Saline infusions

[Milo]

Maybe run them all in at the same rate for the first minute then slow the smaller doses down invisibly with a programmed pump

Having worked in nursing for decades, the infusion pumps make noise that are noisier when they go faster. Also, a rate of 150 ml/ hr would be felt by the patient compared to a 20 ml per hour, in terms of pressure and feeling cold up the arm. 20 ml per hour is known as KVO (keep vein open). Moreover the pump usually displays the rate of infusion, and it is usually near the patient. There would need to be a screen between the pump, the IV bag and perhaps consider temperature of the IV solution. Cold liquid could cause vasoconstriction and in my case being a little cold always help my POTS and capacity to remain upright.

Just some thoughts. I am sure @MelbME has it all covered

Edit: I also have Raynauds

 

[MelbME]

Having worked in nursing for decades, the infusion pumps make noise that are noisier when they go faster. Also, a rate of 150 ml/ hr would be felt by the patient compared to a 20 ml per hour, in terms of pressure and feeling cold up the arm. 20 ml per hour is known as KVO (keep vein open). Moreover the pump usually displays the rate of infusion, and it is usually near the patient. There would need to be a screen between the pump, the IV bag and perhaps consider temperature of the IV solution. Cold liquid could cause vasoconstriction and in my case being a little cold always help my POTS and capacity to remain upright.

Just some thoughts. I am sure @MelbME has it all covered

Always appreciate input like this. Thank you

 

[Jonathan Edwards]

What do you think happened with the Rituximab trial? Went from 67% responding in Fukuda patients to 26% responding in CCC patients. Was it just the definition difference? Why do you think placebo (35%) was better than Rituximab in the phase 3?

Oystein Fluge let me go through the detailed kinetics of all the data from extended phase II. I forget the details now but everything I saw in all those trials was consistent with nobody responding to drug as such - just a combination of expectation effects and chance.

The initial phase II study showed no significant effect at the primary endpoint. The reason for going to phase III was that the six month endpoint data would have been significant if chosen as primary endpoint. I had pointed out in PLOS One comments that six months should have been chosen for primary endpoint because that is when the effect of rituximab is maximal in autoimmune diseases. That meant that it was worth checking that the six month data are not a fluke. As it turned out they must have been a fluke. My confidence in getting a positive result went down a lot when looking at the detailed kinetics because there was no interpretable pattern in the blinded data. For diseases where rituximab works the kinetics are elegantly consistent, even if with some variation in parameters.

The most striking message from the rituximab studies is that people with ME/CFS who get recruited to trials of this sort quite often show major improvement. Moreover, when the treatment is open it looks like a true placebo response from expectation. I don't think you can relate it to a physiological effect of saline. The kinetics indicate an expectation bias. So blinding is crucial.

 

[Jonathan Edwards]

Having worked in nursing for decades, the infusion pumps make noise that are noisier when they go faster.

My very recent experience is of a pump hidden in a box that is completely silent, but they may be pricy!

I think the main problem with blinding is that those receiving 500ml will be desperate for a pee within half an hour.

 

[FMMM1]

"I think the main problem with blinding is that those receiving 500ml will be desperate for a pee within half an hour." --- laughing!

 

[Kitty]

If any of them are ladies my age, showing them a glass of water is enough to make them desperate for a pee!

But seriously, are there problems with giving participants some information, e.g. that the trial includes exploring what the optimum dose (most effective, least uncomfortable) might be? To an experienced eye there might be obvious problems with that, but I genuinely don't know.

 

[Jonathan Edwards]

But seriously, are there problems with giving participants some information, e.g. that the trial includes exploring what the optimum dose (most effective, least uncomfortable) might be?

Dose ranging studies are very standard in the pharmaceutical area. At some stage they are required, to optimise dose. I am not sure what legal requirements are but as an ethics committee member my memory is that as long as patients/subjects are given reasonably sufficient information to make an informed choice about being in a trial the precise details are not always necessary.

