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Hyperbaric Oxygen for Autism? Not so fast PDF Print E-mail
Swift
Written by Joe Albietz   

Treating children with autism can be remarkably frustrating for everyone involved. Its impact on children and their families is life-altering, its cause is unclear, and its therapies are minimally effective at best and costly, dangerous, or exploitative at worst. It is easy to understand how studies which may show a benefit for afflicted children will rapidly draw attention and proponents, regardless of its plausibility.

One such therapy is hyperbaric oxygen (HBO) treatment. There have been some reports that a minority of children with autism have abnormal blood vessels feeding various areas of their brain, potentially limiting the amount of oxygen available to that area of the brain and possibly causing dysfunction of the affected neurons. Notice the hedge terms I use; the evidence is quite weak at this point. Regardless, if this is true, one might expect better functioning of the oxygen deficient neurons with more oxygen delivered. Anecdotes exist describing such a response, but until recently no well designed studies had evaluated the claim.

Enter a recent study published in BioMed Central Pediatrics by Rossignol and colleagues "Hyperbaric treatment for children with autism: a multicenter, randomized, double-blind, controlled trial." (1) Rossignol randomized 62 children with autism into two groups, one of which would receive two 1-hour treatments of HBO per day, 5 days per week for 4 weeks, and a control group subjected to the same environment for the same spans of time with a very brief and minimal pressure change to blind the participants to their group.

Children's outcomes were followed using three behavior scores generated by questionnaires completed by the parents, one of which was also independently completed by the primary care physicians of the children. The study reports significant improvement in the autistic behaviors of children treated with HBO therapy including better eye contact, improved verbal skills, receptive language, reduced stereotypic behavior, reduced irritability, and globally improved function, among others. The authors reported 9/30 children in the treatment group "much or very much improved," vs 2/26 of the controls, and 24/30 in treatment group had any degree of improvement vs 10/26 controls.

On its face, this is a very interesting and potentially exciting finding. A double blinded, randomized, controlled trial with a small but sufficient number of patients studied to make valid statements about the outcome. This is, in fact, exactly what we proponents of evidence and science based medicine have been asking for, and what a relief it would be to have an effective tool to improve the functioning of autistic children. Why then am I not overly enthusiastic about the results?

The first serious concern is the design and execution of the study, which Dr Novella addressed in his blog (2). The numbers involved were not large, the blinding is questionable, there was no follow up beyond the study period, and there may be some conflict of interest for Dr Rossignol.

My second concern is that of biological plausibility. There are a lot of claims and hand waving in the discussion of the article explaining how HBO therapy may decrease inflammation, improve oxygen delivery, prevent brain ischemia, etc. However, most of the claims bottleneck down to one common pathway: more oxygen in the bloodstream delivered to the brain. Instead of getting mired down in detailed discussions of studies which are tangentially topical at best, let's examine HBO's ability to increase blood oxygen content.

HBO can without a doubt increase the amount of oxygen in your blood, and the amount of the increase is directly related to the concentration of oxygen being breathed (room air is 20.9%), and the amount of pressure to which you are subjected. The pressures and concentrations used in the study, 24% and 1.3 atm, are quite low, and we can easily calculate how much extra oxygen patients received during the trial (3).

If we make the reasonable assumption that the children had normal levels of hemoglobin in their blood and live near sea level, then the controls had ~20.7 ml of oxygen in each 100ml of blood, 98.6% of which is bound to hemoglobin, 1.4% dissolved within the blood.

The children given HBO on the other hand would have the underwhelming increase in total blood oxygen content to 21.4 ml of oxygen per 100 ml of blood (this assumes fully saturated hemoglobin). That's a 3% increase in blood oxygen content over baseline that will be lost within seconds of leaving the HBO chamber. Let me put this minimal increase into perspective.

Given the normal range of hemoglobin for humans (~12-16 gm/dl of blood), healthy people have a blood oxygen content ranging from 17 - 22.5 ml of oxygen per 100 ml of blood. It's therefore entirely normal for some healthy people to have 32% more oxygen in their blood than others, which is an order of magnitude greater variance than the 3% increase achieved by HBO.

You can look at this another way. In order for a person with a resting heart rate of 80 to increase their oxygen delivery by 3% (all other things being equal), they could increase their heart rate to 82.4 beats per minute. Contrast that to the fact most people can double and athletes can more than triple their oxygen delivery by this mechanism. A 3% increase is hardly a taxing demand even in critically ill people.

How about another perspective? Living in Denver, I can increase my blood content of oxygen (or that of an autistic child) by almost exactly 3% by descending from Denver's altitude of 5280 ft down to sea level.

Finally, I can increase an average person's blood oxygen content by 3% by providing them with 30% oxygen, which is easily delivered, portable, and can even be worn 24/7.

Given all of the compensatory mechanisms your body has in place to ensure that an adequate amount of oxygen gets to your various organs and tissues, each having wildly different and variable oxygen needs, a 3% increase in blood oxygen content is physiologically insignificant except in the most extreme of conditions. As the hinge upon which most of Rossignol's mechanisms of action swing, the scant increase in blood oxygen provided by HBO is implausible at best.

My other concern with this study is the author's poor handling of the article's discussion. Read without an eye to their citations the discussion flows well, however, most of the assertions made by the authors are supported with the weakest of evidence.

Rossignol asserts that children with autism have a high level of baseline inflammation and that hyperbaric oxygen therapy "possesses strong anti-inflammatory properties." That autistic children have inflammation as a matter of course is contentious, and I'll not cover it here. However, that hyperbaric oxygen therapy can reduce inflammation is a gross misinterpretation of the literature. Of the three studies cited to support their assertion, one concerned traumatic wounds and two evaluated it as a treatment for forms of colitis. All three of these scenarios have significant infectious and ischemic components in superficial areas which would indeed be treated by HBO therapy, and could plausibly reduce inflammation. In the absence of infection or ischemia accessible to HBO treatment, there is no reason to suspect HBO therapy would reduce inflammation, much less that it inherently has "strong anti-inflammatory properties."

Rossignol also ignores the copious body of literature in cellular, animal model, and human studies which establishes that hyperoxia (high levels of oxygen) is one of the more efficient methods of inducing inflammation and oxidative injury, not abating it. There is therefore scant evidence to support HBO therapy's ability to reduce inflammation, and ample evidence to be concerned about the induction of inflammation.

To support his hypothesis that HBO therapy improves cerebral blood flow, Rossignol cites just two articles. The first article is written by Rossignol himself, and is not in fact a research article at all but in fact an opinion piece wherein Rossignol describes the use of HBO therapy in autism (based upon what evidence? This was the first trial of any potential value!). The second citation was also not a peer-reviewed study but instead an author's reply to an actual study published in the Lancet that examined the effect of HBO on children with cerebral palsy and found no effect. Rossignol's best supportive evidence for this hypothesis appears to be nothing more than speculation.

These criticisms (and many others I have not expounded upon) and the lack of physiologic plausibility aside, what if Rossignol is right? Well, as the saying goes, "truth will out." Rossignol is free to build the case for his hypothesis, others will attempt to replicate his results. If HBO therapy actually helps autistic children, then the data from well conducted studies will validate it, and we will have gained a tool to help afflicted children and learned something new in the process. If it doesn't, then we should direct the limited resources at our disposal to more promising avenues of autism research. At this time, HBO therapy remains an expensive, difficult to administer, implausible, and unproven treatment for children with autism.

