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HIGH-ALTITUDE DISEASES An Overview of Illnesses at High Altitude

High Altitude Diseases © Tómas Guðbjartsson 2024 Illustrations: Árni Árnason Book design: bjorgvilhjalms.is Translation: Ölvir Gíslason This book may not be reproduced by any means, such as by photography, printing, recording or by any similar means, in part or in whole, without the prior written consent of the author and publisher.

Reykjavík February 2024

HIGH-ALTITUDE DISEASES An Overview of Illnesses at High Altitude

Tómas Guðbjartsson

TABLE OF CONTENTS ABOUT THE AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 MOST COMMON HIGH-ALTITUDE DISEASES . . . . . . . . . . . . . . . . . 8 WHERE ARE YOU MOST LIKELY TO DEVELOP HIGH-ALTITUDE SICKNESS? . 10 The fourteen highest mountains in the world . . . . . . . . . . . . . . . 12 Cities and towns at high altitude . . . . . . . . . . . . . . . . . . . . . 12 The ten highest ski resorts in the world . . . . . . . . . . . . . . . . . . 13 NORMAL ACCLIMATISATION . . . . . . . . . . . . . . . . . . . . . . . . 14 ACUTE MOUNTAIN SICKNESS . . . . . . . . . . . . . . . . . . . . . . .

17

Signs and symptoms of acute mountain sickness, High-altitude cerebral edema and high-altitude pulmonary edema . . . . . . 18 Lake Louise Criteria for acute mountain sickness . . . . . . . . . . . . . . 19 HIGH-ALTITUDE PULMONARY EDEMA . . . . . . . . . . . . . . . . . . . 20 HIGH-ALTITUDE CEREBRAL EDEMA . . . . . . . . . . . . . . . . . . . .

21

EFFECTS OF HIGH-ALTITUDE ILLNESS ON YOUR BODY? . . . . . . . . . . 22 WHO DEVELOP HIGH-ALTITUDE ILLNESS? . . . . . . . . . . . . . . . . . 23 Risk factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

PREVENTION OF HIGH-ALTITUDE ILLNESS . . . . . . . . . . . . . . . .

26

ACUTE MOUNTAIN SICKNESS AND HIGH-ALTITUDE CEREBRAL EDEMA . . .

26

HIGH-ALTITUDE PULMONARY EDEMA . . . . . . . . . . . . . . . . . . 29 TREATMENT OF ACUTE MOUNTAIN SICKNESS . . . . . . . . . . . . . . . 30 General recommendations . . . . . . . . . . . . . . . . . . . . . . 30 Medicines and other treatments for acute mountain sickness . . . . . . . . 30 Treatment of high-altitude pulmonary edema . . . . . . . . . . . . . . . 31 How is erectile dysfunction medication effective against high-altitude pulmonary edema? . . . . . . . . . . . . . . . . . . . . . . . . . . 31 Treatment of high-altitude cerebral edema . . . . . . . . . . . . . . . . 31 OTHER HIGH-ALTITUDE DISEASES . . . . . . . . . . . . . . . . . . . . . 32 Sleep disturbances . . . . . . . . . . . . . . . . . . . . . . . . . 32 Altitude-related cough . . . . . . . . . . . . . . . . . . . . . . . . 32 Gastrointestinal problems . . . . . . . . . . . . . . . . . . . . . . . 33 Eye conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 Frostbite . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 LISTS OF MEDICINES . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36

ABOUT THE AUTHORS Engilbert Sigurðsson, MD, MSc is a professor of psychiatry at the University of Iceland and consultant psychiatrist at Landspitali - The National University Hospital of Iceland.

After completing his medical degree, he studied psychiatry and graduated with an MSc in epidemiology from London School of Hygiene & Tropical Medicine. Engilbert is an ex­ perienced hiker and mountain skier, both in Iceland and abroad, with ascents that include both Kilimanjaro and Monte Rosa.

Gunnar Guðmundsson, MD, PhD is a a respiratory physician at Landspitali - The Nation­ al University Hospital and professor at the University of Iceland’s Faculty of Medicine.

He completed his medical degree in Iceland, studied pulmonary and critical care medi­ cine at the University of Iowa, and graduated with a PhD degree from the University of Iceland’s Faculty of Medicine. Gunnar was a member of a search and rescue team in his younger years, and is an experienced mountaineer, both in Iceland and in mainland Europe, Africa, the United States and Nepal. For many years, Gunnar has also advised Icelandic mountaineers in their expeditions to the world’s highest peaks.

Magnús Gottfreðsson, MD, PhD is a professor of infectious diseases and senior consultant at Landspitali - The National University Hospital. After graduating with a medical degree from the University of Iceland, he moved to North Carolina, where he trained in internal medicine and infectious diseases. Magnús has climbed Mount Kilimanjaro and numerous mountains in Iceland and the Alps in addition to being an experienced mountaineer and marathon runner. Ólafur Már Björnsson, MD is an ophthalmologist at Sjonlag Eye Center. He trained in ophthalmology in Oslo after completing his medical degree in Iceland. He has trekked to Everest Base Camp, and gone on many mountain ski and hiking expeditions, both in the Alps and in Iceland. He is also an avid photographer.

Tómas Guðbjartsson, MD, PhD is a professor of surgery and senior consultant at the Department of Cardiothoracic Surgery at Landspitali - The National University Hospital.

After completing his medical degree and PhD at the University of Iceland, he trained in general surgery and later cardiothoracic surgery in Lund, Sweden, and Boston, USA. Tómas has climbed Aconcagua, Imje Tse, Kilimanjaro, Mont Blanc, Monte Rosa and Mount Rainer in addition to taking part in mountain ski expeditions in Europe and North America.

He has also many years of experience as a mountain guide and medical consultant for Icelandic mountaineering expeditions overseas.

