Respiratory Management Protocol of Patients with SARS-CoV-2

First of all, a big hat tip to the authors:

Aurio Fajardo C; MD. Medicina Interna. Unidad de Paciente Crítico. MsC en Ventilación Mecánica, Universitat de València. MsC en Medicina Intensiva. Grupo Ventilación Mecánica Chile - Drive Flow Org. Viña del Mar. Chile. @drive_flow_org

Alberto Medina V; PhD. MD. UCIP. Hospital Universitario Central de Asturias. Oviedo. España @alberto_medina_villanueva

Angelo Roncalli; PT. MsC. Hospital Escola Helvio Auto Maceió. Brasil @angelo.roncalli

Enrique Monares Zepeda; Médico Intensivista. Ciudad de México. @enriquemonareszepeda

Federico Gordo-Vidal; MD. Hospital Universitario del Henares. Coslada- Madrid. Grupo de Investigación en Patología Crítica. Francisco de Vitoria, Madrid. España. @fgordo5

Vicent Modesto A; MD. Jefe Clínico UCIP Hospital Universitari I Politècnic La Fe. València, España.

Rodrigo Adasme J; MsC, Pt, CRT. Terapia Respiratoria Hospital Clínico Red de Salud UC-Christus. UNAB. Santiago, Chile.


This is a great review of 45 references to help us take care of patients with COVID-19. There is much left to be learned about this horrendous disease, but we can take cues from prior experience to help us guide our management of the ventilator to cause as little harm as possible. The group of experts listed above, using their multinational expertise, developed this evolving document including algorithms as well as guidelines that will be updated as we learn more. Best of all, it's free to us all. Thank you!

Link to Article

Link to PDF in English

Link to PDF in Spanish


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.

Ivermectin for COVID

This paper was sent to me by @itskatiesway, @bug_drugs, @sanamoh92, @sy_doctornetwork, @paul.neil95, @nascarnora. Thank you all for sending data to me. Also, I am getting somewhere around 50-100 messages per day from the community. Much love to you all. I cannot answer every single question bc I wouldn't be able to live my own life. Thanks for understanding.


Let's get started. It bears repeating that I like simple and cheap stuff. Ivermectin, has been around since 1998 and many of us learned about it as a treatment for scabies. It's about $5 a tab per UpToDate. This paper is quite different than what I am used to reading (since I mainly read clinical trial data which is written a particular way). This is far more science-y than what I am accustomed to understanding. Even this nerd has his limitations.


Let's start off with the first and glaringly obvious limitation to this study. It works in vitro. No data that it work in vivo. Made simple means we have absolutely zero data that it would work in a human body.


Basically they infected cells with SARS-CoV-2 and then added ivermectin. They followed up later to see if there was a reduction of viral RNA at different time points and there was! They noted that "a single dose was able to control viral replication within 24-48 hours" in their system. Don't get too excited now. Again, this is in vitro. They provide some mechanisms which are way over my head.


They recommend trying multiple regimens on COVID-19 patients to assess for a clinical response. At least could postulate, perhaps erroneously, that we could see a change in 24-48 hours. I am not holding my breath but this seems like something that should be attempted early in the disease course, like plaquenil, and may not have too much benefit once the patient is in my hands in the ICU. I can't wait for a good. The best thing is that the Australians discovered this and the know how to put together some great trials with their ANZICS group. A hat tip to the authors!

- EJ

Link to Article

Link to FULL PDF (this link may not work extremely well, go to the article and sort it out there)


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.

Hydroxychloroquine and Azithromycin in Severe COVID-19 Infection

For those of you new to the page/blog, I am a Critical Care physician. My team and I are usually the last line of care patients receive. Many of you are part of my extended team working in ICU's throughout the world. I would honestly love for this combination of HCQ and azithro to work. This study makes us further curb our enthusiasm.

A bit of background:
The two French studies that "showed a benefit" as well as the Chinese study I posted that "showed a benefit" were conducted in patients who were NOT critically ill. This paper was published on March 30th. I'm late to the party, I know. But it correlates with the anecdotal experience I've noted from various facilities who are taking care of critically ill patients.

We get another small study here. n=11. They weren't critically ill when they started the data collection but within 5 days, 1 died and 2 were transferred to the ICU.

Regimen: HCQ 600mg daily x 10 days + Azithromycin 500mg on day 1, 250mg on days 2-5.

Results: 8 patients still had positive RNA at days 5 to 6 after treatment initiation.

