High Flow Oxygen As Acute Therapy is Most Optimal for Headache Relief


Recent findings from a network meta-analysis suggest that high flow oxygen is more efficacious when compared with low flow oxygen for headache relief.

Ioana Medrea MD, MS, assistant professor, Department of Neurology, SUNY Upstate Medical University

Ioana Medrea MD

Findings from a recent network meta-analysis suggest that high flow oxygen is more efficacious in comparison with low flow oxygen for acute relief from cluster headache, suggesting that when patients who can tolerate oxygen are failing with low flow oxygen, an increased flow rate should be implemented.1 

Currently, there is limited evidence on acute treatments for cluster headache and most treatments only compared against placebos in clinical trials, whereas there are few head-to-head comparisons between treatments.

The analysis displayed high flow oxygen as the most effective therapy for headache relief at 15 and 30 min (odds ratio [OR], 9.0; 95% credible intervals [CrI], 5.3-15.9), followed by injectable sumatriptan at the next highest effect (OR, 6.4; 95% CrI, 3.75-11.1). In addition, high flow oxygen was also more effective than low flow oxygen (OR, 2.55; 95% CrI, 1.13-5.8), nasal spray zolmitriptan (OR, 3.75; 95% CrI, 1.72-8.4), octreotide (OR, 4.5; 95% CrI, 1.64-12.5), and noninvasive vagal nerve stimulation (nVNS; OR, 5.2; 95% CrI, 2.29 -11.9). 

This review is the first in identifying the important clinical findings such as patients who have a lack of success with low flow oxygen and can tolerate increased flow rates should be tried on high flow oxygen. As there is a lack of head-to-head clinical trials for acute therapies, the ability to provide guidance on the relative efficacy of the available therapies in comparison with each other may be valuable. Investigator Ioana Medrea MD, MS, assistant professor, Department of Neurology, SUNY Upstate Medical University, and colleagues noted, “Our findings that nVNS may be effective in acute management of episodic cluster and that sphenopalatine ganglion may be effective for chronic cluster also represent important findings worthy of additional study.”

The network meta-analysis consisted randomized controlled trials to identify the evaluation of treatments in adult patients greater than 18 years old of age with cluster headache in accordance with the accepted diagnostic criteria. Bayesian network meta-analyses were conducted for comparing treatments in terms of headache relief at 15 or 30 min, along with the occurrence of adverse events. The researchers reported the OR of relative treatment effects along with the corresponding 95% CrI as well as measures of treatment ranking.

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Additional findings showed that the sumatriptan injectable was also effective for headache relief, better than nasal spray zolmitriptan (OR, 2.67; 95% CrI, 1.21-5.9), octreotide (OR, 3.20; 95% CrI, 1.17-8.8), and nVNS (OR,3.69; 95% CrI, 1.63-8.4). Notably, octreotide (odds ratio 4.1; 95% CrI,1.71-10.5) and sumatriptan (OR, 2.40; 95% CrI, 1.39-4.2) were associated with greater risk of adverse events in comparison with the placebo, while other treatments did not demonstrate increased risk. nVNS was significantly better than placebo (OR, 4.9; 95% CrI, 1.89-14.1) when focused on patients with episodic cluster headache.

In accordance with the most recent systematic reviews and guidelines for CH findings, this analysis review also found oxygen to be effective as acute therapy.2,3 The limitations from this analysis include that the data collection was conducted by a single author and that for most of the treatment comparisons, the linking node that facilitated the conduct of analysis was the placebo.

Medrea et al wrote, “We do not show in our companion scoping review that for the treatment efficacy response there was little variability in the placebo response rates between various treatment modalities, and as such we do not think this influenced our results for the treatment efficacy.”They added that network meta-analyses, in general, can play a critical role in establishing the relative benefits and risks of treatment modalities for a disease and can be confounders such as differing trial characteristics that modify treatment response.1

1. Medrea I, Christie S, Tepper SJ, Thavorn K, Hutton B. Network meta-analysis of therapies for cluster headache: Effects of acute therapies for episodic and chronic cluster. Headache. 2022;62(4):482-511. doi:10.1111/head.14283
2. Robbins MS, Starling AJ, Pringsheim TM, Becker WJ, Schwedt TJ. Treatment of Cluster Headache: The American Headache Society Evidence-Based Guidelines. Headache. 2016;56(7):1093-1106. doi:10.1111/head.12866
3. Francis GJ, Becker WJ, Pringsheim TM. Acute and preventive pharmacologic treatment of cluster headache. Neurology. 2010;75(5):463-473. doi:10.1212/WNL.0b013e3181eb58c8
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