6 Hig-Altitude Diseases

INTRODUCTION This booklet provides an overview of the most common diseases that may occur at high-altitudes; both acute-mountain sickness (AMS), which is the most common form of high-altitude illness, and life-threatening conditions such as high-altitude cerebral edema (HACE) and high-altitude pulmonary edema (HAPE). Acclimatisation, i.e. the body’s natural response to lack of oxygen, is explained in brief, and other common conditions at high-altitude, such as sleep disturbance, gastrointestinal problems, snow blindness and frostbite, are also discussed. Treatment of the most common conditions is reviewed, and at the back is a list of medicines that may be helpful to bring along when mountaineering abroad.

The authors are five doctors who are all avid outdoorsmen and have taken part in overseas montaineering expeditions. In 2019, the authors published a review on high-altitude illness in the Icelandic Medical Journal, and while the present text is partly based on this review, the approach is geared towards general readers as opposed to healthcare professionals.

Tables have also been added and all illustrations are new. Graphic designer Björg Vilhjálms­ dóttir and illustrator Árni Árnason are responsible for the design of the booklet, which is printed on water-resistant paper and in a size that should fit comfortably into a backpack.

Special thanks go out to Mountain Hardwear, and the Iceland Touring Association, which provided funding for this publication, as well as the the companies 66°North, Fjallakofinn and Everest, who also provided support without imposing any conditions on the authors.

Reykjavík, 11 February 2024 On behalf of the authors, Tómas Guðbjartsson, editor

High-Altitude Diseases 7

MOST COMMON HIGH-ALTITUDE DISEASES Those who travel to an altitude of more than 2500 metres (~8,200 feet) experience vari­ ous disorders associated with thin air, usually within a few days. The risk is mainly deter­ mined by the altitude and rate of ascent, and the symptoms may vary greatly and manifest in various organs and organ systems. Before symptoms occur, the body will have re­ sponded to the lack of oxygen by initiating an adjustment process called acclimatisation.

However, the body's response is not always sufficient, or it may over-respond, in which case high-altitude illness may develop. By far, its most common form is acute mountain sickness (AMS), but the more dangerous and potentially life-threatening, high-altitude cerebral edema (HACE) and high-altitude pulmonary edema (HAPE) may also occur. While high-altitude illness is caused by a lack of oxygen and insufficient acclimatisation, the form it takes is determined by the body’s response. The most common symptoms of AMS include headache, fatigue, weakness, nausea, and loss of appetite, but sleep disturbance and gastrointestinal symptoms are also common complaints. The most frequent symptoms of HAPE include severe shortness of breath and lack of energy, while HACE is usually characterised by lack of balance (ataxia), confusion and reduced consciousness. Finally, there are conditions associated with high-altitude that cannot be traced directly to lack of oxygen, such as frostbite and diarrhoea.

SYMPTOMS OF DIFFERENT FORMS OF HIGH-ALTITUDE ILLNESS Acute mountain sickness (AMS)

High-altitude cerebral edema (HACE)

High-altitude pulmonary edema (HAPE)

Fatigue Vertigo Sleep disturbance Nausea/vomiting

Severe headache Clumsiness Confusion Unclear thoughts

Fatigue Fever Coughing Shortness of breath

8 Hig-Altitude Diseases

THE MOST COMMON SYMPTOMS OF AMS INCLUDE HEADACHE, FATIGUE, WEAKNESS, NAUSEA AND LOSS OF APPETITE

High-Altitude Diseases 9

WHERE ARE YOU MOST LIKELY TO DEVELOP HIGH-ALTITUDE SICKNESS? More and more individuals are hiking, skiing, climbing and mountain biking at altitudes exceeding 2500 meters (~8,200 feet). Destinations include the highest altitude areas in the world, such as the Himalayas, where the 20 highest mountains in the world can be found, the South American Andes, the Rocky Mountains in the United States, and the Alps in Europe. Several major cities also have a high altitude and there is no time for acclimatisation when landing at an airport in such cities. One such city is La Paz in Bolivia, whose elevation above sea level makes it the highest capital city in the world.

Many ski resorts are also at a high altitude, so it is common to experience symptoms of acute mountain sickness there, especially when disembarking from the highest lifts.

SEVERAL MAJOR CITIES ARE AT HIGH-ALTITUDE AND THERE IS NO TIME FOR ACCLIMATISATION WHEN LANDING AT AN AIRPORT IN SUCH CITIES

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RELATIVE HEIGHT OF SEVERAL MOUNTAINS

EVEREST (8848 m / 29,029 ft)

ACONCAGUA (6962 m / 22,841 ft) KILIMANJARO (5895 m / 19,341 ft)

MONT BLANC (4808 m / 15,774 ft)

HEKLA (1515 m / 4,970 ft)

High-Altitude Diseases 11

The fourteen highest mountains in the world i.e. the mountains with a height of more than 8,000 metres 1.

Everest

8848 m / 29,029 ft

The Himalayas (Nepal/China)

2.

K2

8611 m / 28,251 ft

Karakoram (Pakistan/China

3.

Kangchenjunga

8586 m / 28,169 ft

The Himalayas (Nepal/India)

4.

Lhotse

8516 m / 27,940 ft

The Himalayas (Nepal/China)

5.

Makalu

8485 m / 27,838 ft

The Himalayas (Nepal/China)

6.

Cho Oyu

8201 m / 26,864 ft

The Himalayas (Nepal/China)

7.

Dhaulagiri

8167 m / 26,795 ft

The Himalayas (Nepal)

8.

Manaslu

8163 m / 26,781 ft

The Himalayas (Nepal)

9.