Subjects should be told that the trial included dummy treatments and a range of doses. Mentioning a range of doses may have the advantage that subjects do not try too hard to guess whether they had the treatment or not. It would be impossible to try to work out which dose one had.

 

[Kitty]

Mentioning a range of doses may have the advantage that subjects do not try too hard to guess whether they had the treatment or not.

Thanks, that was what I was thinking. If people are told this, any who have enough experience to be aware they'd only received a smallish dose might be less inclined to question it or base expectations on it. Similarly, any who spent the next two hours wearing out the carpet leading to the bathroom might assume it was connected to a comfort/acceptability aspect.

 

[RainbowCloud]

Moved posts

Does anyone know if saline IV was tried to see if it helped? Because even if it helped for half an hour then maybe it would’ve allowed Maeve sit up to be fed – that could’ve made a crucial difference given she died due to malnutrition.

I won’t pretend to understand the complexities of IV saline but I’d like to try and understand why some doctors believe it can help and others don’t, because there’s conflicting information.

Some POTS specialists seem to feel saline IV considerably helps their patients and there are patient experiences to the same effect (examples in links below) but @Jonathan Edwards it seemed that you disagreed and thought anything past half an hour wouldn’t have any effect (think I interpreted that right but please correct me if not?!) As someone who has POTS and wants to understand what feels like a crucial question regarding Maeve’s care, please could you (or anyone else) help me try to understand why there are differing opinions and experiences? Thanks!

https://drsanjayguptacardiologist.c...transformative-treatment-for-pots-long-covid/

https://drsanjayguptacardiologist.com/patient-stories/my-experience-of-pots-iv-fluids/

Also, it occurred to me that research into saline IVs specifically on pwME (or both ME and POTS) is probably scarce and so if there is a circa 20% lower blood volume then how can we know whether we can apply the results of other studies to pwME, especially since no one seems to understand why the low blood volume might occur?

Here’s some research I’ve been able to find via a quick search specifically relating to pwME as well as a study that’s planned but hasn’t yet started that will be interesting too. I haven’t been able to read more than the abstract so perhaps these won’t be helpful here but including in case they’re relevant.

https://pubmed.ncbi.nlm.nih.gov/9292244/

https://pubmed.ncbi.nlm.nih.gov/28185102/

https://www.omfaustralia.ngo/saline-formulations-effectiveness-me-cfs-pots-long-covid/#:~:text=The most commonly reported treatment,infusion and a Hartmann's solution.

 

[Haveyoutriedyoga]

Does anyone know if saline IV was tried to see if it helped? Because even if it helped for half an hour then maybe it would’ve allowed Maeve sit up to be fed – that could’ve made a crucial difference given she died due to malnutrition.

I won’t pretend to understand the complexities of IV saline but I’d like to try and understand why some doctors believe it can help and others don’t, because there’s conflicting information.

Some POTS specialists seem to feel saline IV considerably helps their patients and there are patient experiences to the same effect (examples in links below) but @Jonathan Edwards it seemed that you disagreed and thought anything past half an hour wouldn’t have any effect (think I interpreted that right but please correct me if not?!) As someone who has POTS and wants to understand what feels like a crucial question regarding Maeve’s care, please could you (or anyone else) help me try to understand why there are differing opinions and experiences? Thanks!

https://drsanjayguptacardiologist.c...transformative-treatment-for-pots-long-covid/

https://drsanjayguptacardiologist.com/patient-stories/my-experience-of-pots-iv-fluids/

Also, it occurred to me that research into saline IVs specifically on pwME (or both ME and POTS) is probably scarce and so if there is a circa 20% lower blood volume then how can we know whether we can apply the results of other studies to pwME, especially since no one seems to understand why the low blood volume might occur?

Here’s some research I’ve been able to find via a quick search specifically relating to pwME as well as a study that’s planned but hasn’t yet started that will be interesting too. I haven’t been able to read more than the abstract so perhaps these won’t be helpful here but including in case they’re relevant.

https://pubmed.ncbi.nlm.nih.gov/9292244/

https://pubmed.ncbi.nlm.nih.gov/28185102/

https://www.omfaustralia.ngo/saline-formulations-effectiveness-me-cfs-pots-long-covid/#:~:text=The most commonly reported treatment,infusion and a Hartmann's solution.

