Nick Mark MD Profile picture
Jul 25, 2021 13 tweets 9 min read Read on X
Pre-print of the #COVIDSTEROID2 RCT comparing dexamethasone 6mg vs 12mg in hospitalized patients on high flow O2 or MV:
- no difference in survival or days free of MV with higher dose dex but…
- interesting “trend towards benefit” w/ higher dose dex
📄medrxiv.org/content/10.110…
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🔑 Question: we know from #RECOVERY that steroids are beneficial in severe COVID, but what’s the ideal dose?

#COVIDSTEROID2 was a large DB multi center RCT to answer this. It randomized patients on high flow O2 or MV to either 6mg or 12mg of dexamethasone for up to 10 days.
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The 1° endpoint was days alive free of lifesupport (MV, ECMO, RRT). 2° endpoints included 28 day mortality.

Based on prior studies, they powered for a 15% relative mortality reduction (ARR ~4.5%) combined w/ a 10% reduction in life support duration.

This is pretty ambitious.
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They randomized 1000 people (outcomes were available for 971). The two groups had similar baseline characteristics:
-mostly older (median 65), mostly male (~70%)
-comorbidities were frequent (DM, CHF, CAD, CHF)
~1/2 were on High flow O2, 1/4 on MV, & 1/4 on CPAP at enrollment
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The results were interesting.

Compared to 6mg, 12mg of decadron was associated with:
-numerically lower mortality (27.1% vs 32.3%, ARR 5.2%)
-more days free of support (22 vs 20.5)
-lower rates of SAEs (11.3% vs 13.2%)

However NONE of these reached statistical significance
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Slicing the data different ways yields similar findings: the higher dose of dexamethasone is numerically slightly better but doesn’t (quite) achieve statistical significance. ImageImageImage
What can we conclude?

It’s tempting to round “a trend towards benefit” up to “benefit” but this isn’t good science

If we round down a p=0.06 why not, for symmetry, dismiss a p=0.04 as “trending towards insignificant”?

Thresholds may be arbitrary but we shouldn’t just ignore
7/
Perhaps better to put this finding in context in two ways:
1) #RECOVERY demonstrated a huge mortality benefit by ICU standards (NNT 8); it’s hard to power a study to improve on this
2) prior studies (#DEXAARDS) had shown that a higher dose of dex (20mg/day) was safe/effective
8/
The differences b/w studies are germane:
#RECOVERY enrolled all hospitalized people w/ COVID & found a lower dose of 6mg dex was beneficial (but only in people with hypoxemia)
#COVIDSTEROID2 enrolled sicker people (all on O2) and found a “trend towards benefit” at 12 mg dex
9/
#DEXAARDS enrolled people who were even sicker, those on MV who already met criteria for ARDS

This study was pre-COVID but I think we have enough data to say, uncontroversially, that COVID ARDS is ARDS

Thus it’s reasonable to conclude that sicker pts “need” more steroids🤯
10/
Although #COVIDSTEROID2 doesn’t show a clear benefit for higher dose dex, it also demonstrates that 12mg isn’t worse than 6mg. In fact 12mg has numerically fewer serious side effects, including infxn

With diverging KM curves it’ll be interesting to see the 3 & 6 mo follow up
11/ ImageImage
Clinical 🥡:
- this is a *NEGATIVE* study…
- yet there *IS* reason to think that a slightly higher dose dexamethasone (12mg instead of 6mg) may be safe & beneficial in sicker COVID patients (such as those with ARDS on MV)
- looking forward to reading the peer reviewed 📄
12/12
Things NOT to do:
-go above #DEXAARDS dosing; older studies found HARM w/ higher steroid doses in ARDS
-continue for longer than 10 days; NO studies demonstrate benefit for this
-substitute another steroid (unless you need to); no mineralocorticoid effects w/ dex may help
13/12

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More from @nickmmark

Oct 13
#HurricaneHelene damaged the factory responsible for manufacturing over 60% of all IV fluids used in the US, leading to a major national shortage.

As clinicians what can we do to about the #IVFluidShortage and how can we prevent this crisis from happening again?

A thread 🧵
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There are many things we can do as clinicians to improve ICU care & reduce IVF use.

1️⃣Don't order Maintenance IV Fluid!
Almost no patient actually needs continuous IV fluids.
Most either need resuscitation (e.g. boluses) or can take fluid other ways (PO, feeding tube, TPN).
2/
Frequently if someone is NPO overnight for a procedure, MIVF are ordered.
This is wrong for two reasons.
We are all NPO while asleep & don't need salt water infusions!
We should be letting people drink clears up to TWO HOURS before surgery, per ASA.

