Diagnosis and prediction of the occurrence of acute mountain sickness measuring oxygen saturation--independent of absolute altitude?

PURPOSE: Commercialization of trekking tourism enables untrained persons to participate in trekking tours. Because hypoxia is one of the main purported triggers for acute mountain sickness (AMS), pulse oximetry, which measures arterial oxygen saturation (SPO2), is discussed to be a possible and useful tool for the diagnosis of AMS. The purpose of this study was to evaluate possible associations between SPO2 values and the occurrence of AMS. METHODS: In 204 trekkers, SPO2 values (pulse oximetry) were measured and the Lake Louise Self-assessment Score (LLS) was administered over the first 7 days of their trekking tours. RESULTS: During treks at altitudes of 2500-5500 m in Nepal, India, Africa, and South America, 100 participants suffered from mild AMS, 3 participants suffered from severe AMS, and 9 participants reported both mild and severe AMS. The lowest mean SPO2 was 85.5 (95 % confidence interval (CI), 83.9-86.1 %) on day 5. SPO2 and LLS exhibited a weak to moderate negative correlation for all days of the study (ρ ranging from -0.142 to -0.370). Calculation of time-shifted associations of 24 and 48 h resulted in the disappearance of most associations. Susceptibility to headaches (odds ratio (OR) 2.9-7.2) and a history of AMS (OR 2.2-3.1) were determined to be potential risk factors for the development of AMS. CONCLUSION: Since there is no strong altitude-independent association between AMS and SPO2 during the first week of high-altitude adaptation, the implementation of pulse oximetry during trekking in order to detect and predict AMS remains questionable.

Long-term monitoring of oxygen saturation at altitude can be useful in predicting the subsequent development of moderate-to-severe acute mountain sickness.

OBJECTIVE: The use of pulse oximetry (Spo2) to identify subjects susceptible to acute mountain sickness (AMS) is the subject of debate. To obtain more reliable data, we monitored Spo2 for 24 hours at altitude to investigate the ability to predict impending AMS. METHODS: The study was conducted during the climb from Alagna (1154 m) to Capanna Regina Margherita (4559 m), with an overnight stay in Capanna Gnifetti (3647 m). Sixty subjects (11 women) were recruited. Each subject was fitted with a 24-hour recording finger pulse oximeter. The subjects rode a cable car to 3275 m and climbed to 3647 m, where they spent the night. RESULTS: In the morning, 24 subjects (6 women) had a Lake Louise Questionnaire score (LLS) ≥ 3 (AMS(+)), and 15 subjects (4 women) exhibited moderate-to-severe disease (LLS ≥ 5 = AMS(++)). At Alagna, Spo2 did not differ between the AMS(-) and AMS(+) subjects. At higher stations, all AMS(+) subjects exhibited a significantly lower Spo2 than did the AMS(-) subjects: at 3275 m, 85.4% vs 87.7%; resting at 3647 m, 84.5% vs 86.4%. The receiver operating characteristics curve analysis resulted in a rather poor discrimination between the AMS(-) subjects and all of the AMS(+) subjects. With the cutoff LLS ≥ 5, the sensitivity was 86.67%, the specificity was 82.25%, and the area under the curve was 0.88 (P < .0001) for Spo2 ≤ 84% at 3647 m. CONCLUSIONS: We conclude that AMS(+) subjects exhibit a more severe and prolonged oxygen desaturation than do AMS(-) subjects starting from the beginning of altitude exposure, but the predictive power of Spo2 is accurate only for AMS(++).

Assessment of Acute Mountain Sickness: Comparing the Chinese AMS Score to the Lake Louise Score.