Nanga Parbat

8126 m / 26,660 ft

The Himalayas (Pakistan)

10. Annapurna

8091 m / 26,545 ft

The Himalayas (Nepal)

11. Gasherbrum I

8080 m /26,509 ft

Karakoram (Pakistan/China)

12. Broad Peak

8051 m / 26,414 ft

Karakoram (Pakistan/China)

13. Gasherbrum II

8035 m / 26,362 ft

Karakoram (Pakistan/China)

14. Shishapangma

8027 m / 26,335 ft

The Himalayas (China)

Cities and towns at high altitude

Population

Dingboche (Nepal)

4350 m / 14,271 ft

200

La Pax (Bolivia)

3640 m / 11,942 ft

1.900.000

Namche Bazaar (Nepal) 3440 m / 11,286 ft

1700

Cusco (Peru)

3400 m / 11,155 ft

430.000

Leadville (USA)

3094 m / 10,151 ft

2.900

Lukla (Nepal)

2860 m / 9,383 ft

230

Machu Picchu (Peru)

2430 m / 7,972 ft

0

Mexico City (Mexicó)

2240 m / 7,349 ft

21.300.000

Denver (USA)

1564 m / 5,131 ft

716.000

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The ten highest ski resorts in the world 1. Jade Dragon Snow Mountain (China)

4700 m / 15,420 ft

2. Gulmarg (India)

3980 m / 13,058 ft

3. Breckenridge (USA)

3914 m / 12,841 ft

4. Zermatt (Switzerland)

3899 m / 12,792 ft

5. Loveland (USA)

3871 m / 12,700 ft

6. Tochal (Iran)

3850 m / 12,631 ft

7. Chamonix (France)

3842 m / 12,605 ft

8. Elbrus (Russia)

3840 m / 12,598 ft

9. Telluride (USA)

3831 m / 12,569 ft

10. Aspen Snowmass (USA)

3813 m / 12,510 ft

EARTH'S HIGHEST ALTITUDE AREAS

High-Altitude Diseases 13

NORMAL ACCLIMATISATION At sea level, the percentage of oxygen in inhaled air is 21%, the same as on the summit of Kilimanjaro (5895 metres, ~19,341 feet) and Mount Everest (8848 metres, ~29,029 feet).

However, with increased elevation, the atmospheric pressure decreases exponentially, meaning that instead of 760 mm of mercury (equivalent to 1013 millibars or 101.3 kPa) at sea level, the atmospheric pressure is only half of this (50 kPa) on the summit of Kilimanjaro (5895 metres, ~19,341 feet) and a third (34 kPa) on Mount Everest, Earth’s highest mountain.

The amount of oxygen per volume of atmosphere on the summit of Mount Everest is, there­ fore, only a third of the amount per the same volume at sea level.

At heights of more than 2500 metres (~8,200 feet) the effects of reduced oxygen may be felt, and symptoms may occur at lower elevations in individuals with conditions such as cardiovascular disease. To make the most of the available oxygen, your body will begin to acclimatise to the elevation. This is a complex physiological process that begins as soon as you reach a higher elevation, but may take weeks or months to become fully effective.

Thus, a person who has not undergone acclimatisation will only survive for half an hour on the summit of Mount Everest, while specially trained mountaineers who have spent six to eight weeks at a high elevation can ascend Earth’s highest peaks without the aid of supplemental oxygen.

MANY SKI RESORTS HAVE HIGH ELEVATION SO SYMPTOMS OF ACUTE MOUNTAIN SICKNESS MAY BE FELT WHEN DISEMBARKING FROM THE HIGHEST LIFTS

14 Hig-Altitude Diseases

Mount Everest conquered without supplemental oxygen On 8 May 1978, Peter Habeler and Reinhold Messner became the first men to reach the summit of the world's highest mountain, Mount Everest, without the use of supplemental oxygen. The expedition was meticulously planned and is considered one of the greatest mountaineering achievements of all times. Equipment was kept as light as possible, allowing the mountaineers to travel faster on Mount Everest than anyone had done before them. Before their expedition, it was widely believed that it was physiologically impossible to reach the summit without supplemental oxygen, as oxygen levels there are only a third of the levels at sea level. Habeler and Messner proved this wrong, and over two hundred mountaineers have since followed in their footsteps. Reinhold Messner would later become the first person to ascend the 14 highest mountains in the world without the use of supplemental oxygen.

Most of the body's organs acclimatise to higher elevation, but the response of the lungs, heart and blood are most important. When blood oxygen levels decrease, the receptors in the arteries that carry oxygen to the brain are stimulated, resulting in an elevated respira­ tory rate and deeper inhalation, both of which increases gas exchange in the lungs.

ATMOSPHERIC PRESSURE DECREASES EXPONENTIALLY WITH INCREASED ELEVATION. TRIS IS WHY THERE IS LESS MOLECULAR OXYGEN PER LITER OF INHALED AIR AT HIGHER ELEVATIONS

High-Altitude Diseases 15

The faster and deeper breathing lowers the amount of CO2 in the blood while raising pH levels in the blood. The main symptoms of hyperventilation are numbness in the fingers and around the mouth. Exertion may also result in more shortness of breath than before.

Meanwhile, the heart increases its cardiac output by beating faster (a faster pulse) and increasing the contractions of the heart muscle, both of which reduce the time it takes to supply oxygen to tissue such as the brain and muscles. The kidneys gradually join in the response to rising pH levels by increasing the excretion of bicarbonate in the blood (it usually takes the kidneys a few days to fully correct the pH levels). The body also begins to produce more urine, which may exacerbate dehydration. The kidneys start producing more erythropoietin, a hormone that stimulates the synthesis of red blood cells in the bone marrow. Maximum secretion of erythropoietin is reached in two to three weeks, resulting in increased haemoglobin levels.