References

1) Rossignol DA et al. Hyperbaric treatment for children with autism: a multicenter, randomized, double-blind, controlled trial. BMC Pediatrics 2009, 9:21

URL: http://www.biomedcentral.com/1471-2431/9/21

2) Neurologica Blog: Hyperbaric Oxygen for Autism:

URL: http://www.theness.com/neurologicablog/?p=496

3) Calculating blood oxygen content:

PaO2 (Pressure of oxygen within arterial blood)) =

[(Atmospheric Pressure - H2O Vapor Pressure) x % Oxygen in atmosphere] - (Arterial CO2 / Respiratory Quotient)

Sea Level: [(760mmHg - 47mmHg) x 0.2093] - (40 / 0.8) = 100mmHg PaO2

We can then translate this pressure of dissolved oxygen to the volume of dissolved oxygen by knowing that there are 0.003 mls of O2 per mmHg of O2 dissolved in 100 ml of arterial blood, so:

0.003 x 100 mmHg = 0.3 ml O2 dissolved in every 100 ml of arterial blood at sea level

Hemoglobin binds 1.39 ml of oxygen per gram fully saturated, and has a non-linear saturation curve. For my calculations I used 95% saturation at 5280 ft, 98% saturation at sea level, and 15 gm hemoglobin per 100 ml of blood. Add the ml of oxygen bound to hemoglobin to the ml dissolved in blood for the total oxygen content.

 

Disclaimer: Dr Albietz has no ties to industry and no conflicts of interest to disclose.   The views expressed by Dr Albietz are his alone, and do not necessarily represent the views of his department or institution.  The information provided is for educational purposes only and should not replace a therapeutic relationship with a licensed and accredited medical professional.

 

 

 

 

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written by MadScientist, March 28, 2009
1.3 atmospheres is 'hyperbaric'? That's really pushing the term; that's probably about the air pressure down the mineshafts of some of the world's deepest mines and the air pressure when you swim to the bottom of a 10ft deep pool. Strap on some SCUBA and bring the kids down about 35 feet and they'll get about 2 atmospheres. I like the idea of wearing a mask with a small tank of oxygen to make the air about 30% oxygen; that's certainly much cheaper and more convenient than a hyperbaric chamber.

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What's the problem?
written by Skeptic, March 28, 2009
I don't see the problem here. Sure, the study is small and the results are tentative, but NOBODY CLAIMS OTHERWISE. They are merely claming that they have the results they have, and that this -- they hope -- justifies further, more detailed, larger studies.

This is usually the way such studies are made: before you can get funding for a larger, serious study, you need to show tentative positive results in a small, less serious study.

Sure, it might turn out to be a chimera. But one can hardly dismiss the study by the "common sense says it shouldn't work" argument -- "common sense" says natural selection shouldn't work and that the sun revolves around the earth, too.

I think Dr. Albietz's real concern is that the media will jump all over this with "MAGICAL CURE FOR AUTISM FOUND: OXYGEN!" headlines. That may well happen, alas, but if so, it would not be the fault of the scientists who made the study!
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written by MadScientist, March 29, 2009
@Skeptic: One of the points is that there is no need for a hyperbaric chamber. To increase oxygen in the blood by the amounts in the study only requires about a 50% enhancement over what is in air - all done without pressurizing the kids. Some sports training facilities have (large) sealed rooms where the oygen can be adjusted to that level (or lowered slightly to induce an increase in red blood cells) and even that sort of arrangement would be more sensible than a pressurized chamber. Since the treatment is only a few hours a day, why not just get the kids to wear masks as already pointed out? In this instance the use of a hyperbaric chamber is a bit like swatting a fly with a baseball bat.
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Questionable at best
written by Bart B. Van Bockstaele, March 29, 2009
I agree with Joe Albietz. This is highly questionable "research". I had seen a mention of it by the BBC and have commented negatively on it. Unfortunately, neither the article itself nor the abstract were accessible at the time, but I concluded just as well that this is all very implausible.

Also Dan Rossignol works at the ICDRC, an organization that does not have a spotless reputation.
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So?
written by pxatkins, March 29, 2009
I agree with Skeptic. Seems to me there is nothing out of whack at all with a study that reports it's findings, caveats warts and all and encourages further research/study. I'd be more worried about any report that provided proof first time around.

As an aside, I'd just like to mention I am happy to see the last few articles have returned to the more scientific milieu I prefer to see at the JREF. I really don't give a rat's rear about out-tabloiding the tabloids.