Wu, Yu, Wenqi Zhao, Bao Liu, Jianyang Zhang, Zhifeng Zhong, Simin Zhou, Jiaxin Xie, Yuqi Gao, Peng Li, and Jian Chen. Assessment of Acute Mountain Sickness: Comparing the Chinese Ams Score to the Lake Louise Score. High Alt Med Biol 25:164-173, 2024. Objective: To compare the ability of the Chinese AMS Score (CAS) to detect acute mountain sickness (AMS) using the 2018 version of the Lake Louise Score (LLS) as reference. Methods: After flying from Chengdu (altitude: 500 m) to Lhasa (3,658 m), 2,486 young men completed a questionnaire. The questionnaire contained LLS and CAS items. An LLS ≥3 and/or a CAS ≥cutoff were used as the criteria for AMS. Hierarchical cluster analysis and two-step cluster analysis were used to investigate relationships between the symptoms. Results: AMS incidence rates were 33.8% (n = 840) with the LLS and 59.3% (n = 1,473) with the CAS (χ2 = 872.5, p < 0.001). The LLS and CAS had a linear relationship (orthogonal regression, Pearson r = 0.91, p < 0.001). With the LLS as the standard, the CAS had high diagnostic accuracy (area under the curve = 0.95, 95% confidence interval: 0.94-0.96). However, with the CAS, 25.5% (n = 633) more participants were labeled as having AMS than with the LLS (false positives). Two clusters were identified: one with headache only (419 participants, 66.2%) and one without headache but with other symptoms (214 participants, 33.8%). Reducing the weight of headache in the CAS allowed to align CAS and LLS. Conclusion: In comparison to the LLS, the CAS has a sensitivity close to 100% but lacks specificity given the high rate of false positives. The different weight of headaches may be the main reason for the discrepancy.

Temporal changes in biomarkers in individuals with and without acute mountain sickness following rapid ascent.

BACKGROUND: Field studies have reported conflicting results regarding changes in biomarkers at high altitude. This study measured temporal changes in biomarkers and compared the differences between individuals with and without acute mountain sickness (AMS). MATERIALS AND METHODS: This study included 34 nonacclimatized healthy participants. Ten-milliliters of blood were collected at four time points: 3 days before ascent (T0), on two successive nights at 3150 m (T1 and T2), and 2 days after descent (T3). Participants were transported by bus from 555 m to 3150 m within 3 hours. AMS was diagnosed using the self-reported Lake Louise Scoring (LLS) questionnaire. RESULTS: Compared with T0, significant increases in E-selectin and decreases in vascular endothelial growth factor (VEGF) levels were observed at high altitude. Significantly increased C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), and S100 calcium-binding protein B (S100B) levels were observed at T2, and significantly decreased vascular cell adhesion molecule-1 (VCAM-1) levels were observed at T3. Eighteen (53%) participants developed AMS. Changes in E-selectin, CRP, MCP-1, and S100B levels were independent of AMS. Relative to individuals without AMS, those with AMS had significantly higher atrial natriuretic peptide (ANP) and VCAM-1 levels and lower plasminogen activator inhibitor-1 (PAI-1) levels at T1 and higher brain natriuretic peptide and lower VEGF and PAI-1 levels at T3. LLSs were positively correlated with ANP and VCAM-1 levels and negatively correlated with PAI-1 levels measured at T1. CONCLUSIONS: After acute ascent, individuals with and without AMS exhibited different trends in biomarkers associated with endothelial cell activation and natriuretic peptides.

Repeated remote ischaemic preconditioning can prevent acute mountain sickness after rapid ascent to a high altitude.

BACKGROUND: This study assessed the effectiveness of 4 different repeated remote ischaemic preconditioning (RIPC) protocols varying in duration and frequency for preventing acute mountain sickness (AMS) after rapid ascent to high altitude. METHODS: In a randomized but not blinded design, participants were assigned to receive either of the four RIPC treatments at low altitude (Group A, once daily for 1 week; Group B, twice daily for 1 week; Group C, once daily for 4 weeks; and Group D, twice daily for 4 weeks) or control (no specific sham treatment). Participants were then flown to a high altitude (3650 m). The primary outcome was the incidence and severity of AMS evaluated by the Lake Louise score (LLS) after arrival; vital signs were collected simultaneously. RESULTS: A total of 250 participants (50 per group; mean age 38.56 ± 0.76 years) were included. The overall AMS incidence was 26.4%. A total of 20 AMS cases (40%) occurred in the control group, 15 cases (30%) both in the RIPC A and RIPC B groups (RR 1.3; 95%CI 0.8-2.3; χ2 = 1.099; p = 0.29), and 8 cases (16%) both in the RIPC C and D groups (RR 2.5; 95%CI 1.2 - 5.2; χ2 = 7.143, p < 0.01), with significantly lower LLSs in the RIPC C and D groups (F = 6.51, p < 0.001). The scores of gastrointestinal symptoms (F = 7.42, p < 0.001) and dizziness (F = 9.82, p < 0.001) but not headache (F = 0.60, p > 0.05) were lower in the RIPC groups compared to control. The blood oxygen saturation level (SpO2) decreased less in the RIPC B, C and D groups compared to control after arrival at a high altitude (F = 11.42, p < 0.001). The number of RIPC treatments received was moderately correlated with SpO2 (R = 0.38, p < 0.001), and SpO2 was moderately inversely correlated with the LLS (R = -0.48, p < 0.001). CONCLUSION: This study demonstrated that a four-week RIPC intervention but not a one-week regimen reduced AMS incidence and severity; however, a placebo effect might have contributed to these results.

