Acute Mountain Sickness Symptoms After Rapid Ascent to 4900 m
INTRODUCTION: Acute mountain sickness (AMS) is a common condition in individuals ascending rapidly to high altitudes and often presents with headaches, fatigue, and gastrointestinal symptoms. AMS is prevalent above 13,000 ft (4000 m), but some individuals experience it at lower elevations. This pilot study assessed the prevalence and timing of AMS symptoms in unacclimatized individuals exposed to 16,000 ft (4900 m) in a controlled hypobaric environment.
METHODS: A total of 10 healthy, unacclimatized men and women were exposed to an altitude of 16,000 ft (4900 m) for 5 h. Physiological parameters, including heart rate (HR), oxygen saturation (Spo2), and respiratory rate (RR), were recorded alongside AMS symptom severity using the 2018 Lake Louise Questionnaire (LLQ) and divided into low, moderate, and high responders based on severity.
RESULTS: All subjects experienced some degree of AMS symptoms, with LLQ scores increasing over time. Two subjects could not complete the full exposure due to moderate and severe symptoms. HR increased (Δ = 7.0 ± 0.6), while Spo2 remained stable but lower than baseline (Δ = 9 ± 4.2). LLQ score increases were strongly correlated with HR, Spo2, and RR. RR remained stable across subjects but varied between AMS severity groups.
DISCUSSION: This pilot study demonstrated that unacclimatized individuals rapidly exposed to 13,000 ft (4900 m) develop AMS symptoms in a controlled environment. The correlation between LLQ scores and physiological changes offers insight into AMS pathophysiology, supporting the need for further research into AMS susceptibility and genetic factors.
Murphey JT, Hess HW, Schwob J, Monaco BA, Clemency BM, Hostler D. Acute mountain sickness symptoms after rapid ascent to 4900 m. Aerosp Med Hum Perform. 2025; 96(11):958–963.
Acute mountain sickness (AMS) is a prevalent and potentially debilitating medical condition that develops following rapid ascent to high altitude. Characterized by fatigue, loss of appetite, headache, sleep disturbances, and diminished affect,1 AMS typically emerges within 6–12 h of exposure to altitudes exceeding 11,500–13,000 ft (3500–4000 m). However, various reports indicate that some individuals experience AMS at altitudes as low as 8000 ft (2500 m).1–3 The Lake Louise Questionnaire (LLQ),4 most recently revised in 2018, remains the principal tool for symptom-based assessment and classification of AMS severity.5 While the LLQ has demonstrated utility in the field, its performance in controlled laboratory environments and its relationship to objective physiological metrics remain incompletely characterized.
Despite the long-standing history of high-altitude research,6 important gaps persist in the understanding of AMS pathophysiology.1 Proposed mechanisms include a marked increase in extracellular cerebral edema, vasogenic intercellular edema, an acute increase in plasma volume from carbonic anhydrase in the renal system, and an increase in oxidative stress coupled with neuronal damage from increased intracranial pressure.5–7 However, the symptom complex associated with AMS is nonspecific and overlaps with other altitude-related and infectious diseases, complicating early identification and intervention. For example, initial AMS symptoms are often attributed to other benign conditions (e.g., common cold or flu) when outside a controlled setting. Since not easily differentiated from other conditions, treatment may be delayed, leading to the development of more severe conditions—high-altitude cerebral edema (HACE) or high-altitude pulmonary edema (HAPE).7–9 Previously, it was thought that untreated AMS directly caused HACE and, to some degree, HAPE. However, studies have shown that the pathophysiology differs, and the exact mechanisms behind HACE and HAPE are still being investigated.5,6,10 It is important to note that the onset of AMS symptoms varies from person to person. It is generally accepted, however, that mild symptoms will occur within 1–2 h of ascent to high altitude.1,7,10
Field studies of AMS are expensive, time-consuming, and can be complicated by adverse environmental conditions such as wind, cold, and precipitation. Furthermore, subjects in field studies are often trained climbers with previous experience acclimatizing or are in the process of acclimation. This makes generalizability difficult, as AMS is not limited to mountaineers, climbers, or alpinists. The expansion of expedition tourism and the mobile nature of military operations open high-altitude destinations to nearly everyone. Studying unacclimatized individuals without previous hypobaric exposure in a controlled hypobaric environment allows generalization to a much broader population. Controlled hypobaric hypoxia exposure in a hypobaric chamber provides a platform for testing interventions that unacclimated individuals may use.
This pilot study was conducted to evaluate the onset and severity of AMS symptoms in healthy, unacclimated individuals during acute exposure to 16,000 ft (4900 m) in a hypobaric setting. A secondary objective was to assess the feasibility of stratifying AMS severity using the LLQ and to explore its potential utility as a correlative measure in future studies examining physiological and cognitive predictors of AMS. The findings from this study are intended to inform the development of larger-scale studies and support the validation of self-report tools in controlled, yet operationally relevant, environments.
