Trial Report Beneficial effects of intermittent intravenous saline infusion in dysautonomic patients with [ME/CFS]: a case series, 2025, Sjogren et al

[forestglip]

Beneficial effects of intermittent intravenous saline infusion in dysautonomic patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: a caseseries

Per Sjogren, Helena Huhmar, Bo Christer Bertilson, Björn A Bragée, Olli Polo

[Line breaks added]

Purpose
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition with no single, uniformly effective pharmacologic therapy. Dysautonomic features like orthostatic intolerance and postural tachycardia syndrome are common features in ME/CFS, severely affecting the patient´s quality-of-life. Intermittent saline infusion may reduce symptoms associated with dysautonomia, but this has not been tested scientifically in patients with ME/CFS.

In this case-series, 22 patients with ME/CFS and signs of dysautonomia and/or hypovolemia were treated every third week over 9 weeks with intravenous saline (9 mg/mL NaCl), using standard aseptic technique. Symptoms were monitored throughout the treatment regime, and a follow-up evaluation was conducted.

Results
At treatment start, patients were predominantly female (95%), at mean age 46 ± 10 years, and with a mean body hydration percentage of 48 ± 6. Self-reported health status revealed an overall symptom score of 47 ± 13 on a 0-96 scale, a median POTS score of 64 (IQR 16) on a 0-120 scale, and poor measures of quality-of-life (median 25 IQR 25, on a 0-100 scale) and abilityto-work (median 0, IQR 26, on a 0-100 scale).

Following 9 weeks of intermittent saline infusion (mean volume 1600 ± 360 mL), self-reported composite symptom score, quality-of-life and POTS-related symptoms improved significantly (all p<0.001), as did ability-to-work (p<0.05).

Our data derived from a non-controlled case-series indicate health benefits from volume loading with intermittent infusion of saline among patients with ME/CFS, which may stimulate further studies on various forms of intravenous volume loading to patients with ME/CFS and dysautonomia.

Link (Frontiers in Neurology) [Abstract only ahead of publication]

 

[Binkie4]

I have had a couple of saline infusions on the advice of Dr Bansal and improved hugely for a temporary period.

The circumstances were a 3 day hospital admission for cardiac investigations. My local hospital was proposing open heart surgery to replace a leaking valve and I wanted a second opinion. I was nervous about the effects of testing on my ME since I had deteriorated significantly after being examined at my local hospital.

Dr Bansal wrote a letter advising on the management of ME during the extensive testing which included saline infusions. I was fine both during and after testing . The saline was repeated when I returned for further tests. I continued to be well even during stress testing. At the time I was pacing with a heart rate monitor and my heart rate was kept as low as it could be while still achieving the purpose of the tests.

I felt much better with saline and did look up the cost of paying for regular infusions. Cannot remember the cost but it was too much for self pay.

 

[Utsikt]

It appears like Bragee continues to take the treat first, ask questions later approach to things..

 

[John Mac]

Now published:

Frontiers | Beneficial effects of intermittent intravenous saline infusion in dysautonomic patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: a case-series

PurposeMyalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition with no single, uniformly effective pharmacologic therapy. Dys...

www.frontiersin.org

 

[Utsikt]

Forty (40) patients with signs of dysautonomia, POTS and/or hypovolemia during diagnostic assessment, or at clinical follow-up, were considered having clinical indications for IV saline therapy. Eighteen out of 40 individuals were treated only once or twice and did thus not complete the full treatment regime: the reasons for not completing the treatment were predominantly (i) sudden illness preventing attendance at certain treatment session or (ii) due to the effort related to the treatment procedure. Data presented herein are focused on those 22 patients who completed the treatment regime over 9 weeks.

45 % dropout. That’s almost impressive.