The Impact of Nocebo and Placebo Effects on Reported Incidence of Acute Mountain Sickness.

Bärtsch Peter. The impact of nocebo and placebo effects on reported incidence of acute mountain sickness. High Alt Med Biol. 23:8-17, 2022.-Well comparable studies reporting acute mountain sickness (AMS) in nonacclimatized, acutely exposed individuals performed at 3,450-3,650 m (9 studies) and 4,559-4,675 m (18 studies) at real altitude or in hypobaric or in normobaric hypoxic chambers were analyzed with the hypothesis that the study design impacts occurrence of AMS. Individual symptoms and overall scores of AMS were not different between the three modalities of exposure to a comparable degree of hypoxia, indicating that hypobaria has, if at all, minimal influence on AMS. Studies not focusing versus those focusing on AMS report lower scores and prevalence of AMS at 3,500 m, but not at 4,559 m, while frequent assessment may be associated with more severe AMS. These data suggest that focusing on AMS creates expectations of getting AMS (nocebo effects) and increases its prevalence, while not paying attention reduces negative expectations and thus AMS. On the other hand, interventions promising improvement may cause positive expectations (placebo effect). Information about purpose and dangers of a study, repeated assessments for AMS, previous experiences of AMS, and observation of illness in other study participants are major factors contributing to negative expectations and thus nocebo effects increasing AMS. They should be considered when designing studies and subject information and be reported in detail in publications of studies on AMS.

Evaluation of the Lake Louise Score for Acute Mountain Sickness and Its 2018 Version in a Cohort of 484 Trekkers at High Altitude.

Richalet, Jean-Paul, Chantal Julia, and François J. Lhuissier. Evaluation of the Lake Louise Score for acute mountain sickness and its 2018 version in a cohort of 484 trekkers at high altitude. High Alt Med Biol. 22:353-361, 2021. Background: The Lake Louise Score (LLS) is widely used in field studies and chamber studies for the diagnosis of Acute Mountain Sickness (AMS). This score aggregates symptoms that are nonspecific: headache, gastrointestinal symptoms, fatigue, dizziness and sleep disturbance can be due to a variety of causes unrelated to altitude hypoxia. The objectives of this study were to (1) reevaluate the need for a headache score >0 for the diagnosis of AMS, (2) evaluate the role of sleep disturbances, in relation with other symptoms, (3) evaluate the significance of dizziness. Materials and Methods: We analyzed LLS from 484 trekkers at high altitude. Among them, 212 suffered from moderate AMS (mAMS: 3 ≤ LLS < 6) and 115 from severe AMS (sAMS: LLS ≥ 6). Results: Cluster analysis of AMS revealed three main groups presenting the following symptoms: Group 1 includes 254 subjects who had less than 2 symptoms; Group 2 includes 137 subjects who had fatigue, sleep disturbance, and headache, corresponding to mAMS; Group 3 includes 93 subjects who had headache, fatigue, dizziness and sleep disturbance, corresponding to sAMS. A headache score of zero was found in 25% of mAMS and 5% of sAMS subjects. Only the absence of headache associated with the absence of fatigue was specific of absence of sAMS. In subjects with a dizziness score > 1, end-tidal partial pressure of carbon dioxide during a hypoxic exercise test was lower than that in subjects with a dizziness score < 2. Subjects with high ventilatory response to hypoxia may develop dizziness with high altitude exposure. Conclusion: (1) An isolated headache score > 0 should not be mandatory to define AMS, (2) sleep disruption contributes to the diagnosis of AMS, (3) gastrointestinal symptoms and dizziness are weaker contributors to the LLS, (4) dizziness might be linked to a hyperresponsiveness to hypoxia and not to AMS itself.

Assessment of Acute Mountain Sickness Using 1993 and 2018 Versions of the Lake Louise Score in a Large Chinese Cohort.

