Abstract
Background
The variation in heights beyond high altitude has different effects on the cardiorespiratory profile of individuals because of variation in oxygen density with every thousand feet. This study was planned to analyze and compare the effects of difference in altitudes on cardiorespiratory profile from anesthesiologist's point of view.
Methods
A multicenter observational study was done involving two different groups of 600 patients at 10,000 ft (Group A) and 15,000 ft (Group B). Observation and comparison of oxygen saturation, 6-min walk test, and breath holding time was carried out.
Results
Fifty-five percent of subjects in Group A had oxygen saturation of more than 93% in comparison to 5.5% in Group B. This was statistically significant (P < 0.001). Two percent of subjects in Group A in comparison to 63.5% of Group B had oxygen saturation of less than 88% (P < 0.001). Percentage increase of more than 15% of heart rate was found to be statistically significant in all the age groups. Overall, 3.8% of individuals in Group A had breath holding time less than 15 s in comparison to 16.6% of individuals in Group B (P value < 0.001).
Conclusion
The study demonstrates that there is a significant fall in oxygen saturation, significant rise in the heart rate in 6-min walk test, and significant fall in the breath holding time in the group located at 15,000 ft. Heights beyond 10,000 ft should be restricted to life and limb saving surgeries, and logistics should be focused more on “scoop and run” than “stay and play” policy.
Keywords: High altitude, Breath holding time, 6-min walk test
Introduction
High altitude can be associated with harmful effects that generally start developing over approximately 3000 m (9842 feet) above the sea level.1 Individuals at moderate and extreme high altitudes face a continuous state of hypoxia and extravasation of fluid from intravascular to extravascular spaces.1 Despite getting acclimatized and working at these altitudes for more than 6 weeks, they continue to have fatigue and breathlessness on exertion while doing daily chores such as taking bath, mopping the floor, etc. Inspired partial pressure of oxygen in alveoli falls from ≈150 mm Hg at sea level to ≈100 mm Hg at 3000 m and to the extent of 43 mm Hg on the summit of Everest (8400 m).2 It means that exposing such individuals to general anesthesia for emergency or elective surgeries needs deliberate preparation.
With increase in population of individuals staying at these heights, illness or accidents are a huge possibility. This may require general anesthesia in addition to other medical or surgical interventions.
Owing to the paucity of resources and inability to do immediate casualty evacuations because of weather challenges, it was a felt need as an anesthesiologist to determine the surrogate markers that can directly or indirectly help in assessing the cardiopulmonary status of individuals and compare them at different heights for anesthetic management in future times. The aim of the study was to assess and compare the effect of altitude on cardiopulmonary reserves of individuals staying more than 6 weeks at 10,000 ft and 15,000 ft. The following parameters were used as surrogate markers : oxygen saturation (SpO2) levels in different group of individuals posted at moderate and extreme high altitudes, change in heart rate with 6-min walk test (6MWT), and breath holding time (BHT).
Materials and methods
After approval of hospital ethical committee and registration in the Clinical Trial Registry of India (CTRI), this observational study was done at two centers, one at 10,000 ft and another at 15,000 ft involving two different groups of 600 patients between 17 and 55 years who were acclimatized and had stayed at 10,000 ft and 15,000 ft, respectively, for more than 6 weeks. Inclusion criteria were patients aged between 17–55 years and physical status as American Society of Anesthesiologists I (ASA I).
Exclusion criteria were patients below ASA I, history of bronchial asthma, chronic obstructive pulmonary disease or any respiratory disease, history of smoking, stay at moderate and extreme high altitudes less than 6 weeks, history of diabetes mellitus, hypertension, or autonomic disturbances.
After following the inclusion and exclusion criteria, we divided the sample into two groups, Groups A and B, each consisting of 600 participants in each group. All the individuals evaluated were combatants posted at these heights. Group A consisted of individuals at 10,000 ft, and Group B consisted of individuals posted at 15,000 ft. Both the groups were observed, and the documentation was done by respective group of doctors and nursing team posted at locations of study who were trained regarding the observational study.
After written informed consent, individuals were explained about the procedure in detail. Calibrated pulse oximeter that were tested and checked with standardized multiparameter monitor was used for measuring the oxygen saturation. Pulse oximeter was placed on the index finger of individual for 30 s, and after ensuring uniform reading and the waveform, oxygen saturation and the heart rate was noted. After this, the individual was instructed to walk on a plain level ground for 6 min at comfortable pace. After 6MWT, a pulse oximeter was again placed on the index finger of individual for 30 s, and after ensuring uniform reading and the waveform, the oxygen saturation and the heart rate were noted again.
After a detailed counseling, participants in both groups were asked to take maximum possible breath and hold it for the maximum time duration as tolerated and were asked to signal by raising right hand before the beginning of expiration. This duration of forced apnea was noted for each participant using a standard stopwatch. This test was repeated three times for each participant at an interval of every 5 min, and the longest duration of apnea was taken as the final reading for each.
Collection of data
We further subdivided Groups A and B on three different variables into Subgroups 1, 2, and 3 (as shown in Table 1) on the basis of SpO2 (percentage), increase in heart rate after 6MWT, and BHT.
Table 1.
Categorization of individuals into three subgroups.
| Variables | Subgroup 1 | Subgroup 2 | Subgroup 3 |
|---|---|---|---|
| SpO2 (%) | More than or equal to 93(≥) | 89–92 | Less than or equal to 88 |
| 6-min walk test (HR increase in %) |
Less than or equal to 9 (≥) | 10–14 | More than or equal to 15 |
| BHT (s) | More than or equal to 25(≥) | 16–24 | Less than or equal to 15 |
Subgroup 1 consisted of those who had SpO2 of more than or equal to 93, BHT of more than or equal to 25 s, and percent increase in heart rate after a 6MWT of less than or equal to 9% from the base line.
Subgroup 2 consisted of those patients with observed SpO2 of 89–92%, BHT of 16–24 s, and percent increase in heart rate after a 6MWT of less than or equal to 10–14% from base line.
Subgroup 3 consisted of those patients with observed SpO2 of less than 88%, BHT of less than15 s, and percent increase in heart rate after a 6MWT of more than or equal to15% from the base line.
SpO2 after a 6MWT was also noted in all the participants but was not included in the present study.
To minimize the effect of age as a confounding variable in the present study, the data collected were further categorized into further subgroups on the basis of age (as shown in Table 2):
-
1.
Age between 17 and 40 years (A1 at 10,000 ft and B1 at 15,000 ft)
-
2.
Age between 41 and 55 years (A2 at 10,000 ft and B2 at 15,000 ft)
Table 2.
Data collected and tabulated as with P value <0.001 as statistically significant by Mann–Whitney U, Wilcoxon W, and Z tests.
| Group type |
Group A (10,000 ft) |
Group B (15,000 ft) |
P value |
|---|---|---|---|
| Parameters | |||
| SpO2 | |||
| ≥93% | 245 (55.2%) | 32 (5.4%) | <0.001 (chi-square test) |
| 89–92% | 190 (42.8%) | 184 (31.1%) | 0.00014 (chi-square test) |
| ≤88% | 9 (2%) | 375 (63.5%) | <0.001 (chi-square test) |
| HR before 6 min walk test in bpm (median and interquartile range) | 86 (16) | 93 (16) | <0.001 (Mann–Whitney U test) |
| HR after 6 min walk test in bpm (median and interquartile range) | 94 (16) | 97 (16) | <0.001 (Mann–Whitney U test) |
| Percentage increase in HR | |||
| ≤9% | 237 (53.4%) | 407 (69%) | <0.001 (chi-square test) |
| 10–14% | 108 (24.4%) | 82 (13.9%) | <0.001 (chi-square test) |
| >15% | 99 (22.2%) | 102 (17.1%) | 0.039 (chi-square test) |
| BHT | |||
| ≥25 s | 273 (61.4%) | 46 (7.8%) | <0.001 (chi-square test) |
| 16–24 s | 154 (34.8%) | 447 (75.6%) | <0.001 (chi-square test) |
| ≤15 s | 17 (3.8%) | 98 (16.6%) | <0.001 (chi-square test) |
SpO2, oxygen saturation; HR, heart rate; bpm, beats per minute; BHT, breath holding time; 6MWT, 6-min walk test.
Statistical analysis
Categorical variables were reported as frequencies and percentages. Group (individuals staying more than 6 weeks at 10,000 ft and 15000 ft) comparisons were made with the chi-square test/Fisher's exact test. The normality of quantitative data was checked by measures of Kolmogorov–Smirnov tests of normality. Our data were skewed, so continuous data were given as median with interquartile range where applicable. Comparison based on the basis of groups was made by Mann–Whitney U test and chi-square test. Fisher exact test was used to examine the significance of the association (contingency) between the two groups. A P value of 0.001 was considered significant. The analysis was conducted using IBM SPSS STATISTICS (version 22.0) software.
Comparison was done between the two groups. Both the groups were then subdivided into age group as 17–40 years and 41–55 years and compared.
Results
Of a total of 600 participants in both Groups A and B, 146 participants from Group A and nine participants from Group B were excluded from the study because of incomplete data in these subjects.
The loss of 146 subjects from Group A was because of the sudden moving out of troops from that location due to operational requirements. For the same reason, nine subjects from Group B were lost to follow-up.
All the demographic profiles were calculated and presented as median with interquartile range in brackets (Q1–Q3). The median age of Group A was 33 years (8) in comparison to 31 years (8) in Group B (P value > 0.001; Mann–Whitney U test). The median height in Group A was 173 cm (6) in comparison to 174 cm (6) in Group B (P value > 0.001, Mann–Whitney U test). The mean weight of Group A was 70 kg (6) in comparison to 69 kg (6) in Group B (P value > 0.001, Mann–Whitney U test). No statistically significant difference was found in demographic profile.
Body mass index (BMI) in Group A was 23.42 kg/m2 (2.7) in comparison to 23.25 kg/m2 (2.1) in Group B (P value > 0.001 Mann–Whitney U test). Comparison of age, height, weight, and BMI between different groups was statistically insignificant.
After statistical analysis, we found that 55.2% of subjects in Group A had SpO2 of more than 93% in comparison to 5.4% in Group B. There was statistically significant difference (P value < 0.001 by chi-Square test) between the two groups as shown in Table 1 and Fig. 1.
Fig. 1.
Comparison of oxygen saturations at different height in total as well as age-adjusted group.
In the category involving SpO2 of less than 88%, 2% of the total individuals in Group A were included in this group in comparison to 63.5% of the in Group B. This was statistically significant (P value < 0.001, chi-square test).
In this study, it was noticed in 6MWT that the median heart rate after performing the test in Group A was 93 bpm (16). This was almost equal to the opening heart rate in the Group B of 94 bpm (16) and was statistically significant (P value < 0.001, Mann–Whitney U test).
As far as the percentage increase in the heart rate is concerned, there were comparable changes in Group A and Group B (P value 0.039, chi-square test), A1B1 (P value 0.0013, chi-square test), and A2 B2 (P value 0.0075, Fisher exact test) as far as more than 15% increase in heart rate is concerned.
Overall, 61.4% of individuals in Group A had BHT of more than 25 s in comparison to 7.8% of individuals in Group B (P value < 0.001, chi-square test). Similarly, 3.8% of individuals in Group A had BHT less than 15 s in comparison to 16.6% in Group B (P value < 0.001, chi-square test). In age-adjusted group also, there was a significant difference in BHT between Group A1 and Group B1 (P value < 0.001, chi-square test) and Group A2 and Group B2 (P value 0.0001, Fisher exact test) respectively as shown in Table 3 and Fig. 3.
Table 3.
Age-adjusted data collected and tabulated as with P value <0.001 as statistically significant by Mann–Whitney U, Wilcoxon W, and Z tests.
| Group type |
Group A1 (15–40 y; 10,000 ft) | Group B1 (15–40 y; 15,000 ft) | P value | Group A2 (41–55 y; 10,000 ft) | Group B2 (41–55 y; 15,000 ft) | Pvalue |
|---|---|---|---|---|---|---|
| Parameters | ||||||
| SpO2 | ||||||
| ≥93% | 215 (54.8%) | 25 (4.9%) | <0.001 (chi-square test) | 29 (55.8%) | 7 (9.1%) | <0.001 (chi-square test) |
| 89–92% | 171 (43.6%) | 154 (30%) | <0.001 (chi-square test) | 20 (38.5%) | 30 (39%) | 1.0 (chi-square test) |
| ≤88% | 6 (1.5%) | 335 (65.2%) | <0.001 (chi-square test) | 3 (5.8%) | 40 (51.9%) | <0.001 (chi-square test) |
| HR before 6 MWT in bpm (median and interquartile range) | 86 (14) | 93 (16) | <0.001 (Mann–Whitney U test) | 86 (21) | 94 (15) | 0.003 (Mann–Whitney U test) |
| HR after 6MWT in bpm (mean ± SD) | 94 (15) | 98 (16) | <0.001 (Mann–Whitney U test) | 86 (12) | 96 (15) | 0.008 (Mann–Whitney U test) |
| ≤9% | 201 (51.3%) | 359 (69.8%) | <0.001 (chi-square test) | 35 (67.3%) | 49 (63.6%) | 0.6713 (chi-square test) |
| 10–14% | 95 (24.2%) | 73 (14.2%) | <0.001 (chi-square test) | 14 (26.9%) | 9 (11.7%) | 0.026 (chi-square test) |
| >15% | 96 (24.5%) | 82 (16%) | 0.0013 (chi-square test) | 3 (5.8%) | 19 (24.7%) | 0.0075 (Fisher exact test) |
| BHT | ||||||
| ≥25 s | 254 (64.8%) | 41 (8.0%) | <0.001 (chi-square test) | 20 (38.5%) | 5 (6.5%) | <0.001 (chi-square test) |
| 16–24 s | 121 (30.9%) | 393 (76.4%) | <0.001 (chi-square test) | 32 (61.5%) | 54 (70.1%) | 0.310 (chi-square test) |
| ≤15 s | 17 (4.3%) | 80 (15.6%) | <0.001 (chi-square test) | 0 (0%) | 18 (23.4%) | 0.0001 (Fisher exact test) |
SpO2, oxygen saturation; HR, heart rate; bpm, beats per minute; BHT, breath holding time; 6MWT, 6-min walk test.
Fig. 3.
Comparison of breath holding (BHT) time between total as well as age-adjusted group.
Discussion
This is the first study ever done at height of 15,000 ft in a natural atmosphere involving this large group of individuals as known to the authors.
The study was planned to determine and compare the effects of difference in altitude on cardiac and lung functions of the individual from the anesthesiologist's point of view beyond 9000 ft. It is known that high altitude causes changes in oxygen-carrying capacity, lung functions, and the cardiac functions. Most of the studies related to these changes are done between artificially created altitudes of 10,000 to 12,000 ft.
Variations in cardiorespiratory profiles with the increase in heights beyond high altitude is less known. The main reasons for this being less population density and lack of resources.
The aim of this study was to assess and compare the effect of altitude on cardiopulmonary reserves of individuals staying more than 6 weeks at 10,000 ft and 15,000 ft.
As shown in Fig. 1, statistically significant higher number of subjects in Group A had SpO2 more than 93% in comparison to Group B. Our results were similar to a study conducted by Brito et al3 on pediatric Chilean population. However, this study differs from ours in terms of altitude and the number of subjects (120 only).
In previous studies, the oxygen saturation by pulse oximetry was usually between 75% and 80% at 4000–5000 m.4 These included subjects with acute exposure to high altitude, vis-a-vis our study population, who had already spent 6 weeks at respective altitude.
Lesser number of Group A individuals were there in SpO2<88% in comparison to Group B. Maximal oxygen consumption begins to decrease significantly above an altitude of 1600 m. For every 1000 m above that, VO2 max drops by approximately 8–11%.5
Increase in altitude leads to not only progressive reduction of barometric and inspiratory oxygen pressure but also associated with multiple other changes such as progressive reduction of density of air, humidity, and massive decrease in temperature.
6MWT was used in this resource-limited setting. Sinclair et al did 6MWT test and found it to be useful to screen and stratify patients for noncardiac surgeries.6
A statistically significant increase in heart rate was found in Group A in comparison to Group B in all the categories of percentage increase in heart rate as shown in Fig. 2 & Table 2. This is a significant finding as far as cardiorespiratory reserves are concerned. A similar study was done for eight patients with a history of an acute myocardial infarction (ejection fraction >5%) with a low-risk score compared with seven healthy subjects by de Vries et al.7 In this study, both patients and healthy controls showed a similar decrease in exercise capacity and maximum heart rate at 4200 m compared with sea level, suggesting that patients with a history of coronary artery disease may tolerate stay and exercise at high altitude similarly to healthy controls. The number of patients however was significantly lower in comparison to our study.
Fig. 2.
Comparison of percentage increase in heart rate after 6-min walk test (6MWT) in total as well as age-adjusted group.
There was statistically significant difference in BHT in Groups A, A1, and A2 in comparison to Groups B, B1, and B2, respectively. Although a remarkably simple test, the reproducibility and safety of BHT cannot be undermined. Trembach et al did BHT to evaluate peripheral chemoreflex sensitivity in healthy subjects.8 They concluded that BHT is useful in the assessment of peripheral chemoreflex sensitivity in healthy subjects. BHT is directly proportional to lung volume and partial pressure of oxygen in inspired gases. It has been found that BHT remarkably decreases by increase in partial pressure of carbon dioxide in arterial blood (PaCO2);9 however, the subjects in this study were evaluated in plains and have inhaled inspired fraction of oxygen of 1 (FiO2 = 1). Although functional residual capacity increases with aging because of the expansion of alveolar spaces, the PaCO2 has been found to be higher than normal.10 Most of the studies done in the past have BHT between 35 and 40 s, but these studies have been either done in plains or have inspired varied percentage of oxygen.11 BHT values in our study were different from most of the previous studies because of the difference in altitude. Our study also reinforces the fact that with increase in age, cardiorespiratory profile declines at high altitude.
Limitations of the study
The group chosen for this study consisted of healthy individuals only without any significant comorbidities.
The loss of 146 subjects from Group A and nine subjects from Group B may have caused bias in the study. This was unavoidable.
Only pulse oximetry–based assessment of oxygen saturation of the individuals was done. Limited availability of instruments was the reason behind the assessment of oxygen just by pulse oximetry rather than more precise partial pressure of oxygen measurement using arterial blood gas analysis.
Division of pulse oximetry group as <88%, 89–92%, and >93% was done on the assumption that <88% is suggestive of rapid fall in partial pressure of oxygen and >93% is suggestive of good oxygen levels. It is difficult to explain the selection of 89–92% group.
Conclusion
The study demonstrates that there is a significant fall in SpO2 in the group, which is located at 15,000 ft compared with the group at 10,000 ft in total as well as in age-adjusted groups.
There is a statistically significant rise in the percentage increase in heart rate after 6MWT in all the age group located at 15,000 ft compared with the group at 10,000 ft.
There is a statistically significant fall in the BHT in all the age group located at 15,000 ft compared with the group located at 10000 ft. The study is a good indicator that we must plan and segregate our anesthesiology inventory for different altitudes beyond 9000 ft.
Inventory of anesthesiology equipment needs to be tailor made as per the height. Higher altitude requires inventory focusing more on oxygen supplies and availability of arterial blood gas analyzers in comparison to inventory at lower altitudes.
More importantly, it must also be remembered that there is a huge production of inflammatory mediators, changes in stress hormones, and disturbed sleep pattern in addition to deranged cardiorespiratory system, which needs further studies and research at these heights. Till that time, at heights beyond 10,000 ft, elective surgeries should not be done, and only lifesaving surgical interventions should be attempted. As far as lifesaving surgeries are concerned, generally, such patients are prone to increased complications postoperatively. Attention should be narrowed down more to efficient and fast casualty evacuation with well-trained emergency medicine technicians as holding the postoperative patients at such high altitude with limited resources is a big challenge.
Disclosure of competing interest
The authors have none to declare.
References
- 1.Ward M.P., Milledges J.S., Ward M.P. University of Pennsylvania Press; Philadelphia: 1989. High Altitude Medicine and Physiology; pp. 349–352. [Google Scholar]
- 2.Grocott M.P., Martin D.S., Levett D.Z., McMorrow R., Windsor J., Montgomery H.E., Caudwell Xtreme Everest Research Group Arterial blood gases and oxygen content in climbers on Mount Everest. N Engl J Med. 2009;360:140–149. doi: 10.1056/NEJMoa0801581. [DOI] [PubMed] [Google Scholar]
- 3.Brito J., Siques P., Lopez R. Long-term intermittent work at high altitude: right heart functional and morphological status and associated cardiometabolic factors. Front Physiol. 2018 Mar 22;9:248. doi: 10.3389/fphys.2018.00248. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Moon Richard E., Camporesi Enrico M. Clinical care in Extreme Environments: At High and Low Pressure and in Space. 7th ed. Churchill Livingstone; 2010. Miller's Anesthesia. Chapter 80. [Google Scholar]
- 5.West J.B., Hackett P.H., Maret K.H. Pulmonary gas exchange on the summit of Mount Everest. J Appl Physiol Respir Environ Exerc Physiol. 1983;55(3):678–687. doi: 10.1152/jappl.1983.55.3.678. [DOI] [PubMed] [Google Scholar]
- 6.Sinclair R.C., Batterham A.M., Davies S., Cawthorn L., Danjoux G.R. Validity of the 6 min walk test in prediction of the anaerobic threshold before major non-cardiac surgery. Br J Anaesth. 2012 Jan;108(1):30–35. doi: 10.1093/bja/aer322. [DOI] [PubMed] [Google Scholar]
- 7.de Vries S.T., Komdeur P., Aalbersberg S., van Enst G.C., Breeman A., van ’t Hof A.W.J. Effects of altitude on exercise level and heart rate in patients with coronary artery disease and heathy controls. Neth Heart J. 2010 Mar;18(3):118–121. doi: 10.1007/BF03091749. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Trembach N., Zabolotskikh I. Breath-holding test in evaluation of peripheral chemoreflex sensitivity in healthy subjects. Respir Physiol Neurobiol. 2017 Jan;235:79–82. doi: 10.1016/j.resp.2016.10.005. [DOI] [PubMed] [Google Scholar]
- 9.Stock M.C., Downs J.B., McDonald J.S. The carbon dioxide rate of rise in awake apneic humans. J Clin Anesth. 1988;1:96–103. doi: 10.1016/0952-8180(88)90028-1. [DOI] [PubMed] [Google Scholar]
- 10.Pontoppidan H., Geffin B., Lowenstein E. Acute respiratory failure in the adult. 1. A review. N Engl J Med. 1972;287:690–698. doi: 10.1056/NEJM197210052871404. [DOI] [PubMed] [Google Scholar]
- 11.Sasse S.A., Berry R.B., Nguyen T.K. Arterial blood gas changes during breath-holding from functional residual capacity. Chest. 1996;110:958–964. doi: 10.1378/chest.110.4.958. [DOI] [PubMed] [Google Scholar]




