Rebuttal to the PRO Statement

In his article about the use of corticosteroids, Richalet (2015) lumps HAPE, AMS, and HACE into “severe high altitude illness” because of a common sign, increased endothelial permeability, which may at some stage be caused by hypoxia-induced inflammation. However, permeability changes occur in different organs and with a different time course and not always due to inflammation, as indicated by the fact that only a few people with AMS develop HAPE, that many of those susceptible to HAPE have no or only low AMS scores, and that AMS progresses into HACE. This makes organ-specific defects more likely than a common mechanism, which also makes them independent diseases.

Their management, the main focus here being HAPE, involves prevention and treatment. We agree with Richalet (2015) that all potential pathogenic mechanisms, not only increased endothelial permeability, but also hypoxic pulmonary vasoconstriction (HPV) and decreased alveolar fluid clearance, may be prevented by prophylactic intake of DEX. But why take a drug when there are drug-independent means of prevention such as pre-acclimatization and slow ascent (Bärtsch, 1999) and, if needed, excellent pulmonary vasodilators.

Therefore, the main argument for using DEX is treatment of HAPE. Again, we agree on potentially beneficial effects by fighting excessive leakage (Richalet, 2015), exaggerated HPV, and impaired alveolar fluid clearance. However, the benefit of DEX in suppressing these detrimental mechanisms is hampered by the delayed onset of action, which is in the range of many hours, and by high concentrations required. This is well documented in the clinical studies cited by Richalet, and which we also provided in our “con-statement.” So we agree that in the long run, DEX may work, but no rapid effects desirable to prevent deterioration can be expected. Furthermore, it is hard to understand the suggestion to supplement fast-acting drugs such as Ca-antagonists and PDE5 inhibitors with the intake of slow-acting DEX (Richalet, 2015), when those drugs alone do the job. There is no question that DEX and acetazolamide should be given when there are symptoms of severe AMS and HACE (Bärtsch and Swenson, 2013; Bärtsch and Bailey, 2014).

Thus, we agree on the need of a study investigating the sole use of DEX for the treatment of HAPE after it has been diagnosed. However, we wonder what the severely ill HAPE patient (not to mention the ethics committee reviewing such a study) will say if we withhold oxygen and don't decrease PA pressures quickly by proven means to prevent alveolar flooding, but rather only use DEX without good evidence that it works quickly.