Chen, Renzheng, Yong Wang, Chen Zhang, Xiaolin Luo, Jie Yang, Chuan Liu, and Lan Huang. Assessment of acute mountain sickness using 1993 and 2018 versions of the Lake Louise Score in a large Chinese cohort. High Alt Med Biol. 22:362-368, 2021. Background: This study uses Lake Louise Score (LLS) in its original (LLS1993) and new (LLS2018) versions to assess acute mountain sickness (AMS) and aims to provide more clinical information about the AMS scoring system. Methods: We enrolled 1,026 male Chinese soldiers who traveled from an altitude of 500 to 3,700 m by airplane in 2.5 hours. We observed each subject's symptoms after arrival at 3,700 m in 24 and 48 hours. Each item was dropped from LLS1993 to evaluate its sensitivity and effect on AMS diagnosis. The relationship between each symptom and AMS was assessed by correlation analysis. Exploratory and confirmatory factor analyses evaluated the factor structure of LLS, while the ordinal alpha coefficient was calculated to determine its internal consistency. Results: Four hundred fifty-nine subjects were not followed up on day 2. We defined two observed cohorts (cohort 1, n = 1,026 and cohort 2, n = 567). Headache was the most common symptom in 24 hours, while sleep disturbance was the fourth-most common symptom at 24 hours and the most common symptom at 48 hours. When we dropped gastrointestinal symptoms, the drop rate was lowest in each situation (1.0% in cohort 1, 1.3% in cohort 2 at 24 hours, and 5.7% in cohort 2 at 48 hours, respectively). The incidence of AMS decreased from 18.4% at 24 hours to 36.4% at 48 hours when lost sleep disturbance in cohort 2. Moreover, the statistical method of Mantel/Haenszel square test was used for correlation analysis and the results showed a correlation between sleep disturbance and AMS. Besides, both LLS1993 and LLS2018 had acceptable internal consistencies, and all items had good loading coefficients in LLS1993. Conclusions: We have demonstrated that there could be an association between sleep disturbance and AMS diagnosis. Both LLS1993 and LLS2018 applied to young Chinese men.

The Lake Louise Score: A Critical Assessment of Its Specificity.

Moore, James, Martin J. MacInnis, Jon Dallimore, and Matt Wilkes. The Lake Louise Score: A Critical Assessment of Its Specificity. High Alt Med Biol. 21:237-242, 2020. Introduction: The Lake Louise Score (LLS) has low specificity for diagnosing acute mountain sickness (AMS). As this tool is used for research and clinical decision making, it is important to understand the origins of this poor specificity. We reviewed AMS diagnoses in a population trekking at low altitude ("false positives") to critically assess LLS specificity. Method: We retrospectively analyzed data from a sample of 123 adolescents trekking at low altitude to establish the predominant causes of false-positive AMS diagnoses (1993 LLS criteria), separately removing each LLS component to assess its contribution to the final score. Exploratory factor analysis (EFA) was applied to the data to establish component patterns. Results: Removal of LLS components individually showed fatigue contributed slightly more to false-positive AMS diagnoses than sleep quality in this group. An EFA from morning data highlighted sleep quality as a stand-alone factor in the measurement of AMS. Although of smaller significance, an EFA of the evening data highlighted fatigue and headache as the stand-alone factor. Conclusion: Our findings not only supported the recent removal of sleep quality from the LLS, but also demonstrated that fatigue had an equal part to play in the misdiagnosis of AMS in this population. These data highlighted the poor specificity of the LLS and suggest that the measurement of illness at altitude undergo further review.

Carry-Over Quality of Pre-acclimatization to Altitude Elicited by Intermittent Hypoxia: A Participant-Blinded, Randomized Controlled Trial on Antedated Acclimatization to Altitude.