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written by pxatkins, March 29, 2009
its ... for shame ... smilies/sad.gif
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written by tmac57, March 29, 2009
@Skeptic's "Whats the problem?":
As Joe Albietz stated in the article, his problem is #1 Design and execution,#2 biological plausibility(which he expounds on in length,#3 "My other concern with this study is the author's poor handling of the article's discussion. Read without an eye to their citations the discussion flows well, however, most of the assertions made by the authors are supported with the weakest of evidence."
Then he ends with "These criticisms (and many others I have not expounded upon) ..." which indicates that there are probably other concerns , does raise questions, and in science ,that's what people do when any new proposed treatment comes along, they try to pick it apart to see if it withstands scrutiny . If it does, fine, if it doesn't then that's one more useless therapy that gets (hopefully) shot down.
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written by Caller X, March 29, 2009
What's the problem?
written by Skeptic, March 28, 2009
I don't see the problem here.

I think Dr. Albietz's real concern[...] Doctor Who? Where do you get this "Doctor" nonsense?
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written by Chakolate, March 29, 2009
Even if the amount of increase of oxygen is negligible, it may be the pressure that effects the change, if there is any. My grandson is autistic, and he *loves* to be squeezed - the harder the better. I know he's only one data point, but it seems to me to be a fairly common sign of autism.

So even if the conclusion drawn by the experimenter is off, the result may be quite real. What I can't figure out is why such effects should appear to continue after treatment is finished.

As they say, more research is needed.
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written by MadScientist, March 29, 2009
@Human Person Jr: Well put, even if you are feeding a troll. The incident does give us a good idea of the whack-jobs that the JREF has got to sort through though.
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Plausibility is the problem here.
written by BillyJoe, March 29, 2009
Research costs a lot of time, effort, and money. It is important, therefore not to waste resources on treatments with little hope of benefit. The test is plausibility and hyperbaric oxygen doesn't have it.
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written by BillyJoe, March 29, 2009
My grandson is autistic, and he *loves* to be squeezed - the harder the better.

Therefore hyperbaric oxygen might work. smilies/grin.gif
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written by The crazy person living in your attic., March 30, 2009
written by Caller X, March 29, 2009:
written by Skeptic, March 28, 2009:
I think Dr. Albietz's real concern[...]

Doctor Who? Where do you get this "Doctor" nonsense?
Possibly from the disclaimer at the bottom of the article, following the references.
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written by BillyJoe, March 30, 2009
I see x has fallen flat on his cake hole again.
Looks like he won't be offering any services for a while.

smilies/cool.gif

BJ
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written by One Skunk Todd, March 30, 2009
Mad Scientist,
Not meaning to be critical, but based on my experience with autistic kids (5 in my groups of friends, including my nephew smilies/sad.gif ) "just get the kids to wear masks" is not going to be a practical method of treating them. For most of them it's struggle to get them to wear clothes at all.
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written by Chakolate, March 30, 2009
Research costs a lot of time, effort, and money. It is important, therefore not to waste resources on treatments with little hope of benefit. The test is plausibility and hyperbaric oxygen doesn't have it.


But if there was a significantly good result, shouldn't that be followed up? I think the oxygen level part is completely wrong-headed, but the pressure part just might be of use.

Most autism schools have a squeeze machine, because it calms the students. It is often used as a reward for good behavior - auties just love to be squeezed. (
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written by Chakolate, March 30, 2009
Sorry, some of my comment was cut off. (I'm not very good at HTML.)

I know 'auties just love to be squeezed' is a generalization, but it's more true than not, I think.

If the results of the HBO treatment were valid, and if the oxygen part is not likely to be the cause of good results, then isn't it useful to look at the pressure part?
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written by Otara, March 30, 2009
I guess for me the issue is the process. As in ideally noone would use this in standard practise till it gets replicated under more stringent conditions, it probably wouldn't get replicated because the arguments and results arent convincing and it would die off unless someone else identified a reasonable causal pathway or something else came up to warrant further study.

Instead of course what often happens is no further study is done but it gets cited for the rest of the time as 'proof' that the method works. Because people arent aware of the need for things like independent verification or large sample sizes, it can be used to get a cloak of legitimacy that it doesnt really deserve.

I dont have an easy solution for that, ideally some kind of clearer standard is developed for knowing what stage of research a particular medical concept is at and how much credence it should be given as a concept, allowed to be used in advertising or part of normal practise etc. But in practise it would probably be a nightmare.
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written by Chakolate, March 30, 2009
I suspect what will happen is that parents will try it anyway. I know that for my grandson, anything *anybody* suggests, if it won't harm him, we try. If it improves his ability to cope, we use it. If not, we discard it and try something else. Omitting wheat and dairy from the diet, using weighted vests, a trampoline, playing special music through headphones, epsom salt baths - you name it, we've tried it.

If this is just an anomaly, and there's really no benefit to it, the main downside will be the expense (whether borne by insurance or by the parents).

(FYI, he was helped by eliminating wheat, weighted vests, trampoline, epsom salts, and not by eliminating dairy or playing those (very expensive) CD's through his heeadphones.)

BTW, I'm happy to report that his parents *never* fell for the vaccination-causation garbage.
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Wrong Direction?
written by Realitysage, March 30, 2009
What gets me is all the time and resources given to autistic children. Studies show that spending is vastly disproportionate as opposed to the very bright. Might it be better to use those resources on gifted kids instead? They are the ones who will lead the way in innovation and productivity.
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written by Chakolate, March 30, 2009
You may be confusing 'autistic' with 'low-functioning autistic'. My grandson *is* gifted. In his special school, he's doing fifth grade math (he's eight) and complains that it's not hard enough for him.

But that's just one data point. The more general answer to your remark is that autism doesn't have to be disabling. If treatments and therapies are introduced early, then the autie can lead a full and productive life, although never without difficulty.

So the real question is, do you want to spend a few resources now to level the playing field and get the auties up to speed, or do you want to support them for the rest of their lives?
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written by Caller X, March 30, 2009
written by BillyJoe, March 30, 2009
I see x has fallen flat on his cake hole again.
Looks like he won't be offering any services for a while.




Oh come on, he's a pediatrician with four years' experience. What does a foot doctor know about autism?
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written by dr pepper, March 30, 2009
I know someone whose child is on the extremely low functioning end of the scale. It might be worthwhile for him to try some variant of this.
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x
written by BillyJoe, March 30, 2009
I can spot even a really bad joke from a mile off.
Especially from you because it's more or less expected.

But shouldn't you be thinking "dental surgeon" about now?
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autie?
written by BillyJoe, March 30, 2009
autie
To me, they're always children with autism.
But each to their own I guess.
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Realitysage
written by BillyJoe, March 30, 2009
What gets me is all the time and resources given to autistic children.
How dare you be politically incorrect!
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dr pepper
written by BillyJoe, March 31, 2009
I know someone whose child is on the extremely low functioning end of the scale. It might be worthwhile for him to try some variant of this.

Well, yes, if you've completely missed the point.
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Yes, autie
written by Chakolate, March 31, 2009
autie?
written by BillyJoe, March 30, 2009

autie

To me, they're always children with autism.
But each to their own I guess.


But not all auties are children. If you mean that you'd rather think of them as being people first and having a condition second, you have a good point.

I learned the term 'autie' from an online autism support group, and that's what the auties preferred to be called. They make the point that while someone can have, say, asthma and think of themselves as a person with asthma, and know what they'd be like without asthma, an autie is an autie through and through. That is, if you took away the autism, you'd be left with an entirely different person.

As one guy put it, 'When my father says he wishes I didn't have autism, what I hear is that he wishes he had a different son.'
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written by BillyJoe, March 31, 2009
You think I didn't know there are adults with autism???

You were talking about your grandson who I assumed is a child and someone else commented about the resources spent on children with autism. Just following on.

And whatever you say about being autistic through and through, autism is still a disease and I don't understand why someone would want to be defined by their disease.

BJ
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written by Chakolate, April 01, 2009
You think I didn't know there are adults with autism???

You were talking about your grandson who I assumed is a child and someone else commented about the resources spent on children with autism. Just following on.


Okay.

And whatever you say about being autistic through and through, autism is still a disease and I don't understand why someone would want to be defined by their disease.


