JADE Student Edition 2019 JADE JSLUG 2019 | Page 37

Pre-acclimatisation has also been suggested as a preventative measure against altitude sickness and involves spending a period of time at moderate altitude prior to ascending to the final altitude however, studies have shown conflicting results. Whilst some studies demonstrate benefits associated with pre-exposure to hypobaric hypoxia, others demonstrate no significant effect (Forster, 1985; Küpper and Schöffl, 2010; Guo et al., 2016; Luks et al., 2017). One study (Forster, 1985) demonstrated decreased incidence of altitude sickness in sea level residents undertaking frequent and rapid ascents to elevations of 4,200m when a “shift-worker” pattern of 5-days spent at the designated height, followed by the same period spent at sea-level was followed. Another study (Guo et al., 2016) demonstrated a significant increase in performance and reduction of AMS incidence at 4400m after a 4-day short term pre-exposure at 3700m. Furthermore, the use of hypoxic chambers at sea-level for pre-acclimatisation effects has been shown to reduce the incidence of AMS with recommendations suggesting that the pre-acclimatisation process is performed sleeping at simulated altitudes following an ascent profile that replicates the “gold-standard” for typical acclimatisation (Küpper and Schöffl, 2010; Fulco et al., 2013; Luks et al., 2017). Oxygen Enrichment As previously mentioned, reduction of PO2 to below 60mmHg – such as at high altitude – results in rapid decline of SO2 leading to compromised oxygen delivery to the tissues therefore supplementary oxygen has long been considered preventative against AMS. West (2004) compared the effects of ventilatory acclimatisation and oxygen enrichment on the improvement of oxygenation. The study measured alveolar PO2 and reduction in equivalent altitude as a measure of oxygenation and showed that full ventilatory acclimatisation at altitudes of up to 3600m reduced the equivalent altitude sufficiently for supplementary oxygen not to be necessary. At altitudes between 3600-4200m, full acclimatisation reduces equivalent altitude to approximately 3400m. Dependent on the pattern of ascent, oxygen enrichment may or may not be necessary for ascend to these altitudes. For ascent to altitudes of greater than 5050m, oxygen enrichment is suggested in order to optimise mental and physical performance, where an oxygen supplementation of 27% at 5000m is capable of reducing equivalent altitude to around 3200m – generally well tolerated (West, 2004). However, there is conflicting evidence in terms of the use of placebo oxygen. Some studies exploring the effects of placebo in the place of real oxygen supplementation have shown that a placebo is capable of mimicking the effects of oxygen at altitudes as high as 4500-5500m, whilst other studies have shown that placebo oxygen had no effect on reducing the incidence of altitude sickness, other than potentially decreasing fatigue (Fabrizio et al., 2015; Benedetti et al., 2018; Moraga et al., 2018). Chemoprophylaxis Acetazolamide is a carbonic anhydrase (CA) inhibitor. Carbonic anhydrases are enzymes that catalyse the conversion reaction between carbon dioxide + water and carbonic acid (bicarbonate ions + hydrogen ions). The active site of most carbonic anhydrase enzymes contains a zinc ion and it is to this zinc ion that acetazolmide binds to in order to inhibit the enzymes action. Inhibition of renal carbonic anhydrase by acetazolamide results in removal of bicarbonate by urination as well as metabolic acidosis (increased hydrogen ions in the blood causing acidic blood) which increases the ventilatory response and arterial PO2. Typical recommendations for acetazolamide as a prophylactic state that use should start a minimum of one day prior to ascent, and a maximum of five (Wright et al., 1983). Dexamethasone is a glucocorticoid (a type of steroid hormone); its effects most likely mediated through changes to capillary permeability and cytokine release. Due to its significant side effects, dexamethasone is not typically recommended for prophylaxis unless acetazolamide is contraindicated. In one double-blind, randomised trial, 47 climbers were given either 250mg acetazolamide, 4mg dexamethasone, or a placebo every 8 hours as a Article #5 37