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Eur Respir J 2006; 27:165-171
Copyright ©ERS Journals Ltd 2006

Hypoxic ventilatory response in successful extreme altitude climbers

L. Bernardi1, A. Schneider2, L. Pomidori3, E. Paolucci3 and A. Cogo3

1 Dept of Internal Medicine, University of Pavia and IRCCS Ospedale S. Matteo, Pavia, and 3 Dept of Clinical and Experimental Medicine, Section of Respiratory Diseases, University of Ferrara, Ferrara, Italy. 2 Dept of Anaesthesiology, University Medical Center, Regensburg, Germany

CORRESPONDENCE: L. Bernardi, Clinica Medica 2, Universita' di Pavia - IRCCS Ospedale S. Matteo, 27100 Pavia, Italy. Fax: 39 0382526259. E-mail: lbern1ps{at}unipv.it

Keywords: Altitude, hypoxia, ventilation, ventilatory control, ventilatory efficiency

Received: February 11, 2005
Accepted September 2, 2005


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
A very high ventilatory response to hypoxia is believed necessary to reach extreme altitude without oxygen. Alternatively, the excessive ventilation could be counterproductive by exhausting the ventilatory reserve early on.

To test these alternatives, 11 elite climbers (2004 Everest-K2 Italian Expedition) were evaluated as follows: 1) at sea level, and 2) at 5,200 m, after 15 days of acclimatisation at altitude. Resting oxygen saturation, minute ventilation, breathing rate, hypoxic ventilatory response, maximal voluntary ventilation, ventilatory reserve (at oxygen saturation = 70%) and two indices of ventilatory efficiency were measured.

Everest and K2 summits were reached 29 and 61 days, respectively, after the last measurement. Five climbers summited without oxygen, the other six did not, or succeeded with oxygen (two climbers). At sea level, all data were similar. At 5,200 m, the five summiters without oxygen showed lower resting minute ventilation, breathing rate and ventilatory response to hypoxia, and higher ventilatory reserve and ventilatory efficiency, compared to the other climbers.

Thus, the more successful climbers had smaller responses to hypoxia during acclimatisation to 5,200 m, but, as a result, had greater available reserve for the summit. A less sensitive hypoxic response and a greater ventilatory efficiency might increase ventilatory reserve and allow sustainable ventilation in the extreme hypoxia at the summit.

At high altitude, the reduced partial pressure of oxygen (PO2) results in arterial desaturation; respiration is then driven by the arterial chemoreceptors, rather than medullary partial pressure of carbon dioxide (PCO2), and with any physical exertion the necessary increases in ventilation are very large 1, 2.

Previous studies showed that a high hypoxic ventilatory response (HVR) helps in performing work at high altitude 1, 2. By extension, it is generally believed that extreme altitudes could be tolerated without oxygen support only by subjects with the highest HVR, due to the extreme increase in ventilation required to remove carbon dioxide and increase arterial oxygen partial pressure (Pa,O2). However, even with good acclimatisation, an extreme sensitivity to hypoxia may stimulate minute ventilation (V'E) close to, or even above, sustainable limits (e.g. close to the maximal voluntary ventilation (MVV) defined as the maximal ventilation that can be maintained for 12 s 3).

Since 1978, several climbers have nevertheless reached the summit of Mt Everest without oxygen, but, to the current authors' knowledge, there is little information (except anedoctal 4) about the respiratory control in these subjects.

It could be hypothesised that the subjects with a better chance of reaching extreme altitudes without oxygen would be those with the highest HVR, due to their ability to increase Pa,O2 through the maximal increase in ventilation. Alternatively, it could be hypothesised that these subjects would approach their limit (e.g. the MVV) at relatively lower altitudes, whereas subjects with a brisk but not excessive ventilatory stimulus could maintain sustainable ventilation up to extreme altitudes. This could be possible if a relatively lower ventilation were associated with (or compensated by) a higher ventilatory efficiency.

