Orthostatic intolerance

Wasn't there some suggestion that a large, rapid dose of water (either via IV or rapidly drinking a pint of cold water first thing) affects the baroreceptors (?) or something, and triggers a response that isn't just proportionate to the volume taken in? That it's the speed that's crucial?

 

This has been speculated but it makes no sense. Nobody thinks it is safe to infuse fluid IV at a rate of much more than 500ml over half an hour except for diabetic coma and haemorrhage cases. You can drink 500ml of salty consommé in about two minutes if you put your mind to it and that will be pretty much all absorbed through gastric mucosa into the bloodstream within twenty minutes. Putting fluid directly IV has no physiological advantage except when the person cannot take fluid by mouth. The effect on baroreceptors will be the same.

 

What are the solutions for this orthostatic hypotension?

We are unable to find one, despite having our beloved family member try: salt tablets, salted water, large volumes of herbals tea, licorice, midodrine, mestinon, florinef, compression stockings, abdominal binders. Nothing is working. The medications just bring on horrid side effects and are then abandoned, only to be tried again with the same results and then tossed aside in frustration.

My daughter's blood pressure on lying down is plus/minus 100 systolic and about 45-50- diastolic. If she sits up, then the systolic pressure drops 20+ points. We don't even try to measure it standing up. Sitting for 1/2 hour will have the pressure going down so badly that she becomes violently ill.

What causes this in ME? Is it neurogenic?
Is there anything we have not tried. Suggestions will be welcome. Thank you.

PS. forgot to add that saline IVs are not a help at all, these have been tried many many times: useless

 

Do we know if the OI and orthostatic hypotension in ME is due to a) heart/circulation problems, b) adrenals, c) neurological, d) vascular?
Forgive the pedestrian question, but can it be determined what the hypertension is due to at this point in time?
And why is it that the medications I listed above (forgot to add Effortil,fludrocortisone), are not helping to raise the BP, or are causing such unacceptable side effects in so many ME patients?
I do believe that if the BP could be normalised a bit it would make things a little more comfortable for folks.
Surely, this is not rocket science. I was rather distressed to hear during the NIH talks, one doctor describe BP problems as "low hanging fruit." I hardly see it this way, if it can't seem to be managed.

 

This is what I thought about also. I do not agree anymore it's "low hanging fruit". That's how I understood it: Findings up til now seem to indicate there are the following problems (while upright): blood circulation into the small vessels (i.e. into the "periphery", i.e. less oxygen gets there), blood circulation into the brain (i.e. less oxygen gets there), blood circulation into the heart, and the oxygen that arrives in the mitochondria doesn't seem to be used properly.

One of the body's compensation is raising the pulse (which could lead to POTS) and/or the blood pressure (by increasing adrenaline e.g.) - in others, noradrenaline is increased.

Therefore, in my personal view, taking the body's compensatory method by giving medications that decrease BP and/or pulse is like giving a diabetic sugar - the underlying problem will get worse. What needs to be addressed is the oxygen supply via the blood vessels. And secondly, there seems to be this mitochondrial problem that needs to be addressed as well. This doesn't sound too easy to me.

POTS/NMH and the like can have neurological (then called dysautonomia if I understood correctly, a problem in the autonomous nervous system - but the question then is, what led to dysautonomia?) and/or cardiological origins; this needs to be checked.

 

Julia Newton talked about studying the relation between circulation and fatigue in 2014. Five years later her group have produced few papers but nothing very definite. Newton thought that fatigue was due to low cardiac filling pressure. What I think needs to be considered is that things may be the other way around.

People with ME feel terrible. If you feel terrible you lie down. If you lie down enough several control mechanisms that maintain cardiac filling pressure on standing become less efficient. There are at least three - resting plasma volume control, peripheral venoconstriction through autonomic nerves and oncotic pressure control through albumin levels. All of these are known to become less efficient if you spend a lot of time recumbent.

Newton's group published a paper suggesting that OI was not due to 'deconditioning', presumably suggesting not due to inactivity and lying down. However, the physiological changes of lying down are not strictly deconditioning. Astronauts get them even if they exercise.

Newton argued that the OI was not secondary to inactivity because it did not correlate with illness duration. However, that does not seem to me to mean much. Regulatory changes occur over a few weeks, so illness duration may not show up as relevant.

If OI is secondary to recumbency then you would not expect any drugs to help without causing major problems. I personally doubt drugs are appropriate. The real question I see is whether the best treatment of OI is ensuring that whenever possible the PWME does not lie down but sits up or moves about more. I realise that may increase symptoms but it may be the only way to reduce symptoms the longer term. I am not suggesting this as a recommendation, simply pointing out that the recommendations being handed out by physicians at present may be muddled and unhelpful and that we need some better research studies to find out what causes what.

 

@Jonathan Edwards while I’m not disputing the fact that prolonged recumbency worsens OI, the idea that pwME should move a little more does not fit with my personal experience.

