Trial Report Cerebral blood flow and end-tidal CO2 predict lightheadedness during head-up tilt in patients with orthostatic intolerance, 2024, Novak

[Dolphin]

https://link.springer.com/article/10.1007/s10072-024-07673-8

Coelho, F.M.S., de Carvalho Cremaschi, R.M. & Novak, P. Cerebral blood flow and end-tidal CO2 predict lightheadedness during head-up tilt in patients with orthostatic intolerance. Neurol Sci (2024). https://doi.org/10.1007/s10072-024-07673-8

Abstract

Orthostatic intolerance (OI) is a common problem.

Reliable markers of OI are missing, as orthostatic blood pressure and heart rate poorly correlate with orthostatic symptoms.

The objective of this study was to assess the relationship between orthostatic lightheadedness and cerebral blood flow.

In this retrospective study patients with OI were evaluated at the Autonomic Laboratory of the Department of Neurology, Brigham and Women’s Faulkner Hospital, Boston.

The 10-minute head-up tilt test was performed as a part of autonomic testing. Orthostatic lightheadedness was evaluated at every minute of the head-up tilt.

Heart rate, blood pressure, capnography, and cerebral blood flow velocity (CBFv) in the middle cerebral artery using transcranial Doppler were measured.

Repeated-measures design with a linear mixed-effects model was used to evaluate the relationship between orthostatic lightheadedness and hemodynamic variables.

Correlation analyses were done by calculating Pearson’s coefficient.

Twenty-two patients with OI were compared to nineteen controls.

Orthostatic CBFv and end-tidal CO2 decreased in OI patients compared to controls (p < 0.001) and predicted orthostatic lightheadedness.

Orthostatic heart rate and blood pressure failed to predict orthostatic lightheadedness.

The lightheadedness threshold, which marked the onset of lightheadedness, was equal to an average systolic CBFv decrease of 18.92% and end-tidal CO2 of 12.82%.

The intensity of lightheadedness was proportional to the CBFv and end-tidal CO2 decline.

Orthostatic lightheadedness correlated with systolic CBFv (r=-0.6, p < 0.001) and end-tidal CO2 (r=-0.33, p < 0.001) decline.

In conclusion, orthostatic CBFv and end-tidal CO2 changes predict orthostatic lightheadedness and can be used as objective markers of OI.

 

[Murph]

Simple but massive breakthrough to have a measurable correlate of OI. If you can measure it you can manage it.

 

[Turtle]

Simple but massive breakthrough to have a measurable correlate of OI. If you can measure it you can manage it.

I can't access the paper. And even if I could I probably would not be able to figure this out.

I had an end-tidal of 34 (was 39) that is 12,82% but was CBF velocity measured? CBF dropped 25%.
I had no lightheadiness.
Severe cognitive problems were the reason I was tested, no "normal" OI problems.
I belong to the third group, no POTS, no dOH, but heartrate up and BP down a bit. The mixed bag-group.
How would that influence the findings of this paper?

 

[Nightsong]

This study found that the instantaneous changes in CBFv and end-tidal CO2 predict orthostatic lightheadedness during head-up tilt, and can be used as an objective marker of OI. CBFv had a larger effect than end-tidal CO2. The intensity of lightheadedness was also proportional to the decline of CBFv and ET-CO2. The study also confirmed that orthostatic heart rate and blood pressure were poor predictors of orthostatic lightheadedness.

In our patients, an orthostatic decline in CBFv correlated with signs of cerebral hypoperfusion. In most of our patients (except of OCHOS), the decline in orthostatic CBFv was driven by orthostatic hypocapnic hyperventilation, e.g., reduced ET-CO2.

A fascinating paper. Only 22 patients, so a small sample size, and potential referral bias which the authors acknowledge, but will be interesting to see if this replicates.

 

[Ken Turnbull]

@Turtle, I suspect the researchers chose subjects who had complained of frequent orthostatic lightheadedness so that there would be a single common symptom for the subjects to report during the testing.

I am not sure how they chose the subjects in general terms, as it only says that they had OI. Did they all have one particular kind of OI, or were they a mixed group?

One of the Visser, van Campen et al papers noted that quite a few subjects with ME/CFS who did not report OI symptoms on questioning still had a drop in cerebral blood flow. So it is possible that, like you, these folk did not report typical OI symptoms such as lightheadedness.

(Sorry, I can't find which of their many studies found this. Perhaps someone else could jump in with the reference.)

I am sure they will get round to including everyone eventually.

 

[Ken Turnbull]

It's nice that Dr Novak had Brazilian co-authors. We need this knowledge to spread!

 

[Nightsong]

(Sorry, I can't find which of their many studies found this. Perhaps someone else could jump in with the reference.)

"some individuals who did not endorse orthostatic symptoms before the study nonetheless had substantial reductions in cerebral blood flow." (link)

I am not sure how they chose the subjects in general terms, as it only says that they had OI. Did they all have one particular kind of OI, or were they a mixed group?

The study population included patients referred for evalua- tion of chronic orthostatic intolerance which was defined as the presence of symptoms of cerebral hypoperfusion with standing and relief of symptoms by recumbency for six months or longer [1]. The most common orthostatic symptoms were lightheaded- ness or dizziness accompanied by dyspnea.

Inclusion criteria were a history of OI for the duration at least six months, that was unexplained and not attributed to other known diseases such as pulmonary disorder, car- diac arrhythmia, heart failure, metabolic derangement, and genetic disorder [1]. To exclude the effect of technical arti- facts such small temporal bone window, we required that all OI patients had normal supine CBFv and normal brain imaging, either CT or MRI.

For controls, we used patients referred for evaluation of unexplained paroxysmal loss of consciousness which was attributed to vasovagal syncope or vasovagal reaction. Typi- cal history included sudden (seconds) loss of consciousness while upright, provoked by prolonged standing or exposure to hot weather associated with typical syncopal prodromes such as lightheadedness, blurred vision changes and/or dyspnea [15]. Controls had normal cardiac evaluation which ruled out cardiac causes of syncope, they did not have a history of OI except for suspected vasovagal syncope and had normal and asymptomatic head-up tilt tests. Controls were matched to OI patients using age, gender, and BMI as matching criteria.

 

[Ken Turnbull]

@Nightsong, many thanks for filling in those gaps for me.