Nick Mark MD Profile picture
Apr 17 21 tweets 12 min read
At long last, here is part 5️⃣ in my animal #physiology in the ICU series #FOAMed

Case 1: You are called about a very high blood glucose (BG) value: 738 mg/dL (41 mM)!

The RN asks if you want to start an insulin drip. You say no, it’s totally normal because the patient is a:
1/
Answer: Hummingbird

Part of it's adaptation to energy intensive activities (flying, hovering) the Hummingbird maintains a very high blood glucose:
Fasting: >300 mg/dL
Fed: >700 mg/dL

That's right - a fasting hummingbird has a higher blood glucose than almost any fed mammal!
2/
The wrong answers: 🐑
A sheep’s normal blood glucose is 25-50 mg/dL! (among the lowest of all mammals!)

A sheep with a fasting blood glucose of 90 mg/dl would likely be diabetic!
publish.csiro.au/cp/AR9500182
3/
Nectivarous bats do indeed have very high blood glucose: up to ~540 mg/dL (30 mMol). High, but not quite as high as the hummingbird
Like the hummingbird this reflects the 🦇's high sugar diet (nectivarous = sugary) & a high energy needs in order to fly
ncbi.nlm.nih.gov/pmc/articles/P…
4/
Case 2:
Now that you are an expert in comparative blood glucose (BG) levels in different vertebrates, which animal do you think has the highest hemoglobin A1c (glycolated hemoglobin)?

(I've included some BG values as a reference)
5/
Answer: 🐪 Camel

Despite blood glucose levels that are similar to humans, camels have significantly higher glycolated hemoglobin (HbA1c). pubmed.ncbi.nlm.nih.gov/3568621/
Average human A1c 4.9%
Average camel A1c 5.5%

Why? We need to understand what HbA1c is...
6/
Glucose reacts spontaneously with amines on hemoglobin to form a hemoglobin adduct: HbA1c.
(This process is called non-enzymatic glycosylation btw)

The amount of HbA1c reflects two factors:
-how much glucose is present (average BG)
-how long RBCs last (RBC lifespan)
7/
Camels have *higher* HbA1c than us because their RBC lifespan is longer, presumably an adaptation to extreme dehydration. (Their RBCs are also elliptocytes)
Human RBCs last 100-120 days
Camel RBCs last up to 150 days

That's why a camel's HbA1c is higher than ours!
8/
Amazingly, the hummingbird has a fed BG of >700 mg/dL but a hemoglobin A1c that's lower than most humans (3.8%)!

In fact, most birds' HbA1c is <3%! The duck’s A1c is <1%

The reason is that birds have shorter RBC lifespans than humans: just 30-40 days. Hence a lower HbA1c!
9/
Clinical🥡
Like a hummingbird, people with increased RBC turn-over (e.g. hemolysis) can have low HbA1c despite elevated BG.
Be cautious if you see a sudden drop in HbA1c - it may represent either:
-a decrease in average BG *OR*
-a shorter RBC lifespan
ncbi.nlm.nih.gov/pmc/articles/P…
10/
Case #3:
The neuro-ICU calls about an abnormal EEG.

It shows slow waves consistent w/ sleep on the LEFT side & signs of wakefulness on the RIGHT!
The LEFT eye is open & tracks, the RIGHT is closed

You reassure them. This is normal.

In what situation would this ABNORMAL?
11/
Answer: humans* (I’ll explain the * later..)

Cetaceans & birds evolved unihemispheric slow wave sleep (USWS); literally half the 🧠 sleeps at a time!
Example: alternating slow wave sleep in Beluga 🐋 & 🐬. The L & R hemispheres “take turns” sleeping.
citeseerx.ist.psu.edu/viewdoc/downlo…
12/
Why the heck do they do this?

For cetaceans 🐳 unihemispheric slow wave sleep (USWS) enables them to remain awake enough to swim slowly and periodically surface to breath. (Pretty important stuff IMO)

Like us 🐬 sleep ~8 hours a day, but with only half their 🧠 at a time!
13/
Frigatebirds also sleep with half their 🧠 while crossing oceans.
To sleep, they go into shallow turns with the sleeping hemisphere down, so the awake side of the 🧠 can keep monitoring the environment. Then they switch 🧠 sides & turn the other way.
nature.com/articles/ncomm…
14/
Other birds use unihemispheric sleep as an anti-predation strategy

When groups of ducks sleep on a log, the🦆s on the ends use unihemispheric sleep to maintain outward vigilance
In the wild they swap positions, so each duck & 🧠 hemisphere gets sleep!
sciencedirect.com/science/articl…
15/
While humans don’t have USWS, we have something called the first night effect (FNE) where the depth of sleep is discrepant between 🧠 hemispheres when in an unfamiliar place.

Presumably like🦆s sleeping with one eye open, this is a defense mechanism
scientificamerican.com/article/sleepi…
16/
And in what unfamiliar place do people sleep especially poorly? the ICU!

Just look how disrupted the sleep is for these 5 patients in the ICU.
pubmed.ncbi.nlm.nih.gov/11179121/
17/
Interestingly, ICU patients exhibit discrepant sleep depth in each hemisphere & it's associated with failing SBTs!

