Article Text
Abstract
The military has always had an important role in high altitude research. This is due to the fact that mountainous regions often span borders and provide a safe haven to enemies. Deploying troops rapidly into high altitude environments presents major problems in terms of the development of high altitude illness. This paper examines the rationale for carrying out research at high altitude and the opportunities within the UK Defence Medical Services for carrying out this research.
- ALTITUDE MEDICINE
- EDUCATION & TRAINING (see Medical Education & Training)
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Key messages
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Ascent to high altitude leads to significant physiological changes.
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Research at high altitude presents a significant challenge.
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The military needs to better understand adaptation to high altitude to be able to deploy troops safely and effectively in this environment.
Introduction
Barometric pressure changes on ascent to high altitude (HA). Above 2500 m, oxygen saturations can be expected to fall below 90% and physiological changes occur in every body system. On ascent to altitude, there is an increase in RR which has the effect of reducing alveolar carbon dioxide (CO2) which in turn allows a small but crucial increase in alveolar oxygen. This would normally be limited due to an increase in pH slowing the respiratory drive; however, at altitude, bicarbonate is excreted maintaining a normal pH for a lower CO2. The diuresis that brings about increased bicarbonate excretion also creates relative haemoconcentration generating more oxygen carrying capacity per unit of blood. Through these mechanisms, individuals can tolerate profound hypoxia well. This process is termed acclimatisation. At the extremes of altitude, ABGs are quite remarkable with arterial samples drawn at 8400 m showing an arterial oxygen tension (PaO2) of 3.28 KPa, PaCO2 of 1.77 KPa and normal pH1 (Table 1).
The physiological variables recorded during the 2012 Defence Medical Services (DMS) expedition to Bolivia are displayed in Table 2.
However, in some individuals, acclimatisation fails resulting in a spectrum of altitude illness. Acute mountain sickness (AMS) is the most common and includes a headache plus a variety of other, multisystem symptoms (Table 3). HA pulmonary oedema and HA cerebral oedema are life-threatening conditions occurring as a result of failure to acclimatise.
These profound physiological changes in otherwise healthy individuals have led to an interest in investigating the effects of HA in the hope that clinically relevant lessons can be identified.2 ,3
Military importance
Since the end of the cold war, there has been a shift in conflict from large organised Armies to smaller ‘asymmetric’ threats from ideologically motivated groups rather than nation States. It stands to reason that these groups will seek shelter in inhospitable regions, away from easy surveillance and communication and mountains provide just such a haven. During the initial war in Afghanistan, US forces fought at HA to displace the Taliban. An important battle during this phase was Op Anaconda, fought in the Shahi-Kot valley, where 2700 US and Afghan soldiers faced 1000 Taliban fighters at altitudes of 2500–3500 m. During this phase of the conflict, 8% of US casualties evacuated were as a result of altitude illness.4
The problem of identifying when troops are ready to deploy at HA is exacerbated by the fact that the only diagnostic criteria for AMS is the self-reported Lake Louise Score (LLS).5 A self-reported score may not be useful with a cadre of highly motivated and committed soldiers and the score also shares many features with anxiety questionnaires. A biochemical test or predictor for altitude illness would be useful. The NATO review of HA medicine in the Military6 identifies the need for a capability for the ‘early detection and diagnosis of altitude illness prior to onset of severe symptoms that is independent of the victim reporting their symptoms’ and this ‘will reduce altitude illness impact on mission and medical support and evacuation requirements’.
Problems in conducting HA research
There are many problems with conducting high quality research at HA.
Subjects
Many hundreds of thousands of people subject themselves to the potential risks of HA environments for leisure activities annually. To this extent, it is ethically justifiable to take a trekking team on a research expedition knowing that some will become ill. However, what becomes more difficult is tailoring a research protocol to an individual's expectations. If subjects receive a fully funded trip to a beautiful and remote environment, should this be seen as unethical inducement or, alternatively, if subjects are paying a large amount of money to take part in the research trip, how far can protocols be sufficiently relaxed to allow for recreation, and how will this compromise results?
Logistics
Many mountainous areas are remote. This creates difficulties with supplies of power and equipment to carry out research. A considerable amount of planning is required to ensure sufficient capacity and redundancy of equipment and power.
Monitoring of HA illness
Failure of adaptation to HA is manifest as altitude illness and in very many cases monitoring daily LLS is a crucial part of research protocols. However, these scores are self-reported and the very act of raising awareness of the symptoms may increase the reporting. The LLS itself is in no way specific for altitude symptoms and therefore may over-report altitude illness. Somatic symptoms of anxiety are very similar to many of the symptoms that would add to an LLS, further confounding the diagnostic problem.
Interplay with exercise
Exercise has an effect on the process of acclimatisation. It has long been mountaineering practice to recommend some exercise (ie, the act of trekking) when gaining a new altitude and to avoid overexerting oneself. A research protocol that involves covering a known route (such as the trek to Everest base camp) will generate a differing perception of effort for different people, even if walking pace is strictly governed.
