had made all their COVID coverage free until this point. Shady shady (EDIT: it is now free to download). I have to credit my partner Kelly for getting me this paper. My NP Cody texted me about it 45 seconds before Kelly. I love my team.

There’s much to go over here. Too much to fit in the limited character count on IG but I’ll try my best. I could be wrong, don’t trust me, read the data for yourself. There are many details I just can’t cover because I’m trying to live my life. Let’s go!

Investigator initiated: they weren’t randomized from the get-go based on certain criteria, someone chose these patients. If your patients have renal failure or are on CRRT, these data do not apply as they were excluded from the study. The placebo group had more males which it’s the sex harder hit by COVID but the Remdesivir group had more HTN, DM, and CAD. These patients were less ill than the prior study. Interpret that as you may.

Remdesivir, 200mg on day 1, 100mg days 2-10 vs. placebo (2:1); n=158 vs. 78

Primary endpoint: time to clinical improvement within 28 days after randomization. What type of vague endpoint is that? Correct me if I’m wrong but that's a very uncommon endpoint. Either way, there was no statistically significant difference. Now, they admit that it’s not statistically significant, but they said there’s a trend that if they started the study drug within 10 days there’s possibly a benefit for faster clinical improvement. That’s a lot of ifs but this is where I figure there should be a benefit if there was to be one. Even with this caveat in mind, there was no difference in mortality if started early or late.

Secondary endpoints that you and I care about: all-cause mortality at day 28; frequency of invasive mechanical ventilation; duration of oxygen therapy; duration of hospital admission. No difference in any of these. There wasn’t even a difference in viral loads. This is an antiviral drug, by the way.

To be honest with you I’m not even going to go over the adverse effect stuff because I’m not convinced this works and I don’t think I can get my hands on it for my patients even if I wanted it. Well, maybe now since others may feel the same way I do and many aren’t going to want it.

The study was stopped early because they didn’t have enough patients to continue. Why not phone some friends and make the study multicentered? I disagree. I’m not a research conducting guy. I don’t want to further expose my ignorance.

I’m tired. This COVID stuff has exhausted me and I’m not even in an epicenter. I sympathize for all my colleagues in busier places than me. I have a strange survivorship guilt thing going on. I’m here for you all.

-EJ

Wang Y Zhang D Du G et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020; (published online April 29.)

Addendum: the Lancet now made the paper open access. I can't take the credit for them doing that! 

Link to Article

Link to PDF

Resuscitation and Fluid responsiveness, what is it?

You have a patient who is hypotensive. You want to make them not hypotensive. The first thing the vast majority of clinicians reach for is some sort of IV fluid. We give it and cross our fingers that they won't be hypotensive after the fluids were provided. This is what is done in every single hospital throughout the world.

I've already posted before that even in a healthy person, if they get a liter of fluid, 68% of it will be extravasated within 1 hour. Much more and far quicker will that volume be lost in someone who is critically ill; approximately 80% in 30 minutes. No wonder the "response" to that liter of fluid was so short lived.

Fluid overload has many complications which many of you know of already. Perhaps I'll do a post solely on that. This is just one post of many, so feel free to ask questions below and I will address all of them in full posts in the near future.

The whole purpose of providing a fluid challenge is to increase either the cardiac output or stroke volume, not increase MAP. This excellent paper was written by some resuscitation geniuses who I often fanboy over their work. It's completely free and I suggest you download it and read it for yourself. 

Monnet X, Marik PE, Teboul JL. Prediction of fluid responsiveness: an update. Ann Intensive Care. 2016;6(1):111. doi:10.1186/s13613-016-0216-7

Link to Article

Link to FULL FREE PDF

Resuscitation and Fluid Responsiveness: Passive Leg Raising + Stroke Volume

Don't think that I'm anywhere close to being finished on discussing fluid resuscitation and when to stop, I think I could spend a whole career just talking about this once concept. Drowning our patients with fluids is bad, we all know that.

Check out my YouTube video on the matter where I break down this study.

Douglas IS, Alapat PM, Corl KA, Exline MC, Forni LG, Holder AL, Kaufman DA, Khan A, Levy MM, Martin GS, Sahatjian JA, Seeley E, Self WH, Weingarten JA, Williams M, Hansell DM, Fluid Response Evaluation in Sepsis Hypotension and Shock: A Randomized Clinical Trial, CHEST (2020), doi: https://doi.org/10.1016/j.chest.2020.04.025.