Could an “attenuated form" of unihemispheric sleep contribute to worse ICU outcomes? Stay tuned; we need more research!
ncbi.nlm.nih.gov/pmc/articles/P…
18/
Clinical 🥡:
People in the ICU have sleep disruption due to FNE & maybe even an attenuated form of USWS!
RCTs have shown that a very simple intervention - ear plugs - can improve ICU sleep quality & reduce delirium (maybe even prevent mortality too!)
pubmed.ncbi.nlm.nih.gov/26741578/
19/
In part 5️⃣ of this physiology 🧵we learned:
-What animals have the highest & lowest blood glucose & the relationship between HbA1c & RBC lifespan
-How birds/cetaceans sleep w/ 1/2 their 🧠. People have a similar pattern of abnormal 🧠 activity & disrupted sleep in the ICU
20/
Hope you enjoyed part 5️⃣, you may also like the prior #tweetorials in this series. Highlights: how 🦒&🦕 regulate BP, why 🐘 can't get PTX, & how a 🐢 has a lactate >200
1️⃣
2️⃣
3️⃣
4️⃣
21/21

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More from @nickmmark

Apr 6
Here’s a fun ICU riddle - why do these two different patients both have funny colored effluent in their CRRT bags?

#FOAMed #FOAMcc

1/ ImageImage
One patient received methylene blue (causing green urine & effluent) and the other received hydroxycobalamin (causing dark red urine & effluent).

But what do these two cases have in common?

2/ ImageImageImageImage
The explanation is that both of these patients had vasopressor refractory shock.

Both methylene blue and hydrocobalamin can be used for refractory distributive shock.

Methylene blue
ncbi.nlm.nih.gov/pmc/articles/P…

Hydroxycobalamin
ncbi.nlm.nih.gov/pmc/articles/P…

But why?
3/
Read 15 tweets
Apr 1
Q: What do🐍 snakes have to do with ICU pharmacology?
A: A lot! We use 💊medications derived from snake venom every day in fact!

Buckle up for a fun 🧵of #UnusualDrugDiscovery & #HistoryOfMedicine about medications derived from from 🐍☠️snake venom! #FOAMed #FridayFun
1/
First a question: which of the following snake venoms have been used to develop medical therapies?

(don't worry we’ll go over the answer at the end)
2/
It was long known that workers in banana plantations would collapse due to low blood pressure if they were bitten by the Brazilian Arrow Headed Pit Viper Bothrops jararaca.

A Brazilian graduate student - Sergio Ferreira - thought this could be useful...
3/
Read 17 tweets
Mar 31
The #CultOfIvermectin has invented new excuses. Let’s address those:

“eVeRyOnE iN bRaZiL wAs AlReAdY TaKiNg IvErMeCtIn OTC!”

While Ivermectin use in the 30 days prior to screening wasn’t an absolute exclusion criteria, they appear to have de facto excluded those patients.
1/
It’s also worth wondering *why* someone who was taking ivermectin would enroll in a RCT of ivermectin vs placebo.

Also - if ivermectin prophylaxis was so effective - why would so many people on ivermectin be getting COVID in the first place?
2/
“tHeY dIdN’t UsE ZINC!!!!”

The original in vitro studies of ivermectin (Caly et al) didn’t use zinc.

None of the fraudulent “positive” RCTs of ivermectin combined it with zinc.

There has been *one* RCT of early zinc in COVID and it was *NEGATIVE*.
jamanetwork.com/journals/jaman…

3/
Read 5 tweets
Mar 30
The largest trial of #ivermectin in early #COVID is now published @NEJM & the results are *NEGATIVE*

#TOGETHER randomized n=1358 outpatients with COVID in 🇧🇷 to IVM vs placebo. No difference in hospitalizations, mechanical ventilation, or death.

nejm.org/doi/full/10.10…

A 🧵
1/
I’ve written about the #TOGETHER trial before (see my fluvoxamine 🧵below)

Briefly #TOGETHER is a large double blind multi-arm platform RCT. Pretty much the 1st 🥇 gold standard for high quality medical research.

2/
TOGETHER enrolled high risk people with COVID from 12 outpatient clinics in Brazil.

Patients could be enrolled up to 7 days after symptom onset (more on this later).

They were randomized to either placebo or to ivermectin 0.4mg/kg daily for 3 days. (Also more on dose later)
3/
Read 16 tweets
Mar 22
Remember that Vitamin C cures sepsis paper that could never be replicated in 9 RCTs?

Turns out there is a good reason why: it’s very likely fraudulent.

More brilliant statistical sleuthing by @K_Sheldrick.

kylesheldrick.blogspot.com/2022/03/eviden…
1/
To understand the proof you should read Dr Sheldricks post.

To summarize, he observed that in this non-randomized study the baseline characteristics of the pre & post intervention groups are far too perfectly matched. This perfect matching is unlikely to occur by chance.

2/
Specifically, you’d expect to see a range of p values for each baseline characteristic.

(This is especially true in a tiny trial with only n=47 patients)

Instead the range of p values for almost every variable was exactly 1.

This is *extremely* unlikely to occur by chance.
3/
Read 16 tweets
Mar 22
Here’s an idea for an ID board game: Guess Who Bacterial Pathogens

A: “is your bug rod shaped?”
B: “Yes”
A: “is your bug Gram Positive?”
B: “weakly”
A: “does your bug have catalase!?”
B: “Yes!”
A: “You’re Nocardia!!!”
A: “are you monotrichous?”
B: “yes”
A: “are you a facultative anaerobe?”
B: “yes!”
A: “are you Vibrio cholera?!?”
B: “yes!!!”
Ok I’ve decided to make this game in my garage.

Hopefully Hasbo won’t sue and my kids won’t be too mortally embarrassed to play.
Read 4 tweets

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