Ibuprofen Compared to Acetazolamide for the Prevention of Acute Mountain Sickness: A Randomized Placebo-Controlled Trial.

INTRODUCTION: Acetazolamide is recommended for the prevention of acute mountain sickness (AMS); however, its use is limited in some areas because of side effects. Previous studies report ibuprofen to be similar to or slightly inferior to acetazolamide. This randomized, triple-blinded, parallel-group, placebo-controlled trial was designed to compare ibuprofen with acetazolamide for the prevention of AMS. METHODS: Four hundred forty-three healthy Asian Indian men with a mean age of 29 (range: 20-49) years were randomized into three groups A, B, and P at 350m (SL). Acetazolamide (A): 85 mg; ibuprofen (B): 600 mg; or placebo (P): calcium carbonate was administered thrice daily, starting one day prior and continuing for three days after arrival at 3500m (HA). Participants were evaluated for AMS using the Lake Louise Questionnaire and for pulse, BP, SpO2, and respiratory rate twice daily for the first two days during rest and once a day for days three to six at HA. RESULTS: Of the 443 participants recruited at SL, 139 could not be airlifted due to logistical limitations, and 304 were available for follow-up at HA. Among these, 254 had ascended as per protocol. By intent to treat (IT) (N = 304; A = 99, B = 102, P = 103), the incidence of AMS (LLQS>/=3) was 12%, 5%, and 13%, and the incidence of severe AMS was 1%, 2%, and 6%, in groups A, B, and P, respectively. Using per protocol analysis (PP) (N = 254; A = 83, B = 87, P = 84), the incidence of AMS was 12%, 6%, and 13% in groups A, B, and P, respectively. The relative risk for developing AMS vs. placebo was A-0.96 (CI:0.46-2.0, p=0.91), B-0.39 (CI:0.14-1.04, p=0.06), A-0.94 (CI:0.42-2.1, p=0.88), and B-0.45 (0.16-1.24, p=0.12) by IT and PP, respectively. CONCLUSION: Ibuprofen is effective in males for the prevention of AMS with rapid ascent to 3500 m-rest for the first two days. Acetazolamide was superior to ibuprofen in the prevention of moderate-to-severe AMS.

Body fat content correlates with maximum aerobic capacity in healthy sedentary Indian males.

Background: Obesity is a multifactorial public health problem with varying effects on physical fitness determined by maximum aerobic capacity or VO2max. The relationship between body fat content and VO2max has shown varying results. The present study was planned as an experimental study to evaluate the relationship between body fat content and maximum aerobic capacity. Methods: 104 healthy Indian males [Age: 21 (4.87)years; Height: 171.4 (6.14)cm; Weight: 64.1 (8.57)kg] were evaluated for body fat content using body mass index (BMI), bioimpedance, skinfold thickness (SFT), body girth (BG) measurements, waist circumference (WC), and waist-hip ratio (WHR). Maximum aerobic capacity or VO2max for all subjects was determined indirectly from maximum heart rate achieved using an incremental treadmill protocol using Astrand and Astrand nomogram. Results: VO2max, when expressed in L/min, showed a statistically significant positive correlation with body fat irrespective of the method of estimation. VO2max, when expressed in ml/kg/min, showed negative correlation with five of the seven clinical parameters of fat estimation. Of these, a statistically significant negative correlation was seen with SFT. Conclusion: VO2max (L/min) shows a significant positive correlation with all methods of body fat estimation. VO2max (ml/kg/min) shows a significant negative correlation with skinfold thickness. Monitoring of body fat content using skinfold thickness could be studied further for its use in the early identification of young, healthy adult Indian males with low aerobic fitness.

Epidemiology and pathophysiology of vascular thrombosis in acclimatized lowlanders at high altitude: A prospective longitudinal study.

