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

Jun 1
Well designed RCT shows patients randomized to an exercise program had substantially improved survival after adjuvant chemotherapy for colon cancer.
- 5 yr disease-free survival 80.3% vs
73.9% (HR 0.72)
- 8 yr overall survival 90.3% vs 83.2% (HR 0.63)

This is groundbreaking!
1/ Image
Some deets on the CHALLENGE trial

A 55 center trial done over 15 years (2009-2024) that randomized n=889 people with resected colon cancer after adjuvant chemotherapy to either:
- participate in a structured exercise program
- or to receive health-education materials alone

2/
The intervention was pretty comprehensive:
Personal activity consultant (PACs) - essentially trainers - got to know the participant 1:1, introduced them to the gym and came up with personalized activity goals
Regular every 2 week sessions helped participants reach the goals

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Read 16 tweets
May 18
Tragic news today about former president Biden's prostate cancer diagnosis. I wish him well.

As someone who follows presidential health reporting, I noticed something odd: unlike his predecessors, Biden's physician's never reported PSA.

How to interpret this absence? A🧵
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There are two possibilities:
1️⃣ Biden’s PSA was never checked
2️⃣ Biden’s PSA was checked but it wasn't reported

Strictly speaking, not checking PSA could be a medically correct option. Whether or not to test PSA is a complex question and is not the topic of this thread.

2/
Like many VIPs, presidents tend to have excessive testing that is not always strictly evidence-based.

For example, Bush 43 had an exercise treadmill test and a TB test for no apparent reason.

3/ Image
Read 13 tweets
May 4
In honor of #MayThe4thBeWithYou let's consider the most difficult airways in the Star Wars universe:

1. Darth Vader
Species: human
Vader presents several challenges: Vent dependent at baseline, airway burns from Mustafar, limited neck mobility.
Discuss GOC before saving him Image
2. Fodesinbeed Annodue
Species: Trog
All airways require teamwork, but intubating Fodesinbeed Annodue's two heads really will require two operators.
Consider double simultaneous awake fiberoptic intubation
Be sure to consent both heads. Image
You will never find a more wretched hive of scum & challenging airways than Mos Eisley (except maybe at Jabba's)

3.Greedo
Species: Rodian
Micrognathia, posterior airway, no nasal intubation, green skin so no pulse ox
Approach: VL + bronchoscope. Intubate quickly (shoot first) Image
Read 23 tweets
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.

🧵

1/ Image
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

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