Objective

To demonstrate that high oxygen flow rates improve headache response in previously oxygen refractory cluster headache patients.

Background

Effective abortive therapy for cluster headache is essential based on the extreme intensity of the pain. The two most effective cluster abortives are injectable sumatriptan and inhaled oxygen. As most cluster sufferers are cigarette smokers and at high risk of coronary artery disease, many develop contraindications to triptans. Oxygen, the safest of all cluster therapies, is not effective in every patient. In Kudrow's landmark study¹ 75% of patients responded to 100% oxygen at 7 L/min although only 57% of older chronic cluster patients had relief. Rozen et al^.2 documented a gender difference in response to oxygen as only 59% of their female cluster patients responded to oxygen, whereas 87% of men did. In almost every textbook and article written on the subject of cluster treatment, patients are instructed to use 100% oxygen via a non-rebreather face mask at 7-10 L/min. The rationale behind this prescribed oxygen flow rate is unknown but has become doctrine since the Kudrow1 study. Prescribing higher flow rates of oxygen up to 12 L/min has recently been suggested but there is no documentation that this may improve efficacy.³ The abortive effect of higher oxygen flow rates (up to 15 L/min) in cluster patients refractory to standard oxygen therapy is unknown.

Methods

Three cluster headache patients who demonstrated no response to standard oxygen therapy were exposed to higher flow rates of oxygen (up to 15 L/min) to assess response.

Results

Patient 1: 53-year-old man with history of episodic cluster headache since the age of 12. No history of cigarette smoking. Oxygen via a non-rebreather face mask at 7-10 L/min had no effect on his headaches. In the clinic he developed a cluster headache and 100% oxygen at a flow rate of 15 L/min alleviated his head pain. He has now used the oxygen multiple times at home at 15 L/min and has complete headache relief.

Patient 2: 34-year-old woman with chronic cluster headache for 4 years. Smokes 2 packs of cigarettes per day for many years. Oxygen via a non-rebreather face mask at 7-10 L/min never changed the intensity of a cluster headache. At 14 L/min the patient experienced anywhere from 70% to 100% relief of her headaches and this response was reproducible.

Patient 3: 37-year-old man with chronic cluster headache for 16 years. He smokes 1 pack of cigarettes per day for many years. Oxygen via a non-rebreather face mask at 7-10 L/min never had any effect on his headaches. At 15 L/min the patient had complete headache relief. This response has been reproduced consistently multiple times.

Discussion

The basis by which oxygen turns off a cluster headache is unknown but is unique to this primary headache. Oxygen's vasoconstrictive effect on cerebral vessels may play a significant role.⁴ Why 100% oxygen delivered at variable rates would have disparate effects on cluster headache in different individuals is unknown. One study documented that cluster patients with the greatest reduction in cerebral blood flow after oxygen inhalation had the most benefit from oxygen therapy.⁵ Two of the 3 presented patients had a significant smoking history and it may be in that setting that higher flow rates of oxygen are needed to see an abortive response of cluster headache. In the Rozen et al.² investigation, women responded less to standard oxygen therapy than men and in that study 75% of the women had a smoking history versus 61% of the men. Chronic smokers have been shown to have a decreased cerebral vasoconstrictor response to 100% oxygen compared with nonsmokers.⁶ If cerebral vessel constriction and subsequent reduction in cerebral blood flow is one of the keys to oxygen's abortive effect in cluster, cluster patients with a more substantial smoking history would theoretically have less vasoconstrictor response to 100% oxygen, especially at low flow rates and thus a poor response to standard oxygen therapy. Increasing the flow rate of oxygen could conceivably overcome this deficit in cerebral vasoconstrictor response, leading to headache alleviation. Before exposing cluster patients with a smoking history to high flow rates of 100% oxygen it is imperative to determine if they may be at risk of respiratory suppression with high levels of oxygen because of a history of chronic carbon dioxide retention from obstructive lung disease.

Conclusion

From this clinical observation it appears that cluster headache patients should not be deemed refractory to oxygen therapy unless flow rates up to 15 L/min have been utilized. Each of the presented patients had tried oxygen several times at the 7-10 L/min flow rate and experienced no change in headache intensity. On the higher flow rate the patients had complete or near-complete headache alleviation.

MHNI Headache Division Staff

References

1. Kudrow L. Response of cluster headache attacks to oxygen inhalation. Headache 1981;21:1-4.
2. Rozen TD, Niknam R, Shechter AL, Silberstein SD. Gender differences in clinical characteristics and treatment response in cluster headache patients. Cephalalgia 1999;19:323.
3. Matharu MS, Boes CJ, Goadsby PJ. Management of trigeminal autonomic cephalalgias and hemicrania continua. Drugs 2003;63:1637-1677.
4. Drummond PD, Anthony M. Extracranial vascular responses to sublingual nitroglycerin and oxygen inhalation in cluster headache patients. Headache 1985;25:70-74.
5. Hardebo JE, Ryding E. Cerebral blood flow response to oxygen in cluster headache. In: Olesen J, ed. Migraine and Other Mechanisms. New York: Raven Press, 1991;311-314.
6. Rogers RL, Meyer JS, Shaw TG, Mortel KF, Thornby J. The effects of chronic cigarette smoking on cerebrovascular responsiveness to 5 percent CO2 and 100 percent O2 inhalation. J Am Geriatr Soc 1984;32:415-20.