An important part of acclimatisation is that with lower blood oxygen levels it becomes easier for red blood cells to deliver oxygen to tissues. A hormone that stimulates the formation of blood vessels in tissues lacking oxygen is also produced. This increases blood flow and the availability of oxygen to the tissues. Finally, there is a change in the metabolism of mitochondria, which provide energy for cells, to ensure optimal utili­

GAS EXCHANGE TAKES PLACE IN THE ALVEOLI IN THE LUNGS AS OXYGEN MOVES TO THE PULMONARY CIRCULATION AND CARBON DIOXIDE IS EXCRETED Atmosphere

Oxygen-poor blood from the right heart to the lungs

Oxygen-rich blood from the lungs to the left heart

ALVEOLUS

16 Hig-Altitude Diseases

sation of oxygen. To begin with, acclimatisation can keep pace with the reduced oxygen in inhaled air, but at heights of more than 5,000 metres (~16,400 feet), the rate of oxygen desaturation starts to exceed the rate of acclimatisation. At this point, oxygen saturation begins to decrease at a much faster rate with increased elevation, the effects on the body are greater, and the risk of high-altitude illness increases. Withstanding such elevation re­ quires many weeks of acclimatisation, with mountaineers who tackle the summit of Mount Everest, and other mountain peaks with an elevation of more than 8000 metres (~26,000 feet), often showing haemoglobin levels of around 190 g/L, compared to approximately 140 g/L under normal conditions.

ACUTE MOUNTAIN SICKNESS Acute mountain sickness is a collection of symptoms where headache is the main symptom, but other symptoms are also frequently present. Acute mountain sickness is a very common problem, with research from the Rocky Mountains and the Alps indicating that more than a fifth of those who reach heights of 2,500-2,900 metres (~8,200-9,800 feet) experience symptoms, more than 40% of those who reach heights of over 3,000 metres (~9,800 feet), and close to 60% when heights exceed 5,000 metres (~16,400 feet).

ACUTE MOUNTAIN SICKNESS IS USUALLY A PRECURSOR OF HIGH-ALTITUDE CEREBRAL EDEMA

Acute mountain sickness

High-altitude cerebral edema (HACE)

High-altitude pulmonary edema (HAPE)

High-Altitude Diseases 17

Signs and symptoms of acute mountain sickness, high-altitude cerebral edema and high-altitude pulmonary edema SYMPTOM

SIGNS

mild

Headache, loss of appetite, nausea, sleep disturbance

No specific

moderate

Headache (responds to pain killers), loss of appetite, sleep disturbance, dizziness

No specific

serious

Headache (unresponsive to pain killers), severe nausea, vomiting and extreme fatigue

No specific

High-altitude cerebral edema

Headache (unresponsive to pain killers), vomiting

Ataxia, altered state of consciousness (confusion), impaired reflexes

High-altitude pulmonary edema

Restricted mobility, dry cough, shortness of breath at rest, blood in saliva, difficulty breathing

Rapid heartbeat at rest (>100 beats per minute), rapid breathing (> 25/min), blue colour of fingers

Acute mountain sickness

Many of these symptoms can also be caused by conditions other than acute mountain sickness. Specific criteria with different weighing of symptoms is therefore used. The most commonly used international criteria are the scoring system named after Lake Louise in Canada.

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Lake Louise Criteria for Acute Mountain Sickness HEADACHE 1.

2.

3.

4.

None at all A mild headache Moderate headache Severe headache, incapacitating

GASTROINTESTINAL SYMPTOMS 1.

2.

3.

4.

Good appetite Poor appetite or nausea Moderate nausea or vomiting Severe nausea and vomiting, incapacitating

FATIGUE AND/OR WEAKNESS 1.

2.

3.

4.

Not tired or weak Mild fatigue/weakness Moderate fatigue/weakness Severe fatigue/weakness, incapacitating

DIZZINESS/LIGHT-HEADEDNESS 1.

2.

3.

4.

No dizziness/light-headedness Mild dizziness/light-headedness Moderate dizziness/light-headedness Severe dizziness/light-headedness, incapacitating

AMS Clinical Functional Score Overall, if you had AMS symptoms, how did they affect your activities?

1.

Not at all 2.

Symptoms present, but did not force any change in activity or itinerary 3.

My symptoms forced me to stop the ascent or to go down on my own power 4.

Had to be evacuated to a lower altitude

High-Altitude Diseases 19

This means that while a person with actual acute mountain sickness will always have a headache, they must also have recently ascended to an elevation of more than 2,500 metres (~8,200 feet), thus not having completed their acclimatisation. One or more of the following symptoms will also be present: gastrointestinal symptoms (loss of appetite, nausea or vomiting), dizziness, weakness and fatigue. Insomnia, on the other hand, is no longer part of the diagnostic criteria for acute mountain sickness, as it has been shown that up to 40% of people with AMS do not have disturbed sleep. Symptoms typically appear 6-10 hours after reaching a great height, but may commence up to one hour after arrival or one to two days later. Barring further ascent, the symptoms usually go away in one to three days.

HIGH-ALTITUDE PULMONARY EDEMA This dangerous disease is much rarer than acute mountain sickness, with a frequency of around 5% at 5,500 metres (~18,000 feet), and is mostly determined by the rate of ascent. High-altitude pulmonary edema is considered the most fatal form of high-altitude illness for mountaineers. Its symptoms may appear two to four days after ascending to an elevation of more than 3,000 metres (~9,800 feet). It is caused by fluid retention in the lungs and the first symptoms are dry cough, shortness of breath with activity and lack of energy when climbing or walking up a slope. The increased retention of fluid in the lungs, and the resulting drop in oxygen saturation, often manifests in increasing shortness of breath when walking on level ground, and even breathing difficulties. Sputum may also

IN HIGH-ALTITUDE PULMONARY EDEMA, PULMONARY CAPILLARIES LEAK FLUID INTO THE ALVEOLI, IMPAIRING GAS EXCHANGE IN THE LUNGS

20 Hig-Altitude Diseases

become frothy and blood-coloured. It is important to keep in mind that common symp­ toms of acute mountain sickness, such as headache and nausea, only occur in about half of all cases of imminent high-altitude pulmonary edema, and at its earliest stages, HAPE may be difficult to distinguish from respiratory infections, which are very common at high altitude.