The opportunity to participate in the recent Italian Everest-K2 expedition (spring–summer 2004) allowed the current authors to test a relatively high number of elite climbers before and during their acclimatisation. The study then tested whether the climbers who could reach the highest summits without oxygen were characterised by a higher or lower ventilatory sensitivity to hypoxia, as compared to those who did not succeed or needed supplemental oxygen. The study also tested whether successful climbers had a more efficient respiration, and whether any differences were present even before exposure to high altitude, or became apparent only during acclimatisation.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
Subjects
The study was approved by the institutional ethics committee, and all subjects gave informed consent to participate. Eleven Italian male elite climbers with previous experience of climbing in the Alps, Himalayas and Andes were studied. All subjects were healthy, nonsmokers, and were not taking any drugs or medications before and during the study. Anthropometric data are shown in table 1Go.


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  		Table 1— Anthropometric and baseline haematological data

 
Protocol
All subjects were studied sitting, in a comfortable position, at ambient temperature and humidity, as follows: 1) at sea level, 1 month before the expedition; and 2) at 5,200 m, after 15 days of total stay at altitude, including 6 days of stay at altitudes between 3,800 and 5,200 m and 9 days from the arrival at North Face Everest Base Camp (5,200 m), i.e. when the acclimatisation process should already have begun. After the second evaluation, the climbers reached progressively higher camps, until the Everest summit (8,848 m), 29 days later. Thereafter, they descended to sea level for 2 weeks and left for K2 base camp (5,000 m). After 61 days from the second evaluation, they eventually reached the summit of K2 (8,611 m).

Recordings were taken during: 1) spontaneous breathing (4 min without a pneumotachograph and 4 min with the pneumotachograph); 2) slow breathing at 6 breaths·min–1 (2 min); 3) 12-s MVV; 4) a slow vital capacity manoeuvre; and 5) progressive isocapnic hypoxia (arterial oxygen saturation (Sa,O2) from resting values to 70%). This was obtained by a re-breathing circuit, in which a variable part of the expired air was passed into a reservoir containing soda lime prior to return to the re-breathing bag, in order to maintain end-tidal carbon dioxide pressure (PET,CO2) clamped at 4.8 kPa (36 mmHg; a value that could be reached both at sea level and altitude). The HVR was evaluated as the slope of the linear regression line relating the increase in ventilation to the drop in oxygen saturation 5. During recordings 2 to 5, the expiratory flow was monitored by a heated Fleish pneumotachograph (Metabo, Epalinges, Switzerland) connected to a mouthpiece. During all recordings, oxygen saturation (3740 Ohmeda Pulse Oximeter; Ohmeda, Englewood, CO, USA) and expired CO2 (COSMOplus; Novametrix, Wallingford, CT, USA; connected to the mouthpiece, or to nasal tubes during recording 1) were monitored, as well as the electrocardiogram (by chest leads) and blood pressure (by sphygmomanometer). During the first recording, respiration was monitored by inductive belts 6 around the chest, in order to measure the respiratory rate without possible artefacts induced by the pneumotachograph 7. The pneumotachograph was recalibrated after each re-breathing manoeuvre by a 3-L syringe. The capnograph was calibrated before and after each subject by a known gas reference (5% CO2 gas mixture). The saturimeter was calibrated by breathing 100% O2 mixture. All signals were acquired on a Macintosh G3 at 300 samples·s–1. Interactive software analysis written by one of the current authors (L. Bernardi) calculated mean heart rate, tidal volume (VT), V'E, mean expiratory CO2, PET,CO2, and Sa,O2, for each breath, according to previous formulae 3, for each sequence. During the sea-level recording session, the subjects underwent simple haematological examinations by standard methods to evaluate haemoglobin content, red blood cell count and haematocrit.

Ventilatory reserve
Since hypoxia stimulates ventilation, one could assume that for a given level of hypoxaemia, each subject ventilates at a given per cent of MVV. According to reports indicating that oxygen saturation at the summit of Mt Everest is in the range of 70% 2, the present authors defined the ventilatory reserve as = 100x(MVV– V'E(Sa,O2 = 70))/MVV) (fig. 1Go). This is based on the same formula commonly used to define the ventilatory reserve during exercise at sea level (breathing reserve = 100x(MVV–V'E)/MVV) 3. In addition, the reserve was also reported as the difference MVV–V'E(Sa,O2 = 70), in L·min–1.



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  		Fig. 1— Schematic diagram showing the relationship between the ventilatory response to hypoxia and the ventilatory reserve. Data were obtained after 15 days at altitude (9 days at 5,200 m). The significances reported refer to the difference in hypoxic ventilatory response (HVR) mean slopes between the two groups (which were drawn from 95% oxygen saturation (Sa,O2) down to 70%), and to the mean ventilatory reserve between the two groups. Complete numerical data are reported in table 3. The ventilatory reserve was calculated by subtracting the ventilation reached at Sa,O2 = 70% from maximal voluntary ventilation (MVV). The value of 70% was chosen because this is an average value found on the summit of Mt Everest 2. The subjects who eventually reached the summit of Mt Everest or K2 without oxygen were characterised by a lower ventilatory response during acclimatisation, allowing them to maintain a ventilatory reserve at rest of 66.6% when Sa,O2 = 70%, whereas those who could not had a reserve of only 26.7%, as a consequence of a higher HVR. *: p<0.05; **: p<0.01. V'E: minute ventilation.

 
Ventilatory efficiency
Ventilatory efficiency could be defined in different ways. At sea level, an established marker of ventilatory efficiency can be obtained by the dead space/tidal volume ratio (VD/VT), by measuring the CO2 levels in the arterial blood and expired air 3, 8. The current authors obtained a simple indirect estimate of this variable, similar to standard commercial methods, by the single breath test "SBT-CO2" and Bohr formula 8: VD/VTestimated = (Pa,CO2–PE,CO2)/Pa,CO2 (where Pa,CO2 is the noninvasive estimate of arterial PCO2, based on end-tidal PCO2, and PE,CO2 is mixed expired CO2). In addition, the current authors defined a simple, global and noninvasive estimate of ventilatory efficiency, relative to a particular level of ambient hypoxia, as the amount of ventilation required to achieve a given level of oxygen saturation. This was evaluated as the simple ratio Sa,O2/V'E.

Statistical analysis
Data are presented as mean±SD and analysed by mixed design ANOVA (repeated measures in two groups 9), to test for differences between groups and between sea level and altitude. Due to the 2x2 comparisons (two groups and two conditions), exact significance levels could be obtained by unpaired (between groups) and paired (between conditions) t-test, when overall significances were ascertained by ANOVA.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
Five of the 11 subjects studied reached one (Everest n = 2, K2 n = 2) or both (n = 1) summits without oxygen supplementation. Two of the remaining six subjects reached the Mt Everest summit but needed oxygen supplementation. The present authors thus divided the climbers into two groups: "summiters without oxygen" (five subjects) and "other climbers" (six subjects).

The main anthropometric and haematological characteristics of the groups were not different (table 1Go). At sea level, no significant differences between the two groups were found in any of the variables (table 2Go).


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  		Table 2— Data obtained at sea level

 
After 15 days of stay at altitude, all subjects increased their resting ventilation and hypoxic ventilatory response, and decreased their PET,CO2 and Sa,O2 levels, as compared to sea level. However, the "summiters without oxygen" showed significantly lower V'E, lower respiratory rate, lower HVR and higher PET,CO2 levels (table 3Go). The differences in ventilatory variables remained, even after correction for body surface area (table 3Go). Correction for height, body mass index and body weight gave similar results (not reported in the tables). The ventilatory reserve was markedly higher in the "summiters without oxygen" group (fig. 1Go). The ratio Sa,O2/V'E was also higher in the "summiters without oxygen" group, and the VD/VT ratio was lower. There were no significant differences in vital capacity and maximal voluntary ventilation. At altitude, a significant correlation between the ventilatory reserve and Sa,O2/ V'E (fig. 2Go) was found.


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  		Table 3— Data obtained after 15 days of exposure to high altitude(9 days at 5,200 m)

 


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  		Fig. 2— Correlation between ventilatory efficiency and ventilatory reserve. The data were obtained after 15 days at altitude (9 days at 5,200 m) for "summiters without oxygen" ({circ}) and "other climbers" (•) groups. Sa,O2: oxygen saturation; V'E: minute ventilation. r = 0.69; p = 0.018.

 
Compared to spontaneous breathing, slow breathing increased the Sa,O2/ V'E ratio and decreased the VD/VT ratio in the "other climbers" group, so that values were no longer different from the "summiters without oxygen" group. As expected, exposure to hypoxia tended to increase heart rate and blood pressure, but the increase was less marked in the "summiters without oxygen" group (tables 2Go and 3Go).


