High-Flow Oxygen for Treatment of Cluster Headache A Randomised Trial

Authors:  Anna S. Cohen, PhD, MRCP;  Brian Burns, MD, MRCP; Peter J. Goadsby, MD, PhD,DSc,FRACP,FRCP
Source:  JAMA, Vol 302, No. 22, December 9, 2009


Cluster Headache is a stereo typical primary headache syndrome characterized by attacks of unilateral excruciating pain usually in the eye, periorbital region, and temple with associated cranial autonomic symptoms such as conjunctival injection, lacrimation, nasal blockage, rhinorrhea, ptosis, and eyelid edema. During attacks patients are often restless, agitated, or both. Attacks typically last for 15 to 180 minutes untreated and have a frequency of 1 every other day for up to 8 attacks a day.
Attacks usually occur in bouts, or clusters, lasting for weeks or months, separated by remissions lasting months or years. Episodic cluster headache is defined as bouts of attacks lasting 7 days up to a year with breaks of 1 month or more between bouts. Bouts are usually circannual, occurring once a year, with a mean bout duration of 8 weeks. Chronic cluster headache is defined as occurring for more than a year without remission or with remissions lasting less than a month. Cluster headache attacks may also occur with clocklike regularity during the day and may be precipitated by sleep, usually occurring 90 minutes after the onset of sleep. Cluster headache affects more men than women (male-female ratio of 2.5:1) and has an estimated prevalence of 0.3% in the general population. Cluster headache is probably the most severe pain known to humans. Most female patients describe each attack as worse than childbirth.
Context: Cluster headache is an excruciatingly painful primary headache syndrome, with attacks of unilateral pain and cranial autonomic symptoms. The current licensed treatment for acute attacks is subcutaneous sumatriptan.
Objective: To ascertain whether high-flow inhaled oxygen was superior to placebo in the acute treatment of cluster headache.
Design, Setting, and Patients: A double-blind, randomized, placebo-controlled crossover trial of 109 adults (aged 18-70 years) with cluster headache as defined by the International Headache Society. Patients treated 4 headache episodes with highflow inhaled oxygen or placebo, alternately. Patients were randomized to the order in which they received the active treatment or placebo. Patients were recruited and followed up between 2002 and 2007 at the National Hospital for Neurology and Neurosurgery, London, England.
Intervention: Inhaled oxygen at 100%, 12 L/min, delivered by face mask, for 15 minutes at the start of an attack of cluster headache or high-flow air placebo delivered alternately for 4 attacks.
Main Outcome Measures:  The primary end point was to render the patient pain free, or in the absence of a diary to have adequate relief, at 15 minutes. Secondary end points included rendering the patient pain free at 30 minutes, reduction in pain up to 60 minutes, need for rescue medication 15 minutes after treatment, overall response to the treatment and overall functional disability, and effect on associated symptoms.
Results: Fifty-seven patients with episodic cluster headache and 19 with chronic cluster headache were available for the analysis. For the primary end point the difference between oxygen, 78% (95% confidence interval, 71%-85% for 150 attacks) and air, 20% (95% confidence interval, 14%-26%; for 148 attacks) was significant (Wald test, 2 5=66.7, P.001). There were no important adverse events.
Conclusion: Treatment of patients with cluster headache at symptom onset using inhaled high-flow oxygen compared with placebo was more likely to result in being pain-free at 15 minutes.
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