HIGH-ALTITUDE CEREBRAL EDEMA Like high-altitude pulmonary edema, high-altitude cerebral edema is a life-threatening form of high-altitude illness. It is believed to be caused by a fluid imbalance in the small vessels of the brain due to insufficient acclimatisation. Symptoms usually do not appear until altitudes of 3,000 metres (~9,800 feet) or more. Unsteadiness when walking, also called ataxia, is usually the first noticeable symptom while people with more advanced cerebral edema experience balance disorders that may turn rapidly into drowsiness, and even disorientation and reduced consciousness. Risk factors include a history of highaltitude illness, insufficient acclimatisation and heavy physical exertion. High-altitude cere­ bral edema is less common than high-altitude pulmonary edema, with a frequency of 0.5-1% at an altitude of 4,000-5,000 metres (~13,000-16,400 feet). Symptoms of acute mountain sickness, such as headache and nausea, and even symptoms of high-altitude pulmonary edema, usually precede the onset of high-altitude cerebral edema, although high-altitude cerebral edema has been known to develop without such preceding symptoms.

HIGH-ALTITUDE CEREBRAL EDEMA IS A COMPLEX CONDITION AND IN SEVERE CASES PRESSURE INSIDE THE SKULL IS INCREASED

High-Altitude Diseases 21

THE SYMPTOMS OF HIGH-ALTITUDE ILLNESS OVERLAP, LIKE THE PATHOGENESIS OF THE SYNDROMES, EXCEPT THAT THE LATTER IN HIGH-ALTITUDE PULMONARY EDEMA (HAPE) IS SLIGHTLY DIFFERENT TO THAT OF ACUTE MOUNTAIN SICKNESS (AMS) AND HIGH-ALTITUDE CEREBRAL EDEMA (HACE)

ACUTE MOUNTAIN SICKNESS

HAPE HACE

ACUTE MOUNTAIN SICKNESS

HAPE

HACE

Symptoms

Pathogenesis

EFFECTS OF HIGH-ALTITUDE ILLNESS ON YOUR BODY? The pathogenesis, or the mechanisms by which it develops, of acute mountain sickness is complex, but can be traced to the body’s response to insufficient oxygen levels. The pathogenesis of high-altitude pulmonary edema is slightly different from the pathogenesis of acute mountain sickness and high-altitude cerebral edema, which some consider to be an extreme form of AMS. There is considerable overlap in the main forms of high-altitude illness, although high-altitude pulmonary edema may occur without symptoms of acute mountain sickness.

Acute mountain sickness and high-altitude cerebral edema There is still much unknown about what triggers the complex trajectory of these diseases, although it seems like those who develop acute mountain sickness typically have lower blood oxygen saturation levels than those who remain asymptomatic. Various factors are thought to be involved, such as insufficient respiratory rate increase when oxygen pres­ sure decreases, reduced gas exchange in the lungs due to edema and abnormal fluid retention in the body, plus other factors. It is clear that lack of oxygen triggers hyper­ ventilation, which lowers carbon dioxide levels in the blood and causes the blood vessels to the brain to dilate. This increases blood flow to the brain, but in severe cases of acute

22 Hig-Altitude Diseases

THE ELEVATION AT WHICH VOU SLEEP IS A VERY IMPORTANT FACTOR IN AVOIDING HIGH-ALTITUDE ILLNESS

mountain sickness and high-altitude cerebral edema, capillary leakage makes the brain swell with fluid, increasing pressure inside the skull.

High-altitude pulmonary edema In these individuals, lack of oxygen is believed to result in localised pulmonary hyper­ tension which causes increased blood flow to other areas of the lungs, capillary leak and ultimately pulmonary edema.

WHO DEVELOP HIGH-ALTITUDE ILLNESS? The biggest risk factor for high-altitude illness is rapid ascent at high altitude. A history of high-altitude illness is also a known risk factor, especially in the case of high-altitude pulmonary edema, where more than half of individuals with such a history become sick again, with similar symptoms, if they return to the same elevation. The elevation of where you sleep is also important. There is no difference in frequency of high-altitude illness by gender, but age is a factor, as people between 50 and 70 are at a lesser risk of developing acute mountain sickness than those who are younger, while the risk increases again after the age of 70. Overexertion and infections, particularly respiratory infections, are known risk factors for high-altitude pulmonary edema.

High-Altitude Diseases 23

THERE IS NO DIFFERENCE IN THE FREQUENCY OF HIGH-ALTITUDE ILLNESS BY GENDER, BUT AGE IS A FACTOR

High exercise capacity and physical training do not protect against high-altitude illness, and there is much to indicate that athletes who compete in endurance sports such as marathons and swimming are no less susceptible than others. Studies of some of the most prominent mountaineers in history, including Reinhold Messner, have furthermore shown that they do not have more exercise capacity than top athletes in various endurance sports.

There are many indications that genetics may partly explain differing susceptibility to the disease. Thus, ethnic Tibetans who have lived at high altitudes for centuries are much less susceptible to high-altitude illness than Chinese people who have moved to Tibet from the lowlands in the last few decades. The heredity of high-altitude illness and the body’s response to lack of oxygen is a complex and still largely unexplained phenomenon. Several genetic variations have been described, with the so-called angio­ tensin-converting (ACE)-gene, providing the strongest link.

