Index Measured at an Intermediate Altitude to Predict Impending Acute Mountain Sickness

The HUNT Study

Pietro Amedeo Modesti; Stefano Rapi; Rita Paniccia; Gregorz Bilo; , Miriam Revera; Piergiuseppe Agostoni; Alberto Piperno; Giulia Elisa Cambi; Angela Rogolino; Annibale Biggeri; Giuseppe Mancia; Gian Franco Gensini; Rosanna Abbate; Gianfranco Parati


Med Sci Sports Exerc. 2011;43(9):1675-1679. 

In This Article

Abstract and Introduction


Purpose: Acute mountain sickness (AMS) is a neurological disorder that may be unpredictably experienced by subjects ascending at a high altitude. The aim of the present study was to develop a predictive index, measured at an intermediate altitude, to predict the onset of AMS at a higher altitude. Methods: In the first part, 47 subjects were investigated and blood withdrawals were performed before ascent, at an intermediate altitude (3440 m), and after acute and chronic exposition to high altitude (Mount Everest Base Camp, 5400 m (MEBC1 and MEBC2)). Parameters independently associated to the Lake Louise scoring (LLS) system, including the self-reported and the clinical sections, and coefficients estimated from the model obtained through stepwise regression analysis were used to create a predictive index. The possibility of the index, measured after an overnight stay at intermediate altitude (Gnifetti hut, 3647 m), to predict AMS (defined as headache and LLS ≥ 4) at final altitude (Capanna Margherita, 4559 m), was then investigated in a prospective study performed on 44 subjects in the Italian Alps. Results: During the expedition to MEBC, oxygen saturation, hematocrit, day of expedition, and maximum velocity of clot formation were selected as independently associated with LLS and were included in the predictive index. In the Italian Alps, subjects with a predictive index value ≥ 5.92 at an intermediate altitude had an odds ratio of 8.1 (95% confidence limits = 1.7–38.6, sensitivity = 85%, specificity = 59%) for developing AMS within 48 h of reaching high altitude. Conclusion: In conclusion, a predictive index combining clinical and hematological parameters measured at an intermediate step on the way to the top may provide information on impending AMS.


Nowadays, owing to the modern tourist industry, access to high altitudes is made easy. Within 6–12 hafter arrival at altitudes greater than 2500 m and consequent acute exposition to hypobaric hypoxia, nonacclimatized mountaineers may experience nonspecific symptoms including headache, nausea, anorexia, insomnia, fatigue/lassitude, vomiting, and dizziness.[14] When these symptoms are assessed and rated in severity on a scale of 1–3 with the generally accepted Lake Louise scoring (LLS) system,[22] the presence of acute mountain sickness (AMS) can be clinically diagnosed at the presence of a headache and at least one of the other symptoms.

Although not generally life-threatening, AMS is a clinical and pathophysiological continuum with high-altitude cerebral edema,[14,25] a potentially fatal condition marked by the onset of ataxia and altered consciousness.[2,14] As very few medications for AMS treatment are available, subjects with AMS should descend or be evacuated when LLS does not abate or worsen at any point within 24–48 h.[25] At high altitude, this decision may, however, be hindered by accessibility of the hut, the geographic layout, and mostly by weather conditions. In addition, evacuation can sometimes be severely delayed among the local staff engaged in the expedition, who may deny AMS symptoms because they worry about losing their jobs.[7] Therefore, a great interest exists regarding the possibility to screen subjects who may undergo a life threat.[25]

Rate of ascent, heavy exercise, and individual susceptibility are the recognized important determinants for the onset of AMS.[24] Individual susceptibility, however, can only be ascertained after a first episode,[25] and although a relationship between oxygen saturation (SaO2) and the subsequent development of AMS[9] was observed, at present there is no way to predict AMS.[24] Mild to moderate AMS was found to be associated with different pathophysiological changes, including relative hypoventilation,[20] impaired gas exchange (interstitial pulmonary edema),[13] fluid retention and redistribution,[27] and increased sympathetic drive.[5] Studies performed on mountaineers after a rapid ascent by foot to high altitude in the Alps (>4000 m) revealed that AMS with a score ≥ 4 was also associated with mild but significant shortening of activated partial thromboplastin time in the absence of any evidence of thrombin generation or fibrin formation;[3] no blood coagulation changes were observed in mountaineers not reaching the same AMS score.[4]

The complexity and the dynamic nature of AMS might represent significant obstacles toward the identification of a single parameter for predicting the disease. Therefore, the aim of the present study was to develop for the first time a predictive index, combining simple clinical and hematological parameters (i.e., hematocrit, oxygen saturation, etc.), which may be used at intermediate altitude to predict the onset of AMS at high altitude. A two-phase study was thus designed: in the first phase, we analyzed data collected within the frame of the HIGH altitude CArdiovascular REsearch (HIGHCARE) project at Mount Everest Base Camp (MEBC, 5400 m) to estimate the parameters to be included in the equation for deriving the clinical prediction index; in the second phase, an expedition to Monte Rosa (Italian Alps) was set up to validate the clinical prediction model by using data obtained after an overnight stay at the Gnifetti hut (3647 m) to predict an onset of AMS at the final high-altitude destination (Capanna Margherita (CM) hut, 4559 m).


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