Intermittent normobaric hypoxia (IH) is increasingly used to pre-acclimatize for a sojourn to high altitude. There is a number of hypoxia - protocols observing the hypoxic ventilatory response (HVR), but little is known about the carry - over quality of the Lake Louise Score (LLS). We thus studied a week - long, 1 h per day poikilocapnic hypoxia protocol on whether acclimatization could be carried over for one week. Rationale for this was that it usually takes one week to get from Europe, Britain or the United States to the base camp of a major mountain. Forty-nine healthy volunteers of both sexes were exposed to daily bouts of 1 h at an inspiratory fraction of oxygen (FiO2) of 0.11 or 0.21 (control) for 7 consecutive days. Seven days after cessation of IH or sham exposures participants were again subjected to hypoxia (FiO2 = 0.11) for 6 h and measurements of isocapnic HVR and blood gases out of the arterialized earlobe were taken and LLS was assessed. In those with IH exposures LLS was reduced which was not the case in those with sham exposure (87 vs. 50%). Changes in HVR or the arterial hemoglobin saturation were not observed. Gender neither affected LLS nor HVR nor blood gases or carry -over quality. We found that our week - long, hypoxia protocol grants a reduction in LLS that can be carried over the time span of one week. In this way, antedated acclimatization may improve safety and comfort on the mountain.

Incidence of Mild Cognitive Impairment with Ascending Altitude.

Background: This study aimed to longitudinally quantify the prevalence of mild cognitive impairment (MCI) in individual trekkers at three different ascending altitudes (Site 1: ∼3500 m, Site 2: ∼4400 m, and Site 3: ∼5100 m). We correlated these findings with the presence of acute mountain sickness (AMS). Materials and Methods: We performed serial assays using the environmental quick mild cognitive impairment (eQMCI) score on 103 English-speaking 18- to 65-year-old volunteers trekking to Everest Base Camp in Nepal during spring 2016. We defined MCI as a score less than 67 (lower scores indicating more cognitive impairment). Additional data collected included the Lake Louise Score, demographics, and other possible confounders. Results: eQMCI scores significantly decreased with ascent from Site 1 to 2 (a score of 78.95 [SD = 7.96] to 74.67 [SD = 8.8] [Site 1-2 p = 0.04]), but then increased on ascent to Site 3 to 83.68 (SD = 8.67) (Site 1-3 p = <0.0001, Site 2-3 p = <0.0001). However, subjects who fulfilled eQMCI criteria for MCI increased despite the overall improvement in score: 6.8% (N = 7) at Site 1, 18.7% (N = 14) at Site 2, and 3.3% (N = 2) at Site 3. Incidence of AMS at Sites 1, 2, and 3 was 22.3% (N = 23), 21.3% (N = 16), and 48.3% (N = 29), respectively. Of those with MCI, 1.94% met criteria for AMS at Site 1 (p = 0.0017), 2.67% at Site 2 (p = 0.6949), and 3.33% at Site 3 (p = <0.0001). Conclusions: There is a significant incidence of MCI at high altitude, even in those without subjective findings of AMS. Interestingly, subjects with a decline in cognitive function show an increasing trend for developing AMS at higher altitude. Future research on the clinical impact of MCI on a subject's health, judgment, and performance remains to be elucidated.

Acute mountain sickness, chemosensitivity, and cardiorespiratory responses in humans exposed to hypobaric and normobaric hypoxia.

We examined the control of breathing, cardiorespiratory effects, and the incidence of acute mountain sickness (AMS) in humans exposed to hypobaric hypoxia (HH) and normobaric hypoxia (NH), and under two control conditions [hypobaric normoxia (HN) and normobaric normoxia (NN)]. Exposures were 6 h in duration, and separated by 2 wk between hypoxic exposures and 1 wk between normoxic exposures. Before and after exposures, subjects (n = 11) underwent hyperoxic and hypoxic Duffin CO2 rebreathing tests and a hypoxic ventilatory response test (HVR). Inside the environmental chamber, minute ventilation (V(E)), tidal volume (V(T)), frequency of breathing (fB), blood oxygenation, heart rate, and blood pressure were measured at 5 and 30 min and hourly until exit. Symptoms of AMS were evaluated using the Lake Louise score (LLS). Both the hyperoxic and hypoxic CO2 thresholds were lower after HH and NH, whereas CO2 sensitivity was increased after HH and NH in the hypoxic test and after NH in the hyperoxic test. Values for HVR were similar across the four exposures. No major differences were observed for Ve or any other cardiorespiratory variables between NH and HH. The LLS was greater in AMS-susceptible than in AMS-resistant subjects; however, LLS was alike between HH and NH. In AMS-susceptible subjects, fB correlated positively and Vt negatively with the LLS. We conclude that 6 h of hypoxic exposure is sufficient to lower the peripheral and central CO2 threshold but does not induce differences in cardiorespiratory variables or AMS incidence between HH and NH.