Acute Mountain Sickness Symptom Severity at the South Pole: The Influence of Self-Selected Prophylaxis with Acetazolamide

Introduction

Acetazolamide, a carbonic anhydrase inhibitor, remains the only FDA approved pharmaceutical prophylaxis for acute mountain sickness (AMS) though its effectiveness after rapid transport in real world conditions is less clear.

Methods

Over 2 years, 248 healthy adults traveled by airplane from sea level (SL) to the South Pole (ALT, ~3200m) and 226 participants provided Lake Louise Symptom Scores (LLSS) on a daily basis for 1 week; vital signs, blood samples, and urine samples were collected at SL and at ALT. Acetazolamide was available to any participant desiring prophylaxis. Comparisons were made between the acetazolamide with AMS (ACZ/AMS) (n = 42), acetazolamide without AMS (ACZ/No AMS)(n = 49), no acetazolamide with AMS (No ACZ/AMS) (n = 56), and the no acetazolamide without AMS (No ACZ/No AMS) (n = 79) groups. Statistical analysis included Chi-squared and one-way ANOVA with Bonferroni post-hoc tests. Significance was p≤0.05.

Results

No significant differences were found for between-group characteristics or incidence of AMS between ACZ and No ACZ groups. ACZ/AMS reported greater LLSS, BMI, and red cell distribution width. ACZ/No AMS had the highest oxygen saturation (O₂Sat) at ALT. No significant differences were found in serum electrolyte concentrations or PFT results.

Discussion

Acetazolamide during rapid ascent provided no apparent protection from AMS based on LLSS. However, it is unclear if this lack of effect was directly associated with the drug or if perhaps there was some selection bias with individuals taking ACZ more likely to have symptoms or if there may have been more of perceptual phenomenon related to a constellation of side effects.     

急性高原病的预防性用药

急性高原病是暴露于高原时,因高原低氧而在数小时至数天内出现的临床症候群,若不及时诊治,会发展为较为严重的高原肺水肿和高原脑水肿。随着我国对西部地区投入力度的增加,内地人员进入高原地区日渐增多,因此如何保证进入高原的人员健康,是医药科研工作的一项重要任务。为使人们有效快速地预防急性高原病,本文对国内外使用较为普遍的药物以及它们的作用机制进行了概述;并对有良好应用前景的药物进行了介绍。     

急性高原病的预防性用药

急性高原病是暴露于高原时,因高原低氧而在数小时至数天内出现的临床症候群,若不及时诊治,会发展为较为严重的高原肺水肿和高原脑水肿。随着我国对西部地区投入力度的增加,内地人员进入高原地区日渐增多,因此如何保证进入高原的人员健康,是医药科研工作的一项重要任务。为使人们有效快速地预防急性高原病,本文对国内外使用较为普遍的药物以及它们的作用机制进行了概述;并对有良好应用前景的药物进行了介绍。     

Association between Body Water Status and Acute Mountain Sickness

Purpose

The present study determined the association between body fluid variation and the development of acute mountain sickness (AMS) in adults.

Methods

Forty-three healthy participants (26 males and 17 females, age: 26±6 yr, height: 174±9 cm, weight: 68±12 kg) were passively exposed at a FiO₂ of 12.6% (simulated altitude hypoxia of 4500 m, PiO₂ = 83.9 mmHg) for 12-h. AMS severity was assessed using the Lake Louise Score (LLS). Food and drink intakes were consumed ad libitum and measured; all urine was collected. Before and after the 12-h exposure, body weight and plasma osmolality were measured and whole-body bioimpedance analysis was performed.

Results

The overall AMS incidence was 43% (38% males, 50% females). Participants who developed AMS showed lower fluid losses (3.0±0.9 vs. 4.5±2.0 ml/kg/h, p = 0.002), a higher fluid retention (1.9±1.5 vs. 0.6±0.8 ml/kg/h, p = 0.022), greater plasma osmolality decreases (−7±7 vs. −2±5 mOsm/kg, p = 0.028) and a larger plasma volume expansion (11±10 vs. 1±15%, p = 0.041) compared to participants not developing AMS. Net water balance (fluid intake – fluid loss) and the amount of fluid loss were strong predictors whether getting sick or not (Nagelkerkes r² = 0.532). The LLS score was related to net water balance (r = 0.358, p = 0.018), changes in plasma osmolality (r = −0.325, p = 0.033) and sodium concentration (r = −0.305, p = 0.047). Changes in the impedance vector length were related to weight changes (r = −0.550, p<0.001), fluid intake (r = −0.533, p<0.001) and net water balance (r = −0.590, p<0.001).