Bottom line: in this subset of patients, there was no rapid clearance of COVID-19 by giving this combination. It wasn't as 100% as the Gautret/Raoult studies that I have taken apart in the past. This study is also fraught with flaws. No control group, small, no baseline characteristics. They do not define what made these patients "severe" as opposed to mild or moderate. They could have also waited the full 10 days of therapy. I guess they were in a rush to pump out data or they're going to publish the full data in a couple days and have two publications for their CV instead of just one. Sigh.

I am personally not excited about the HCQ/Azithro combo in my critically ill patients.

Molina JM, Delaugerre C, Goff JL, Mela-Lima B, Ponscarme D, Goldwirt L, de Castro N, No Evidence of Rapid Antiviral Clearance or Clinical Benefit with the Combination of Hydroxychloroquine and Azithromycin in Patients with Severe COVID-19 Infection, Me ́decine et Maladies Infectieuses (2020), doi: https://doi.org/10.1016/j.medmal.2020.03.006

Link to Abstract

Link to FULL 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.

The Cytokine Storm and the -mab

One of the beauties of practicing in the ICU is that although many of my patients take up a lot of resources, the pharmacy-cost component of it isn't too high. I like my cheap IV fluids, norepinephrine, run-of-the-mill antibiotics, heparin, PPI's, tube feeds, sedation meds, etc. None of these are too outlandishly expensive. People generally do well. Reading the ongoing studies regarding COVID-19 I have come across tocilizumab over and over again. Some people around here may already take it or know someone taking it for for their rheumatoid arthritis. Time to take a quick dive into this. This medication is currently being used off-label.


Tocilizumab is an IL-6 receptor antagonist, a monoclonal antibody (hence the -mab at the end of the name). Per UpToDate, this "leads to a reduction in cytokine and acute phase reactant production." Sounds good, right? It's supposed to treat the "cytokine storm" or more formally "cytokine release syndrome". Let's simply define that bad-boy while we are here. We still have a lot to learn and clinical trials are ongoing.


Cytokine release syndrome is a "supraphysiologic response to immune therapy (in this case we're looking at it in COVID-19) that activates or engages T cells and/or other immune effector cells. The systemic reaction is associated with increased levels of inflammatory cytokines and activation of T lymphocytes, macrophages, and endothelial cells" -UpToDate.

The postulation is that this CRS is what is causing people to decide to die. "In more severe CRS, patients may have hypotension and uncontrolled SIRS with circulatory collapse, vascular leakage, peripheral and/or pulmonary edema, renal failure, cardiac dysfunction, and multiorgan system failure." Sounds like what is being described in the COVID literature.

Labs:

Elevated labs: CRP, ferritin, IL-6, and other nonspecific markers of inflammation. I plan to trend these daily.


Adverse effects:

We need to recognize that we are effectively knocking out the immune system to an extent with this medication and could potentially cause harm. There's a black box warning about this. Increased LFTs are commonly noted here (less than 36%). For the nurses, we can see a local site reaction as well.


Cost: it's expensive.


Not FDA approved: currently there is a phase III clinical trial as of 3/26. There are other clinical trials ongoing that have beat the FDA to the punch. Hopefully we will have that data sooner rather than later. There are numerous studies listed on clinicaltrials.gov.





https://www.drugs.com/price-guide/actemra

Link to UpToDate

Chinese non-peer reviewed data

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.

Proning patients on NIV or HFNC

Disclaimer: I am a consultant for a company mentioned in this paper but I am not being compensated in any way, shape or form for this post.

People have asked if it is safe to prone patients who are in ARDS and use either non-invasive ventilation or high flow nasal cannula. In this paper, which is completely FREE for you to download looked at 20 patients who were in ARDS (causes listed on the paper). This was not a randomized trial. It was an observational cohort. They included patients with with moderate ARDS per the Berlin Criteria.

Important teaching point is the Berlin Criteria for ARDS (PaO2/FiO2)
Mild P/F 200-300
Moderate P/F ≤200
Severe: P/F ≤100

Also important to know that moderate ARDS has a mortality of 32% and severe ARDS has a 45% mortality.

55% of patients avoided intubation (it's a small study). But when you consider the fact that these patients with COVID generally stay on the vent for more than 10 days anecdotally, require significant sedation and perhaps paralytics, and eventually move on to be trached, it may be worth consideration. 3 of the 9 patients who were intubated moved on to needing ECMO.

