Stories from the Front Lines (✨COVID-19 Healthcare Workers only: posting rules imposed)

Riviera Paradise

@Wetworks thanks for your excellent posts. Could I please ask some questions:

Are you seeing any evidence of HCQ+AZT treatment being effective and if so for what patients are the treatment protocols being applied?

Riviera Paradise

From you post on ACEis and BRA, my understanding is that you saw a worst outcome for patients on BRA? Was this true for any age group?

Rasputin

As an anesthesiologist, I take exception to what @Wetworks said regarding my response. The situation is constantly developing and to disregard established standards in favor of limited data is to tread in unchartered waters at your own risk. Have you managed patients on long term mechanical ventilation, managed a hypertensive crisis, or even attempted to titrate from one antihypertensive to another on a relatively healthy patient let alone one who is hemodynamically unstable on a ventilator? It’s not a plug and chug situation for many if not most patients. The medical community is straining to contain this pandemic while at the same trying to treat millions with other unrelated conditions. This is not designed to be medical advice but to offer alternate insights to consider. And yes patients are to follow the advice of their physicians.

Rasputin

As an anesthesiologist, I take exception to what @Wetworks said regarding my response. The situation is constantly developing and to disregard established standards in favor of limited data is to tread in unchartered waters at your own risk. Have you managed patients on long term mechanical ventilation, managed a hypertensive crisis, or even attempted to titrate from one antihypertensive to another on a relatively healthy patient let alone one who is hemodynamically unstable on a ventilator? It’s not a plug and chug situation for many if not most patients. The medical community is straining to contain this pandemic while at the same trying to treat millions with other unrelated conditions. This is not designed to be medical advice but to offer alternate insights to consider. And yes patients are to follow the advice of their physicians.

Tony C.

Fascinating video, even for a layperson. Thanks!

Wetworks

Not sure there's anything to take exception with, to be honest. I disagree that switching patients meds out of an abundance of caution is a particularly big deal, especially since their cohorts are experiencing deleterious escalations in their BP before crashing (in other words, the meds aren't helping them, aka, they are likely hurting them), you don't. You would know this is what's happening if you were getting the information first hand; I am, my impression is you are not. Anesthesiology is super busy in my place as the ER attendings are ridiculously busy with keeping up with intubations and managing ICUs until admission, plus the regular ER stuff. Your whipping out your skillset in an attempt to chop down my argument is telling. I'm sure you can speak expertly to your profession, probably even outside your scope of practice too, and likely better than I on a number of other things as well. However, this is very real, my colleagues and I are seeing it. You want to start pooling the data and making the argument for/against to chart the waters, be my guest. But your previous canned response is potentially very harmful, as it suggests that all is well simply because we don't know anything more at this moment.

And to answer your questions, yes I've done all those things, and then some, but I will refrain from making it a pissing contest. Just so we are clear, this all started because you took exception to me offering "alternate insights to consider" where patients health may be concerned. That's informed consent, and it doesn't end with an agreement to fulfill a prescription.

Here's a video that spells it all out. And yet the MD at the end advises the same thing, a wait and see status quo. While I could understand doing so in normal circumstances, doing so now seems so.....passive and wrong.

M'Bob

You two remind me of the parable, which I can't put my finger on at the moment, of the people who are all touching different parts of an elephant, like the trunk, tail, and ears, but don't know they're on the same animal.

I think you're both right, but coming at it from different angles. Conservative and peer-reviewed medicine is the only intelligent way to practice, and doctors struggle everyday to fight against quackery and unproven interventions. Except in war-time, which we are presently in, where the rules are changing so rapidly, drastically, and with so many caveats, that one can't always defer to the play book to make immediate and possibly life-saving decisions.

M'Bob

Orthopedic and sports physical therapist.

A question: does evidenced-based medicine tell you how to chooes between two patients that need a ventilator?

M'Bob

Orthopedic and sports physical therapist.