Conclusions

Participants developing AMS within 12 hours showed a positive net water balance due to low fluid loss. Thus measures to avoid excess fluid retention are likely to reduce AMS symptoms.     

Association of Arterial Oxygen Saturation and Acute Mountain Sickness Susceptibility: A Meta-analysis

Acute mountain sickness (AMS) is the most common high altitude illnesses experienced during rapid ascent to a higher altitude without prior acclimation. It is mainly characterized by a headache which may be accompanied with nausea, vomiting, anorexia, dizziness, lethargy, fatigue, and sleep disturbance. If not diagnosed and treated in a timely manner, AMS can develop into deadly high altitude pulmonary edema or high altitude cerebral edema. In the previous studies of individual variation in susceptibility to AMS, arterial oxygen saturation ( \(S_{{{\text{O}}_{2} }}\) ) was identified as being associated with AMS. However, other studies have reported no association between AMS and arterial oxygen saturation. In this study, the association between \(S_{{{\text{O}}_{2} }}\) and AMS was assessed through a meta-analysis of published data. The literature databases PubMed, Web of Science, LWW, Science Direct, and Embase were queried for papers published before 15 April 2014. A fixed-effects model and a random-effects model were applied (Revman 5.0) on the basis of heterogeneity, and the study quality was assessed in duplicate. Twelve studies with 614 AMS patients and 1,025 control subjects were analyzed. There was a significant association with differences in \(S_{{{\text{O}}_{2} }}\) and the risk of developing AMS. \(S_{{{\text{O}}_{2} }}\) values are associated with AMS incidence.     

Principal Component Analysis and Risk Factors for Acute Mountain Sickness upon Acute Exposure at 3700 m

Objective

We aimed to describe the heterogeneity in the clinical presentation of acute mountain sickness (AMS) and to identify its primary risk factors.

Methods

The participants (n = 163) received case report form questionnaires, and their heart rate (HR), oxygen saturation (SpO₂), echocardiographic and transcranial Doppler variables, ability to perform mental and physical work, mood and psychological factors were assessed within 18 to 22 hours after arriving at 3700 m from sea level (500 m) by plane. First, we examined the differences in all variables between the AMS-positive and the AMS-negative groups. Second, an adjusted regression analysis was performed after correlation and principal component analyses.

Results

The AMS patients had a higher diastolic vertebral artery velocity (V_d; p = 0.018), a higher HR (p = 0.006) and a lower SpO₂. The AMS subjects also experienced poorer sleep quality, as quantified using the Athens Insomnia Scale (AIS). Moreover, the AMS population exhibited more negative mood states, including anxiety, depression, hostility, fatigue and confusion. Five principal components focused on diverse aspects were also found to be significant. Additionally, more advanced age (p = 0.007), a higher HR (p = 0.034), a higher V_d (p = 0.014), a higher AIS score (p = 0.030), a decreased pursuit aiming capacity (p = 0.035) and decreased vigor (p = 0.015) were risk factors for AMS.

Conclusions

Mood states play critical roles in the development of AMS. Furthermore, an elevated HR and V_d, advanced age, elevated AIS sores, insufficient vigor and decreased mental work capacity are independent risk factors for AMS.     

A Prospective Epidemiological Study of Acute Mountain Sickness in Nepalese Pilgrims Ascending to High Altitude (4380 m)

Background

Each year, thousands of pilgrims travel to the Janai Purnima festival in Gosainkunda, Nepal (4380 m), ascending rapidly and often without the aid of pharmaceutical prophylaxis.