METHODS
Subjects
A total of 10 healthy (N = 10, 8 men) unacclimated individuals without previous high-altitude exposure were recruited from the community. The study protocol was approved in advance by the University at Buffalo Institutional Review Board (IRB# FWA00008824). Each subject provided written informed consent before participating. After written consent was obtained from each subject, familiarization with the 2018 LLQ was provided before the protocol visit. To ensure the safety and reliability of our results, each subject underwent a physical examination with a study physician, which included musculoskeletal, neurological, cardiovascular, and pulmonary assessments. Subjects with any history of neurological, metabolic, pulmonary, or cardiovascular disease or illness, those who had traveled to moderate or high altitude within 1 wk of testing, and those who self-reported as claustrophobic were excluded. In addition, subjects who reported being smokers or currently taking any medications that are known to affect pulmonary, cardiovascular, or neurological function were excluded. Subjects abstained from taking antioxidant supplements for 24 h, alcohol, caffeine, nicotine, and exercise for 12 h, and food for 2 h before the testing.
Procedure
Subjects reported to the Center for Research and Education in Special Environments laboratory. The laboratory is located 600 ft (183 m) above sea level. They voided their bladder and were weighed in clothing before entering the hypobaric chamber. Euhydration was confirmed by urine-specific gravity ≤1.020 (Master-Sur/Nα; Atago USA Inc., Bellevue, WA, United States). The hypobaric chamber was decompressed to 16,000 ft (4900 m) at a rate of ∼1000 ft (325 m)/min and remained at that pressure for a maximum of 5 h. Up to three subjects underwent altitude exposure simultaneously. Heart rate (HR) and arterial oxygen saturation (Spo2) were recorded every 5 min (Masimo SET Rainbow, Irvine, CA, United States), blood pressure (BP) and respiratory rate (RR) were measured manually every 15 min, and AMS severity was assessed every 30 min via the LLQ. Mean arterial blood pressure (MAP) was calculated by:
Hypobaric hypoxia exposure was terminated if subjects were unable to equalize inner ear pressure during ascent, their Spo2 dropped below 70% and could not be stabilized through pressure breathing,11 they exhibited an LLQ score greater than 7, experienced severe nausea or headache, showed signs or symptoms of HACE or HAPE, or upon their request. When a termination criterion was met, the subject was provided 100% supplemental oxygen for the remainder of the experimental session while data collection continued for other subjects. Subjects were then returned to sea level and monitored until their vital signs returned to baseline.
Statistical Analysis
Mean and standard deviations were calculated for anthropometric characteristics. Spo2, HR, RR, LLQ, and MAP changes across altitude exposure were compared for statistical significance (GraphPad Prism, Boston, MA), and a robust nonlinear regression was used to identify any outliers. Analysis of variance was used to examine differences within and between subjects; a Tukey post hoc analysis was used to determine where the analysis of variance differences were. Pearson’s correlation coefficients were used to compare physiological measurements to AMS symptom scores. Preliminary analysis revealed subjects fell into one of three groups: no clinical AMS (None, LLQ = 1), mild AMS (Mild, LLQ = 4), and moderate AMS (Mod, LLQ = 6+). A one-way analysis of variance was used to reveal differences between groups. Data are presented as means ± SD with an alpha level ≤0.05.
RESULTS
Anthropometric data are presented in Table I. All subjects were well-hydrated before experimental testing (urine specific gravity = 1.009 ± 0.001). HR and Spo2 differed from baseline (Δ = 27 ± 3.8, P < 0.001; Δ = 9 ± 4.2, P < 0.0001, respectively). HR increased over time (Δ = 7.0 ± 0.6, P = 0.04), while Spo2 remained stable throughout the 5-h exposure (Fig. 1A and B). MAP (Δ = 3.1 ± 13.7, P = 0.57) and RR (0.3 ± 0.5, P = 0.25) did not change over time or from baseline but were different between subjects who experienced only a high-altitude headache and those who had Mild and Mod AMS (Δ = 1.3 ± 0.15, P = 0.006; Δ = 3.16 ± 0.33, P < 0.001, respectively) and between Mild and Mod AMS (Δ = 1.91 ± 0.17, P < 0.05) (Fig. 2A and B).
Citation: Aerospace Medicine and Human Performance 96, 11; 10.3357/AMHP.6661.2025
Citation: Aerospace Medicine and Human Performance 96, 11; 10.3357/AMHP.6661.2025
Of the 10 subjects, 2 could not complete the 5-h experimental exposure. One subject lasted 1 h and 30 min, while the other lasted 1 h and 5 min before being placed on supplemental oxygen. Both reported an LLQ score of 6 just before the administration of oxygen. One subject experienced severe gastrointestinal symptoms and headache, while the other experienced severe lightheadedness respective to the total exposure times previously stated.
