Hypoxemia and acute mountain sickness: which comes first?

Hypoxemia is usually associated with acute mountain sickness (AMS), but most studies have varied in time and magnitude of altitude exposure, exercise, diet, environmental conditions, and severity of pulmonary edema. We wished to determine whether hypoxemia occurred early in subjects who developed subsequent AMS while resting at a simulated altitude of 426 mmHg (approximately 16,000 ft or 4880 m). Exposures of 51 men and women were carried out for 8 to 12 h. AMS was determined by Lake Louise (LL) and AMS-C scores near the end of exposure, with spirometry and gas exchange measured the day before (C) and after 1 (A1), 6 (A6), and last (A12) h at simulated altitude and arterial blood at C, A1, and A12. Responses of 16 subjects having the lowest AMS scores (nonAMS: mean LL=1.0, range=0-2.5) were compared with the 16 having the highest scores (+AMS: mean LL=7.4, range=5-11). Total and alveolar ventilation responses to altitude were not different between groups. +AMS had significantly lower PaO2 (4.6 mmHg) and SaO2 (4.8%) at A1 and 3.3 mmHg and 3.1% at A12. Spirometry changes were similar at A1, but at A6 and A12 reduced vital capacity (VC) and increased breathing frequency suggested interstitial pulmonary edema in +AMS. The early hypoxemia in +AMS appears to be the result of diffusion impairment or venous admixture, perhaps due to a unique autonomic response affecting pulmonary perfusion. Early hypoxemia may be useful to predict AMS susceptibility.

Role of hypobaria in fluid balance response to hypoxia.

To estimate the separate and combined effects of reduced P(B) and O2 levels on body fluid balance and regulating hormones, measurements were made during reduced PB (altitude, ALT; P(B) = 432 mm Hg, F(I(O2)) = 0.207), reduced inspired O2 concentration (normobaric hypoxia, HYX; P(B) = 614 mm Hg, F(I(O2)) = 0.142), and lowered ambient pressure without hypoxia (normoxic hypobaria HYB; P(B) = 434 mm Hg, F(I(O2)) = 0.296). Nine fit and healthy young men were exposed to these conditions for 10 h in a decompression chamber. Lake Louise AMS scores, urine collections, and blood samples were obtained every 3 h, with recovery measurements 2 h after exposure. AMS was significantly greater during ALT than HYX, as previously reported (J. Appl. Physiol. 81:1908-1910. 1996), because the combination of reduced P(B) and P(O2) over the 10 h favored fluid retention by reducing urine volume, while plasma volume (PV) remained higher than during HYX. At ALT the plasma Na+ fell significantly at 6 h, probably from dilution of extracellular fluid, and antidiuretic hormone (ADH) was highest (p = 0.006 versus HYB). The PV, urine flow, free water clearance, and plasma renin activity (PRA) rose significantly during recovery from ALT as AMS symptoms subsided, suggesting increased intravascular fluid and reduced adrenergic tone. During HYB, the plasma aldosterone (ALDO) and K+ levels were significantly elevated, and PRA was highest and ADH lowest, without fluid retention. During HYX, fluid balance was similar to HYB, but PV and ALDO were significantly lower, and ALDO increased significantly in recovery from HYX. The fluid retention at ALT in AMS-susceptible subjects appears related to a synergistic interaction involving reduced P(B) and ADH and ALDO.

Early fluid retention and severe acute mountain sickness.

Field studies of acute mountain sickness (AMS) usually include variations in exercise, diet, and environmental conditions over days and development of clinically apparent edemas. The purpose of this study was to clarify fluid status in persons developing AMS vs. those remaining without symptoms during simulated altitude with controlled fluid intake, diet, temperature, and without exercise. Ninety-nine exposures of 51 men and women to reduced barometric pressure (426 mmHg = 16,000 ft. = 4,880 m) were carried out for 8-12 h. AMS was evaluated by Lake Louise (LL) and AMS-C scores near the end of exposure. Serial measurements included fluid balance, electrolyte excretions, and plasma concentrations, regulating hormones, and free water clearance. Comparison between 16 subjects with the lowest AMS scores near the end of exposure ("non-AMS": mean LL = 1.0, range = 0-2.5) and 16 others with the highest AMS scores ("AMS": mean LL = 7.4, range = 5-11) demonstrated significant fluid retention in AMS beginning within the first 3 h, resulting from reduced urine flow. Plasma Na+ decreased significantly after 6 h, indicating dilution throughout the total body water. Excretion of Na+ and K+ trended downward with time in both groups, being lower in AMS after 6 h, and the urine Na+-to-K+ ratio was significantly higher for AMS after 6 h. Renal compensation for respiratory alkalosis, plasma renin activity, aldosterone, and atrial natriuretic peptide were not different between groups, with the latter tending to rise and aldosterone falling with time of exposure. Antidiuretic hormone fell in non-AMS and rose in AMS within 90 min of exposure and continued to rise in AMS, closely associated with severity of symptoms and fluid retention.

Body temperature, autonomic responses, and acute mountain sickness.

A few studies have reported increased body temperature (T(o)) associated with acute mountain sickness (AMS), but these usually include exercise, varying environmental conditions over days, and pulmonary edema. We wished to determine whether T(o) would increase with AMS during early exposure to simulated altitude at rest. Ninety-four exposures of 51 men and women to reduced P(B) (423 mmHg = 16,000 ft = 4850 m) were carried out for 8 to 12 h. AMS was evaluated by LL and AMS-C scores near end of exposure, and T(o) was measured by oral digital thermometer before altitude and after 1 (A1), 6 (A6), and last (A12) h at simulated altitude. Other measurements included ventilation, O(2) consumption and autonomic indicators of plasma catecholamines, HR, and HR variability. Average T(o) increased by 0.5 degrees F from A1 to A12 in all subjects (p < 0.001). Comparison between 16 subjects with lowest AMS scores (mean LL = 1.0, range = 0 to 2.5) and 16 other subjects with highest AMS scores (mean LL = 7.4, range = 5 to 11) demonstrated a transient decline in T(o) from A1 to A6 in AMS, in contrast to a rise in non-AMS (p = 0.001). Catecholamines, HR, and HR variability (increased low F/high F ratio) indicated significant elevation of sympathetic activity in AMS, where T(o) fell, but no change in metabolic rate. The apparently greater heat loss during early AMS suggests increased hypoxic vasodilation in spite of enhanced sympathetic drive. Greater hypoxic vasodilation and elevated HR in AMS in the absence of other changes suggest that augmentation of beta-adrenergic tone may be involved in early AMS pathophysiology.

Plasma volume by Evans blue: effects of eating and comparison with other methods at altitude.

HYPOTHESIS: Measurements of plasma volume (PV) and its changes (delta%PV) by Evans blue (EB) dye are presumed to be valid only in fasting subjects. In addition, delta%PVEB with acute altitude exposure has not been compared with other methods employing the concentration or dilution of naturally occurring blood (hematocrit (Hct), hemoglobin (Hb)) and plasma (density, proteins) components, but should be similar if capillary permeability and the sampled vein/whole body Hct ratio remain unchanged. METHODS: PVEB was determined in six subjects while fasting or eating on different days, with injection and sampling in the same arm, 4-h extrapolation to time zero and correcting readings with the 620-740 A method. For 93 experiments at altitude, delta%PVEB was obtained similarly from a 3-h extrapolation near the end of a 12-h chamber exposure to 426 mm Hg (-4,880 m =16,000 ft) and at the same time on the preceding control day. RESULTS: Mean PVEB with and without eating was not significantly different (SE of absolute difference = +/- 2.8%). The EB decay curves had significantly more scatter with eating than fasting. The fasting vs. non-fasting values for the single 20-min post-injection point also gave a close comparison (r = +0.97). At altitude the loss in PV measured with EB was significantly greater (delta%PVEB = -6.3%) than losses estimated from Hct-Hb (-2.9%), plasma protein (-3.7%), and plasma density (-3.9%). The expected larger PV loss in subjects tolerant to altitude sickness compared with intolerant ones was most clearly shown by delta%PVEB (8.8%). CONCLUSIONS: Obtaining more samples can offset reproducibility lost by eating. The delta%PVEB were largest and nearest to values previously reported at altitude, perhaps because the single baseline and altitude samples utilized by the other methods are more sensitive to subtle, transient fluctuations in body water and vasomotor tone associated with apprehension, vomiting, fluid intake, and regional vasodilation and constriction.