A question: does evidenced-based medicine tell you how to choose between two patients that need a ventilator?

sah

Being at war has some think outside the box. Try and match 2 patients to share a vent. Or have support personal hand bag the one who does not get the machine.
Option 3, is triage resources to where or who will likely benefit more.

BenBagbag

EMT

Regarding ethics of allocating ventilators when demand is greater than supply...

Too Many Patients…A Framework to Guide Statewide Allocation of Scarce Mechanical Ventilation During Disasters (Link)

My thoughts on COVID-19
1) Reason for ACE inhibitor use as risk for severe COVID-19, due to
2) Microvascular thrombosis in severe COVID-19
3) Possible Role for tPA / heparin / DEFIBROTIDE to treat late-stage severe COVID-19, possible PVOD
4) Possible role for prophylaxis against this thrombotic cascade of MILD cases discharged from ER with anti-platelets for 14 days ??
5) A pathway proposed via PAI-1 surge resulting in thrombosis from ACEI cessation and COVID-19 cytokine storm
This is a possible pathway that could explain role of HTN, ACE inhibitors being associated with severe COVID-19, and the potential role for tPA in COVID-19 treatment. Please be patient and read my thoughts and let know what your thoughts are.
1) A common thread in the fatality of COVID-19 has been the well described, VERY SUDDEN, development of cardiomyopathy and idiopathic AKI and need for CRRT. To think that ARDS or septic shock is causing fatality is not accurate, as most reports clearly mention patient even coming off the vent, coming off vasopressors, even almost ready for downgrade from ICU, and suddenly crashing with low EF, AKI, and death within 2 days. To think the virus somehow has not affected the heart and kidneys until day 11 of severe illness is also not too convincing. There has to be a sudden event, such as thrombosis.
2) In several reports and autopsies by Italian and Chinese, MICROTHROMBI have been identified in cardiac tissue and renal tissue of severe fatal COVID-19. Even massive PEs and large arterial thrombosis were noted in young healthy people with severe COVID-19.
3) We do know that some infections are PRO-THROMBOTIC, as in DIC with thrombosis, such as Dengue fever. Elevated PAI-1 levels are associated with significantly worse outcomes in Dengue.
4) We also have some anecdotal evidence that patients with HTN (inevitably a lot on chronic ACE inhibitors) possibly have higher incidence of severe illness from COVID-19.
5) Fact: ACE inhibitor REDUCES PAI-1 production.
6) Fact: PAI-1 inhibits tPA, thereby causing thrombosis, as described in MI literature. PAI-1 antigen levels are higher in men, and higher with advancing age, among many other factors.
7) Fact: Dengue, as an example, causes elevated PAI-1, described in literature, and Dengue is pro-thrombotic.
8) IL-6, and other cytokines increase PAI-1 release/production during acute inflammatory response.
9) Could it be that ACE inhibitor depletes PAI-1 levels in the serum --> COVID-19 causes a relative surge in PAI-1 level (just as in Dengue due to IL-6 and other cytokine release) --> Sudden surge in PAI-1 levels (particularly if PAI-1 already depleted due to ACE inhibitor use or due to well described genetic polymorphisms) lead to a very large thrombotic surge (by inhibiting tPA) --> lead to vast micro-thrombosis and sudden collapse with microvascular thrombi causing sudden cardiomyopathy and AKI as seen in fatal COVID-19 cases?
10) Could there be a role for tPA infusion or anticoagulation in severe cases of COVID-19? Yes, tocilizumab will stop the IL-6 from wreaking more havoc, but what if the cat is out of the hat, and the thrombotic cascade has begun due to PAI-1 surge (as well evidenced by continuous rise in D-dimer despite its short half-life compared to ALL other inflammatory markers with longer half-life (ferritin, CRP) coming DOWN, even pressors and oxygen requirements coming down). Perhaps a role for tPA even in moderate cases to prevent the fatal thrombotic outcome that has been seen on autopsies in the fatal cardiomyopathy that occurs, in the AKI that occurs?
OR DIRECT PAI-1 inhibitors: tiplaxtinin? Other novel compounds reported and not in use?
Or high-dose STATINS? There is established association with statin use and decrease in PAI-1.