Lake Louise Scores increased over time (3.0 ± 1.0, P < 0.001, Fig. 3A). Subjects were grouped into NONE (0–2), MILD (3–5), or MOD (6–9) based on their peak LLQ score (Fig. 3B). Regardless of LLQ score, however, all subjects experienced a high-altitude headache. Additionally, two subjects reported gastrointestinal symptoms, one mild and one moderate. Fatigue and lightheadedness were reported by six subjects exhibiting mild to moderate AMS symptoms. The average onset time for subjects who experienced MOD AMS was 2:25 (hh:mm). The average onset time for MILD AMS was 1:03 (hh:mm). The LLQ demonstrated a strong positive correlation with HR [r(8) = 0.78, P < 0.05]. Conversely, LLQ exhibited a strong negative correlation with Spo2 [r(8) = −0.9, P < 0.05] and RR [r(8) = −0.7, P < 0.05]. No significant correlation was found between LLQ and MAP (Fig. 4).
Citation: Aerospace Medicine and Human Performance 96, 11; 10.3357/AMHP.6661.2025 Citation: Aerospace Medicine and Human Performance 96, 11; 10.3357/AMHP.6661.2025
DISCUSSION
This study established an experimental protocol for inducing AMS symptoms in a controlled hypobaric environment. The results provide insight into the physiological and symptomatic responses to hypoxia. Subjects showed increased HR and LLQ scores over time, indicating physiological stress and symptom development during exposure. In contrast, MAP and RR remained stable over the 5-h exposure across all subjects, suggesting these parameters did not significantly change once subjects reached 16,000 ft (4900 m). However, those who experienced no clinical AMS had higher RR when compared to those who experienced Mild and Mod AMS symptoms (Fig. 2B). Spo2 also remained stable during hypobaric exposure but was reduced from baseline (Δ = 19 ± 4.2, P < 0.001).
Correlative analyses revealed that higher LLQ scores, indicative of more severe AMS symptoms, were associated with increased HR and lower Spo2 and RR, reflecting the body’s attempt to maintain adequate oxygen levels and sufficient ventilation under hypoxic stress. No relationship was found between LLQ and MAP, indicating that subjective AMS symptoms were not directly related to changes in arterial pressure. Further analysis showed that increased RR was associated with higher MAP, while a complex association was observed between RR, HR, and Spo2, emphasizing the connection between respiratory and cardiovascular reactions. These findings are consistent with known physiological responses to acute hypobaric hypoxia, such as resting minute ventilation and SpO2, which have been independently shown as AMS predictors.12 There was a positive (r = 0.75) relationship between MAP and RR and a modest inverse relationship between MAP and LLQ, Spo2, and HR (r = −0.14, −0.26, and −0.7, respectively).
The findings align with existing literature on AMS, which identifies hypoxia as a primary trigger for AMS symptoms such as headache, nausea, and fatigue.13–15 Hypoxemia is a critical factor in AMS development, leading to increased cerebral blood flow, potentially contributing to cerebral edema and intracranial pressure.16,17 The increased RR shown between subjects who experienced Mild and Mod AMS symptoms compared to those in the None group sheds light on why some subjects were more susceptible to a low-pressure hypoxic environment than others. Given the differences in RR between groups was not a result of exposure time, it is likely RR is not directly related to AMS severity; rather, RR is driven by O2 and CO2 sensing drive RR. This further supports the notion that individual susceptibility and the body’s response to hypoxia play crucial roles in AMS development.9,17 Recent research highlights the importance of understanding the molecular and cellular mechanisms underlying AMS.18–20 For instance, hypoxia-inducible (HIF-1) and vascular endothelial growth factors are implicated in the body’s response to hypoxia, influencing vascular permeability and cerebral edema.21,22 The interplay between these factors and physiological responses, such as increased HR and altered RR, provide a deeper understanding of AMS pathophysiology.1 Based on the literature, it is likely that the subjects who experienced worse AMS have an increased HIF-1 response, a blunted hypoxic ventilatory response (HVR), are more sensitive to changes in CO2 and O2, or possibly a combination. As HIF-1, HVR, and O2/CO2 sensitivity are linked to genetics, future studies should include observations of both to elucidate how much influence genetics has on AMS in unacclimatized individuals. Individual variability in O2/CO2 chemosensitivity is multifactorial, extending beyond genetic determinants, HVR, and HIF-1 signaling. Notably, heightened sympathetic activation—linked to increased peripheral chemoreceptor activity—has been implicated in a myriad of diseases, including hypertension, depression, Type II diabetes, ulcerative colitis, and chronic inflammatory diseases.23 Although the present cohort was screened to exclude cardiovascular, pulmonary, renal, and metabolic conditions, they were not screened for generalized anxiety, depression, or chronic stress. These factors have been associated with elevated sympathetic tone and diminished parasympathetic modulation, potentially contributing to augmented O2/CO2 sensitivity. This, in turn, may underlie the elevated RR, more rapid onset, and increased severity of AMS symptomology that was observed during the study.24,25
In this model of rapid exposure to hypobaric hypoxia, subjects experienced a range of AMS symptoms, including headaches, gastrointestinal issues, fatigue, and lightheadedness. Approximately a third of the subjects experienced severe symptoms, one-third had moderate, and the remaining had minor symptoms and did not reach the clinical threshold for mild AMS. Peak symptom severity was associated with the time of symptom onset. Subjects who experienced the most severe symptoms reported the earliest onset of mild symptoms, highlighting the importance of not dismissing any mild symptoms that occur early during altitude exposure to avoid unnecessary AMS progression. This observation could potentially serve as a valuable diagnostic aid for self-monitoring during rapid ascent.
