Nick Mark MD Profile picture
Nov 1, 2022 15 tweets 6 min read Read on X
Here’s another pulmonary physiology question that *everyone* who gives O2 to patients ought to know:

What is the primary mechanism by which supplemental oxygen can increase PaCO2 in someone with severe COPD?

1/
This is a hard question! You probably learned that "its bad to give someone with COPD ‘too much’ O2 because they might stop breathing”

Turns out hypoxic respiratory drive causing apnea is a MYTH..but there is an important truth here:

A🧵on Oxygen induced hypercapnia!
2/ Image
Every myth has a little kernel of truth:

In the 80s it was shown that giving people with severe COPD (GOLD stage IV) high flow oxygen (15 lpm) made their minute ventilation (VE) drop then return (almost) to normal, but PaCO2 rose significantly.

Why?

ncbi.nlm.nih.gov/pmc/articles/P…
3/ Image
Initially it was theorized that this increase in PaCO2 was due to loss of hypoxic respiratory drive. This is probably the story you were told in medical or nursing school.

The only problem is this isn't true!

👀 If we look close there are a few problems with this theory...
4/ Image
PaCO2 should be inversely proportional to minute ventilation. If you double you VE you should (roughly) half your PaCO2.

But that's NOT what happened!

Ultimately VE fell by only ~5% (from 10 to 9.5 l/min) but PaCO2 increased by 35% (from 63 to 85 mmHg)!

What did we miss?
5/ Image
Clearly the 5% decrease in minute ventilation (VE) can't possibly explain a 35% rise in PaCO2!

If we do the math, the change in minute ventilation can explain at most 4.8 mmHg of the ~22 mmHg rise in PaCO2.

MYTH busted! This must be more than just a change in ventilation!
6/ Image
It turns out that in addition to carrying oxygen, Hemoglobin also carries carbon dioxide.

It does this 3 ways:
1. Dissolved as CO2 (10%)
2. Bound to hemoglobin as HbCO2 (30%)
3. Buffered as bicarbonate (60% of CO2)
CO2 + H2O --> H2CO3 --> H+ + HCO3-

7/ Image
Hemoglobin picks up CO2 in the tissues (where it is unloading O2), and unloads CO2 in the lungs (where it is picking up O2).

For this reason, dexoygenated Hb is better at carrying CO2 & oxygenated Hb is not good at carrying CO2.
8/ Image
For this reason, administration of high concentrations of Oxygen can "push" CO2 off of hemoglobin and into solution, increased PaCO2.

That's he Haldane Effect - the phenomenon where binding of oxygen to hemoglobin promotes the release of carbon dioxide (raising PaCO2).

9/ Image
Although the Haldane effect is very real it's effect isn't huge; it increases the PaCO2 by about 10%.

This means Haldane can only explain about 6 mmHg of the 22 mmHg increase in PaCO2! This is an important contributor but it isn't explaining most of the rise in CO2.

10/
Sidebar: this doesn't mean the Haldane effect is inconsequential.
If my PaCO2 rose from 40 to 44 mmhg I probably wouldn't notice.
But in someone who chronically retains CO2 this could be a big issue. Going from a PaCO2 of 80 to 88 mmHg could be enough to cause CO2 narcosis...
11/
So what causes O2 induced hypercapnea then?

Recall that different lung areas get differential ventilation. (This is especially true in people with parenchymal disease like COPD)

Fortunately the lung regulates blood flow, decreasing perfusion (Q) to poorly ventilated areas.
12/ Image
But what if we provide 'too much' supplemental oxygen?

This can cause the loss of hypoxic vasoconstriction increasing perfusion to the poorly ventilated alveoli.

(Maybe a better term would be HYPERoxic vasodilation! h/t @sargsyanz for suggesting this perfect term!)

13/ Image
This - the loss of hypoxic vasoconstriction to poorly ventilated lung areas - turns out to be the primary reason for oxygen induced hypercapnea.

ncbi.nlm.nih.gov/pmc/articles/P…

14/ Image
Bottom line:
Giving supplemental O2 to someone w/ severe COPD really *can* cause oxygen induced hypercapnea.

It occurs for three reasons:
1. Loss of hypoxic vasoconstriction --> worse V/Q matching (major reason)
2. Haldane effect
3. Decreased respiratory drive

15/15 ImageImage

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More from @nickmmark

Mar 9
Every year, there is a predictable spike in fatal car accidents, medical errors, & heart attacks.

It’s estimated that there are thousands of excess deaths, a 1% increase in energy consumption, & billions of dollars in lost GDP.

The cause? Daylight savings transitions.

🧵

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Earth's axis of rotation and orbital axis are not precisely aligned. The 23.5 degree difference - 'axis tilt' - gives us our seasons and a noticeable difference in day length over the course of the year.

2/
For millennia this seasonal variation was an accepted fact of life.

In 1895, George Hudson, a New Zealand entomologist, was annoyed that less afternoon light meant less time for bug collecting.

He realized that clocks could be adjusted seasonally to align with daylight.

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Read 27 tweets
Feb 14
Musk is so stupid. Exhibit #10544

There aren’t thousands of 150 year olds getting paid social security. There are null values in a database he doesn’t understand how to read… Image
When unidentified people get admitted to the hospital the default DOB is 1/1/1900. The EHR shows their age as 125 yo.

But *almost* everyone is smart enough to understand this is just a result of missing data… Image
Nice summary here debunking Elon’s “duplicate SSNs” claim.

thedatageneralist.com/elon-musk-does…
Read 4 tweets
Feb 8
Important point re indirects:

Unlike other Trump moves, this is arguably GOOD news for researchers!

If the NIH budget is unchanged (a big if), this allocates more money to researchers; if you go from an indirect of 75% to 15% it means you can fund 3 grants instead of 2.
Some context:

Between 1947 and 1965, indirect rates ranged from 8% to 25% of total direct costs. In 1965, Congress removed most caps. Since then indirects have steadily risen.

2/
A lot of indirects go to thing like depreciation of facilities not paying salaries of support staff.

This accounting can be a little misleading.

If donors build a new $400m building, the institution can depreciate it & “lose” $20m/year over 20 years. Indirects pay this.

3/
Read 4 tweets
Jan 22
🚨Apparently all NIH Study Sections have been suspended indefinitely.

For those who don’t know, this means there won’t be any review of grants submitted to NIH

Depending on how long this goes on for, this could lead to an interruption in billions in research funding.
With a budget of ~$47.4B, the NIH is by far the biggest supporter of biomedical research worldwide.

Grants are reviewed periodically by committees of experts outside of the NIH.

When these study sections are cancelled, it prevents grants from being reviewed & funded.
Hopefully this interruption will be brief (days)

A longer interruption in study sections (months) will inevitably cause an interruption in grant funding. This means labs shutdown, researchers furloughed/fired, & clinical trials suspended. This will harm progress & patients!
Read 8 tweets
Oct 13, 2024
#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, 2024
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

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