3/ pubs.asahq.org/anesthesiology…Image
Read 16 tweets
Oct 1
New favorite physiology paper: Central Venous Pressure in Space.

So much space & cardio physiology to unpack here including:
- effects of posture, 3g shuttle launch, & microgravity on CVP
- change in the relationship between filling pressure (CVP) & LV size
- Guyton curves!
1/

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To measure CVP in space they needed two things:
📼 an instrument/recorder that could accurately measure pressure despite g-force, vibration, & changes in pressure. They built & tested one!
🧑‍🚀👩‍🚀👨‍🚀 an astronaut willing to fly into space with a central line! 3 volunteered!
2/
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The night before launch they placed a 4Fr central line in the median cubital vein & advanced under fluoro.

🚀The astronauts wore the data recorder under their flight suit during launch.

🌍The collected data from launch up to 48 hrs in orbit.
3/
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Read 16 tweets
Jul 16
The media silence on this is deafening.

Did he have a head CT? What did it show?
Did he have stitches? Tetanus shot?

The NYT ran nonstop stories about Biden’s health after the debate but can’t be bothered to report on the health of someone who was literally shot in the head?
To the people in the replies who say it’s impossible because of “HIPPA”
1. I assume you mean HIPAA
2. A normal presidential candidate would allow his doctors to release the info. This is exactly what happened when Reagan survived an assassination attempt.
washingtonpost.com/obituaries/202…
My advice to journalists is to lookup tangential gunshot wounds (TGSW).

Ask questions like:
- what imaging has he had?
- what cognitive assessments?
- has he seen a neurosurgeon or neurologist?
- he’s previously had symptoms like slurred speech, abnormal gait - are these worse?
Read 4 tweets
Jun 30
You've probably heard "don't give lactated ringers because it raises lactate"

This statement is ~98% false, but there's one crucial practice-changing fact that you need to know.

A 🧵 all about lactic acid and lactated ringers!
1/
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First off, we should ackowledge the obvious: Lactated ringers does in fact contain lactate... 28 mEq/L in fact

BUT there's one little detail to remember:
Lactate ≠ Lactic acid

When we measure "lactate" we care about the ACID (H+) which lowers pH & causes organ dysfunction
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But the correlation between pH & lactate is really bad!

Look at this analysis of lactate vs pH in 171 ICU patients.

There is a *weak* correlation in people with arterial lactate > 5, but even w/ lactate =10, pH ranged from 7.5 to 7.05. Quite a spread!

3/ ncbi.nlm.nih.gov/pmc/articles/P…
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Read 10 tweets
Jun 13
If you intubate you need to read the #PREOXI trial!
-n=1301 people requiring intubation in ED/ ICU were randomized to preoxygenation with oxygen mask vs non-invasive ventilation (NIV)
-NIV HALVED the risk of hypoxemia: 9 vs 18%
-NIV reduced mortality: 0.2% vs 1.1%

#CCR24
🧵
1/

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Hypoxemia (SpO2 <85%) occurs in 10-20% of ED & ICU intubations.

1-2% of intubations performed in ED/ICU result in cardiac arrest!

This is an exceptionally dangerous procedure and preoxygenation is essential to keep patients safe.

But what’s the *BEST* way to preoxygenate?
2/
Most people use a non-rebreather oxygen mask, but because of its loose fit it often delivers much less than 100% FiO2.

NIV (“BiPAP”) delivers a higher FiO2 because of its tight fit. It also delivers PEEP & achieves a higher mean airway pressure which is theoretically helpful!
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Read 15 tweets
Jun 12
Results from #PROTECTION presented #CCR24 & published @NEJM.
- DB RCT of amino acid infusion vs placebo in n=3511 people undergoing cardiac surgery w/ bypass.
- Reduced incidence of AKI (26.9% vs 31.7% NNT=20) & need for RRT (1.4% vs 1.9% NNT=200)

Potential game changer!

🧵
1/
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I work in a busy CVICU & I often see AKI following cardiac surgery.

Despite risk stratification & hemodynamic optimization, AKI remains one of the most common complications after cardiac surgery with bypass.

Even a modest reduction in AKI/CRRT would be great for my patients.
2/ From Nature reviews nephrology  https://www.nature.com/articles/nrneph.2017.119
During cardiac surgery w/ bypass, renal blood flow (RBF) is reduced dramatically. This causes injury, especially in susceptible individuals.

But what if we could use physiology to protect the kidneys?

Renal blood vessels dilate after a high protein meal increasing RBF & GFR!
3/ https://www.jtcvs.org/article/S0022-5223(18)33243-4/fulltext
Read 11 tweets

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