The onset of AMS was consistent with known patterns of AMS development.26 These symptoms reflect the body’s acute response to hypoxia and the challenges of maintaining homeostasis at high altitudes, and the reported LLQ scores indicate a significant variation in high altitude affinity between individuals. Though all subjects experienced the minimum criteria for AMS diagnosis—a high-altitude headache—AMS severity over the 5-h exposure time varied considerably, with some subjects meeting termination criteria and needing supplemental oxygen well before the end of exposure to others only experiencing a mild headache. Since all subjects were free from other illnesses and had not traveled to high altitudes in the past, none of the symptoms of AMS could be associated with a diagnosed illness or chronic disease. These findings further support a possible genetic correlation to how individuals respond to acute exposure to high altitude outside of people with known evolutionary genetic mutations for survival at high altitude, as is seen in Andean and Tibetan populations.22,27
The study had several limitations that must be considered when interpreting the results. The small sample size limits the generalizability of the findings. However, since this was a pilot study, the distribution of symptom severity allows us to power a future trial to examine the genetic influences on AMS severity, as genome-wide association studies such as Maclinnis et al., Ronen et al., and Yu et al. need larger cohorts to elucidate differences.28–30 Additionally, the biological sex imbalance may have influenced the results, as gender differences in AMS susceptibility have been reported.31–33 The stringent exclusion criteria, while necessary for safety, may result in a sample that is not representative of the general population who access high altitudes, particularly those at higher risk of AMS due to underlying health conditions or smoking. However, two-thirds of this healthy cohort experienced moderate to severe AMS symptoms in a relatively short exposure. Although a hypobaric chamber provides a controlled setting, it cannot perfectly replicate all aspects of true high-altitude exposure, such as cold temperatures and physical exertion associated with climbing, but it allows the isolation of the effects of hypobaria from these potentially confounding co-conditions found in nature.17 The maximum exposure duration of 5 h may not be sufficient to observe the full spectrum of AMS symptoms, which can develop over a longer period at high altitudes.9,27,34
This study successfully validated the experimental protocol for inducing AMS symptoms in a controlled hypobaric environment. The protocol safely elicited mild symptoms of AMS in all subjects and moderate symptoms in 30% of subjects. The strong correlations between LLQ scores, HR, Spo2, and RR provide valuable insights into the physiological and symptomatic responses to hypoxia. These findings align with recent research on AMS and highlight the complex interactions between cardiovascular and respiratory systems in response to acute hypobaric stress. Future research should focus on further exploring these relationships and investigating potential interventions to mitigate the adverse effects of AMS, with an emphasis on understanding the underlying molecular and cellular mechanisms.8,19
A) Heart rate (HR) and B) blood oxygen saturation (Spo2) over time (P < 0.001) from baseline (BL) and HR time effect (P = 0.04). Individual data points by group (AMS Severity) are for moderate AMS (Mod), mild AMS (Mild), and no AMS (None). All data are shown as mean ± SD.
A) Mean arterial pressure (MAP) and B) respiratory rate (RR) for moderate AMS (Mod), mild AMS (Mild), and no AMS (None). Individual data points by group (AMS Severity) show None differed from Mod and Mild (***P < 0.001, **P = 0.006, respectively) and between Mild and Mod (*P < 0.05). All data are shown as mean ± SD.
A) Group Lake Louise Questionnaire (LLQ) scores and time effect (P < 0.001). B) Individual LLQ scores (P < 0.01) and time effect (P < 0.001). All data are shown as mean ± SD.
Pearson’s correlation heat map for all research variables. LLQ: Lake Louise Questionnaire score; RR: respiratory rate; MAP: mean arterial pressure; Spo2: arterial oxygen saturation; and HR: heart rate.
Contributor Notes