Methods

During the 2012 Janai Purnima festival, 538 subjects were recruited in Dhunche (1950 m) before ascending to Gosainkunda. Through interviews, subjects provided demographic information, ratings of AMS symptoms (Lake Louise Scores; LLS), ascent profiles, and strategies for prophylaxis.

Results

In the 491 subjects (91% follow-up rate) who were assessed upon arrival at Gosainkunda, the incidence of AMS was 34.0%. AMS was more common in females than in males (RR = 1.57; 95% CI = 1.23, 2.00), and the AMS incidence was greater in subjects >35 years compared to subjects ≤35 years (RR = 1.63; 95% CI = 1.36, 1.95). There was a greater incidence of AMS in subjects who chose to use garlic as a prophylactic compared to those who did not (RR = 1.69; 95% CI = 1.26, 2.28). Although the LLS of brothers had a moderate correlation (intraclass correlation = 0.40, p = 0.023), sibling AMS status was a weak predictor of AMS.

Conclusions

The incidence of AMS upon reaching 4380 m was 34% in a large population of Nepalese pilgrims. Sex, age, and ascent rate were significant factors in the development of AMS, and traditional Nepalese remedies were ineffective in the prevention of AMS.     

MRI Evidence: Acute Mountain Sickness Is Not Associated with Cerebral Edema Formation during Simulated High Altitude

Acute mountain sickness (AMS) is a common condition among non-acclimatized individuals ascending to high altitude. However, the underlying mechanisms causing the symptoms of AMS are still unknown. It has been suggested that AMS is a mild form of high-altitude cerebral edema both sharing a common pathophysiological mechanism. We hypothesized that brain swelling and consequently AMS development is more pronounced when subjects exercise in hypoxia compared to resting conditions. Twenty males were studied before and after an eight hour passive (PHE) and active (plus exercise) hypoxic exposure (AHE) (F_iO₂ = 11.0%, P_iO₂∼80 mmHg). Cerebral edema formation was investigated with a 1.5 Tesla magnetic resonance scanner and analyzed by voxel based morphometry (VBM), AMS was assessed using the Lake Louise Score. During PHE and AHE AMS was diagnosed in 50% and 70% of participants, respectively (p>0.05). While PHE slightly increased gray and white matter volume and the apparent diffusion coefficient, these changes were clearly more pronounced during AHE but were unrelated to AMS. In conclusion, our findings indicate that rest and especially exercise in normobaric hypoxia are associated with accumulation of water in the extracellular space, however independent of AMS development. Thus, it is suggested that AMS and HACE do not share a common pathophysiological mechanism.     

Carbohydrate-Binding Non-Peptidic Pradimicins for the Treatment of Acute Sleeping Sickness in Murine Models

Current treatments available for African sleeping sickness or human African trypanosomiasis (HAT) are limited, with poor efficacy and unacceptable safety profiles. Here, we report a new approach to address treatment of this disease based on the use of compounds that bind to parasite surface glycans leading to rapid killing of trypanosomes. Pradimicin and its derivatives are non-peptidic carbohydrate-binding agents that adhere to the carbohydrate moiety of the parasite surface glycoproteins inducing parasite lysis in vitro. Notably, pradimicin S has good pharmaceutical properties and enables cure of an acute form of the disease in mice. By inducing resistance in vitro we have established that the composition of the sugars attached to the variant surface glycoproteins are critical to the mode of action of pradimicins and play an important role in infectivity. The compounds identified represent a novel approach to develop drugs to treat HAT.     

The Use of Corticosteroid (Dexamethasone) in the Treatment of Acute Laryngotracheitis

Many practitioners have considered that steroids, with their anti-inflammatory properties, should be efficacious in the treatment of acute laryngotracheitis. To examine this theory, 200 consecutive cases of acute laryngotracheitis admitted to The Hospital for Sick Children, Toronto, were included in a double-blind study using dexamethasone-21-phosphate and placebo according to a random selection code. All other therapy was kept constant. Each patient was assessed by one observer according to seven clinical parameters.The results of this study were subjected to statistical analysis and significantly favoured the steroid-treated group in four parameters only. In view of the risks inherent in steroid therapy, this degree of difference is not sufficient to warrant routine use of this drug for patients with acute laryngotracheitis.