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
ACKNOWLEDGEMENTS
 REFERENCES
 
Main findings
The climbers who could reach the highest summits without oxygen were characterised by a lower ventilatory sensitivity to hypoxia, as compared to those who did not succeed or needed supplemental oxygen. They also showed a slower breathing rate, lower V'E, more efficient respiration, and a higher ventilatory reserve. All these differences became apparent only during acclimatisation, probably suggesting the result of an adaptive (rather than constitutive) response to prolonged hypoxia.

Possible explanations
Lower sensitivity to hypoxia increases ventilatory reserve for extreme altitudes
Ventilation cannot increase indefinitely and subjects with very high ventilatory response to hypoxia may reach their ventilatory limits at lower altitudes. The current authors have set this limit at MVV, and calculated a ventilatory reserve as the difference between this value and the ventilation relative to the level of Sa,O2 (70%) found at the summit of Mt Everest 2. Figure 1Go shows that in subjects with higher HVR ("other climbers" group) the ventilation was rather close to MVV when Sa,O2 reached 70%. Therefore, during the ascent to extreme altitudes, they might have increased ventilation close to their individual limits (by exhausting their reserve) already at an altitude well below the summit, then being forced to either descend or to use supplemental oxygen.

Conversely, the "summiters without oxygen" (due to their relatively lower sensitivity to hypoxia) could increase their ventilation more gradually while ascending to higher altitudes, and thus reach very high levels of ventilation only at the summit, but still remain below their limits.

Indeed, measurements of ventilation during the first 15 days of acclimatisation at 3,800–5,200 m, even during a hypoxic stimulus, do not accurately reflect the ventilations reached at extreme altitude. Rather, further adaptation will continue to take place as a function of time and altitude, with the result of increasing the ventilatory sensitivity to hypoxia and further decreasing the ventilatory reserve in all subjects. However, those with the lowest reserve will be more prone to exhaust their reserve at lower altitudes.

Despite lower V'E, subjects in the "successful climbers" group had similar Sa,O2 levels, suggesting that lower V'E could be compensated by a higher ventilatory efficiency.

Lower sensitivity to hypoxia and high ventilatory reserve are associated with higher ventilatory efficiency
After 15 days of acclimatisation, both indices of ventilatory efficiency were better in the "successful climbers" than in the "other climbers" group. As well as the VD/VT ratio (a well-known index of efficiency), the present authors have also calculated another index (the Sa,O2/V'E ratio), which expresses how much ventilation is required to increase oxygen saturation to a given value. At sea level, due to the high values of ambient PO2, the changes in Sa,O2 are very small despite large changes in ventilation. However, at high altitude, Sa,O2 is much more variable, and depends essentially on the level of alveolar ventilation. An efficient breathing pattern (characterised by a lower proportion of overall dead space/total ventilation) will require a lower total (alveolar+dead space) ventilation to obtain a given level of Sa,O2. Although alveolar ventilation could not be measured directly, both indices of efficiency suggested that the "successful climbers" had a higher relative proportion of alveolar/total ventilation during acclimatisation to altitude.

Slower breathing could link lower HVR and higher respiratory efficiency
The increased efficiency and the higher ventilatory reserve were found to be linked (fig. 2Go). A common underlying factor could be the breathing rate, which was markedly lower in the "summiters without oxygen" group during acclimatisation (table 3Go). Breathing slowly and/or deeply may improve gas exchange at sea level 6, 8, 10–14, at altitude 15 and in experimental models 16, and, in addition, slower breathing reduces the HVR 17, 18. The lower respiratory rate in the "summiters without oxygen" group was not an artefact caused by the mouthpiece 7. The difference remained even when recording was carried out with only the inductive belt (tables 2Go and 3Go) and without the mouthpiece.

A confirmation of the importance of slowing breathing rate can be seen by the data obtained when all subjects were forced to breath at a fixed slow respiratory rate (6 breaths·min–1): both indices of ventilatory efficiency (VD/VT and Sa,O2/V'E) improved in the "other climbers" group and all group differences disappeared even at altitude (table 3Go). These findings were obviously transitory, but similar effects can be maintained by specific respiratory training 6, 18.

With increasing altitude and hypoxia the respiratory rate is expected to increase; however, the advantages of maintaining a relatively lower breathing rate and a proportionally higher VT remain. This could be anticipated by the lower V'E at 70% Sa,O2, seen in the "summiters without oxygen" (fig. 1Go).