The short answer without me giving away any bias for the aforementioned reasons is that it could be done. The data supporting it is in this article. No, it is not a magic bullet. Not everyone will dodge the endotracheal tube. But one could start asking their patients to do this even in their Emergency Department.

Also, I cannot comment on the concern of aerosolization of the virus by NIV or HFNC at this juncture. I honestly don't know the answer. What I do know is that we may run out of vents if we intubate everyone early. Always wear as much PPE as you can reasonably get your hands on.

Ding L, Wang L, Ma W, He H. Efficacy and safety of early prone positioning combined with HFNC or NIV in moderate to severe ARDS: a multi-center prospective cohort study. Crit Care. 2020;24(1):28. Published 2020 Jan 30. doi:10.1186/s13054-020-2738-5

-EJ
Link to Abstract

Link to PDF

Link to Berlin Criteria

COVID-19 Eval and Management in the Emergency Department

I have to tip my hat on this one to my wife who found this and sent it to me but also to the authors. I agree with mostly everything on here. A link to this article and everything else I've ever posted is on eddyjoemd.com, on my stories, and on my highlights under "COVID-19".

Key take-aways from the Emergency Medicine News guideline of sorts for COVID-19 patients.

With regards to the labs:

- check a CMP, with magnesium and phosphorus.

- here's why. First of all, checking LFT's is necessary for calculating SOFA scores. In the setting of rationing off ventilators (hopefully it never gets to that), SOFA scores are going to be used for this. LFT's are part of the CMP.

- There's very poor data regarding Mg levels and QT intervals but repleting this electrolyte early does not cause harm and makes us feel all warm and fuzzy inside. Phos is also very important for respiratory muscle function. These patients have potentially been sick and not eating well. They may be hypophosphatemic. No data to prove this.

- D-dimer. Hopefully this will be the clinical turning point where people stop thinking about d-dimer only as a rule in or rule out of a PE. Sigh.


Poor prognostic factors:

Listed in the website but important to keep in mind.

Imaging:

I understand that in the ED you need to obtain some baseline imaging. But for those of us taking care of patients in the ICU and wards, we really need to consider how it's going to change the management of the patient. Remember that the radiology techs are being exposed as well. We need to take care of them, too.

Fluids:

PLEASE I BEG OF YOU DO NOT GIVE THESE PATIENTS FLUIDS FOR THEIR LACTATE! I have provided a body of data on this page to support not doing this. They also support starting vasopressors earlier. I have also provided data to support this practice and I do it myself.

I also despise maintenance fluids. If you're a doc or nurse on a COVID unit and you have patients receiving 0.9% saline at 125cc/hr, you really really need to consider the fact that you may be causing harm. Especially when the thought process at this moment for the renal failure is microangiopathic. DO NOT give fluids to try to flush out the kidneys and make the numbers pretty. This does not work like that.

Intubation and O2 therapy.

They make a lot of valid points here. Please check them out for yourself.

Definitely worth reading on your own time.

-EJ

Link to Website

Nutrition in the Critically Ill with COVID-19

We can always count on the ASPEN team to come through for us regarding nutritional recommendations for our patients with COVID-19. A hat tip to them. A hat tip also to my pharmacist teammate, Amanda, for sending this to me (and many other literature goodies). This is free so download your own copy and don't trust me.

Let's take a look. First of all, to make one thing clear, there's no RCT on how to provide nutrition particularly to COVID patients. These recommendations need to be extrapolated from other data. This document was updated today. I enjoyed how they took into account preserving PPE in their recs.

The recs:

- start EN within 24-36 hours of admission to the ICU or within 12h of intubation.

- start with trickle/trophic feeds and ramp it up as stated in the document.

- use weight based equations for the correct amount of nutrition

- trophic feeds if patients are on vasopressors (not if increasing VP doses, though). My understanding is that most of these patients are hemodynamically stable. If the patient is getting sicker, do not feed.

- no recommendations regarding patients on paralytics.

- start with gastric feeds, if this fails, try prokinetics, if this fails, feed post-pyloric. I know there are logistical issues with this at different institutions. They also recommend against post-pyloric feeding tubes needing fluoro for placement due to limiting exposure to HCW.

- continuous feeds recommended over bolus feeds (less PPE)

- they make recommendations about TPN that I won't mention here

- they recommend checking triglyceride levels in patients on propofol within the first 24 hours due to a subset of patients who develop secondary HLH. Not going down this road right now.

- they do not recommend checking gastric residuals. This is something I've covered in the past and it will save PPE.

