Aspirin for prophylaxis against headache at high altitudes: randomised, double blind, placebo controlled trial

At altitudes of 3000-5000 m about 20-50% of skiers and mountaineers experience headache, the main symptom of acute mountain sickness.¹ Although most mountaineers know that they should avoid climbing great heights too early on and too fast, they may not always act accordingly. The use of drugs to prevent and treat headaches at high altitudes is therefore widespread, aspirin being one of the most commonly taken. We tested the efficacy of aspirin as prophylaxis against headache at high altitudes.

Subjects, methods, and results

Twenty nine volunteers with a history of headache at high altitude were randomly assigned in a double blind fashion to receive placebo (eight men, six women, mean age 38 (SD 12) years) or 320 mg aspirin (nine men, six women, mean age 38 (14) years). After examination at low altitude (600 m), subjects were transported to high altitude (3480 m) for 24 hours. We gave them three tablets, one every 4 hours, starting 1 hour before arrival at high altitude. We scored headache on a four-point scale (0=none, 1=mild, 2=moderate, 3=severe) and measured heart rate, blood pressure, and arterial oxygen saturation 1 hour before and 3, 7, 10, and 19 hours after arrival. In addition, subjects exercised for 2 minutes by stepping 60 times up and down a 24 cm step, at low altitude and within 2-5 hours after arrival at high altitude during which we continuously monitored gas exchange, heart rate, and oxygen saturation.

Seven subjects given placebo and only one given aspirin developed mild to severe headache (P=0.01 for differences in proportions). Although mean oxygen saturation was not different between the two groups 3 hours after arrival at high altitude, the individual values were accurate predictors of the subsequent development of headache. Those who had taken aspirin developed headache at lower oxygen saturation than those who had taken placebo (<83% v <88%; figure). The difference between mean heart rates at the end of the exercise test at high and low altitudes was smaller in those who had taken aspirin (134 (7) v 118 (10) beats/min) than in those who had taken placebo (142 (13) v 116 (15)) (P=0.01, analysis of variance for repeated measures), in whom ventilation responses to exercise tended to be higher (P=0.07). In the placebo group, the difference in heart rate at high altitude was positively correlated with maximum headache scores (r=0.8, P<0.01) and inversely related to saturation values 3 hours after arrival at high altitude (r=–0.8, P<0.01; figure).

Comment

The incidence of headache at high altitude increases when arterial oxygen saturation and associated oxygen partial pressure decline with increasing altitude.² In this study, however, aspirin prevented headache without improving oxygenation. Pretreatment with aspirin raised the headache threshold, which was indicated by toleration of lower saturation values. Moreover, intake of aspirin was associated with less pronounced cardiorespiratory responses to short term exercise at high altitude. Since acute hypoxia augments prostaglandin concentrations,³ and prostaglandins increase ergoreceptor activation and accompanying sympathetic stimulation,⁴ aspirin probably prevents headache by diminishing these responses. Prostaglandins also enhance nociception, and reduced hyperalgesia may therefore have contributed additionally to the prophylactic efficacy of aspirin. Nevertheless, within the first few days of exposure to high altitude, symptoms of acute mountain sickness usually disappear even without drugs. Simultaneously, sympathetic responsiveness decreases due to desensitisation of adrenoceptors,⁵ again indicating some relation between sympathetic activity and development of headaches at high altitude. If this relation is true, aspirin may support adaptation to high altitude by reducing sympathetic activity mediated by prostaglandins.

Figure.

Relation between arterial oxygen saturation values 3 hours after arrival at high altitude, and difference in heart rate after exercise at high and low altitudes in subjects taking placebo or aspirin. s shows subjects who developed headache at high altitude