IF it helps for half an hour, providing symptomatic relief for half an hour (and I acknowledge that's an IF), then, is it possible that either the saline OR the assumed-to-b related half hour of relief causes some sort of consequential change, that then helps the person feel more well for the next few days (as subjectively reported and assumed to be a result of the saline, in some anecdotal cases)?

 

[Jonathan Edwards]

As someone who has POTS and wants to understand what feels like a crucial question regarding Maeve’s care, please could you (or anyone else) help me try to understand why there are differing opinions and experiences?

The simple problem is that we have no reliable evidence of there being benefit. I don't discount the conceivability that there is some ongoing benefit but it is physiologically unlikely and nobody has shown the benefit so far in adequately controlled studies.

'Specialists' in ME/CFS hand out all sorts of treatments claiming they know they work. The BPS hand out GET and CBT saying they know they work. Physicians hand out midodrine, fludriocortisone, IV saline and so on saying they know they work but doctors have been doing that for centuries. When blood letting was abolished doctors were furious because they 'knew it worked'. Both doctors and patients are gullible. We know that. IV saline is the perfect placebo - a dramatic intervention with a 'scientific' rationale. It is bound to make people think they have improved. But before pharmacologists believe anything works the least they ask for is a dose response curve. If something really works there is a dose where nothing happens - much too small - there are doses where you get increasing benefit with giving more, and there is a level above which there is no further good and there may be harm. We have no suggestion of that for IV saline. The chances that people are being given the 'right' dose are zero because nobody has found out what the right dose is.

It is all make believe and medicine has been built on make believe for centuries. What changed in 1970, more or less, is that medicine suddenly became more than make believe. But the doctors who made a living out of make believe have never quite got to handle that. I don't deny that IV saline might do some good but it has all the hallmarks of a placebo effect. The placebo effect is the reason why we have trials costing 10 million dollars rather than half a million. It is that important.

 

[Jonathan Edwards]

is it possible that either the saline OR the assumed-to-b related half hour of relief causes some sort of consequential change, that then helps the person feel more well for the next few days

If the idea is that this is a disordered signalling loop then yes that certainly makes sense. You might nudge the loop back into an upward spiral. But almost certainly you could get the same with drinking a cup of soup. Of course if drinking is impossible that is no good but I think there are two different problems here. One is inability to take anything by mouth, the other is putative low blood volume from some abnormal regulation.

 

[RainbowCloud]

Thanks @Haveyoutriedyoga and @Jonathan Edwards – I feel like I have a better rounded understanding of it now. And I agree, we desperately need reliable studies on this (and so many other things) before we can categorically say what is or isn’t helpful. I was taken from moderate to severe by a ‘treatment’ in the past and haven’t recovered since and I’m sure many others have experienced similar. It’s scary and unfair to have to experiment when your health is so precarious.

Given Maeve didn’t have the benefit of proper research into saline IV, I can’t help but think that the benefits of trying it outweighed the risks of starvation. It’s sad there are so many what ifs like this.

By the way, sorry I posted pretty much the same question as @Lou B Lou – I hadn’t quite caught up far enough at the time to notice I was asking the same thing!

 

[mango]

IF it helps for half an hour, providing symptomatic relief for half an hour (and I acknowledge that's an IF), then, is it possible that either the saline OR the assumed-to-b related half hour of relief causes some sort of consequential change, that then helps the person feel more well for the next few days (as subjectively reported and assumed to be a result of the saline, in some anecdotal cases)?

According to "anecdotal cases" ie experiences shared for example in Swedish dysautonomia groups, there are some people who are currently getting IV saline twice a week for a number of weeks on a trial basis. They have reported that it helps them so much that they are even able to go to work part time, which includes travelling to a workplace outside the home. So for some people it's clearly about more than just "feeling better", and the effects seem to last for several days for them. They are obviously less severely affected than Maeve was, so not a comparison but it does suggest that the effect can at least sometimes be much more than "only minor and only very temporary".

