Risk Factors Associated With High Altitude Sickness: A Case-Control Study

INTRODUCTION

The primary environmental factor at high elevations is a decrease in barometric pressure. This decrease leads to a reduction in the partial pressure of oxygen at each stage of the process that carries oxygen from the air to the cells' mitochondria. This hypobaric hypoxia initiates a sequence of physiological responses that generally enable an individual to endure and adjust to the low-oxygen environment. However, there are instances where these responses become maladaptive, resulting in one of three forms of acute altitude illness: acute mountain sickness (AMS), high-altitude cerebral oedema (HACE), and high-altitude pulmonary oedema (HAPE). These diseases may occur within several hours or up to 5 days after ascending to a particular height and can range in severity from mild, having minimal impact on the scheduled travel itinerary, to a life-threatening condition..(1) Acute mountain sickness (AMS) is characterized by non-specific symptoms that emerge at altitudes of ⩾2500 m among unacclimatized individuals. These symptoms usually appear with a delay of 4-12 hours after arriving at a new altitude, and tend to be most intense after the first night spent there. When appropriate measures are taken, these symptoms typically resolve on their own.(2) Acute mountain sickness (AMS) is a collection of symptoms that typically involves a headache and at least one other symptom such as nausea/vomiting, fatigue, dizziness, or difficulty sleeping. It usually appears 6-12 hours after arriving at high altitude and generally resolves within 1-3 days. If left untreated, AMS can progress to high-altitude cerebral edema (HACE), which is characterized by altered mental status such as impaired mental capacity, drowsiness, stupor, and ataxia. Coma and even death can occur as soon as 24 hours after these symptoms develop.(3) High altitude pulmonary edema (HAPE) is a type of pulmonary edema that is non-cardiogenic in nature and may not be preceded by acute mountain sickness. Typically, it occurs between one and four days after arriving at altitudes higher than 2500 m.(4) There are several risk factors associated with altitude sickness, including the elevation of the individual's home, maximum altitude, sleeping altitude, rate of ascent, latitude, age, gender, physical condition, intensity of exercise, pre-acclimatization, genetic make-up, and pre-existing diseases. Both men and women are at similar risk of developing AMS, although some studies suggest that women may be slightly more susceptible. Contrary to popular belief, older individuals do not appear to be at higher risk of AMS. In fact, some studies suggest that younger individuals may be more susceptible. A previous history of AMS is a significant predictor for developing AMS upon subsequent exposure to comparable altitudes(5) It is unclear if other factors such as age, obesity, gender, level of fitness, and nicotine or alcohol consumption are significant risk factors for altitude sickness in mountaineering populations. The primary determinants of AMS appear to be the level of acclimatization, rate of ascent, and individual susceptibility. Further research is needed to fully understand the impact of these additional factors on the development of altitude sickness in mountaineering populations.(6) Meta-analyses of observational field studies have demonstrated that prophylactic acetazolamide can reduce the symptoms of acute mountain sickness. The drug is typically prescribed at doses between 125 mg and 1 g per day, with most patients receiving 125 mg or 250 mg twice daily. However, it is important to note that acetazolamide does not prevent the symptoms of acute mountain sickness when an individual ascends too quickly.(7) The Mustang study site is known for its several high-altitude attractions, including the world-renowned Thorong La Pass (5416m) in the Annapurna trekking circuit, the Muktinath Temple (3800m), Lo Manthang (3840m), and the Kora La Pass (4660m). In recent years, improvements to major roadways have increased connectivity to these attractions, resulting in an increased flow of visitors and shorter travel times. However, this has also led to a higher likelihood of individuals rapidly ascending from lower elevations to a hypobaric hypoxia environment, thereby increasing the risk for developing high-altitude illness during the initial few days of travel.(8)

LITERATURE REVIEW In a study done among trekkers climbing a 5400 m high pass in the Nepalese Himalaya the overall prevalence of AMS was 63%. AMS was positively correlated with rate of ascent and negatively correlated with pre-trek acclimatization. Women suffered more frequently and more seriously from AMS. Body mass index (weight/length2) was significantly correlated with AMS in men. No significant association was found between AMS and age, smoking habits, use of oral contraceptives, previous high altitude experience, special pre-trek training, size of trekking party or whether the trek was agency- or self-organised. Of trekkers, 80% had elementary knowledge of the diagnosis and treatment of AMS.(9) In a one-year study conducted at Mustang District Hospital, it was found that approximately one-fourth (25.7%) of the 105 patients exhibiting symptoms were not meeting the criteria of LLS to be classified as AMS patients. Out of the remaining three-fourths (74.3%) who were diagnosed with AMS, 61.5% had mild symptoms, 35.9% had moderate symptoms, and only 2.6% had severe symptoms. In the dataset, there was only one case of HACE and two cases of HAPE. Among patients with AMS, approximately 73.1% reported experiencing gastrointestinal symptoms, 84.6% reported dizziness, and a majority of 97.4% reported fatigue. Ascent rate was strongly associated with the likelihood of developing severe AMS among travellers with AMS symptoms.(10) A preliminary study sponsored by the Himalayan Rescue Association of AMS among pilgrims to a holy lake (Gosaikunda) at 4154 m in Nepal, revealed that out of 5163 pilgrims who came to the lake, 229 (4.4%) developed AMS. The severity of the illness correlated with the rapidity of ascent, but there was no difference in severity between men and women.(11) A study was conducted in a total of 162 mountaineers (assuming that the more experienced mountaineers of the Western Alps are less susceptible to developing AMS than recreational mountaineers of the Eastern Alps or tourist populations), 79 in the Eastern Alps (3454 m) and 83 in the Western Alps (3817 m) on the morning after their first night at high altitude. A diagnosis of AMS was based on a Lake Louise Scoring, thirty of 79 subjects (38.0%) suffered from AMS at 3454m in the Eastern Alps as did 29 of 83 (34.9%) at 3817m in the Western Alps. After adjustment for altitude, the prevalence in the Western Alps constituted 24.5%, which differed significantly (p=0.04) from that found in the Eastern Alps. The lower mountaineering experience of mountaineers in the Eastern Alps turned out to be the only factor for explaining their higher AMS prevalence.(12) A study was done on 27 mountaineers on the day of arrival at the Capanna Margherita (4559 m) and on the next morning. Susceptibility was assessed based on previous AMS episode and pre exposure was defined as having spent more than 4 d above 3000 m during the 2 months preceding the climb to the Capanna Margherita. Slow ascent was defined as ascending in more than 3 d. In susceptible individuals, the prevalence of AMS was 58% with rapid ascent and no preexposure, 29% with preexposure only, 33% with slow ascent only, and 7% with both preexposure and slow ascent. The corresponding values for nonsusceptible individuals were 31%, 16%, 11%, and 4%. The overall odds ratio for developing AMS in susceptible versus nonsusceptible individuals was 2.9 (95% confidence interval, 2.1- 4.1). Age, gender, training, body mass index, alcohol intake, and cigarette smoking had no significant effect in bivariate analyses or in multivariate logistic regressions. In conclusion individual susceptibility, rate of ascent, and preexposure are the major, independent determinants for prevalence of AMS.(6) In a meta-analysis done studying acetazolamide for the prevention of AMS, when all of the reported symptoms were pooled together, the average ES was -0.38, indicating that drug prophylaxis was effective in reducing the most common symptoms of AMS. When examined individually, the ES for preventing headache was -0.54, nausea was -0.29, and insomnia was -0.42.(7)

RESEARCH AIM AND OBJECTIVES Primary Objective: To identify risk factors for high altitude sickness, including AMS, HACE, and HAPE

Specific Primary Objectives: