Effect of Oral Glucose on Arterial Blood Gas and Oxygen Saturation on Exposure to Simulated Altitude of 12,000 Feet

End Tidal Carbon Dioxide (ETCO₂) and Respiratory Rate (RR)

The ETCO₂ level in fasting Group-I did not show any change from 0 to 30 min. However, in Group-II during fasting, an increase between 0 to 30 min (p = 0.044) was observed. The ETCO₂ values in all subjects during fasting showed a significant difference between 0 to 60 min (p<0.0001) and 30 to 60 min (p<0.0001) in both the groups. Significant increase was also observed between 0 to 60 min (p<0.0001) and 30 to 60 min (p<0.0001) in both the groups when glucose was administered. There were no significant difference observed between the two groups with glucose administration (p = 0.278) between 0 to 30 min. This was not expected as the Respiratory rate across the subjects, and when group comparison was made, was found to be elevated significantly in both conditions ie with and without glucose from 0 to 30 min, 0-60 min and from 30-60 min. That is to say that while the ETCO₂ showed a consistent increase, the RR showed a corresponding increase. This finding is against the expectations and what has been recorded in the literature. In a recent study carried out by Sahota in 2011 and earlier report by Ernsting (1965) [3, 10, 11], a consistent reduction in ETCO₂ in subjects exposed to hypobaric hypoxia has been reported. While Ernsting measured changes within 10-20 min, Sahota reported changes in 90 minutes of exposure. In our study, the ETCO₂ and RR (Table 4 and 7) were measured after 30 and 60 min to study the early effects of exposure with and without glucose.

Nancy et al studied subjects to a simulated altitude of 4600m (15,180 feet) with and without carbohydrate ingestion. They reported a decrease in PaCO₂ from a mean of 36.4 ± 4.05 mm of Hg at the beginning of the study to 32.8 ± 4.41 after 150 min of hypoxia exposure in subjects who had not taken a carbohydrate rich solution, while in the group who had taken a carbohydrate rich solution the reduction after 150 min was to 33.9 ± 3.97 mm of Hg [12]. The increase observed was bare marginal after glucose ingestion and at the end of 150 min and hence the effects observed in the various studies can hardly be compared.

Hansen et al [13] exposed four subjects to a simulated altitude of 11,000 feet after either a high carbohydrate diet or low carbohydrate diet. The fall in PaCO₂ was to an extent of 29.1 ± 2.9 mm of Hg in subjects when on low carbohydrate in comparison to a fall of PaCO₂ to 30.4 ± 2.3 mm of Hg in high carbohydrate group. Similarly, Golja et al reported that CO₂ fraction in the expired air increased significantly (p<0.001) in the carbohydrate intake group as compared with the control group who had not taken carbohydrate rich solution prior to exposure to acute hypobaric hypoxia [14]. The results of the present experiment showed a variable changes with initial decrease followed by increase but to lesser than the basal values (Table 6 and 7) this is not in agreement with the studies published earlier [3, 11, 12, 14].

Arterial Oxygen Saturation (SpO₂)

The SpO₂ level in fasting showed statistically significant difference between 0 to 30 min (p<0.001) & 0 to 60 min (p<0.001) in both the groups without glucose. Statistically significant difference was also observed between 0 to 60 min (p<0.0001) and 30 to 60 min (p<0.001) in both the groups when glucose was administered. There were no significant difference observed between the two groups with glucose administration (p = 0.288) as well as fasting state (p = 0.308) between 30 to 60 min.

Although the difference between the oxygen tension of the alveolar gas and that of the blood entering the pulmonary capillaries is markedly reduced on exposure to altitude, the diffusion characteristics of the alveolar-capillary membrane are such that the tension of oxygen leaving the pulmonary capillaries still equals that of alveolar gas when the individual is at rest. But the effects of reduction in atmospheric oxygen tension are evident through arterial oxygen tension (PaO₂) and oxygen saturation of haemoglobin (SpO₂). PaO₂ decreases from 95 mm of Hg at ground level on breathing air to 56 mm of Hg at 8,000 feet, 43 mm of Hg at 12,000 feet and to 37 mm of Hg at 15,000 feet. Similarly, a comparable decrease in SpO₂ from 97% at ground level to 93% at 8,000 feet on breathing air, 84% at 12,000 feet and 78% at 15,000 feet. So it can be derived that at a PaO₂ of 43 mm of Hg at 12,000 feet the SpO₂ is about 84% [3]. Hansen et al reported that at 11,000 feet of simulated hypoxia, subjects maintained PaO₂ of 59.4 ± 5.8 mm of Hg with low carbohydrate diet while the same subjects maintained a PaO₂ of 63.7 ± 3.0 mm of Hg after a high carbohydrate diet [13].