- feeding proned patients: you could feed the gastric chamber. This is something that I have been asked.

It's only an 8 page document. Check it out for yourself!

-EJ

Link to Abstract

Link to FULL FREE PDF

I agree with Joint Commission!

Is this the part of the movie where the villain switches sides and fights with the heroes? 

The PR folks over at the Joint Commission said "now's our chance!!" 

They stated "We must protect those who are working so heroically to care for people afflicted with COVID-19."

That PR team needs a raise!

Here are some key points: Download the PDF over at eddyjoemd.com

"The Joint Commission supports allowing staff to bring their own standard face masks or respirators to wear at work when their healthcare organizations cannot routinely provide access to protective equipment that is commensurate with the risk to which they are exposed."

"No Joint Commission standards or other requirements prohibit staff from using PPE brought from home."

Regarding N95 respirators vs. Surgical MasksThey state that the CDC changing their recommendations from N95 to surgical masks "may have been precipitated by the emergence of PPE shortages". Ohhhhhh burn!

They state that the understand why healthcare workers have concerns about the adequacy of surgical masks.

Regarding wearing a mask throughout the dayThey state "it is reasonable for staff to want to wear a mask throughout the day".

For our ED friends and colleagues: "Staff in the ED are at particularly high risk because of the high number of patients they see who may be asymptomatic carriers of the virus and the fact that they may have to emergently intubate patients and would be at significant risk without a respirator to protect against aerosolized virus".

The Joint Commission is not siding with hospital administrators on this one, team. We will applaud them, once. I'm still going to drink and eat at the nurses station bc that's where the fun people are.

Link to Statement

Link to FULL PDF

ACE inhibitors and ARBs in COVID-19

We've been hearing a bunch regarding ACE-inhibitors and ARBs in COVID-19 infections. The NEJM finally put out an article on it. Let's review it in plain english and see if it can help us treat our patients. Spoiler alert: like they said in the second paragraph of the article :the data in human are too limited to support or refute these hypothesis and concerns".

Okay I read this paper and didn't get much out of it. Data to be determined.

Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19 [published online ahead of print, 2020 Mar 30]. N Engl J Med. 2020;10.1056/NEJMsr2005760. doi:10.1056/NEJMsr2005760

Link to Article

Link to FREE FULL 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.

Hydroxychloroquine for COVID-19

This is some actual data regarding the effects of hydroxychloroquine in COVID-19! A hat tip to the authors. This is not the most robust study with the most conventional endpoints but it's something. It is very small but I'd rather it exist than not exist at this juncture. These patients are not ICU level patients. 

Disclaimer: this is a not a peer reviewed article at the time of my writing. This is also my interpretation of the study.

The authors wanted to see the effects of hydroxychloroquine in patients with COVID-19. No azithro was harmed in this study that I can tell.

n=62, RCT
31 received standard treatment PLUS a 5 days course of HCQ 400mg daily
Mean age: 44.7 (not the oldest folks, older tend to be sicker.)
All 62 patients also received antivirals, antibiotics (zero mentions of azithro in the article), immunoglobulins +/- steroids.
Noteworthy excluded patients (cannot discuss all of these): severe and critically ill patients. Renal failure. Others. Bottom line is that these patients are not SICK SICK SICK. 
There's no subgroup analysis to see how the +/- steroids may have influenced the results.

Endpoints and Results (assessed at baseline and after 5 days of treatment)
Time to clinical recovery: body temperature, cough remission time. Fewer patients in the control group had fevers, despite this, fever resolved quicker in the HCQ group. Fewer patients had cough in the control group. Also despite this, fewer patients had cough in the HCQ group. Bottom line, patients with HCQ felt better. This is a strange endpoint.

Radiological results: 

CT scan on day 0 and on day 6. Improved pneumonia in 80.6% of HCQ arm versus 54.8% in the control arm. NNT=3.9. 

61.3% of the patients in the HCQ group had a significant absorption of their pneumonia.

4 patients progressed to severe illness in the control group. That's almost 13% of the group. None in HCQ group.

Adverse reactions: 

in the HCQ group, one patient had a rash, another had a headache. 

The authors concluded that HCQ could shorten the time to clinical recovery and promote the absorption of pneumonia. The mechanisms by which this occurs are postulated in the article. This would support giving HCQ to patients who are not critically ill as we do not know its effects on that population, yet. 

-EJ

Link to FULL FREE Article

Link to Abstract

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.