How much oxygen is enough?

ICU oxygen therapy

Only a few years ago, back when I was in medical school, I was taught that the goal of oxygen therapy should be to push saturation above 95%, and that anyone who comes in to hospital with a saturation below that should receive oxygen therapy (with the exception of people with chronic obstructive pulmonary disease, whose bodies have adjusted to lower oxygen levels). For those who aren’t used to the terminology, the definition of oxygen saturation is the proportion of haemoglobin molecules in the arteries that are “saturated” with oxygen. A normal level for a healthy person is usually 97% or higher.

In the last few years, however, there’s been a bit of a shift in thinking. It started with the realization that people with heart attacks who were treated oxygen didn’t do any better than those who weren’t. This is a good example of a medical reversal – it seemed logical to give oxygen to people with heart attacks, because a heart attack is a blockage in one of the arteries that supply the heart, which means that the heart muscle isn’t getting enough oxygen. By increasing the oxygen level in the blood stream, even if only a small amount of that oxygen is able to get past the blockage, it should do some good. At least that was the thinking.

Unfortunately, logic often turns out be wrong, at least in medicine. As it turns out, oxygen isn’t the utterly benign substance it’s often made out to be. First, oxygen causes blood vessels to constrict, so by pushing up the oxygen saturation you could actually be worsening the blockage. Second, oxygen has an unfortunate tendency to form reactive oxygen species (ROS), which can wreak all kinds of havoc in our cells. We’ve evolved mechanisms to deal with these, but when a part of the body is depleted of oxygen for a while, many of our defences to deal with ROS are diminshed. If you then push up the oxygen arriving in an area enormously, say an area of heart muscle that’s been deprived of oxygen for a while but that now once again has good flow thanks to an intervention to remove the blockage, you might actually increase the damage to that area.

Long story short, it turned out that oxygen wasn’t good to give to people with heart attacks. It might even be bad. Thankfully, that practice has now stopped in most places. The realization that oxygen might actually be harmful in certain situations has led to a change in thinking about oxygen therapy. No longer is it viewed uncritically as a universal panacea that can be doled out generously to everyone who comes in through the doors of the hospital. At least that’s the case in theory. In practice, lots of patients still get oxygen who don’t need it.

When hospital staff see a patient who is out of breath, they will often will shove a mask on their face and crank up the oxygen, regardless of what the patient’s saturation level is. On a superficial level, I guess this makes some sense. If someone’s breathless, they must need oxygen, right?

Wrong. There are many things that can cause a sensation of breathlessness, and a lack of oxygen is just one of them. Our bodies are actually not very good at detecting changes to the oxygen level in the blood stream. If a patient has a saturation of 90% and is out of breath, then the breathlessness is not caused by the somewhat low oxygen. I’ll repeat that sentence, just to be sure you didn’t miss it. If a patient has a saturation of 90% and is out of breath, then the breathlessness is not caused by the somewhat low oxygen. Our bodies are in fact amazingly poor at noticing the oxygen level in the blood stream, and don’t really start to pay attention until the oxygen saturation drops well below 80%.

For the most part, our breathing rate is determined by the level of carbon dioxide in the blood stream (or to be more technically correct, the pH), not by the level of oxygen. It is much more central to our continued life on this planet to keep carbon dioxide within strict limits than it is to make sure that oxygen is always kept at a very high level. That’s why people who engage in free diving will often intentionally hyperventilate before going under the water. The purpose isn’t to increase the oxygen content in the bloodstream (which is anyway already at 100% or thereabouts). It’s to decrease the carbon dioxide content, which will allow them to hold their breath longer, since it will take longer for the carbon dioxide levels to reach the point where their bodies force them to take a breath.

Ok, that was a rather long preamble, but I think I’ve set the stage sufficiently now. A study was published recently in the New England Journal of Medicine that sought to answer the question of what a reasonable level of oxygen supplementation is in patients who are having trouble oxygenating themselves.

This was a randomized trial carried out at 35 intensive care units (ICU’s) in seven different European countries. In order to be included in the trial, participants had to be over the age of 18 and have respiratory failure for which they were receiving at least ten liters of oxygen. Unusual causes of respiratory failure which require special treatment, such as carbon monoxide poisoning and cyanide poisoning, were excluded from the study.

Participants were randomized to an oxygen saturation target of either 90% or 96% (technically they were randomized to a PaO2 of 60 mmHg or 90 mmHg, but it’s roughly the same thing). The study wasn’t blinded, since treating a patient to a specific target requires knowing what their saturation is.

