CO Poisoning Question

[Duke Dive Medicine]

Great conversation all! A few thoughts:

The mechanism of CO removal via hyperbaric oxygen is the diffusion gradient. That is, by greatly increasing the partial pressure of O2 in the lungs, the CO will be more likely to diffuse into them.

As @Zef alluded to (great posts BTW), CO also binds to myoglobin, meaning that the muscles act as a carbon monoxide sink. Also, carbon monoxide does not just bind to hemoglobin and myoglobin, it binds to heme proteins in the mitochondria (the metabolic organ of cells) and interferes with cellular metabolism. This is why carboxyhemoglobin level is not an accurate predictor of outcomes. A patient can come in with a high COHb level with a short exposure and be just fine. Another patient who is exposed to lower concentrations of CO but for a longer time may come in with a relatively low COHb level but with enough cellular damage that the incident is not survivable.

The classic cherry red lips and nail beds sign is largely a myth.

Best regards,
DDM

 

[Zef]

(Edited to state that this was typed and posted at the same time as Duke Dive Medicine's post above)

Here is an interesting resource on transport and exchange of gas between the lungs, blood, and tissues:

22.5 Transport of Gases – Anatomy and Physiology

It does not however explain how CO is dissociated from hemoglobin...unless it follows a similar path as O2 and follows a pressure gradient causing it to diffuse into the body's tissues where exogenous CO does not normally serve a metabolic function, and is then picked back up by the blood as the PP of CO becomes lower in the blood and higher in the tissue. I assume only a small amount of CO is exhaled due to its strong affinity for the heme portion of the erythrocytes and for the most part the majority of the molecules of CO just continue to recirculate throughout the body occupying the hemoglobin and preventing molecules of O2 from attaching and efficiently circulating until the body can naturally break down the CO via oxidative metabolism in the mitochondria of tissue cells.

I may be mistaken but I think the reason why hyberparic treatment with high concentrations of O2 speeds up the the process of the eliminating CO from the blood/body is because the higher PP O2 caused by increasing the atmospheric pressure has an effect of increasing cellular metabolism...this increase could facilitate the transport of CO into the mitochondria where it is metabolized and then filtered from the blood as a component waste product.

A couple of other resources:

Carbon monoxide and mitochondria—modulation of cell metabolism, redox response and cell death

The independent effects of atmospheric pressure and oxygen partial pressure on gas exchange of the chicken embryo - ScienceDirect

-Z

 

[Duke Dive Medicine]

(Edited to state that this was typed and posted at the same time as Duke Dive Medicine's post above)

Here is an interesting resource on transport and exchange of gas between the lungs, blood, and tissues:

22.5 Transport of Gases – Anatomy and Physiology

It does not however explain how CO is dissociated from hemoglobin...unless it follows a similar path as O2 and follows a pressure gradient causing it to diffuse into the body's tissues where exogenous CO does not normally serve a metabolic function, and is then picked back up by the blood as the PP of CO becomes lower in the blood and higher in the tissue. I assume only a small amount of CO is exhaled due to its strong affinity for the heme portion of the erythrocytes and for the most part the majority of the molecules of CO just continue to recirculate throughout the body occupying the hemoglobin and preventing molecules of O2 from attaching and efficiently circulating until the body can naturally break down the CO via oxidative metabolism in the mitochondria of tissue cells.

I may be mistaken but I think the reason why hyberparic treatment with high concentrations of O2 speeds up the the process of the eliminating CO from the blood/body is because the higher PP O2 caused by increasing the atmospheric pressure has an effect of increasing cellular metabolism...this increase could facilitate the transport of CO into the mitochondria where it is metabolized and then filtered from the blood as a component waste product.

A couple of other resources:

Carbon monoxide and mitochondria—modulation of cell metabolism, redox response and cell death

The independent effects of atmospheric pressure and oxygen partial pressure on gas exchange of the chicken embryo - ScienceDirect

-Z

It's a fine point, but the idea behind hyperbaric oxygen therapy is to get the exogenous CO away from the mitochondria, rather than send it there. If the mitochondria bind it in excess, it interferes with cellular metabolism.