11) Could this explain why HTN (inevitably a lot on ACE inhibitors) has been somewhat anecdotally associated with worse outcomes? A lower PAI-1 state in hemostasis with tPA in the body due to chronic ACE inhibitor use, followed by a sudden huge surge of PAI-1 due to the prothrombotic (via PAI-1) nature of COVID-19 (and a sudden surge in PAI-1 due to holding ACE inhibitors that we naturally hold in sepsis) causing microvascular thrombosis and fatality?
12) Could a plausible explanation in worse outcomes in patients on ACE inhibitor be that, as patient inevitably goes to septic shock, ACE inhibitor is held --> leads to rebound elevation in PAI-1 naturally --> this elevation works synergistically with PAI-1 elevation from the inflammatory cascade that COVID-19 causes (as documented in Dengue) --> leads to a large surge in PAI-1 --> thrombotic cascade and death.
13) If you have a case with CRP improving, Ferritin improving, sepsis improving, IL-6 improving, but D-dimer rising and patient not improving, would it not make sense that the discordant D-dimer rise (which has the shortest half-life of all three and should technically be falling if it were only due to acute inflammation) is due a thrombotic cascade? Perhaps consider treating this subset first to see if fatal outcomes can be prevented?
14) Could it be that some of the mild cases discharged will go to cytokine storm, microvascular thrombosis, and show up late-stage with hypoxia without any significant lung auscultation findings (as has been reported), because of this process? And succumb to a quick death in this late stage?
15) Should we risk stratify mild cases based on IL-6 level and D-dimer level before discharging a seemingly mild case? Should we prophylaxis everyone we send out with some sort of agent to avoid thrombosis if we cannot tell exactly who gets it and who doesn't?
16) Should we across the board just assume every case's "thrombotic" tendency from cytokine storm is at the same intensity? I understand from this study that prophylaxis dose of LMWH was used and is being used in US. Could there be cases that need a therapeutic dose in someone with a higher thrombotic propensity depending on their cytokine storm, depending on their IL-6 level? What about those cases that roll into ER without prior care at late stage, very elevated D-dimer, discordant findings? Is a prophylactic dose of Lovenox SC enough to stem the thrombotic cascade? Could they need a higher dose? Could some late presenters need tPA?
17) Could PVOD be the reason we are hearing reports that patients in ARDS turn course and behave more like a "cardiogenic" pulmonary edema without LV issues noted on echo, which is essentially a post-arterial outflow issue, as that could happen in PVOD. And if this worsening in A-a gradient is associated with rise in D-dimer (and small vessel PE is not found on CT), then PVOD is a possibility as with other thrombosis elsewhere. If having ACUTE thrombosis causing PVOD-like picture, then perhaps treatment with anticoagulant, tPA, or Defibrotide (as in hepatic VOD) may help.
18) Can Italian, Chinese, or WA/NY doctors tell the rest of us how well did patients do that were NOT on ACEI/ARB but on chronic ASA/Plavix or anticoagulation? If they did the best, then the writing is on the wall regarding this thrombotic cascade.
Thoughts?
Disclaimer: I'm your average not too bright GI doctor 10 years out from any biochemistry. Smarter people need to chime in. Maybe run this by the smartest physician in your facility and see if it makes any sense to try this please. Please don't try this based alone on this thread. Although Chinese and Italian doctors are recommending anticoagulation per many reports.
Disclaimer #2: Please don't stop your ACE inhibitors based on this. These are just theoretical possibilities. I'm NOT recommending any change in meds or practice for anyone. These are just food for thought and for smarter people to analyze.

Wetworks

RN, ED

This was posted to my feed today. Interesting theory as to why pts who are seemingly on the rebound go south. It was posted as a thought experiment by a GI doc.




Still doesn't explain (from what I understand), why we are seeing patients on ACEs go south while still on their medication though. Or am I missing something (little deep for my educational background)?