Modelling HA in the laboratory
Using chambers (hypobaric or normobaric) to model hypoxia is appealing as an exercise stimulus can be carefully controlled. There is, however, debate about whether or not these two entities are similar. This depends in part on what the model is being used for be it sports science, altitude medicine or aviation medicine. Rapid ascent in a hypobaric chamber does seem to be associated with more pronounced respiratory changes than the equivalent FiO2 (SaO2 62.3% vs 69.5%) with a 5 min exposure to 7500 m equivalent.7 However, in this study, the reported symptoms were similar prompting the authors to conclude that normobaric hypoxia was a useful model (for aviation training). This pattern of more pronounced hypoxaemia, hypocapnia and alkalosis (with hypobaric hypoxia) has been found in other studies and may be due to changes in dead space ventilation.8 One other factor is the calculation of the correct FiO2 which is often not clear from descriptions of research protocols.9 The saturated vapour pressure of water () is constant at any altitude (pressure) and amounts to a value of 47 mm Hg. The ambient PO2 must be reduced by 47 mm Hg as gases are saturated with water vapour on inspiration. In hypobaric environments, this leads to a greater reduction of inspired oxygen content than in normobaric environments. As an example, a reduction of pressure to 430 mm Hg in a hypobaric chamber with a normal FiO2 (0.209) leads to an ambient oxygen tension of 90 mm Hg (430×0.209); the same oxygen tension can be generated with an FiO2 of 0.119 in normobaricity (760 mm Hg×0.119). However, to calculate the inspired oxygen tension, the SVP of water must be taken into account using the equation:
Hence, in normobaricity, the PiO2 is 85 mm Hg whereas in hypobaricity it is 80 mm Hg and the FiO2 in normobaricity must be set lower to get an equivalent stimulus. Interestingly, no studies have yet been published comparing normobaric and hypobaric chambers with a field study at HA.
Hypoxia research within the DMS
For the reasons outlined above, there is a military interest in HA adaptation and disease. Over the past 6 years, members of the DMS have taken part in four research expeditions with the aim of combining research with military adventurous training. The primary research aim of the expeditions has been focused on hormonal adaptation to hypoxia with the aim of finding a marker that can be used to diagnose (or exclude) AMS. One specific biomarker that has been investigated is brain natriuretic peptide (BNP). This is increased in some animal models of hypoxia, rises with increased pulmonary artery pressures and with inflammation and stress. BNP also causes a natriuresis which is important in acclimatisation to HA; for these reasons, we hypothesised that it may be a useful marker of AMS.
In 2009, we undertook a field study at altitude in Nepal during the course of a trek to Everest base camp, using an ascent profile of a typical recreational trek. BNP was measured using point of care monitors (Alere Triage Biosite Pro, Cheshire, UK) which reduced any reliance on electrical power or ability to freeze samples. We found that BNP (mean±SEM) rises between sea level (7.1±1 pg/mL) and 5150 metres (17.7±5.1 pg/mL, range 6.70–119 pg/mL, p=0.001) in a cohort of 23 subjects.10 We also found that mean LLS (mean±SEM) for those with a BNP response versus no BNP response at 5150 m were significantly different: 3.3±0.5 versus 0.75±0.5 (p=0.034) on day 10 and 3.3±0.4 versus 0±0 (p=0.003) on day 11. This contradicted previously published data.11 ,12 The major difference in our study was that the research took place during a trek rather than a study where mechanised transport had been used to gain altitude. As exercise is a key part of a trek at HA or any military campaign at HA, this finding was worthy of further investigation.
In 2011, we ran a second field study with 20 subjects repeating the same trek to Everest base camp. This time blood samples were taken, centrifuged and frozen in addition to using a point of care monitor. BNP and NT-proBNP (pg/mL, mean±SEM) rose significantly from Kathmandu (approximately 1300 m) (9.2±2 and 36.9±6.6, respectively) reaching a peak at 5150 m, immediately following ascent/descent to 5643 m. At this altitude, BNP and NT-proBNP were 32.3±8.8 and 301.1±96.3 (p=0.003 and p<0.001 vs Kat, respectively).13 At 5150 m, BNP levels were significantly higher among the four subjects with severe (LLS >6) AMS (58.4±18.7) compared with those without (BNP 22.7±8.6, p=0.048) (Figure 1). There were significant correlations between change in body water from baseline to 5150 m with both BNP and NT-proBNP (r 0.77, p=0.001, r 0.745, p=0.002, respectively).
These findings suggested that BNP was an important marker of fluid retention and potential altitude illness. One potentially useful role of BNP is to assess illness severity in an austere environment. While a high BNP may not diagnose altitude illness per se, there may be a role for the use of such biomarkers to rule out significant illness. During 2012, a large scale field study was conducted in the Cordillera Real region of Bolivia. Early in the expedition, one member became unwell with a clinical diagnosis of HA pulmonary oedema.14 This is a life-threatening condition and descent to a lower altitude is the best treatment. In this case, there was no easy retreat to lower altitude. During the next 24 h, we were able to show improvement in pulmonary artery pressures (with cardiac echo) and a reduction in BNP. The climber recovered and was later able to climb a 6100 m mountain. This is the real value of a biomarker for altitude illness, supporting clinical decisions and allowing appropriate decisions where there are only difficult and possibly dangerous options for descent.
Summary
Ascent to HA environments places a significant and predictable physiological stress on human beings. While acclimatisation does occur, altitude illness is a significant risk. Mountains provide national boundaries and a potential haven for enemies in the current climate of small scale, asymmetric warfare. Understanding the process of acclimatisation and identification of those at risk is of significant importance to the military. Studies can be conducted in hypobaric or normobaric chambers, but there are many variables affecting the usefulness of studies in chambers and further research is required to establish the model. In order to better investigate biomarkers, large scale studies and investigation of those who present unwell to medical services are the next logical steps to be taken.
References
Footnotes
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Contributors AM contributed to the manuscript and has organised a number of high altitude research expeditions, DW has contributed to the manuscript and collected and analysed the BNP data used in the manuscript.
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Funding DMS expeditions have been supported by grants from Drummond Foundation, JS Expeditions Trust, Surgeon General's Department.
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Competing interests None.
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Provenance and peer review Not commissioned; internally peer reviewed.