Best regards,
DDM

 

[Akimbo]

A patient can come in with a high COHb level with a short exposure and be just fine. Another patient who is exposed to lower concentrations of CO but for a longer time may come in with a relatively low COHb level but with enough cellular damage that the incident is not survivable.

You've opened the gates now!

1. Are standard lab tests performed before releasing CO victims from the hospital?
2. Do many survivors suffer long term damage?
3. Does Duke always treat CO poisoning in a chamber? If not, what guides the decision?
4. Does Duke treat many CO victims?
5. Are they mostly accidental or suicide attempts? Hopefully, inexpensive CO alarms is reducing the accidents.

The classic cherry red lips and nail beds sign is largely a myth.

Interesting. Is that related to the severity of the CO poisoning or human variability?

 

[Zef]

It's a fine point, but the idea behind hyperbaric oxygen therapy is to get the exogenous CO away from the mitochondria, rather than send it there. If the mitochondria bind it in excess, it interferes with cellular metabolism.

Best regards,
DDM

So basically increase the dissociation curve by flooding the body with lots of O2 at an increased PP, making it more likely that increased amounts of CO would be exchanged due to the disproportionate gradient between the CO in the blood and O2 in the alveoli?

I am guessing that the increased affinity of CO for hemoglobin compared to O2 is why the timeframe to eliminate the CO from the body is significantly reduced but not altogether eliminated. Is that correct?

-Z

 

[Duke Dive Medicine]

You've opened the gates now!

1. Are standard lab tests performed before releasing CO victims from the hospital?
2. Do many survivors suffer long term damage?
3. Does Duke always treat CO poisoning in a chamber? If not, what guides the decision?
4. Does Duke treat many CO victims?
5. Are they mostly accidental or suicide attempts? Hopefully, inexpensive CO alarms is reducing the accidents.

Interesting. Is that related to the severity of the CO poisoning or human variability?

Haha no worries!
1. Carboxyhemoglobin level is pretty standard on admission, along with arterial blood gases. Other labs are based on patient presentation and symptoms.
2. Some do, not sure what the criteria for "many" is. It depends on the level of damage.
3. Not always. Criteria, interpreted somewhat liberally, are any sign of cardiac damage (elevated enzymes, ECG changes, symptoms), neurological symptoms/periods of unconsciousness, and/or carboxyhemoglobin level greater than 20% at any point in the incident (we do back-calculations based on predicted half-life).
4. It's largely seasonal. We see more in the winter due to home heating incidents, and during power outages when people use generators either inside the house or too close to the eaves on the outside.
5. Mostly accidental, but some suicide attempts. We'd love it if more people would spread the word about CO detectors!

Best regards,
DDM

 

[Duke Dive Medicine]

So basically increase the dissociation curve by flooding the body with lots of O2 at an increased PP, making it more likely that increased amounts of CO would be exchanged due to the disproportionate gradient between the CO in the blood and O2 in the alveoli?

I am guessing that the increased affinity of CO for hemoglobin compared to O2 is why the timeframe to eliminate the CO from the body is significantly reduced but not altogether eliminated. Is that correct?

-Z

Yes to both. I'll reproduce the relevant section from the Hyperbaric Oxygen Therapy Indications (13th edition, I still need to order #14!) from the UHMS. This is from the section on carbon monoxide poisoning by Lindell Weaver, MD of Intermountain Health in Utah.

"Breathing oxygen hastens the removal of COHb. The half-life of COHb in adults breathing air at sea level is approximately five to six hours (22), but reduced alveolar ventilation would lengthen the half-life. With administration of normobaric oxygen, the COHb half-life is 74 +- 25 minutes (mean +- 1 SD). (23) Hyperbaric oxygen accelerates COHb dissociation compared to breathing pure oxygen at sea-level pressure. (22, 24, 65-67) Additionally, HBO2, but not ambient pressure oxygen treatment, has several actions that have been demonstrated in animal models to be beneficial in ameliorating CNS injuries. These include an improvement in mitochondrial oxidative processes, (50,68), inhibition of lipid peroxidation, (69) impairment of leukocyte adhesion to injured microvasculature, (70) and reduction of brain inflammation caused by the CO-induced adduct formation of myelin basic protein. (71)"

Weaver L (2014) Carbon Monoxide Poisoning, in Undersea and Hyperbaric Medical Society Hyperbaric Oxygen Therapy Indications, 13th edition, Best Publishing (Fl)

 

[DandyDon]

Such interesting posts. I may not understand it all, but some.

