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Ok, here is a little #Tweetorial about #COVID19 and whether, outside of a controlled trial, we should be using different:
1. rules for anti-coagulation/ lytics
2. ventilatory settings in ARDS
3. anti-virals/ anti-inflammatories
1. rules for anti-coagulation/ lytics
2. ventilatory settings in ARDS
3. anti-virals/ anti-inflammatories
First, we have to acknowledge that we already have protocols & norms for these things.
Hospital & ICU VTE prophylaxis,
ARDS ventilatory management,
& administration of experimental agents outside of trials
Hospital & ICU VTE prophylaxis,
ARDS ventilatory management,
& administration of experimental agents outside of trials
I will expand on experimental agents:
As a rule, we do not give experimental drugs to healthy ppl without proof, rarely if sick w something where most recover w time, sometimes when hospitalized and most recover w time, and occasionally when critically ill & most don't recover
As a rule, we do not give experimental drugs to healthy ppl without proof, rarely if sick w something where most recover w time, sometimes when hospitalized and most recover w time, and occasionally when critically ill & most don't recover
Second, if you already have rules/ norms in place for say VTE management or ARDS, the first question is:
Is this new condition fundamentally different than conditions I am used to seeing wrt to pathophysiology/ risk?
Let's consider COVID19
Is this new condition fundamentally different than conditions I am used to seeing wrt to pathophysiology/ risk?
Let's consider COVID19
When it comes to COVID19, we still lack compelling data that the risk is fundamentally different than severely ill hospitalized patients who are severely ill with anything.
Available data is fragmented, cherry picked, evolving and not very persuasive.
Available data is fragmented, cherry picked, evolving and not very persuasive.
Much has been said about "microthrombi" in COVID--- that is nothing new. We have known about microthrombi in critically ill ARDS for a long time https://twitter.com/awgaffney/status/1249712028400390144
Even the histopath of COVID lungs looks like ARDS https://twitter.com/MiscSusan/status/1249844204630614019?s=20
And, let us not forget most people with the disease, fortunately, do not die of the disease. The case fatality rate is debated, but it ain't > 50%.
Probably fair to say 96, 97, 98% chance of natural recovery among those diagnosed
Probably fair to say 96, 97, 98% chance of natural recovery among those diagnosed
So for the first pre-requisite: Is the condition fundamentally different from traditional VTE considerations in hospitalized individuals, pulmonary issues in cases of respiratory failure/ hypoxia and risk of progression?
The answer is probably no.
The answer is probably no.
If no, do not pass go.
There is prima facie no reason, no logic, no evidence to abandon norms/ rules/ practices based on dozens of RCTs to "try something new"
But let's assume the opposite
There is prima facie no reason, no logic, no evidence to abandon norms/ rules/ practices based on dozens of RCTs to "try something new"
But let's assume the opposite
Let's assume, for the sake of argument, we actually believed the risks/ pathophys is fundamentally different.
If you were persuaded thrombosis risk is new, lung pathophysiology is novel, risk of progression is unprecedented, then what you have is a hypothesis..
If you were persuaded thrombosis risk is new, lung pathophysiology is novel, risk of progression is unprecedented, then what you have is a hypothesis..
You hypothesize that say: higher dose enoxaparin will work better than standard prophy dose, if say the d-dimer is >500 or 1000; you hypothesize that higher TV is ok, you hypothesize some zn or vit c, or HCQ or toci will help
Like this is a hypothesis: https://twitter.com/jungleland/status/1249881667600171008?s=20
Like this is a hypothesis: https://twitter.com/jungleland/status/1249881667600171008?s=20
The question is then: Is the hypothesis right?
To answer that you need a randomized trial. Why? Because none of these things are magic bullets.
If they were, someone would report a 100% cure rate. Instead, they at best have meager effect sizes, which need RCT to validate
To answer that you need a randomized trial. Why? Because none of these things are magic bullets.
If they were, someone would report a 100% cure rate. Instead, they at best have meager effect sizes, which need RCT to validate
You have a hypothesis
I think this is different/ new. I think DOAC might be better than enox 40.
