Alex Wright

Acute Mountain Sickness: Pathophysiology, Prevention, and Treatment

Barometric pressure falls with increasing altitude and consequently there is a reduction in the partial pressure of oxygen resulting in a hypoxic challenge to any individual ascending to altitude. A spectrum of high altitude illnesses can occur when the hypoxic stress outstrips the subjects ability to acclimatize. Acute altitude-related problems consist of the common syndrome of acute mountain sickness, which is relatively benign and usually self-limiting, and the rarer, more serious syndromes of high-altitude cerebral edema and high-altitude pulmonary edema. A common feature of acute altitude illness is rapid ascent by otherwise fit individuals to altitudes above 3000 m without sufficient time to acclimatize. The susceptibility of an individual to high-altitude syndromes is variable but generally reproducible. Prevention of altitude-related illness by slow ascent is the best approach, but this is not always practical. The immediate management of serious illness requires oxygen (if available) and descent of more than 300 m as soon as possible. In this article, we describe the setting and clinical features of acute mountain sickness and high-altitude cerebral edema, including an overview of the known pathophysiology, and explain contemporary practices for both prevention and treatment exploring the comprehensive evidence base for the various interventions.

Acute altitude illnesses

#### Summary points Acute altitude illnesses are potentially serious conditions that can affect otherwise fit individuals who ascend too rapidly to altitude. They include high altitude headache, acute mountain sickness, high altitude cerebral oedema, and high altitude pulmonary oedema. The number of people travelling to altitude for work (soldiers, miners, construction workers, and astronomers) or for recreation (skiing, trekking, mountain biking, and climbing) is rising, and increased media attention towards these activities has also raised the profile of altitude related illness. Typical scenarios in which such illness might occur are a family trek to Everest base camp in Nepal (5360 m), a fund raising climb of Mount Kilimanjaro (5895 m), or a tourist visit to Machu Picchu (2430 m). Awareness of potential altitude related problems is important even for healthcare practitioners working at lower altitude, because patients may ask for advice about the safety of a proposed journey and how to prevent illness at altitude. #### Sources and selection criteria We searched Medline and Google Scholar with no …

Cerebral venous system and anatomical predisposition to high-altitude headache

As inspired oxygen availability falls with ascent to altitude, some individuals develop high‐altitude headache (HAH). We postulated that HAH results when hypoxia‐associated increases in cerebral blood flow occur in the context of restricted venous drainage, and is worsened when cerebral compliance is reduced. We explored this hypothesis in 3 studies.

Effects of breathing air containing 3% carbon dioxide, 35% oxygen or a mixture of 3% carbon dioxide/35% oxygen on cerebral and peripheral oxygenation at 150 m and 3459 m

The effects of gas mixtures comprising supplementary 3% carbon dioxide, 35% oxygen or a combination of 3% CO(2) plus 35% O(2) in ambient air have been compared on arterial blood gases, peripheral and cerebral oxygenation and middle cerebral artery velocity (MCAV) at 150 m and on acute exposure to 3459 m in 12 healthy subjects. Breathing 3% CO(2) or 35% O(2) increased arterial blood oxygen at both altitudes, and the CO(2)/O(2) combination resulted in the most marked rise. MCAV increased on ascent to 3459 m, increasing further with 3% CO(2) and decreasing with 35% O(2) at both altitudes. The CO(2)/O(2) combination resulted in an increase in MCAV at 150 m, but not at 3549 m. Cerebral regional oxygenation fell on ascent to 3459 m. Breathing 3% CO(2) or 35% O(2) increased cerebral oxygenation at both altitudes, and the CO(2)/O(2) combination resulted in the greatest rise at both altitudes. The combination also resulted in significant rises in cutaneous and muscle oxygenation at 3459 m. The key role of carbon dioxide in oxygenation at altitude is confirmed, and the importance of this gas for tissue oxygenation is demonstrated.

Near-infrared spectroscopy in the assessment of cerebral oxygenation at high altitude

Hypoxia plays a key role in the pathogenesis of acute mountain sickness (AMS), but individual susceptibility is variable and cerebral symptoms do not always correlate with PaO2 measurements. Cerebral hypoxia may be more relevant than PaO2. We studied trends in cerebral regional oxygen saturation by the technique of near-infrared spectroscopy in 20 subjects ascending rapidly to 4680 m. Subjects were enrolled in a placebo-controlled, double-blind trial of medroxyprogesterone for the prevention of AMS. The fall in cerebral oxygen saturation was less than in the periphery. At 4680 m, cerebral oxygenation correlated with peripheral saturation but not with PaCO2 or with cerebral symptoms scores. At 4680 m, subjects on medroxyprogesterone had higher cerebral and peripheral saturation compared with those on a placebo. We conclude that cerebral oxygenation monitored with the Critikon 2020 system provided important information on the complex relationship of hypoxia to AMS and that other factors, such as changes in blood flow or capillary permeability, may be equally important.