24 Hig-Altitude Diseases

THERE ARE MANY INDICATIONS THAT GENETICS MAY PARTLY EXPLAIN DIFFERING SUSCEPTIBILITY TO HIGH-ALTITUDE ILLNESS

Risk factors RISK

DESCRIPTION

Low

A person with no prior history who ascends to an altitude of less than 2,800 metres (~9,200 ft). A person who takes two days to ascend to an altitude of 2,500-3,000 metres (~8,200-9,800 ft) and increases their sleeping altitude by less than 500 metres (~1,600 ft) a day, taking an extra day for acclimatisation for every 1,000 metres (~3,200 ft) of altitude gain.

Moderate

A person with prior history who ascends to an altitude of 2,500-2,800 metres (~8,200-9,200 ft) in one day. No history of high-altitude illness and ascends to an altitude of more than 2,800 metres (~9,200 ft) in one day. Any person with a daily altitude gain of more than 500 metres (~1,600 ft) (increase in sleeping altitude) at an altitude of more than 3,000 metres (~9,800 ft) but who takes an extra day for acclimatisation for every 1,000 metres (~3,200) of altitude gain.

High

A person with prior history who ascends to an altitude of more than 2,800 metres (~9,200 ft) in one day. Any person with a history of high-altitude cerebral edema.

Any person who ascends to an altitude of more than 3,500 metres (~11,500 ft) in one day. Any person with a daily altitude gain of more than 500 metres (~1,600 ft) (increase in sleeping altitude) at an altitude of more than more than 3,000 metres (~9,800 ft) but with no extra days for acclimatisation. Very rapid ascent. Example: Kilimanjaro in less than seven days.

High-Altitude Diseases 25

PREVENTION OF HIGH-ALTITUDE ILLNESS Various methods can be used to prevent high-altitude illness, both general recommen­ dations and medicines. Below is a special joint discussion of preventing acute mountain sickness and high-altitude cerebral edema, as well as a look at preventive treatment for high-altitude pulmonary edema.

ACUTE MOUNTAIN SICKNESS AND HIGH-ALTITUDE CEREBRAL EDEMA General recommendations Here, the golden rule of mountaineering applies: to allow enough time for acclimati­ sation. This is something that is much too frequently forgotten. You should avoid ascend­ ing straight from sea level to an altitude of more than 2,700-3,000 metres (~8,900-9,800 feet). It is best to stay overnight at an average altitude of perhaps 2,500-2,800 metres (~8,200-9,200 feet) before continuing the ascent. After this, it is recommended that daily altitude gain does not exceed 500-600 metres (~1,600-2,000 feet) between places of sleep, with a day of rest for each 1,000-1,200 metres (~3,200-4,000 feet) of altitude gain.

The sleeping altitude is often more important than the altitude ascended to during the day, i.e. most acclimatise as they finish their trek of the day with a descent to the place of sleep. You should walk calmly and steadily and not overexert yourself, especially if you have been subjected to high-altitude illness before.

THE MOST COMMONLY USED SPECIALISED MEDICINE TO PREVENT HIGH-ALTITUDE ILLNESS IS ACETAZOLAMIDE

26 Hig-Altitude Diseases

MEDICINES The medicines most commonly used for the prevention and treatment of high-altitude illness can be seen in the table below. All medications must be administered after con­ sultation with a physician.

Paracetamol and anti-inflammatory agents such as ibuprofen and celecoxib are effective for high-altitude headaches, but the most commonly used specialised medicine is aceta­ zolamide.

Medicine

Indication

Ingestion

Acetazolamide

Prevention of AMS, HACE Treatment of AMS, HACE

Oral Oral

Dexamethasone

Prevention of AMS, HACE Treatment of AMS, HACE

Oral Oral Intravenous or intramuscular

Ibuprofen

Prevention of AMS

Oral

Nifedipine

Prevention of HAPE Treatment of HAPE

Oral Oral

Tadalafil

Prevention of HAPE

Oral

Sildenafil

Prevention of HAPE

Oral

Salmeterol

Prevention of HAPE

Inhalation

AMS: acute mountain sickness, HACE: high-altitude cerebral edema, HAPE: high-altitude pulmonary edema.

High-Altitude Diseases 27

What kind of medicine is acetazolamide (Diamox®) and how effective is it?

This medicine, originally developed to treat glaucoma, inhibits renal reabsorption of bicarbonate and sodium, thus increasing the amount of bicarbonate excreted in the urine, which leads to acidification of the blood (metabolic acidosis). To correct the blood pH, the body will respond by increasing oxygen uptake in the lungs. Results on the efficacy of this medicine have varied, but recent studies indicate that it may reduce the rate of acute mountain sickness by as much as half, although users will experience increased tingling in their hands and feet and carbonated beverages, such as soft drinks, will have an unpleasant taste.

THE STRUCTURE OF ACETAZOLAMIDE IS RELATIVELY SIMPLE

28 Hig-Altitude Diseases

It is up to each individual whether to take acetazolamide, but it is not considered neces­sary as an altitude illness prevention for all who ascend to great heights, although those who have experienced more than a touch of acute mountain sickness should consider such treatment to reduce the likelihood of developing symptoms of high-altitude illness. Those who intend to travel from sea level to a sleep altitude of more than 3,000 metres (~9,800 feet) without allowing for acclimatisation, should consider taking this or other medicine that prevents high-altitude illness. You will begin taking acetazolamide 24 hours before ascending and stop when you are back to below 2,500 metres (~8,200 feet), or if you stay at the same altitude for more than 4–5 days. Those who are allergic to sulfa drugs should avoid acetazolamide due to potential cross sensitivity. To ensure that the medicine is well tolerated, it is often recommended to test it at sea level about two weeks prior to the in­ tended use.

