Effects of acetazolamide and dexamethasone on cerebral hemodynamics in hypoxia

Abstract

Previous attempts to detect global cerebral hemodynamic differences between those who develop headache, nausea, and fatigue following rapid exposure to hypoxia [acute mountain sickness (AMS)] and those who remain healthy have been inconclusive. In this study, we investigated the effects of two drugs known to reduce symptoms of AMS to determine if a common cerebral hemodynamic mechanism could explain the prophylactic effect within individuals. With the use of randomized, placebo-controlled, double-blind, crossover design, 20 healthy volunteers were given oral acetazolamide (250 mg), dexamethasone (4 mg), or placebo every 8 h for 24 h prior to and during a 10-h exposure to a simulated altitude of 4,875 m in a hypobaric chamber, which included 2 h of exercise at 50% of altitude-specific VO(2max). Cerebral hemodynamic parameters derived from ultrasound assessments of dynamic cerebral autoregulation and vasomotor reactivity were recorded 15 h prior to and after 9 h of hypoxia. AMS symptoms were scored using the Lake Louise Questionnaire (LLQ). It was found that both drugs prevented AMS in those who became ill on placebo (~70% decrease in LLQ), yet a common cerebral hemodynamic mechanism was not identified. Compared with placebo, acetazolamide reduced middle cerebral artery blood flow velocity (11%) and improved dynamic cerebral autoregulation after 9 h of hypoxia, but these effects appeared independent of AMS. Dexamethasone had no measureable cerebral hemodynamic effects in hypoxia. In conclusion, global cerebral hemodynamic changes resulting from hypoxia may not explain the development of AMS.

Fig. 1.

Top: autoregulation index (ARI) responses from normoxic baseline to 9 h of hypoxia for all trials. On placebo, cerebral autoregulation was impaired after 9 h of hypobaric hypoxia. Acetazolamide reduced ARI scores in normoxia, but prevented further impairment in autoregulation after 9 h of hypoxia. Dexamethasone improved autoregulation in normoxia, but had no measureable effect in hypoxia. Bottom: circular markers indicate acute mountain sickness (AMS)-susceptible subjects (n = 6) identified during the placebo trial. Autoregulation was similar in AMS-susceptible and AMS-resistant subjects across all trials.