Cluster Headache—Acute and Prophylactic Therapy

Avi Ashkenazi, MD; Todd Schwedt, MD


Headache. 2011;51(2):272-286. 

In This Article


Oxygen inhalation has been used for the treatment of acute CH attacks for decades.[1] The major advantage of oxygen is the virtual lack of AEs. As opposed to triptans, oxygen can be given to patients with a history of cardiovascular or cerebrovascular disease. The mechanism of action of oxygen on CH has long been related to its vasoconstrictive effect.[14] More recently, however, it has been shown that oxygen inhibits neuronal activation in the trigeminal nucleus caudalis when this activation is initiated by stimulation of the parasympathetic outflow through the facial nerve.[15] Oxygen has been evaluated as an acute treatment of CH in a number of studies.[16] In an open study, Kudrow examined the efficacy of oxygen for acute CH attacks in 52 patients.[17] Oxygen 100% was inhaled via a facial mask at a rate of 7 liters/minute (L/min) for 15 minutes. Thirty-nine (75%) patients experienced significant pain relief within 15 minutes. The best response was observed in younger (<50 years old) patients who had ECH. Fogan examined the efficacy of oxygen for acute CH in a double blind crossover study.[18] Nineteen men were treated with either oxygen, or air inhalation, at a rate of 6 L/min. After treatment, average pain relief score was significantly higher for oxygen, as compared with air. Rozen examined the effect of high flow oxygen on CH pain in 3 patients who had been refractory to oxygen given at the standard flow rate of 7–10 L/min.[19] All 3 patients (2 with CCH and 1 with ECH) had complete or near-complete headache response after inhaling 100% oxygen at a rate of 14–15 L/min. Two of the patients were heavy smokers. The author suggested that patients who fail to respond to oxygen at the standard flow rate should be tried on higher flow. In a recent large controlled trial, Cohen et al examined the efficacy of high flow oxygen in the treatment of acute CH attacks.[20] A total of 109 patients treated 4 CH attacks with either oxygen (12 L/min) or inhaled air, given via a facial mask for 15 minutes. Oxygen was significantly superior to placebo with regards to the primary end point (elimination of pain or "adequate pain relief" at 15 minutes—78% vs 20%, with oxygen and air, respectively).

Hyperbaric oxygen (HBO) has also been studied as a treatment for acute CH attacks.[21,22] Weiss et al treated a CH patient with hyperbaric (2 atmospheres) 100% oxygen, after she had been refractory to conventional oxygen therapy.[21] Two attacks were treated with HBO, with prompt and complete pain relief. Di Sabato et al treated 7 ECH patients with HBO in a placebo controlled study.[22] Six patients responded well to treatment, with interruption of their attack. Moreover, in 3 of the responders the CH period ended after HBO treatment. Placebo treatment had no effect on pain.

In summary, normobaric oxygen is an effective treatment of acute CH attacks in the majority of patients. It is well tolerated and has virtually no AEs. As opposed to triptans, there is no limitation to the number of times per day it can be used. A proper technique of use is crucial for good results with oxygen therapy. The patient should be instructed to use the oxygen via a non-rebreathable mask, at a rate of 7–10 L/min, in a sitting position, for at least 15–20 minutes. Patients may increase the flow rate up to 15 L/min if needed. The optimal flow rate should be determined individually for each patient. The major disadvantage of oxygen therapy is its inconvenience of use, particularly when the patient is out of home. Portable oxygen tanks are available for patients who wish to use it in these circumstances. Oxygen therapy for CH should be used with caution, or even avoided, in patients with chronic obstructive pulmonary disease, because of the risk of respiratory depression. HBO may be considered for refractory CH patients. However, because this is not a readily available therapy, and there is no evidence for a sustained effect of it on CH,[23] the majority of patients are not likely to benefit from it.


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