Dexamethasone is a glucocorticoid medication that may help to prevent cerebral edema by reducing leakage in brain capillaries. This medicine should only be used as a prevent­ive treat­ ment after consultation with a physician, for instance if acetazolamide is not well tolerated or if its use is contraindicated. Intake of glucocorticoids for more than 10 consecutive days is not recommended due to the risk of adverse reactions, and it is important to keep in mind that symptoms of high-altitude illness may recur when treatment is discontinued.

Various other medicines have been studied for their potential to prevent high-altitude illness, including magnesium citrate and ginkgo biloba, but most studies do not support their efficacy.

HIGH-ALTITUDE PULMONARY EDEMA In general, the preventive guidelines that apply for acute mountain sickness also apply for high-altitude pulmonary edema, although it is especially recommended to avoid over-exertion, especially for those who have a respiratory infection. Those who have had high-altitude pulmonary edema before should ascend very carefully and consult a physician before ascending to a high-altitude. The use of so-called phosphodiesterase inhibitors, such as tadalafil and sildenafil, which are used primarily for the treatment of erectile dysfunction, is rarely appropriate for preventive purposes, except in isolated cases of patients who have previously suffered from high-altitude pulmonary edema, and then only after consultating a physician.

High-Altitude Diseases 29

HYPERBARIC BAGS CAN BE USED TO TREAT ACUTE HIGHALTITUDE ILLNESS BUT THEY ARE RARELY AVAILABLE

TREATMENT OF ACUTE MOUNTAIN SICKNESS General recommendations Most important is to descend to a lower altitude at once, and this must always be done if conditions permit. If symptoms are mild, staying put may be an option. A descent of 500–1,000 metres (~1,600-3,200 feet) is often enough to reduce symptoms significantly.

After resting and acclimatisation, further ascent may be attempted if the symptoms were mild. Those who have had cerebral or pulmonary edema are advised against attempting to ascend further. It is always recommended to drink plenty of liquids and quench thirst as soon as it arises to avoid dehydration and reduce the effects of acute mountain sickness.

Fluid overload should be avoided, however, as it may result in lower blood sodium and acute mountain sickness-like symptoms.

Medicines and other treatments for acute mountain sickness Medicines may be used exclusively if symptoms are mild or if conditions do not allow for descent to a lower altitude, for instance due to weather or darkness. Medicines most commonly used for patients with severe symptoms of acute mountain sickness can be seen in the table on page 27. Full doses of painkillers such as paracetamol, ibuprofen or celecoxib may be used for mild symptoms, especially headache. Acetazolamide should be administered as soon as possible after the onset of symptoms while more potent medication, such as dexamethasone, may be used as an alternative, after consultation

30 Hig-Altitude Diseases

with a physician. Acetazolamide is mostly used for mild cases of acute mountain sickness.

If symptoms subside once medicine has been administered, descending to a lower altitude may not be necessary. Dexamethasone, on the other hand, is preferred in cases of moderate or severe acute mountain sickness. It is never recommended to ascend to a higher altitude before symptoms have subsided. Administering oxygen nasally reduces symptoms quickly but it is rarely available, as oxygen cylinders are cumbersome and heavy. Some cabins have portable hyperbaric (Gamow) bags, in which the patient can be placed and pressure applied with a foot or hand pump, resulting in a decrease in effective altitude of up to 3,000 metres (~9,800 feet).

Treatment of high-altitude pulmonary edema It is especially important in these cases to bring the patient to a lower altitude, but a hyper­ baric bag may be useful when transporting the patient is not possible. Administering oxygen, e.g. 1–2 litres/min nasally via a nasal mask, is effective but rarely available at high altitudes. Phosphodiesterase inhibitors, such as tadalafil or sildenafil, can be admini­ stered, in consultation with a physician, to decrease pulmonary artery pressure, for which nifedipine tablets can also be used. Diuretics and morphine are not recommended for the treatment of high-altitude pulmonary edema, as diuretics may increase dehydration.

How is erectile dysfunction medication effective against high-altitude pulmonary edema?

Sildenafil was originally studied as an antihypertensive agent, but did not prove to be sufficiently effective. However, many men did not want to stop taking the drug at the conclusion of clinical trials. That is how its effectiveness as treatment for erectile dysfunction was discovered. These medicines increase the production of nitrous oxide (NO) in the pulmonary arteries, dilating them without having an effect on blood pressure elsewhere in the body. That is why they are used to treat high-altitude pulmonary edema and unexplained pulmonary hypertension. Studies on their efficacy in treating high-altitude pulmonary edema are limited, but never­ theless sufficient to recommend their use.

Treatment of high-altitude cerebral edema Most important is to move the patient further down the mountain, as far far down as condi­tions allow. This is always the case unless descent is prevented by external condi­ tions. In such circumstances, administering oxygen, if available, may be appropriate, if oxygen is available, and the same applies to hyperbaric bags. Dexamethasone in tablet form is sometimes used, administered intravenously or intramuscularly, if conditions allow.

High-Altitude Diseases 31

SLEEP DISTURBANCES ARE AMONG THE MOST COMMON COMPLAINTS AT HIGH-ALTITUDES

OTHER HIGH-ALTITUDE DISEASES Sleep disturbances These are some of the most common altitude-related complaints, and may be caused by various environmental noises that disturb sleep, but also by unfamiliar sleeping condi­ tions, such as sleeping in a tent or a crowded cabin. Lack of oxygen is believed to be the main cause of such sleep disturbances. Symptoms include irregular, periodic breathing, which is common at high altitudes, but can often be treated with acetasolamide. Those who experience severe sleep disturbances despite acetazolamide may take sleeping medicine such as zolpidem, which is less likely to suppress breathing than other sleeping medicine.

Altitude-related cough Coughing is common at higher altitudes where the cough reflex is more sensitive.