Background: Previous literature suggests that thrombosis is more common in lowlanders sojourning at high altitude (HA) compared to near-sea-level. Though the pathophysiology is partly understood, little is known of its epidemiology. To elucidate this, an observational prospective longitudinal study was conducted in healthy soldiers sojourning for months at HA. Methods: A total of 960 healthy male subjects were screened in the plains, of which 750 ascended, to altitudes above 15,000ft (4,472m). Clinical examination, haemogram, coagulogram, markers of inflammation and endothelial dysfunction, were studied at three time points during ascent and descent. The diagnosis of thrombosis was confirmed radiologically in all cases where a thrombotic event was suspected clinically. Subjects developing thrombosis at HA were labelled as Index Cases (ICs) and compared to a nested cohort of the healthy subjects (comparison group,(CG)) matched for altitude of stay. Findings: Twelve and three subjects, developed venous (incidence: 5,926/105 person-years) and arterial (incidence: 1,482/105 person-years) thrombosis at HA, respectively. The ICs had enhanced coagulation (FVIIa: p<0.001; FXa: p<0.001) and decreased levels of natural anticoagulants (thrombomodulin, p=0.016; tissue factor pathway inhibitor [TFPI]: p<0.001) and a trend to dampened fibrinolysis (tissue plasminogen activator tPA; p=0.078) compared to CG. ICs also exhibited statistically significant increase in the levels of endothelial dysfunction and inflammation markers (vascular cell adhesion molecule-1[VCAM-1], intercellular adhesion molecule-1 [ICAM-1], vascular endothelial growth factor receptor 3 [VEGFR-3], P-Selectin, CD40 ligand, soluble C-reactive protein and myeloperoxidase: p<0.001). Interpretation: The incidence of thrombosis in healthy subjects at HA was higher than that reported in literature at near sea-level. This was associated with inflammation, endothelial dysfunction, a prothrombotic state and dampened fibrinolysis. Funding: Research grants from the Armed Forces Medical Research Committee, Office of the Director General of Armed Forces Medical Services (DGAFMS) & Defence Research and Development Organization (DRDO), Ministry of Defence, India.

High-altitude pulmonary oedema: Newer treatment modalities for an age-old problem.

Background & objectives: High-altitude pulmonary oedema (HAPE) continues to challenge the healthcare providers at remote, resource-constrained settings. High-altitude terrain itself precludes convenience of resources. This study was conducted to evaluate the rise in peripheral capillary saturation of oxygen (SpO2) by the use of a partial rebreathing mask (PRM) in comparison to Hudson's mask among patients with HAPE. Methods: This was a single-centre, randomized crossover study to determine the efficiency of PRM in comparison to Hudson's mask. A total of 88 patients with HAPE referred to a secondary healthcare facility at an altitude of 11,500 feet from January to October 2013 were studied. A crossover after adequate wash-out on both modalities was conducted for first two days of hospital admission. All patients with HAPE were managed with bed rest and stand-alone oxygen supplementation with no adjuvant pharmacotherapy. Results: The mean SpO2on ambient air on arrival was 66.92±10.8 per cent for all patients with HAPE. Higher SpO2values were achieved with PRM in comparison to Hudson's mask on day one (86.08±5.15 vs. 77.23±9.09%) and day two (89.94±2.96 vs. 83.39±5.93%). The difference was more pronounced on day one as compared to day two. Interpretation & conclusions: Mean SpO2values were found to be significantly higher among HAPE patients using PRM compared to those on Hudson's mask. Further studies to understand the translation of this incremental response in SpO2to clinical benefits (recovery times, mortality rates and hospital stay) need to be undertaken.

Is it time to revise the acclimatization schedule at high altitude? Evidence from a field trial in Western Himalayas.

