AUTHORS’ ABSTRACT: 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 high- flow inhaled oxygen or placebo, alternately. Patients were randomized to the order in which they received the active treatment or placebo. Patients were recruited and fol- lowed up between 2002 and 2007 at the National Hospital for Neurology and Neu- rosurgery, 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 deliv- ered 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 clus- ter 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, 25=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.
Dr. Sewell’s comment:
In the last couple of months, there has been a spate of news articles about cluster headache. USA Weekend Magazine: “Oxygen may ease cluster headaches”; Personal Liberty Digest: “High-flow Oxygen Can Relieve Cluster Headaches, New Study Suggests”; Pain.com: “Oxygen Proves as Possible Treatment for Cluster Headaches”, and so on. Those of you have been using oxygen for years are no doubt bemused by this. New study shows that the Pope is Catholic? Will modern science next tell us what bears do in the woods? Just what is all the fuss about?
It is true that we have known for years that oxygen helps cluster headache. Lee Kudrow, the granddaddy of cluster headache research (a cluster headache researcher who coincidentally suffers from cluster headache himself), first reported this in 1981, and this treatment is now incorporated into standard guidelines. I myself have found it more effective than triptans, to the point that when someone tells me that oxygen doesn’t work for them, my first thought is that they either aren’t using a proper non-rebreather mask or else just haven’t turned the flow rate up high enough. Everyone knows that oxygen works.
But what exactly is the scientific evidence? Surprisingly, not much. Dr. Kudrow’s original observations, a small study of 19 patients published by Dr. Fogan of UCLA in 1985 confirmed them, and that’s it. In a way, oxygen is a victim of it’s own success—there are no randomized placebo-controlled trials showing that parachutes are effective in preventing death caused by jumping out of an airplane; it’s so obvious that nobody has bothered. And yet it matters—insurance companies love to call something an “experimental treatment” and deny coverage; the modern crop of doctors raised with “evidence-based medicine” like to see an evidence base for their medicine, and most cluster headache patients have found that getting oxygen therapy is more of a headache than the cluster attacks it’s supposed to treat.
Enter Dr. Anna Cohen, of the Headache Group at Queen Square, London. She is a member of Dr. Goadsby’s group, and I know that Dr. Goadsby has been going on about the need to formally study oxygen for years, so I’m not sure how much of this is her idea. The paper itself is beautifully written, however, one of the clearest scientific papers I’ve ever read, and I encourage readers of this blog to click on Cohen’s name at the top here and read it for yourselves; it almost doesn’t need my interpretation. For that, I’m sure Dr. Cohen deserves credit; it’s always the first author that does the actual writing.
So how did they do it? She took 109 cluster headache patients (episodic or chronic), and had each of them treat four cluster attacks with a tank of what was either pure oxygen or just room air, nobody was quite sure which until the study was over. The subjects used high-flow (12 L/min) for fifteen minutes, and if that didn’t work, they could use a “rescue medication”; what that was wasn’t listed but I presume it was Imitrex. Dr. Cohen was mostly interested in what proportion of people were pain-free (or had adequate relief) after 15 minutes, but also looked at whether subjects remained pain free at half an hour and one hour, whether other symptoms of a cluster attack (other than pain) were affected, and how many people needed rescue medication.
What did she find? At the fifteen-minute point, 78% of subjects who used oxygen were pain-free, versus only 20% of patients receiving room air. At the one-hour point, 95% of the oxygen users had reduced pain (meaning, 1 point or more decrease on a 4-point pain scale) versus 38% of air users. Only 30% of oxygen breathers needed “rescue medication” at the 15-minute point, versus 76% of the air breathers. 81% of the oxygen breathers also had less runny nose, droopy eye, etc (associated symptoms) versus 40% of the air breathers. It was a clear win for oxygen. Did it work any differently with chronic cluster headache patients than episodic? Here Dr. Cohen waffles a little bit, saying that only a fifth of the group had chronic cluster headache, and some of them had used oxygen before… but it appears to work just as well no matter what the subtype.
So finally, we have scientific proof that inhaled oxygen treats cluster headache! The 78% success rate is impressive, and privately I wonder if it could have been even higher if Dr. Cohen had cranked the flow rate up to, say, 15L/min. Oxygen is a great alternative for anyone who can’t take triptans, and is mercifully free of side effects. This study will help doctors and patients in their battles with insurance companies everywhere.
I was discussing oxygen with Dr. Kudrow at a meeting of the American Headache Association in Los Angeles a few years ago. “You know,” he mused, “a farmer came to me just after the War and told me that he was using oxygen from a welding tank in his barn to abort his cluster attacks. I dismissed it as nonsense. It was twenty years later that I realized he was right. I wish I’d paid attention then!” One wonders what else cluster headache patients are telling us that we’re not paying attention to!