Breathing is also accelerated and the air is dryer, which dries up the respiratory tract and may result in coughing. This especially applies to people with asthma or other respiratory diseases. In addition, mountain air is often very dusty, and bacterial and viral infections are easily transmitted in cramped spaces such as tents. Rest and descending to a lower altitude is effective in alleviating the problem, but medicines with codeine can also be used to control coughing.

32 Hig-Altitude Diseases

DIARRHEA AND VOMITING ARE FREQUENT CONDITIONS AT HIGH-ALTITUDE

Gastrointestinal problems Changes in diet and digestion are often part of travel in different cultures. Sanitary facili­ ties and fresh water are usually not easily accessible at high-altitudes, and preserving food is difficult. Bacteria can be killed by boiling, if circumstances allow. Filtration can be used as an alternative, but gastrointestinal viruses may pass through filters so this method is not completely safe. Chlorine and iodine tablets have also been used to kill germs, in which case the water must be reasonably clear and ideally filtered beforehand.

In addition to this, water may be purified without external substances, e.g. by using an UV lamp or solar energy. Diarrhea, often accompanied by abdominal pain, is another frequent affliction. In such conditions, it is important to drink plenty of liquids containing sugars and electrolytes.

Antibiotics are not recommended to treat altitude-related diarrhea except in obvious cases of serious bacterial infection, in which case an antibiotic like ciprofloxacin is most often used. Unnecessary antibiotic use, however, often compromises the body's natural gut microbiota, which can lead to further gastrointestinal symptoms and increase the risk of antibiotic-resistant bacteria in the digestive system. Flatulence is a frequent problem that may be caused by both a change in diet and more air being swallowed due to rapid breathing.

High-Altitude Diseases 33

Eye conditions The most common eye condition at high altitude is acute keratitis, often called snow-blind­ ness. It is caused by powerful ultraviolet radiation at high altitudes, as well as dry and cold air. Acute keratitis is characterised by eye pain, redness, foreign object sensation, excessive tearing, photophobia and vision impairments. Symptoms are often not felt until several hours from exposure to radiation and they usually subside in one to three days.

For treatment, artificial tears are used and sometimes antibiotic eye drops with antiinflammatory steroids. Snow blindness can be prevented by using glacier glasses that protect the cornea from UVA and UVB radiation.

Lack of oxygen may cause high-altitude retinopathy and macular hemorrhage that only be­ comes apparent at altitudes of over 4,000 metres (~13,000 feet). This is often accompanied by impairment of vision, which is usually reversible, and these patients often also suffer from high-altitude cerebral edema.

SNOW BLINDNESS IS AN INFLAMMATION OF THE CORNEA THAT MAY RESULT IN TEMPORARY BLINDNESS

34 Hig-Altitude Diseases

Frostbite Skin damage due to frost results in frostbite, which can be either superficial, when the top layer of the skin freezes, or deep frostbite where deeper layers of tissue are damaged. The parts of the body most sensitive to frostbite are the face, ears, hands and feet, where the surface is proportionally large and no large muscles to heat the tissue. In cases of surface frostbite, the skin will become white or grey and sore to the touch. The frostbitten part is cold and stiff, while the tissues under the skin remain soft. The symptoms are mainly a stinging sensation and pain. In cases of deep frostbite, the skin is even colder and harder and does not move when pushed. The colour of the skin will be white or grey-white. Pain is not as pronounced as in cases of surface frostbite and over time, blisters may develop.

Frostbite is treated by moving the patient from the cold and to a warm place while remov­ ing clothing and anything else that may be in the way of the injury. It is important to pre­ vent the frostibite area from freezing again, but rubbing the area is not recommended.

A variety of heating techniques may be applied as conditions permit, such as inserting an affected body part into a warmer armpit or groin area or using a warm, damp cloth. If conditions allow, the frostbite area is then heated for 15-60 minutes in water that is 3739 degrees Celsius (~100° F). It is important to administer painkillers as frostbite is often very painful. Dry and clean bandages are then applied to prevent infections.

FROSTBITE ON FINGERS IS A SERIOUS ALTITUDE-RELATED COMPLICATION

High-Altitude Diseases 35

LISTS OF MEDICINES Mountain expedition to an altitude of 2,500–6,000 metres (~8,200-20,000 feet) • • • • • • •

Paracetamol Paracodeine Ibuprofen Acetazolamide Antibacterial eye ointment Ciprofloxacin Sildenafil / tadenafil

Mountain expedition to an altitude of over 6000 metres (~20,000 feet) • • • • • • • •

Paracetamol Paracodeine Ibuprofen Acetazolamide Antibiotic eye ointment Ciprofloxacin Sildenafil / tadenafil Dexamethasone

36 Hig-Altitude Diseases

The authors standing in front of the Landspitali – The National University Hospital of Iceland in Reykjavik. From the left: Ólafur Már Björnsson, Gunnar Guðmundsson, Magnús Gottfreðsson, Engilbert Sigurðsson and editor Tómas Guðbjartsson.

Photograph by Kristinn Ingvarsson.

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High-Altitude Diseases 37

High-Altitude Diseases This booklet provides an overview of the most common diseases that may occur at high-altitudes; both acute mountain sickness (AMS), which is the most common form of high-altitude illness, and life-threatening conditions such as high-altitude cerebral edema (HACE) and high-altitude pulmonary edema (HAPE).

Acclimatisation, i.e. the body’s natural response to lack of oxygen, is explained in brief, and other common conditions at high altitude, such as sleep disturbance, gastrointestinal problems, snow blindness and frostbite, are also reviewed. Treatment of the most common conditions is discussed, and at the back is a list of medicines that may be helpful to bring along when mountaine­ ering at high altitudies.

ISBN 978-9935-25-243-2