Autism is *not* a disease. And most auties don't think of it as such. It's an alternative neurological condition. Many auties will tell you that being autistic is just as valid a neurological hookup as yours.

That's the point I was making about the difference between having autism and having a disease. If you're autistic, then being autistic is part and parcel of who you are, and completely inseparable from your selfhood.
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written by BillyJoe, April 01, 2009
Autism is *not* a disease.

Dictionary definition of disease:
"A pathological condition of a part, organ, or system of an organism resulting from various causes, such as infection, genetic defect, or environmental stress, and characterized by an identifiable group of signs or symptoms."
But call it a disorder if you will.

It's an alternative neurological condition.

That depends on what you mean by "alternative"
If given a choice, it's certainly not a coin toss.

Many auties will tell you that being autistic is just as valid a neurological hookup as yours.

And that depends on what you mean by "valid".
It's certainly not just as desirable.

That's the point I was making about the difference between having autism and having a disease. If you're autistic, then being autistic is part and parcel of who you are, and completely inseparable from your selfhood.

I see your point, but that is not to deny that autism is a disease or disorder take your pick

BJ
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written by Chakolate, April 02, 2009
I see your point too, and we're just going to have to disagree. It's not surprising to me. If you had told me a few years ago that being autistic can be considered just as desirable as being neurotypical, I would have thought you were insane. It's only after talking to many auties that I now see it from their point of view.
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Chakolate
written by BillyJoe, April 02, 2009
I think you've been talking only to people with high functioning autism. Sadly, they are in a minority.

There have also been people who have had strokes that have resulted in the emergence of high artistic talent. These people appreciate the gift that their stroke has given them, but they are in a minority.

BJ
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written by Chakolate, April 02, 2009
Can you cite your source for saying that the high-functioning auties are in the minority?
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You want a link???
written by BillyJoe, April 03, 2009
If I were on the forums I would certainly do so but as it is this is a chit chat show so I'll just say that the number of people with autism I'd rather be than an average person without autism is in a clear minority. smilies/wink.gif

BJ
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written by Steel Rat, April 13, 2009
I was thinking maybe the HBO effect causes autism.

What?

Not that HBO?

Oh.

Never mind!

SR
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expert analysis...
written by lumenary, July 20, 2009
I don't disagree with the blogger regarding many of his criticisms of the paper, (patient selection, number of patients, methods of assessment), but his take on oxygen therapy misses something, which is, basically, the concentration of other gases and their changes during normobaric and hyperbaric oxygen therapy.
One of the downsides of putting an individual on 100% oxygen would be a subsequent drop in the partial pressure of carbon dioxide in the blood. As CO2 drops, so would cerebral perfusion, so, paradoxically, you may not get the same degree of tissue oxygenation. You can mimic the same effect by hyperventilating. In one study that had smokers and non-smokers breathe 100% oxygen for 5 minutes, retinal blood flow and optic head blood flow were reduced 33% and 37%, respectively, in non-smokers and 10% and 13%, respectively, in smokers.
His logic gets completely fuzzy in regards to heart rate and oxygen delivery. He claims that one can increase their oxygen delivery by 3% by raising their heart rate from 80 to 82.4 beats per minute. He fails to recognize that cardiac output (the amount of blood delivered per minute) will not change just because one raises the heart rate. As heart rate goes up, stroke volume decreases, keeping cardiac output exactly the same. If cardiac output is unchanged, then oxygen delivery will be unchanged, not increased. During exercise, blood delivery to muscles is increased by limiting blood flow to other areas. It is not "a fact" that athletes double our triple their oxygen delivery. They don't.
This author fails to understand that oxygen delivery is more than just oxygen--it's oxygen, hemoglobin, 2,4-diphosphoglycerate, acid-base, dissociation curves, etc...

I'm not saying that there is a proven benefit to hyperbaric oxygen, I'm just stating that his rationale for stating that it does nothing is ridiculous. He spews out 8-10 paragraphs of pseudoscience on oxygen dynamics, which is ironic given the website.
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