Background
Acute high altitude illness, also known as acute mountain sickness, may present with a variety of symptoms. It is caused by the decreasing level of oxygen at increasingly high altitudes; and it can be experienced when reaching a high altitude when travelling, hiking or climbing mountains or other elevated areas. People going to altitudes over 4000 metres, females, people younger than mid-adulthood , and people with a history of migraine are at greater risk of suffering from altitude sickness. The most common symptoms are headache, loss of appetite , insomnia, and nausea. However, severe forms can include confusion, difficulty walking, progressive cough, shortness of breath, and even death.
Review question
What are the benefits and risks of different treatments for people suffering from high altitude illness?
Study characteristics
We included 13 studies with a total of 468 participants. Most studies included participants with mild or moderate forms of mountain sickness, and only one study included the severe neurological (disorder of the nervous system) form. Follow-up was usually less than one day. We also identified two ongoing studies.
Key results
We found studies evaluating the following interventions: simulated descent with a hyperbaric chamber (medical use of oxygen in a special chamber at greater than atmospheric pressure to increase the availability of oxygen in the body); oxygen; medicines: acetazolamide, dexamethasone, ibuprofen, paracetamol, gabapentin, sumatriptan, nitric oxide, and magnesium sulphate. None of the studies reported the effects of these interventions on all-cause mortality. The report of complete relief from acute mountain sickness symptoms, and adverse events was infrequent. Studies related to simulated descent with the use of a hyperbaric chamber did not find additional benefits or harms related to this intervention (3 studies, 124 participants). In addition, studies related to administration of medicines found some benefits in terms of reduction of symptoms with the use of acetazolamide (2 studies, 25 participants), and dexamethasone (1 study, 35 participants), without an increase in side effects.
Quality of the evidence
The quality of the evidence we found was low, and thus our certainty in the findings is limited. There was insufficient information on how the studies were conducted, and in some cases there was evidence of tampering at some stages of the trials. Furthermore, the number of persons in each study was very small (< 30 participants), and therefore the results were not clear (imprecise). Some studies were not blinded (that is, participants knew what experimental treatment they were receiving), and this could have affected how the participants evaluated their own symptoms.
There is limited available evidence to determine the effects of non-pharmacological and pharmacological interventions in treating acute high altitude illness. Low-quality evidence suggests that dexamethasone and acetazolamide might reduce AMS score compared to placebo. However, the clinical benefits and harms related to these potential interventions remain unclear. Overall, the evidence is of limited practical significance in the clinical field. High-quality research in this field is needed, since most trials were poorly conducted and reported.
Acute high altitude illness is defined as a group of cerebral and pulmonary syndromes that can occur during travel to high altitudes. It is more common above 2500 metres, but can be seen at lower elevations, especially in susceptible people. Acute high altitude illness includes a wide spectrum of syndromes defined under the terms 'acute mountain sickness' (AMS), 'high altitude cerebral oedema' and 'high altitude pulmonary oedema'. There are several interventions available to treat this condition, both pharmacological and non-pharmacological; however, there is a great uncertainty regarding their benefits and harms.
To assess the clinical effectiveness, and safety of interventions (non-pharmacological and pharmacological), as monotherapy or in any combination, for treating acute high altitude illness.
We searched CENTRAL, MEDLINE, Embase, LILACS, ISI Web of Science, CINAHL, Wanfang database and the World Health Organization International Clinical Trials Registry Platform for ongoing studies on 10 August 2017. We did not apply any language restriction.
We included randomized controlled trials evaluating the effects of pharmacological and non-pharmacological interventions for individuals suffering from acute high altitude illness: acute mountain sickness, high altitude pulmonary oedema or high altitude cerebral oedema.
Two review authors independently assessed the eligibility of study reports, the risk of bias for each and performed the data extraction. We resolved disagreements through discussion with a third author. We assessed the quality of evidence with GRADE.
We included 13 studies enrolling a total of 468 participants. We identified two ongoing studies. All studies included adults, and two studies included both teenagers and adults. The 13 studies took place in high altitude areas, mostly in the European Alps. Twelve studies included participants with acute mountain sickness, and one study included participants with high altitude pulmonary oedema. Follow-up was usually less than one day. We downgraded the quality of the evidence in most cases due to risk of bias and imprecision. We report results for the main comparisons as follows.
Non-pharmacological interventions (3 studies, 124 participants)
All-cause mortality and complete relief of AMS symptoms were not reported in the three included trials. One study in 64 participants found that a simulated descent of 193 millibars versus 20 millibars may reduce the average of symptoms to 2.5 vs 3.1 units after 12 hours of treatment (clinical score ranged from 0 to 11 ‒ worse; reduction of 0.6 points on average with the intervention; low quality of evidence). In addition, no complications were found with use of hyperbaric chambers versus supplementary oxygen (one study; 29 participants; low-quality evidence).
Pharmacological interventions (11 trials, 375 participants)
All-cause mortality was not reported in the 11 included trials. One trial found a greater proportion of participants with complete relief of AMS symptoms after 12 and 16 hours when dexamethasone was administered in comparison with placebo (47.1% versus 0%, respectively; one study; 35 participants; low quality of evidence). Likewise, when acetazolamide was compared with placebo, the effects on symptom severity was uncertain (standardized mean difference (SMD) −1.15, 95% CI −2.56 to 0.27; 2 studies, 25 participants; low-quality evidence). One trial of dexamethasone in comparison with placebo in 35 participants found a reduction in symptom severity (difference on change in the AMS score: 3.7 units reported by authors; moderate quality of evidence). The effects from two additional trials comparing gabapentin with placebo and magnesium with placebo on symptom severity at the end of treatment were uncertain. For gabapentin versus placebo: mean visual analogue scale (VAS) score of 2.92 versus 4.75, respectively; 24 participants; low quality of evidence. For magnesium versus placebo: mean scores of 9 and 10.3 units, respectively; 25 participants; low quality of evidence). The trials did not find adverse events from either treatment (low quality of evidence). One trial comparing magnesium sulphate versus placebo found that flushing was a frequent event in the magnesium sulphate arm (percentage of flushing: 75% versus 7.7%, respectively; one study; 25 participants; low quality of evidence).