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Less-Invasive Science: Not Always Better Science

One of the disturbing trends I have been observing in physiology is the tendency to move away from many of the gold standard, invasive measurements classically described in the scientific literature to non-invasive measures which may or may not accurately reflect the parameter of interest.

One of these non-invasive measurements (which is not used in any of the manuscripts on my desk) that has become the bane of my existence is to use the saturation of hemoglobin in arterial blood (SPO2) as a surrogate for the partial pressure of arterial blood (PO2). SPO2 is measured with a device called a pulse oximeter.

Pulse oximeter

 Figure 1: A fingertip pulse oximeter. This device indicates that this individuals arterial hemoglobin is 98 percent saturated and his heart rate is 73 beats/min.

In order to measure the PO2, you have to place a catheter (a piece of tubing) into an artery and draw blood from it. The PO2 is then measured by a device called a blood gas analyzer. You can click here for a post about the time I had a catheter placed in my brachial artery for this very purpose. Measuring PO2 is certainly much more invasive than measuring SPO2. 

What’s the big deal and what does it all mean? The PO2 is a reflection of the amount of oxygen dissolved in the blood (see Henry’s Law for you physiology lovers). Declines in PO2 indicate an inability of the lungs to properly transport oxygen from the alveoli to the capillaries. Why isn’t it enough to measure the SPO2? Because the PO2 and SPO2 are related like this:

odcurve.jpgFigure 2: The oxygen hemoglobin dissociation curve. 

Normally the PO2 in our arterial blood is about 100mmHg. At that PO2, hemoglobin is 100 percent saturated. But notice that at 90 mmHg, hemoglobin is still about 100 percent saturated. At 80 mmHg, hemoglobin is still about 95 percent saturated with oxygen. Indeed, to get to a point where hemoglobin is 80 percent saturated, you have to decrease PO2 to 50mmHg, or by half. That is a huge decline in PO2 to see a much smaller change in hemoglobin saturation.

The point is, declines in PO2 are what we use to measure impairments in the lung’s ability to oxygenate the blood and it takes a big change in PO2 to change SPO2 at all. When people use SPO2 to conclude that gas exchange in the lung is not impaired, they are just plain incorrect. You can’t make that conclusion when you cannot examine the entire range of possible PO2s. So why do some people try to get away with using it? I suspect because either investigators, or their IRBs, are reluctant to place arterial catheters in human research participants. 

The trend in human research over the last 10 years has been toward less and less invasive studies. The trend may have been driven by the small number of research deaths at the University of Rochester, Johns Hopkins University, University of California-Los Angeles, and the University of Pennsylvania that some argue could not be prevented by even the current amount of IRB oversight.

Still. In some ways demanding less non-invasive measures is good — it causes investigators to stop and consider the safety and comfort of their research participants. But in many ways this is bad. The literature is now chock full of studies where the results are based on a non-invasive, indirect measure and the conclusions must be interpreted with this in mind. I frequently wonder how much these studies really tell us. Especially when every one must be interpreted with a margarita rim’s worth of salt.

I also wonder about the ethics of performing studies using non-invasive, non-gold standard measurements. I understand the argument that patient comfort and safety should be considered. However, the safety record for many of the gold standard, invasive measurements is actually quite good. Because many of the non-invasive measures are less accurate, many of these studies require higher sample sizes. Is it ethical to study 100 participants, subjected to some physiological manipulation, with a non-invasive measurement when 6 participants with the invasive measurement would be sufficient?

Invasive physiological measurement techniques are not easy to use, but they offer important advantages over non-invasive measurements. We may be approaching a point in physiology where we need to seriously reconsider our decision not to use them.

*This blog post was originally published at On Becoming a Domestic and Laboratory Goddess*


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10 Responses to “Less-Invasive Science: Not Always Better Science”

  1. This post, from an unidentified author/research goddess, concerns me. Have you ever seen a patient lose a thumb from a misdirected radial artery stick that severed the vessel? Some doctors don’t adequately consider how much more invasive, painful and potentially dangerous is taking an arterial blood sample than a drawing venous blood.

  2. PalMD says:

    What was the point of that comment, ES? Seriously. Were grown up professionals here discussing professional issues. Are you saying art sticks are never justified, or are you upset that a good writer who isn’t an MD had the audacity to put a toe on our turf?

  3. This comment from a physician concerns me. Why would you draw venous blood if your intent was to measure an arterial blood gas? Have you ever seen someone intubated because some twit accidentally drew venous blood?

  4. shadowfax says:

    And for that matter, no, no I have never seen a thumb fall off from an arterial stick, either. That’s after ten years and thousands of ABGs and art lines. I suppose it could happen, but what with the dual blood supply of the hand it should be pretty damn rare, and by all indications it is.

    Now from my point of view *as a clinician* SpO2 is just fine for measuring oxygenation. You need to understand its limitations and you need to correlate it with an ABG if there’s reason. But it generally works fine for patient management. Maybe her research needs to be more rigorous — I don’t really know what her projects demand. but 95 times out of 100 you can follow the pulse ox and you’ll be fine.

  5. I was pointing to the risks of drawing an arterial blood gas (ABG). These should be weighed in the decision to do the procedure, or not.

  6. PalMD says:

    Risks and benefits of ANY intervention should be weighed. We all know that. But you chose to bring it up here, and some of us are wondering what the significance is.

    I’ve seen a nasty complication of a radial art stick in a thrombocytopenic cancer patient. That sucked. I’ve also done hundreds of them with no complications, gathering pretty important data.

    What would be interesting would be some studies of the utility of ABGs in various situations.

  7. Isis the Scientist says:

    I’m sorry, Elaine. I don’t understand it all. I wrote a post about how clinical scientists are using measurements that by their nature do not yield the information they claim they do. Why would you suggest a venous blood draw to measure arterial blood gases?if you have some risk/benefit insight I am not aware of, I am happy to entertain it.

  8. Isis the Scientist says:

    Pal’s commentary on risk is interesting. Most of what we know about risk is from the sickest patients who may have other confounders. We know little about risk in entirely healthy patients, er, participants.

  9. Of course you can’t learn about the oxygen saturation of arterial blood from a venous sample.

    My intention was to point out the relative risk of drawing an arterial specimen, which is significantly greater than that for ordinary (venous) phlebotomy. Some intern and resident doctors may not sufficiently weigh out that risk when they decide to draw an ABG for what might be academic reasons, or for convenience. (Sometimes the veins are “spent” and it’s relatively easy to find the pulse-artery.)

  10. I don’t know what you mean by “significantly”, although Susan Robb has a great article on communicating the risk of arterial and venous blood sampling. Thankfully there are IRBs to independently assess the risk of these “academic” samples.

    But, I guarantee this is not a phenomenon limited to early career physicians. I know plenty of senior physicians who do not always properly assess risk.

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