 

[MrMagoo]

According to "anecdotal cases" ie experiences shared for example in Swedish dysautonomia groups, there are some people who are currently getting IV saline twice a week for a number of weeks on a trial basis. They have reported that it helps them so much that they are even able to go to work part time, which includes travelling to a workplace outside the home. So for some people it's clearly about more than just "feeling better", and the effects seem to last for several days for them. They are obviously less severely affected than Maeve was, so not a comparison but it does suggest that the effect can at least sometimes be much more than "only minor and only very temporary".

If we start from the theory that ME isn’t one thing, it’s a collection of illnesses which overlap or are similar, makes sense that some people find a treatment useful and others don’t.

 

[Jonathan Edwards]

According to "anecdotal cases" ie experiences shared for example in Swedish dysautonomia groups, there are some people who are currently getting IV saline twice a week for a number of weeks on a trial basis.

If there is actually atrial going on it would be useful to know. But if this is just open label treatments then there is the usual problem of expectation bias. 'Feeling better' is ultimately what matters in ME/CFS, and we have nothing else to measure, so I am not sure in what sense it would be 'more than'.

 

[Jonathan Edwards]

If we start from the theory that ME isn’t one thing, it’s a collection of illnesses which overlap or are similar, makes sense that some people find a treatment useful and others don’t.

Yes, but that applies to things like rheumatoid arthritis, which isn't one thing either. When we do controlled trials we build in to the design the assumption that some will benefit and some not.

But if you do not do properly controlled trials there is no way of knowing whether any of the improve,emts are actually due to the treatment. And if you do properly controlled trials and a proportion benefit that shows up. What the ME rituximab trial showed was that although several people thought they were getting benefit, in a properly controlled trial nothing at all showed up - making is reasonably certain that nobody was benefitting from the drug.

 

[Peter T]

'Feeling better' is ultimately what matters in ME/CFS, and we have nothing else to measure, so I am not sure in what sense it would be 'more than'.

‘Feeling better’ is no doubt a good thing, and I would be happy if I could feel better all the time, but that is not enough. I could ‘feel better’ a lot of the time if I could get enough rest and avoid PEM and avoid anything else that might trigger PEM such as being upright or light or sound, as could everyone with ME who is not at the severe/very severe end of the spectrum.

Presently my life is a continuous struggle to find a balance between not feeling awful and to actually live some form of life.

What I really want is to be able to do more and not to be made worse by activity and hypersensitivities. I suspect if I ‘felt better’ without having a treatment for PEM, I would increase my activity until I crashed. I suspect ‘feeling better’ by itself would be a dangerous gift, that for me activity levels and activity patterns are ultimately the primary measure of improvement not ‘feeling better’.

 

[Jonathan Edwards]

What I really want is to be able to do more and not to be made worse by activity and hypersensitivities. I suspect if I ‘felt better’ without having a treatment for PEM, I would increase my activity until I crashed. I suspect ‘feeling better’ by itself would be a dangerous gift, that for me activity levels and activity patterns are ultimately the primary measure of improvement not ‘feeling better’.

What I mean by feeling better is all the time. 'PEM' is just not feeling better after exertion. That counts. So yes we have to find a way of dealing with what stops people feeling better all the time but to me that is not PEM. PEM is the result of whatever that is.

If the people taking IV saline are going to work and crashing that is clearly not a recommendation for IV saline.

 

[Keela Too]

Maybe a better phrase would be “doing better”?

I think overall I am currently “doing better” than over the winter.

Yet I’m not necessarily “feeling better” as I tend to run at a certain “feeling okayish” level and adjust how much I DO to not “feel worse”.

Likewise any “feeling better” I experience, tends to get used to DO more, so in the end I pan out at a similar level of “feeling okayish”!!!!

Does that sorta make sense.