Infusion protocol​

The IV infusion of physiological saline solution was performed by standard aseptic technique using saline (Braun, 9 mg/mL NaCl) during a 3 h-session and administrated at room temperature, starting with a slow drip rate with subsequent adjustments to achieve a final infusion volume of 1,000–2000 mL, and repeated every third week over 9 weeks (i.e., a maximum of 3 infusions) with subsequent follow-up.

Figure 1. Changes in overall symptom score (mean, SEM) in relation to intermittent infusion of intravenous saline, 3 times over 9 weeks, in patients with ME/CFS who completed the treatment regime: (i) At-treatment-start, prior to first infusion (n = 22) (ii) + 3 weeks, prior to the second infusion (n = 21), (iii) + 6 weeks, prior to third and last infusion. (n = 21), and (iv) End-of-treatment, 1 week after last infusion (n = 19) N differs due to incomplete questionnaire response. Scores are derived from a questionnaire administered to patients prior to each treatment session. Including the 24 most prevalent symptoms in ME/CFS. The composite score ranges from 0 to 96, with 96 representing worst possible overall symptoms. p-values from Wilcoxon signed rank test.

Figure 2. Self-reported changes in POTS score, Quality-of-life and Working ability Before (At-treatment-start) and After (1 week after treatment stop) intermittent infusion of intravenous saline over 9 weeks, in 17 patients with ME/CFS who completed the treatment regime as well as the follow-up questionnaire. The POTS score could take a value of maximum 120, and Quality-of-life and Working ability could take maximum values of 100. p-values from Wilcoxon signed rank test.

These results look very unimpressive compared to Fluge and Mella’s saline infusions..

Discussion​

Data from this non-controlled case-series indicate health benefits from volume loading with intermittent infusion of saline among patients with dysautonomia and ME/CFS. QoL and ability to work improved significantly following three treatments over 9 weeks, and an overall improvement in a range of individual symptoms was evident, especially symptoms related to POTS/dysautonomia. These results provide a justification for further work to determine the optimal target group, frequency and methods, for volume loading in patients with ME/CFS who suffer from debilitating dysautonomia.

Of course, they determine that the infusions are effective based on a small open-label trial with subjective outcomes, and all we have to do is to optimise it.

The beneficial effects observed in our study are most likely explained by volume loading counteracting existing hypovolemia, as mean body hydration percentage prior to treatment-start was 48 ± 6% in the 22 completers, and as low as 44 ± 5% in those (n = 8) who reported the highest benefit of the treatment. We were, however, unable to detect any significant changes in hydration percentage over the treatment period, which might be explained by the insensitive methodology applied (BIA) prohibiting intra-individual conclusions.

Then they try to explain away the lack of findings.

Whether some variant of intermittent volume loading can yield sustainable health effects remains to be shown. In the present study, we were not able to detect any sustainable effects and with limited improvements in objective measures. For example, POTS diagnosis was unaffected by intermittent volume loading. This may be due to the time-delay (on average 9 days) between the last infusion and POTS assessment and the results from tilt table test may had been different if performed closer to the infusion session. However, subjective benefits were present among many of our patients and according to previous publications, volume loading does not necessarily have to be concomitant with more objective measures (29).

Apparently, it doesn’t matter that the objective outcomes didn’t match the subjective ones, because we’ve seen that before.

Improvements in subjective measures may increase the patient’s compliance to other interventions with a feed-forward mechanism (19), rendering volume loading as a potentially important bridge therapy for patients suffering from dysautonomia and ME/CFS. Some of the beneficial effects in our study were counteracted by the effort that came with visiting the clinic, which, not unexpectedly, gave rise to PEM in many of our patients. However, it is interesting to note that among our patients, all with severe degree of ME/CFS (n = 5) completed the infusion protocol, indicating that disease severity does not influence the capacity to complete this particular treatment.

I don’t understand how feeling better might make you more compliant with other interventions. If anything, feeling worse would make me put more effort into getting things right. Not to mention that there are no interventions that would have beneficial effects, other than pacing and getting help to be able to avoid PEM in your everyday life.