Together with the slower breathing rate, subjects in the "summiters without oxygen" group showed a lower increase in heart rate and blood pressure from sea level to altitude (tables 2Go and 3Go). Due to the reciprocal influences between chemo- and baro-reflexes 19, these findings indicate that, together with a lower increase in ventilation, these subjects had a lower need to increase sympathetic activation, which could help maintain exercise capacity at extreme altitudes. Further studies are necessary in order to examine in deeper detail the cardiovascular control during adaptation to high altitude in similar subjects.

Very high sensitivity to hypoxia may be counterproductive
From the alveolar air equation 1, 2, at extreme altitudes, it is known that very high ventilation is needed in order to drive the PCO2 down to a low enough level to maintain an alveolar PO2 compatible with life. Accordingly, it has been suggested that the higher the ventilatory response, the better the climbing performance should be at moderate–high altitudes 1. However, it has been found that with increasing ventilation the work of breathing also increases, and there is a critical ventilation level at which the increase in respiratory work blunts the increase in arterial PO2 20. Similarly, subjects with very high HVR may incur a greater work of breathing that may be counterproductive at extreme altitude 21. This was demonstrated in a group of subjects exercising at 5,050 m, where only the subject with the lowest increase in maximal ventilation at high altitude (as compared to sea level) remained below his critical ventilation during exercise 22. Therefore, a very high HVR is useful at moderate–intermediate altitudes, when the increase in ventilation remains well below critical limits, whereas at extreme altitudes the metabolic cost of excessive breathing may be counterproductive.

The HVR is traditionally evaluated by breathing at constant CO2 (see Methods). In real life, the hypocapnia resulting from hyperventilation in turn reduces the ventilatory stimulus and, hence, maintains the ventilatory reserve. However, if this effect were determinant, it should have favoured those subjects with higher ventilatory responses. Instead, the current findings indicate that there is little advantage in increasing ventilation without a parallel increase in efficiency.

Conclusions
A key requisite to achieving the highest altitudes without supplemental oxygen seems to be a high ventilatory efficiency, which may limit the stimulus for an excessive increase in ventilation. This may have several important benefits, as follows: 1) it reduces the work of breathing, which, at extreme altitudes, becomes extremely relevant and may cancel the advantages of increased ventilation 20–22; 2) it reduces the thermal exchanges and, hence, the thermal loss 1; and 3) it allows a sufficient ventilatory reserve to allow the needed ventilation at altitudes where the extreme hypoxia would otherwise stimulate ventilation beyond sustainable values.

These findings agree with the concept that a well-functioning HVR is necessary 1 to climb to altitude, and a very brisk response is certainly useful to perform work at intermediate altitudes. However, the current findings suggest that HVR should be only moderately increased, in order to allow very high (yet sustainable) ventilation at extreme levels of hypoxia. High ventilatory efficiency is essential to maintain adequate level of arterial PO2 despite a lower increase in V'E. In this respect, a slower breathing rate could be an important factor, as it combines the increase in efficiency and the reduction in HVR. The differences between climbers became evident only when acclimatisation had begun, suggesting that was the result of a different adaptation strategy.

There are practical implications of these findings. Training in slow breathing may speed up and simplify the adaptation process to high altitude, and help withstand severe levels of hypoxaemia by improving respiratory efficiency, even at sea level. This may apply to relevant cardiovascular and respiratory diseases, like chronic heart failure 6, 23, 24 and chronic obstructive pulmonary disease 25, 26.

In conclusion, summiters without oxygen may have unconsciously adopted a breathing strategy that allowed them to maintain a higher ventilatory efficiency during acclimatisation, and perhaps as a consequence, a lower increase in hypoxic ventilatory response. This could have given them a sufficient ventilatory reserve to climb without oxygen supplementation. Therefore, a very high hypoxic ventilatory response may not be necessary to climb in extreme hypoxia without oxygen supplementation, provided that ventilatory efficiency is optimised.


   ACKNOWLEDGEMENTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
REFERENCES
 
The authors would like to thank A. da Polenza (Ev-K2-CNR Project, Head of "K2-2004 50 years later" Italian Expedition to Everest and K2) on behalf of all members of the Expedition, and E. Bernieri (IMONT) for funding this study and for providing technical and logistical support. The authors are grateful to P. Sleight (Oxford, UK) for revising the English.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 

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