Treatment of acute migraine by a partial rebreathing device: A randomized controlled pilot study

Abstract

Background Impaired brain oxygen delivery can trigger and exacerbate migraine attacks. Normoxic hypercapnia increases brain oxygen delivery markedly by vasodilation of the cerebral vasculature, and hypercapnia has been shown to abort migraine attacks. Stable normoxic hypercapnia can be induced by a compact partial rebreathing device. This pilot study aimed to provide initial data on the device's efficacy and safety. Methods Using a double-blinded, randomized, cross-over study design, adult migraine-with-aura patients self-administered the partial rebreathing device or a sham device for 20 minutes at the onset of aura symptoms. Results Eleven participants (mean age 35.5, three men) self-treated 41 migraine attacks (20 with the partial rebreathing device, 21 with sham). The partial rebreathing device increased mean End Tidal CO2 by 24%, while retaining mean oxygen saturation above 97%. The primary end point (headache intensity difference between first aura symptoms and two hours after treatment (0-3 scale) - active/sham difference) did not reach statistical significance (-0.55 (95% CI: -1.13-0.04), p = 0.096), whereas the difference in percentage of attacks with pain relief at two hours was significant ( p = 0.043), as was user satisfaction ( p = 0.022). A marked efficacy increase was seen from first to second time use of the partial rebreathing device. No adverse events occurred, and side effects were absent or mild. Conclusion Normoxic hypercapnia shows promise as an adjunctive/alternative migraine treatment, meriting further investigation in a larger population. Clinical study registered at ClinicalTrials.gov with identifier NCT03472417.

Keywords: CO2 therapy; Migraine; headache; hypercapnia; rebreathing.

Figures

Figure 1.

Schematic of the partial rebreathing device. 1: Flexible-volume rebreathing reservoir, having in its walls laser perforations; 2: Mouthpiece; 3: Mouthpiece opening, connecting the inside of the reservoir with the mouth of the user; 4: Bypass valve opening; 5: Adjustable slider, regulating the flow through the bypass valve.

Figure 2.

Photo of the active device (left) and the sham device (right), showing (a) the folded rebreathing reservoirs; (b) bypass valves; (c) reservoir connectors, shown dismounted from mouthpiece boxes (d); (e) sham device airflow redirection holes, with protruding structure for preventing accidental blocking by fingers, (f) sham device one-way check valve.

Figure 3.

Box/scatter plots of the continuous-variable end points. (a) Active-sham differences of symptom scores of headache, nausea, light/sound sensitivity and functional disability, comparing zero and two hours. (b) Active-sham differences of end-of-period scores of subjective treatment effect, treatment preference, satisfaction with device and likelihood to use in future (for the subjective treatment effect and treatment preference, some data points are missing). Circles are individual patient data points, horizontal black bars indicate means, dark grey boxes indicate confidence intervals (mean ± 1.96 standard errors of the mean), light grey boxes indicate the interval of the mean ± one standard deviation, and the red horizontal line indicates the zero-line (corresponding to no difference between active and sham device). For the parameters in Figure 3(a), values below zero correspond to a better effect of the active over the sham. For the parameters in Figure 3(b), values above zero correspond to a better effect of the active over the sham.

Figure 4.

Comparison of active vs. sham device effect on pain relief at two hours (left) and pain freedom at two hours (right), showing differences between first use and second use of device.

Figure 5.

Changes in symptom severity during the first two hours, for headache (top left), nausea (top right), light/sound sensitivity (bottom left) and functional disability (bottom right). Mean values and corresponding 95% confidence intervals are shown.