HAPE was diagnosed according to the 1991 International Hypoxia Sy

HAPE was diagnosed according to the 1991 International Hypoxia Symposium criteria, and HACE was diagnosed according to the Lake Louise criteria.[7] All groups were accompanied by physicians trained in assessment and treatment of HAI. Group physicians served as clinical evaluators for assessment of the study endpoints.

The secondary endpoint was diagnosis of AMS according to the Lake Louise criteria.[7] Symptoms were evaluated twice daily (self-assessment questionnaire) and at the summit. We used a one-sided Fisher’s exact test for the efficacy comparison, assuming that adding tadalafil to acetazolamide was superior to acetazolamide check details alone. Between the years 2006 and 2009, we assessed 68 participants in five groups Ribociclib molecular weight for study eligibility. Fifty-five climbers met the inclusion criteria and 51 had completed the study protocol: 24 in the tadalafil group and 27 in the control group (Table 1). Four climbers did not complete the study protocol and were not included in the final analysis (tadalafil, n = 3: 1 ankle sprain, 1 epistaxis, and 1 fever; control, n = 1: fever). All participants live at altitude <800 m, and none of them had any activity >2,000 m during the preceding 6 months. Tadalafil

and the control group participants had similar baseline characteristics (Table 1). Overall, 8 of the 51 (15.7%) participants developed severe HAI (Table 1). Severe HAI rates were significantly lower in the tadalafil group when compared with the control group [4.2% vs 25.9%; odds ratio (OR) = 8.05 (0.91–71.1), p = 0.03]. A reduction in the incidence of HAPE in the tadalafil group accounted for most of the difference (4.2% vs 22.2%, p = 0.06). All patients diagnosed with severe HAI developed the condition during the summit day. During ascent days 4 and 5, higher AMS symptom scores were noted in the tadalafil group compared with controls (day 4: 1.7 ± 1.4 vs 0.9 ± 1.3, p = 0.02; Pembrolizumab day 5: 2.1 ± 1.6 vs 1.0 ± 1.4, p = 0.01). We studied trekkers

with no previous history of HAPE or HACE and found that adding tadalafil to acetazolamide reduced the rate of severe HAI compared with acetazolamide-treated controls. Most of the difference between the groups was attributed to the reduction of HAPE rate in the tadalafil group. This finding is in concordance with the work of Maggiorini and colleagues who showed a reduction in HAPE incidence in susceptible individuals by using tadalafil or dexamethasone.[2] In contrast with Maggiorini’s study, we included trekkers without a previous history of HAPE. PDE5 inhibitors act by blocking the breakdown of cyclic GMP, an intracellular mediator of nitric oxide vasodilatory effects, thereby inhibiting hypoxic pulmonary vasoconstriction and pulmonary hypertension. This mechanism explains the possible efficacy in preventing HAPE in both susceptible and non-susceptible individuals. Severe HAI poses a major risk to trekkers, especially at extreme altitudes.

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