Our provisional results in this small series will need to be confirmed in a randomized, blinded trial. Future intervention studies could evaluate the effects of volume loading providing precalculated inadequate vs. adequate volumes of saline with a blinded design.

A bit too late to start talking about this right at the end.

Finally, side-effects of our treatment protocol were few and harmless.

If some patients dropped out because the intervention was too much, and some of those that stayed got PEM, I wouldn’t call it harmless!

 

[ME/CFS Science Blog]

Social media summary:


1) The Bragée clinic in Sweden published an uncontrolled study to test if intravenous saline improves symptoms in ME/CFS patients with dysautonomia.

2) This is an interesting question because salt solutions that go directly into the vein are often used as a placebo control in trials that test intravenous medications. Therefore, it is important to determine if saline alone improves symptoms.

3) The Bragée trial included 40 ME/CFS patients with signs of dysautonomia, POTS and/or hypovolemia. They got 9 mg/mL of NaCl every third week over 9 weeks.

4) Unfortunately, 18 patients (45% of the total) could not complete the trial. Main reasons were sudden illness preventing attendance or effort related to the treatment procedure. One patient reported a treatment-related decrease in quality of life and working ability.

5) The 22 that remained, reported improvements on various measures, but the size of the effect is hard to interpret because the authors did not use standardised questionnaires. For working ability the improvement (from median 0 to 15) was not statistically significant.

6) Among 19 responders at follow-up, 8 (42%) wanted to continue the infusions, 10 (53%) were unsure, whereas 1 (5%) did not want to continue.

7) The researchers also note a lack of improvement on objective measures. They "were not able to detect any sustainable effects, and with limited improvements in objective measures. For example, POTS diagnosis was unaffected by intermittent volume loading."

8) They also measured body composition using bioelectrical impedance analysis (BIA). Patients had a mean body hydration percentage of 48, which is low but still in the normal range (45-60 for women). Saline infusions did not lead to a significant change in hydration percentage.

9) Although there may be a temporary benefit, the authors caution: "Long-term infusion of intravenous saline is not recommended as clinical trials are lacking and may further be compromised by the need for chronic central venous catheter with its attendant complications"

10) The research team led by Chris Armstrong plans to test the effect of saline infusions in a more rigorous manner using various solutions in the SIMPLE study:
https://www.omf.ngo/simple-study-impact-of-saline.../

 

[Jonathan Edwards]

Saline infusions did not lead to a significant change in hydration percentage.

That is interesting. If it is reliable it makes the plausibility of the approach even less.

 

[Utsikt]

Whether some variant of intermittent volume loading can yield sustainable health effects remains to be shown. In the present study, we were not able to detect any sustainable effects and with limited improvements in objective measures. For example, POTS diagnosis was unaffected by intermittent volume loading. This may be due to the time-delay (on average 9 days) between the last infusion and POTS assessment and the results from tilt table test may had been different if performed closer to the infusion session. However, subjective benefits were present among many of our patients and according to previous publications, volume loading does not necessarily have to be concomitant with more objective measures (29).

I’ve been looking at reference 29 to see if I can find any mention of volume loading. These are the only related quotes I’ve found (I left out speculations about cause):
A Prospective, 1-Year Follow-up Study of Postural Tachycardia Syndrome

Patients were counseled on optimal conservative measures to treat their orthostatic symptoms at baseline assessment and re-reviewed at the 1-year follow-up. Specific recommendations included appropriate fluid hydration, …

Urinary sodium excretion was measured using 24-hour urine collection. A total of 18 patients (38%; n=48) at baseline and 12 patients (27%; n=45) at follow-up had a 24-hour sodium excretion of less than 100 mEq, possibly compatible with a hypovolemic state (Table 4).15

The percentage of patients in our study (38%, n=18) classified as hypovolemic (sodium excretion <100 mEq/24 h) was slightly higher than in comparable studies (29%, n=30)

Interestingly, we found no correlation between elevated norepinephrine levels and presumed hypovolemia (on the basis of 24-hour urine output) or 24-hour sodium excretion.