Self-Assessment of Acute Mountain Sickness in Adolescents: A Pilot Study

OBJECTIVE To perform a pilot study exploring the prevalence of acute mountain sickness (AMS) in adolescents on ascent to altitude and evaluating whether this age group is capable of self-assessment of AMS using the Lake Louise scoring system. METHODS Twelve teenagers aged 15 to 18 years old (5 girls) traveled for 21 days between 2400 and 5500 m. Each member of the expedition completed a Lake Louise self-assessment questionnaire on a daily basis. Group leaders (nonmedical) were informed about any subject with a score of 3 or more. Appropriate treatments were then initiated. Detailed analysis of data was undertaken on return to the UK. RESULTS There was 100% completion of 252 questionnaires. Eleven of the 12 subjects (91.7%) had symptom scores greater than or equal to 3, consistent with a diagnosis of AMS, on at least one day (range, 0-8). Symptoms of AMS were more common in the female group members (P = .041). CONCLUSIONS AMS is a common problem among adolescents. There are increasing numbers of adolescents traveling to high altitudes, and there appears to be a lack of information about the prevalence of AMS in this age group. Motivated adolescents seemed capable of self-monitoring for AMS using the Lake Louise questionnaire. Combined with an appropriate ascent profile and support, we feel this approach may contribute to safety in the mountains and merits further study.

Magnetic Resonance investigation into the mechanisms involved in the development of high-altitude cerebral edema

Rapid ascent to high altitude commonly results in acute mountain sickness, and on occasion potentially fatal high-altitude cerebral edema. The exact pathophysiological mechanisms behind these syndromes remain to be determined. We report a study in which 12 subjects were exposed to a FiO2 = 0.12 for 22 h and underwent serial magnetic resonance imaging sequences to enable measurement of middle cerebral artery velocity, flow and diameter, and brain parenchymal, cerebrospinal fluid and cerebral venous volumes. Ten subjects completed 22 h and most developed symptoms of acute mountain sickness (mean Lake Louise Score 5.4; p < 0.001 vs. baseline). Cerebral oxygen delivery was maintained by an increase in middle cerebral artery velocity and diameter (first 6 h). There appeared to be venocompression at the level of the small, deep cerebral veins (116 cm3 at 2 h to 97 cm3 at 22 h; p < 0.05). Brain white matter volume increased over the 22-h period (574 ml to 587 ml; p < 0.001) and correlated with cumulative Lake Louise scores at 22 h (p < 0.05). We conclude that cerebral oxygen delivery was maintained by increased arterial inflow and this preceded the development of cerebral edema. Venous outflow restriction appeared to play a contributory role in the formation of cerebral edema, a novel feature that has not been observed previously.

Changes in pupil dynamics at high altitude--an observational study using a handheld pupillometer.

Gross pupil dynamics are used as an indirect measure of brain function. Changes in hypoxia and intracranial pressure are thought to alter pupil responses to light. This study assessed a portable handheld pupil measuring device (pupillometer) in the field investigating the changes in pupil size, speed of reaction, and rate of constriction/dilatation with hypoxia induced by changes in altitude. A correlation between pupil dynamics and acute mountain sickness was sought. Seventeen volunteers were studied following acute exposure to 3450 m and then during a trek to 4770 m in Ladakh, India. The pupillometer was used to record maximum and minimum pupil diameter in response to a standard light source with calculation of latency, constriction and dilatation velocities. Acute mountain sickness (AMS) was recorded using Lake Louise self completed questionnaires both in the morning and afternoon on each day. Acute altitude exposure resulted in a significant reduction of percentage change in pupil size (36.5% to 24.1% p=<0.001), significant delay in pupillary contraction (latency; 0.208 to 0.223 seconds p=0.015) and a significant slowing of the rate of contraction (constriction velocity; -2.77 mm/s to -1.75 mm/s p=0.012). These changes reverted to normal during a period of acclimatization. A significant diurnal variation in pupil size was also observed. There was no significant difference between subjects with and without AMS. The handheld pupillometer is a suitable robust tool for monitoring changes in pupil dynamics in the field. With acute exposure to hypobaric hypoxia associated with an ascent to a moderate altitude, there is a general slowing of pupil function which reverts to normal within a few days of acclimatization. There appears to be a marked diurnal variation in pupil size. The measurements clearly demonstrated an effect of hypoxia on cerebral function, but these changes did not relate to moderate AMS.

Medroxyprogesterone at High Altitude. The Effects on Blood Gases, Cerebral Regional Oxygenation, and Acute Mountain Sickness

OBJECTIVE To study the effect of medroxyprogesterone on blood gases and cerebral regional oxygenation at high altitude, alone and in conjunction with acetazolamide, and to assess the effect on acute mountain sickness (AMS). DESIGN Two placebo-controlled trials during rapid ascent to high altitude. PARTICIPANTS In the first trial, 20 participants, and in the second trial, 24 participants. SETTING During rapid ascent to 4680 m and on rapid ascent to 5200 m. INTERVENTION In the first trial, participants were randomized to receive medroxyprogesterone 30 mg or a placebo twice a day. In the second trial, participants were randomly assigned to one of 4 groups: a placebo twice daily, medroxyprogesterone 30 mg twice daily, acetazolamide 250 mg plus a placebo twice daily, or acetazolamide 250 mg plus medroxyprogesterone 30 mg twice daily. MAIN OUTCOME MEASURES Blood gas changes and symptom scores of AMS in both trials and cerebral regional oxygen saturations in the first trial only. RESULTS Medroxyprogesterone improved peripheral oxygen saturations in both trials and improved PaO2 in combination with acetazolamide. Cerebral regional oxygen saturation was not altered by medroxyprogesterone. The reduction in symptom scores and in the extent of AMS was not significant in this limited study. CONCLUSIONS Medroxyprogesterone acts as a respiratory stimulant, but the clinical benefit regarding the development of AMS was unproven at high altitude. Combined medroxyprogesterone and acetazolamide gave the best PaO2.

Do changes in gastro‐intestinal blood flow explain high‐altitude anorexia?

Eur J Clin Invest 2010; 40 (8): 735–741