Nancy et al reported that both arterial oxygen tension and saturation trended upwards across most subjects from 45 min through 2 hours after carbohydrate ingestion, but only reached statistical significance at 60 min. Seven subjects ingested additional carbohydrates in the form of fruit juice 2 hours after the initial carbohydrate administration, these subjects maintained higher arterial oxygen compared to subjects who did not consume carbohydrates. This trend suggested additional effect with repeated carbohydrate intake [28]. Golja et al reported that in subjects without carbohydrate ingestion, SpO₂ decreased from 99% to 86 % during exposure to hypoxia. In the Carbohydrate trial group SpO₂ decreased from 99% to 90% in the comparable period of hypoxia exposure. The difference between the two trials was statistically significant (p < 0.001) throughout the hypoxic exposure [14]. Results of the present study on the decrease in SpO₂ on exposure to acute hypobaric hypoxia and effects of carbohydrate ingestion are in agreement with previous reports [3, 12, 13, 14, 15].

Arterial Blood Gases (ABG) Parameters

The PaO₂ level during fasting showed significant reduction between 0 to 30 min (p<0.001) & 0 to 60 min (p<0.001) in both the groups well as between 30 to 60 min in Group 2 (p = 0.041). Significant reduction was also observed when glucose was administered. The PaCO₂ level in both fasting and post glucose administration showed significant reduction between 0 to 30 min & 0 to 60 min in both the groups as well as when analyzed across the subjects (Table 4,5 and 6,7). However, significant reduction was only observed between 0 to 60 min in both the groups and between 30 to 60 min (p = 0.008) in Group 1 when glucose was administered. The Bicarbonate level in fasting did not show any statistically significant difference between 0 to 30 min, 0 to 60 min and between 30 to 60 min in both the groups without glucose. Statistically significant difference was only observed between 0 to 30 min (p = 0.018) in Group 1 and when analysed across the subjects (p<0.009) when glucose was administered. The pH levels did not reveal any changes either between the groups or across all subjects at any stage with or without glucose (Table 4 and 7). No correlation between the parameters of ABG (Other than PaCO₂) was observed with the ETCO₂.

In 2012, Naidu analyzed the data of vast number of studies to see a correlation between PaCO₂ and ETCO₂ in neonates [16]. In analyzing the data presented, it became clear that whilst ETCO₂ monitoring could not replace the Gold Standard of measuring PaCO₂ it could provide useful information if used as a trending tool. This was further supported by studies by Rozycki et al, Wu et al, Bhat and Abhishek and Nangia et al from 1997 - 2003 [17, 18, 19, 20]. They found that a good correlation existed between ETCO₂ and PaCO₂ in patients without underlying lung disease. Haggerty et al [21] demonstrated a good degree of agreement by evaluating the use of the capnometer across two groups, they did not provide any confidence limits or intervals and a correlational relationship between ETCO₂ and PaCO₂ was not established. In the present study, no such correlation between ETCO₂ and PaCO₂ was found. The ABG parameters did not change significantly from fasting to post glucose administration in both the groups and across the subjects.

The gradient, or the difference between the PaCO₂ and ETCO₂ values, is a result of relationship between ventilation, airflow to the alveoli, and perfusion (referred to as V/Q or ventilation-perfusion matching or ratio). Calculating the gradient requires obtaining a simultaneous ABG sample and ETCO₂. In normal healthy lungs there is a good match of alveolar ventilation and perfusion to the pulmonary capillaries resulting in ETCO₂ that closely matches or correlates with the PaCO₂. Therefore, PaCO₂ may be estimated by using actual ETCO₂ in normal subjects without any significant cardio-pulmonary disorders. The estimate is generally reliable if the ETCO₂ trend is stable. In healthy subjects, the gradient is generally 2-5 mm Hg [22, 23]. In this study, however, a correlation between PaCO₂ and ETCO₂ was not observed.

Blood Pressure & Heart Rate changes

The Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) level did not show any changes during the runs with or without glucose at any stage (Table 2, 3, 8 and 9). The results are in keeping with earlier published literature on effects of acute hypoxia on blood pressure. In a similar study, Golja et al reported that SBP remained statistically insignificant throughout the experiment [3, 14, 24, 25].

The heart rate increased significantly on exposure to hypoxia at 12,000 feet. The increase was highly significant (p<0.001) from 0 to 30 and 60 min both with and without glucose. The increase was also significant from 30 to 60 min in both the protocols. The Heart rate values did not vary significantly between the groups nor was any significant change seen from fasting to post glucose intake exposure across the subjects (Table 2, 3, 8 and 9). As a rule the mean arterial blood pressure does not change significantly during hypoxia from that of an individual breathing air at sea level [3, 24, 26]. The findings in this study are consistent with the findings of earlier researches. While in a similar study by Golja et al, HR was significantly elevated in the carbohydrate trial group compared to the control group without carbohydrate. The difference in HR between the two trials groups decreased toward the end of the experiment and did not reach statistical significance as is also seen in the present experiment [14].

In the study by Sahota [10] resting HR was significantly increased after ingestion of glucose than without glucose during the initial period of the experiment and remained higher throughout the experiment. In both the parts of the experiment that is with or without ingestion of glucose, the subjects were kept in a quiet environment at simulated altitude of 12,000 feet without indulging in any activity. But, the HR after ingestion carbohydrate in form of glucose was higher than without glucose. Berne et al. reported a small, but significant increase in HR following D-glucose ingestion and also observed an increase in sympathetic outflow in human muscle nerves in normoxia following carbohydrate ingestion, as determined by micro-neurography. Further, the results of Welle et al demonstrated that ingestion of carbohydrates, but not proteins or fat, increases plasma nor epinephrine level; this suggests that the activity in sympathetic nerve terminals is increased following carbohydrate ingestion. Similar results were also published by Young et al. It is yet to be answered as to whether this increase in increase in sympathetic activity is restricted to specific organs (heart, skeletal muscle) or whether it is a generalized response of the sympathetic nervous system to ingestion of carbohydrates [27, 28, 29]. Rowe et al suggested that hyperinsulinemia following carbohydrate ingestion results in a dose-dependent increase in sympathetic nervous system activity independent of changes in blood glucose. A hyper insulinimic response is expected after ingestion of glucose during the present study [30].

Whatever the mechanism of increase in heart rate it leads to increase in cardiac output without change in stroke volume and improves oxygen delivery during hypoxia more after ingestion of carbohydrates prior to hypoxia exposure [27, 28, 29].

Respiratory Responses to Hypoxia

The Respiratory Rate (RR) in fasting showed a significant increase from 14±1.32 to 20±1 and to 22± 1.9 (0 to 30 and 60 min without glucose – table 8 refers) similar increase was seen in both the groups without glucose as well as when glucose was administered. Eckman et al exposed 3 male subjects repeatedly to 15000 feet and 17000 feet for 1-2 hrs in an aircraft. They reported that minute ventilation following the protein meal was 7.0 per cent and 4.7 per cent less than the ventilations found with the carbohydrate meal or mixed diet. While, the average respiratory rate following a carbohydrate diet was 15.9 breaths per minute as compared to 14.9 and 14.4 breaths per minute in protein diet and mixed diet respectively [31]. Golja et al reported that minute inspiratory volume increased significantly in the carbohydrate trial as compared to the control trial [14]. The result of the present study is not commensurate with the observations of the above mentioned studies. Acute hypoxia leads to an increase in ventilation by increase in both rate and depth of breathing. In the present study, ventilation was collected in form of respiratory rate only which showed a significant increase in both the scenarios. While the above mentioned studies not only measured respiratory rate but also ventilation, volumes, concentration of oxygen and carbon dioxide in the expired air. This perhaps could be the reason for the difference in findings with the previous studies vis-à-vis the present one.