A patient can come in with a high COHb level with a short exposure and be just fine. Another patient who is exposed to lower concentrations of CO but for a longer time may come in with a relatively low COHb level but with enough cellular damage that the incident is not survivable.

Now that's surprising to read. It is a wicked threat.

The classic cherry red lips and nail beds sign is largely a myth.

People keep clinging to that idea don't they, but when I was a kid it was all we had before technology bloomed.

Are they mostly accidental or suicide attempts? Hopefully, inexpensive CO alarms is reducing the accidents.

You know, with catalytic converters, CO suicides are less common. My barber's mom went out that way years ago, but she tells me there have been at least two attempts in my farmtown of 2,000 that failed.

CO alarms for the homes are indeed getting cheaper, but too many still don't have them. I've given a few to my daughter but she keeps losing them. They live in an all electric home, but do have a connected garage and a fireplace, both serious threats.

We'd love it if more people would spread the word about CO detectors!

There's not much you can do when they hear and ignore.

 

[Duke Dive Medicine]

You know, with catalytic converters, CO suicides are less common. My barber's mom went out that way years ago, but she tells me there have been at least two attempts in my farmtown of 2,000 that failed.

Very true, it's harder now than it was before catalytic converters, but it still happens. Years ago we had back-to-back cases involving vehicles with pushbutton starts that were inadvertently left running in garages. I had a conversation with the NHTSB about it.

 

[Zef]

Yes to both. I'll reproduce the relevant section from the Hyperbaric Oxygen Therapy Indications (13th edition, I still need to order #14!) from the UHMS. This is from the section on carbon monoxide poisoning by Lindell Weaver, MD of Intermountain Health in Utah.

"Breathing oxygen hastens the removal of COHb. The half-life of COHb in adults breathing air at sea level is approximately five to six hours (22), but reduced alveolar ventilation would lengthen the half-life. With administration of normobaric oxygen, the COHb half-life is 74 +- 25 minutes (mean +- 1 SD). (23) Hyperbaric oxygen accelerates COHb dissociation compared to breathing pure oxygen at sea-level pressure. (22, 24, 65-67) Additionally, HBO2, but not ambient pressure oxygen treatment, has several actions that have been demonstrated in animal models to be beneficial in ameliorating CNS injuries. These include an improvement in mitochondrial oxidative processes, (50,68), inhibition of lipid peroxidation, (69) impairment of leukocyte adhesion to injured microvasculature, (70) and reduction of brain inflammation caused by the CO-induced adduct formation of myelin basic protein. (71)"

Weaver L (2014) Carbon Monoxide Poisoning, in Undersea and Hyperbaric Medical Society Hyperbaric Oxygen Therapy Indications, 13th edition, Best Publishing (Fl)

The passage you quoted is great and supports what I have read but it does not clearly discuss the mechanism of dissociating CO from the blood....

...My understanding is that each erythrocyte has 4 heme receptor sites that can bond with (in the context of this discussion) O2 or CO. The affinity of CO to heme is with regards to the chemical bond it makes compared to the chemical bond O2 makes. Is it correct that inundating the body with O2 at higher PP results in it being more likely that all 4 receptors of an available erythrocyte will be occupied by O2 thereby keeping CO from having a place to bond?

If the above notion is true, then is it a misnomer that CO "displaces" O2 in the blood? Or does the displacement something that is realized in erythrocytes that do not have all 4 sites bonded with O2? I know that CO on one site affects the propensity of the other sites to bond with molecules of CO and O2, but I just wanted to drill into the actual mechanism of how the CO is displaced from the red blood cells....I haven't found much info that delves into the chemical of physical properties of the transport/dissociation mechanism...lots of info out there about how CO2 is transported and disassociated/removed from the blood/body, but other than various sources repeating to one degree or another what you quoted, I can't seem to find much on the actual mechanism of what is happening at the molecular level/cellular level for CO.

Thanks for the feedback and clarifications you have provided.

-Z