See Jeff gets it: He knows these are hypotheses https://twitter.com/jungleland/status/1249874962501926913?s=20
I think this is different/ new. I think DOAC might be better than enox 40.
See Jeff gets it: He knows these are hypotheses https://twitter.com/jungleland/status/1249874962501926913?s=20
Hypotheses to be tested.
Not ideas to be implemented
Not ideas to be implemented
Finally, lets turn to the desperate situations: folks admitted the ICU, who require intubation
Available data is limited, but outcomes appear grim in this group.
What should we do?
Available data is limited, but outcomes appear grim in this group.
What should we do?
Should we just try many things at once:
Zinc, Vit C, Toci, Kaletra, Remdesivir compassionate use, even, eculizumab, TPA
If you do this, how will you know if the patient was made better or worse by some, all or a combination of these?
Zinc, Vit C, Toci, Kaletra, Remdesivir compassionate use, even, eculizumab, TPA
If you do this, how will you know if the patient was made better or worse by some, all or a combination of these?
Did they live because of the kitchen sink or in-spite of it?
Did they die because of the kitchen sink or despite it?
Did they die because of the kitchen sink or despite it?
The TPA story really set me off.
I mean, we debate TPA in settings where PE is the KNOWN and SOLE cause of illness
Because its harms are MASSIVE and DEVASTATING https://twitter.com/VPrasadMDMPH/status/1250134294044889088?s=20
I mean, we debate TPA in settings where PE is the KNOWN and SOLE cause of illness
Because its harms are MASSIVE and DEVASTATING https://twitter.com/VPrasadMDMPH/status/1250134294044889088?s=20
Hemorrhage after TPA is catastrophic.
Intracranial bleeds horrific.
We debate TPA so much in a setting most favorable for TPA, proven clot, and no other major issue
Intracranial bleeds horrific.
We debate TPA so much in a setting most favorable for TPA, proven clot, and no other major issue
To just give TPA for a hypoxic pt who already has a reason for hypoxia (COVID19), for whom PE is not even known for sure, knowing TPA data-- under best of circumstance is so lousy; knowing harm is so catastrophic
I find reckless and cavalier https://twitter.com/VPrasadMDMPH/status/1249841934979350528?s=20
I find reckless and cavalier https://twitter.com/VPrasadMDMPH/status/1249841934979350528?s=20
If you have ever seen TPA hasten death, I imagine you would think again.
Also, to speak to news reporters whose coverage will only promote off label use, ughh!
Don't speak to reporters about unproven Rx
Also, to speak to news reporters whose coverage will only promote off label use, ughh!
Don't speak to reporters about unproven Rx
What has happened to us, docs?
Yes, we are scared, and yes there is uncertainty, but you don't walk away from decades of VTE guidance, decades of vent management, decades of guiding principles for experimental drugs based on a hunch, a guess, fragmented data, a preprint
Yes, we are scared, and yes there is uncertainty, but you don't walk away from decades of VTE guidance, decades of vent management, decades of guiding principles for experimental drugs based on a hunch, a guess, fragmented data, a preprint
First, you build the case that this is different
Next, you come up with clear hypotheses and
Then, you test them
Testing them is a massive uphill battle.
Next, you come up with clear hypotheses and
Then, you test them
Testing them is a massive uphill battle.
Most hypotheses-- gorgeous, eloquent, marvelous hypotheses-- fail in rigorous testing
Most swings in the dark connect with air
Come on, the chance that these maneuvers are going to yield success is vanishingly low, even if rationale is sound
Most swings in the dark connect with air
Come on, the chance that these maneuvers are going to yield success is vanishingly low, even if rationale is sound
Let's sit back and remember that we did train for this. We do know how to manage clots, and dypnea, and hypoxia. We have rules that we learned the hard way.
Save cowboy medicine for the rodeo
Save cowboy medicine for the rodeo
Heroism is practicing attention to detail, lots of love, evidence based, medical care and we are already damn good at it.
for all else, RCT
for all else, RCT
Covid 19's spike protein promotes binding to the ACE2 receptor; let's not let it bind to our neurons