2,928 patients were included in the trial, a nice big number that should show a difference in mortality if there is one, especially considering that the mortality rate in patients treated in ICU’s is high.

The median actual saturation level in the low oxygen group ended up being 93%, while the median in the high oxygen group ended up being 96%. In other words, not a huge difference. Maybe the nurses felt squeamish about letting the oxygen sit at 90%, as my experience tells me they are wont to be. Obviously, this will make the study a little less useful than it could have been.

Let’s get to the results.

At the 90-day point after recruitment in to the study, 42,9% of patients in the low oxygen group had died, as compared with 42,4% in the high oxygen group. This absolute difference of 0,5% was nowhere close to being statistically significant (p-value 0,64).

When it comes to serious adverse events, 36,1% of participants in the low oxygen group suffered a serious adverse event, as compared with 38,1% in the high oxygen group. Again the difference was nowhere close to being statistically significant (p-value 0,24).

In other words, there was no meaningful difference between the groups in terms of either mortality or serious adverse events. This was a big, high quality study, and it is telling us that we don’t need to push patients’ oxygen saturation up over 95%. If the saturation happens to be at 93% then that’s just fine, no extra oxygen required.

If every nurse, nursing assistant, and doctor became aware of this, hospitals could probably cut down on oxygen use enormously, and since the perceived need for oxygen therapy is one of the main reasons for keeping patients in hospital rather than sending them home, it would frequently also allow for earlier discharge. Considering that hospitals in many western countries are constantly operating at 100% capacity (which was the case long before the advent of covid-19), this could free up a lot of hospital beds.

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36 thoughts on “How much oxygen is enough?”

  1. People in the ICU with a covid infection are often intubated for more oxygen supply.
    Apparently that might not be as useful as expected, if I read this article correctly, but what should or could be done then? They do appear out of breath, I understand. Just sending them home seems rather harsh.

    1. There are many ways of delivering oxygen. The first level is with nasal cannula, 2nd level then with a mask that goes over the face, and then there is something called “high-flow” (which you can have with or without rebreather mask), in which you can adjust the flow steadily upward if required.

      An 82-year old family member survived severe Covid-19 in January 2021 but at one point required delivery of 60 litres of oxygen per minute via high flow for about 36 hours (that’s 129 600 litres just for that day and a half).

      It is only when saturation is not maintained with these interventions that being put on a ventilator would be considered.The ventilators mechanically force oxygen into the lungs – often causing damage.

      In his case there were other younger people who would have had priority; luckily the 60 litres per minute via high flow and re-breather mask however got him through.

  2. Random thought: if it’s true that burning mostly glucose increases CO2 exhaled in breath vs burning mostly fat, and also that our bodies aren’t exquisitely sensitive to oxygen levels, might it also be true that a ketogenic diet could lead to lower oxygen saturation via a reduction in breath frequency/volume? And, going further out on a series of ever-smaller limbs, perhaps this could be advantageous, at least with regard to ROS?

    Lots of assumptions/guessing in there. It just occurred to me while reading your most recent email, and I thought I’d ask if you happened to have relevant data? Not that there’s any particular reason you should. But I didn’t find anything when searching…so why not ask? Feel free to ignore all of the above unless it actually interests you! I won’t be offended if there’s no reply.

    On another topic, I’m not absolutely convinced that heart attacks are synonymous with localized oxygen depletion in the first place, but that’s a separate rabbit hole.

    Regardless, thanks for the thought-provoking emails/posts.

  3. I’ve seen reports of covid patients talking lucidly with 80% O2 sat.

    I’d surmise that their CO2 was close to normal limits.

    How do you test for hypercapnia? ABGs, or is that obsolete?

  4. I read your review of the O2 study. Thank you for that insight. During the review you described that CO2 regulated our breathing. How does that mechanism work? Are there limits to CO2 i.e. What happens when CO2 gets low? What happens when CO2 gets high? Is there any study that shows these limits?

    1. CO2 dissolved in blood forms carbonic acid, which lowers pH. The breathing centre in the brain is sensitive to changes in pH. When pH drops, the breathing rate increases, and when pH rises, breathing slows down.

      1. I used to work in a chemical plant where CO2 and N2 were used. We always did tests to monitor for the presence of these. However, one incident with N2 comes to mind. An engineer leaned into a tank manway and collapsed immediately. He had completely stopped breathing but resumed because he had managed to collapse in fresh air. It was explained at future safety meetings that the brain automatically stopped the persons breathing.
        We measured the atmosphere for O2, CO2 and N2 but the device alarmed at numbers that now that I think of it may have been arbitrary. What limit causes the cessation of breathing or causes hyperventilation?