Overall, they found that there was a trend towards improvement in symptoms during the follow up.

I can’t find anything about «volume loading» as an intervention, and there are no mentions of IV fluids. So I don’t think they have support for saying that interventions that are supposed to increase the blood volume doesn’t have to result in changes in objective measurements for blood volume (or any other objective measurements for that matter).

 

[Hoopoe]

To be a worthwhile treatment, any positive effect would have to be larger than the negative effect of a visit to the clinic and having a mildly invasive procedure done.

In my experience drinking salt water is an effective intervention for the symptoms they intend to treat, but the effect wears off quickly, so it's best implement an approach of drinking salt water over the course of the day. At the end of the day this led to reduced symptoms, presumably due to the reduction in cumulative stress associated with the suboptimal blood volume.

One can see how salt water infusions just cannot work in practice (effect is modest, wears off quickly, visit to the clinic is too stressful/energy consuming) but they probably lead to positive feedback from patients who feel relieved for a few hours while in the clinic. And they lead to positive feedback from patients due to placebo effects which complicates things.

 

[Turtle]

Social media summary:


1) The Bragée clinic in Sweden published an uncontrolled study to test if intravenous saline improves symptoms in ME/CFS patients with dysautonomia.


10) The research team led by Chris Armstrong plans to test the effect of saline infusions in a more rigorous manner using various solutions in the SIMPLE study:
https://www.omf.ngo/simple-study-impact-of-saline.../

The study by Chris Armstrong and his team seems to be de-prioritized. See quote of the SIMPLE study in ME/CFS Science quote above.

 

[wigglethemouse]

From the OMF website: Source

Results / Reason for Discontinuation:
This project has been de-prioritized as the team discusses starting a personalized trial in collaboration with PrecisionLife.

 

[hotblack]

Maybe a little tangential but recently I was wondering about the usefulness of saline as a placebo in trials. Or maybe my usefulness. Because I can tell if I’m being given saline, I can ‘smell’ it.

Before (or around the start of) my ME/CFS I was in hospital a couple of times and this cropped up, I was being given various things but each time there was a saline flush I got this, what I can only describe as a sort of slightly citrusy ‘smell’. The nurses seemed surprised when I would spot the saline as opposed to other things so this may not be common though. It became a bit of a game. Has anyone else experienced this? Is it a known thing they check patients involved in trials for?

 

[Jonathan Edwards]

Is it a known thing they check patients involved in trials for?

I think it is very unlikely that you can sense saline. Your blood plasma contains exactly the same saline as its main vehicle (maybe 90%). It is just possible that you can sense the dilution of other things but I have doubts since it will all be mixed up before it reaches your chemosensitive zones. Saline flushes may well contain all sorts of other things like small amounts of preservative or heparin, but they are going to be present the same in drug infusion and saline dummy almost certainly. The drug bag is likely to contain 95% of the same saline.

 

[hotblack]

I think it is very unlikely that you can sense saline

Useful, thanks. Just reporting my experiences and from the few occasions it seemed that was what was happening. I obviously have not performed a wide ranging or exhaustive study. And certainly can’t explain why it was happening.

I got the same ‘smell’ at times when getting loads of sea water up my nose swimming and surfing too which is another reason I tied it to salt/saline. Sounds like it could have been coincidental or something else though and wouldn’t be an issue for trials.

 

[Utsikt]

Useful, thanks. Just reporting my experiences and from the few occasions it seemed that was what was happening. I obviously have not performed a wide ranging or exhaustive study. And certainly can’t explain why it was happening.

I got the same ‘smell’ at times when getting loads of sea water up my nose swimming and surfing too which is another reason I tied it to salt/saline. Sounds like it could have been coincidental or something else though and wouldn’t be an issue for trials.

Even if you could sense it, if the medication is also delivered in a solution with saline, the differences probably aren’t enough for you to be able to sense a differences between the two.