Link to Article

Link to PDF

Resuscitation and Passive Leg Raise: Don't use the arterial blood pressure to determine fluid responsiveness

Passive leg raising (PLR) is a technique I am going to cover extensively as I am writing a lecture where this will be a hot subtopic. I've covered it before on my blog and instagram. It's all in the effort to NOT drown our patients in IV fluids when they're hypotensive. 

When I was a younger whipper snapper in training, I thought I could perform the passive leg raise assessments by picking up some legs, looking at the BP increase and call it a day. Boy, was I wrong. I learned some further principles behind why I was wrong but today I found the data as to how wrong I was. Needless to say, I was very wrong. Did I mention I was wrong? Glad we're clear. I wasn't born knowing everything and still have a ton to learn.

In this paper they placed a swan in their patients and did some other stuff that I will cover at a later date. As some background and to define certain principles, a person who is fluid responsive is one who receives an amount of fluid, in this case PLR is approximately 300cc, is one who has an increase in their stroke volume or cardiac index/output. It is NOT someone who's blood pressure goes up just because they got fluids. Looking at the sensitivity and specificity of looking at the arterial blood pressure versus the measures generated via thermodilution, you can see how looking at the BP is absolute poop and should not be used. 

I altered a copyrighted photo to help illustrate the area under the curve. I'll take it down if I upset anyone. At the end of the day I'm just trying to save lives. Haney Mallemat @criticalcarenow has done some great coverage on End-tidal CO2 so check out his work on the matter. 

Monnet X, Bataille A, Magalhaes E, et al. End-tidal carbon dioxide is better than arterial pressure for predicting volume responsiveness by the passive leg raising test. Intensive Care Med. 2013;39(1):93–100. doi:10.1007/s00134-012-2693-y



Link to Abstract

Standard BP Measurements in the Critically Ill

Taking a quick COVID break and let's get back to some simple critical care basics: measuring blood pressure. We do this on all of our patients at least hourly for the stable patients and continuously on our unstable patients. Ultimately, though, we need to do this right. After all, this is critical care and the details matter.

I have already detailed my concerns with oscillometric BP cuffs in the past and have even created a youtube video about it meaning I'll skip that here. Ultimately, the values generated by the oscillometric devices leave much to be desired. When someone is sick (everyones definition of what sick is varies) they need an arterial line. Plain and simple. No healthcare professional has ever complained about having an arterial line. Win-win for all involved.

This paper touches on a 5 step approach to using an arterial line.
Step 1. Catheter insertion sites. I am a fan of brachial artery catheterization, ultrasound (US) guided. I tend to look at the radial artery first via US and eyeball the caliber of the vessel. I weigh on complexity of the procedure if they're on jet fuel to keep them alive and quickly scurry up the arm. I don't want to spend 2 hours sticking an artery like we have all done at one point or another. Someone who gloats about how good they are at a-lines hasn't been humbled enough. I asked my nurse colleagues to grab me a dart as well as the femoral line kit. Before anyone gives me a hard time about my preference for brachial artery preference, please note the complication rate is 0.2%. I have placed a number of axillary lines but this is an option of last resort for me. I choose the femoral route in code situations where I knock out a "dirty double" and place both the central line and arterial line depending on what blood return I get from the stick. 

Step 2. Catheter length: I use the 4.45cm catheter for radial arteries and the 16cm catheter for all others. When you place the US probe over the brachial artery you'll quickly see why the 4.45cm catheter won't cut it, especially in an extremity with significant adipose tissue. 

Step 3 is being skipped.

Step 4 and 5 are primarily for my critical care nursing colleagues as they describe the leveling and zeroing of the transducer, as well as checking the quality of the waveforms. They go further into dampening and a number of key concepts that are much better explained by the authors than I can ever do. 

You should definitely check out this article for yourself as it is worth your time. Did I mention that it's free?

Saugel, B., Kouz, K., Meidert, A. et al. How to measure blood pressure using an arterial catheter: a systematic 5-step approach. Crit Care 24, 172 (2020). https://doi.org/10.1186/s13054-020-02859-w

Link to website

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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.

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



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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

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FDA definition of "compassionate use"



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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.

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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

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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

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