I certainly agree that pwME need to maintain a certain level of activity (whatever that looks like for a very severe/severe person) or sit upright for as long as they are able to, to prevent these additional physiological changes and OI worsening.

However I experienced OI for many years when I was undiagnosed and very mildly affected. I was working full time walking at a good pace around the hospital wards and during 23 hour on call shifts. By lunchtime and certainly by the end of the shift I would feel like I was on a boat, extremely brain fogged and was struggling to walk with postural and postprandial tachycardia.

With some rest these symptoms would die down. So my OI would exacerbate during PEM and clearly was not related to deconditioning.

I then had to stop working completely a few years ago as I was struggling to make it up a single flight of stairs at work with severe muscle pain and weakness. I was then bedbound for a year making it to the toilet and back, this felt like chronic flu. Now I’m moderately affected but still housebound and can’t stand up for long due to muscle pain/weakness which still remains.

My VO2 max at onset was 45% of expected! So exertion intolerance is a big factor for me not baseline fatigue.

If I try and push the boundaries of activity or not lay down/rest when I need to my OI flares along with my muscle pain and weakness.

So my feeling is that OI is tightly related to whatever pathology is going on in the brain in pwME which flares during PEM. Whether it’s immune driven changes in autonomic control, we cannot say yet. I also feel that the oxygen extraction problems that are appearing in Systrom’s work may be of significance too.

So I don’t think we can speculate how to best manage OI/PoTS etc until we have an understanding of the pathology. Until then pwME can only be guided by what feels right and if too much upright activity is making things worse overall then you’d be silly to ignore that and push through.

 

This topic is confusing.

Although I agree that it sounds plausible that being supine for longer periods will lead to certain problems - maybe including POTS/NMH - there seem to be several examples indicating this doesn't have to be the case. @jaded's story for one.

I was diagnozed ca. 1.5 years after onset. Until that I still tried to keep my activity level. After the diagnosis, I started pacing, and for this I had to sit/lie in bed, too. Now here comes the supine for longer periods. But I still was upright for some hours per day, I don't lie in bed, I half sit at ca. 45°, and I still do sth like "sport".

But ca. 3 years after onset (and 1.5 years after diagnosis, i.e. after starting pacing), I realized POTS symptoms; POTS was diagnosed, and along with it small fiber neuropathy. If the direction "supine -> POTS -> fatigue" was correct, I should have developped POTS much faster after I started pacing (which included more time in bed)?

What I observe is that SFN and POTS are getting worse, and it seems parallel to each other.

Another example is someone who, despite working in an upright position for a while, got worse and worse, including POTS. Another one is that of a child that needed to cut activity because of POTS, so the direction was "POTS -> rest/supine". So I guess there is something else going on than "just" too much supine position.

 

yep

 

I think I made the usual error of using 'OI' as a shorthand for the sort of reduced cardiac filling pressure that might cause severe OI of the sort Perrier was describing.

So, of course, yes, there must be something else - which there would be if the cardiovascular changes are secondary to some other reason for feeling terrible in the sort of way that makes it difficult to tolerate standing. The something else is whatever starts the OI symptomatology off and may then be aggravated by being supine, leading to the reduced filling pressure on standing.

I thin the problem is that POTS is not an understood process. It is still just a clinical observation. We do not know what sparks off the tachycardia or whether it is the same in early or late situations.

Maybe we are all agreed that someone needs to sort out the actual sequence of events here. It is a pity that Julia Newton 's group does not seem to have nailed this.

 

@Jonathan Edwards my "OI" symptoms are worse in the morning. I'm feeling so much better after 6pm. Others have mentioned this too. Any ideas why?

 

This is a characteristic of POTS. The "worse in the morning" bit at least.

 

Day 1 seems to end at 6 hrs 52 mins? The playback seems to have got stuck for me too.

 

I found it - about two thirds of the way through.

The message is that he finds low filling pressure. That makes some sense but he did it back to front - finding the low pressure and then discovering the patients had ME. That is OK as long as it can be repeated the other way around, otherwise he may be studying a very small subgroup of ME.

 

here is a reference to Dr. Systrom's current Phase 3, double-blind, randomized control clinical trial (The Exercise Response to Pharmacologic Cholinergic Stimulation in Preload Failure) using pyridostigmine, an exercise test and it includes his hypothesis for the trial.

https://clinicaltrials.gov/ct2/show/NCT03674541?cond=ME/CFS

 

Here then is a basic question: if we do not know if this severe problem is immune or autonomic control driven, why can we not find out? Is it that at this point there are no possibilities for distinguishing, or is it that the work has not been done? Thanks

 

Yes, I absolutely agree, there just isn't a detailed enough attention to the sequence of events; and unless this is done, we will continue to sit in a muddle. But who out there is going to do this?

 

I am worried, as I keep repeating, about mestinon. This medication was used for ME by Dr Teitelbaum and Dr Holtorf some 20 years ago, if not more. They ran these Fatigue-fibromylagia clinics.
Many ME patients were unable to tolerate this medication. So, I just find it very discouraging that the wheel is being reinvented, as it were.