      2. I might be just a little confused. Maybe there’s a typo somewhere. Is this bit written backwards?
        Sebastian Rushworth, M.D. says:
        14 April, 2021 at 21:27
        CO2 dissolved in blood forms carbonic acid, which lowers pH. The breathing centre in the brain is sensitive to changes in pH. When pH drops, the breathing rate increases, and when pH rises, breathing slows down.

  5. Sebastian, as usual you are a fresh breath of medical wind….I wrote a chapter a few years ago about the dangerous side of oxygen
    But the real trick and the future of medicine is in combining hydrogen gas with oxygen…….70 years ago the deepest sea divers at 700 meters would breathe 96% hydrogen and only 4% oxygen…only way to survive down there…..whether a person is in ICU dying, or one is facing a chronic disease or just life extension hydrogen makes life easier because like in hydrogen energy, the by product is water….meaning hydrogen converts the worst oxidents into water……so in the heart attack scenerio you mentioned would be safe to give more oxygen as long as you give hydrogen. The hydrogen inhalers I promote generate 66% H and 33% O……..I just published about this last week…

  6. thank you so much for the information.
    I live at 6300 feet and am 80 yrs old. My oxygenation is 95 during the day and per my apple watch is 90 at night. My aerobic capacity is approximately double that of an average 80 yr old. i dont eat carbohydrates. I am less worried now about the night reading of 90…??

  7. Interesting as usual. Just one question….when you use numbers, why do you use commas as decimal points instead of periods. I don’t know anyone else who does this. Is it a Swedish thing?

      1. Bev: It’s a European thing. With numbers, commas in place of decimal points, and decimal points in place of commas. Strange but true.

  8. Thank you. Another interesting article and discussion. One of my interests of free flow of blood cells throughout the body, capillary size, vascular constriction and dilation, avoidance of clotting, rouleaux and agglutination. You make a good point that effects in the body from certain treatments may be counter-intuitive.

    1. Last year I had 10 sessions in a hyperbaric oxygen chamber. I felt no benefit. I asked the staff now it worked but they actually didn’t seem to have a clear explanation. I have HCOM but most of the clients has MS and found it beneficial.

      1. Isabel: “Tripping over the Truth,” by Travis Christofferson has some interesting information about HBOT in cancer therapy.

  9. Dr. Rushworth,

    I see a lot of people comparing Sweden to other nordic countries as far as covid deaths go. Does Sweden have a lot more dark-complected immigrants than other nordic countries? If so, then I would expect their vitamin D levels to be lower than the light-complected people with a higher tendency towards compromised immune systems in winter. (I’m sorry that discussing skin complexions is a political hot topic, but it’s necessary to do so because of public health concerns.) And I have heard that Sweden has had mild flu years recently compared with other nordic countries. Please point me to where you have written about this.

    Thank you.

  10. A few months back a morbidly obese friend in his 40s was admitted to hospital with low blood oxygen saturation levels. He was given oxygen therapy and it raised his oxygen saturation levels. They then took him off oxygen and his saturation level began to drop. Even so he told his wife he felt fine and wanted to go home. However, the doctors decided to intubate him. He died within hours. I wonder if he would still be with us had he been sent home. 

  11. I have COPD and when in hospital contracted a lung infection. Was given oxygen through nose tubes. I found that very helpful and reassuring.
    Surely by helping me breathe, the treatment was helping me get rid of carbon dioxide.
    I was there for a broken ankle and had no arteries or heart problems. I had been vegetarian for a few years at the time but that was when I became a RECOVERING alcoholic.

  12. I see an earlier commenter has already suggested the use of nitrogen with oxygen. If the the purpose of hypoxia is merely to shed carbon dioxide then hypothetically Argon would be a suitable gas. I was only able to find one article by Zhou testing a high argon low oxygen mix in vivo and in vitro in oxygen deprived rat brain cells with very promising results

    1. My guess, without in any way being an expert on the technology, would be that it is thanks to increased production of reactive oxygen species, which are a central mechanism by which our immune cells destroy bacteria.

  13. I recently came across an article that claimed the Sanger method for DNA sequencing was more accurate than PCR tests. The author suggested that to confirm PCR tests the Sanger method should be used. Is this an accurate claim? If so what would it reveal? Is it used for that purpose?
    There are a host of questions but I will not try to list everyone.
    Is their an article in this for you?

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