BACKGROUND: In Western Himalayas, Indian Army soldiers take 11 days (6 days of acclimatization and 5 days of travel) on a sea-level to high altitude road (SH road) to reach a high altitude location (HAL) situated at an altitude of 11,500 feet from sea-level location (SLL) at an altitude of 1150 feet while following acclimatization schedule (AS). AS has an extra safety margin over the conventional 'mountaineering thumb rule' of not exceeding 500 m sleeping altitude above 3000 m altitude. We carried out this randomised field trial to study the feasibility of moving large number of troops rapidly from SLL to HAL on SH road in western Himalayas in 4 days under pharmaco-prophylaxis. METHODS: Based on the pharmaco-prophylaxis, at SLL 508 healthy lowland soldiers were divided into two groups: 'A' (n = 256) with Acetazolamide + Dexamethasone and 'B' (n = 252) with Acetazolamide + Placebo. They travelled rapidly by road to HAL in 4 days and prevalence of acute mountain sickness (AMS), high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE) during the ascent was measured. RESULTS: Prevalence of AMS was found to be 1.56% and 1.59% in group 'A' and group 'B' respectively during the ascent with no cases of HAPE and HACE. CONCLUSION: At least on SH road, troops can be inducted rapidly to HAL from SLL in 4 days under pharmaco-prophylaxis with Acetazolamide with minimal occurrence of acute high altitude illnesses.

Anthropometric evaluation of school-going native highlanders (4-19 years of age) from the Leh-Ladakh region in India.

BACKGROUND: The native population of the Ladakh region faces the unique challenges of a high-altitude environment with distinct physiological adaptations in comparison with lowlanders. However, no comprehensive data on standard anthropometric parameters for the school-going children in this populace is available. OBJECTIVES: We aimed to study the various anthropometric parameters in the school-going native highlander population and computed measures of central tendency. The nutritional status of the community was also be determined by comparing with World Health Organization (WHO) scores for height for age (HFA), weight for age (WFA) and body mass index (BMI) for age. DESIGN: A cross-sectional, descriptive study was devised to assess the anthropometric parameters. We measured height, weight, mid-upper circumference (MUAC), triceps skinfold (TSF) thickness, sub-scapular skinfold (SSF) thickness, waist, hip and abdominal circumference. Statistical analysis was conducted to determine the mean [±2 standard deviation (SD)], median, range, minimum and maximum. The z-scores for HFA, WFA and BMI for age was computed using WHO reference data. SUBJECTS: A total of 346 school-going native highlander children (4-19 years of age) were studied. RESULTS: Among the study population, the mean height was 141.17 ± 39.08 cm, the mean weight was 38.27 ± 25.40 kg. The gender difference in height, MUAC, sub-scapular skinfold (SSF) thickness, TSF thickness and the abdominal circumference was found to be statistically significant. Of the subjects 23.46% were stunted (i.e. HFA below -2 SD of the WHO standard) and 7.01% were underweight (WFA below -2 SD of the WHO standard). CONCLUSION: The nutritional status of the Ladakhi population was assessed by comparison with the WHO reference data. Nomograms for anthropometric data in school-going children (4-19 years of age) of Ladakh were created. These can be used for further studies and planning targeted intervention strategies on this geographically isolated and evolutionary distinct highland population.

Comparison of Optic Nerve Sheath Diameter between both eyes: A Bedside Ultrasonography Approach.

CONTEXT: Optic nerve sheath diameter (ONSD) has long been accepted as a reliable proxy of intracranial pressure especially in critical care and bedside settings. The present consensus is to measure ONSD in both eyes and take average value, which is cumbersome and a potential cause of discomfort to the patient. AIM: We aim to compare the values of ONSD of the right and left eye in a random sample as measured by bedside ocular ultrasonography (USG) in Indian adults. SETTINGS AND DESIGN: This was a prospective study conducted from September 2012 to March 2013 in the Department of Internal Medicine of a tertiary care hospital situated at moderate high altitude (11,500 ft) in India. MATERIALS AND METHODS: Patients admitted with high altitude pulmonary edema (HAPE) were recruited by convenience sampling. The ONSD of both eyes were measured 3 mm behind the globe using a 7.5 MHz linear probe on the closed eyelids of supine subjects. STATISTICAL ANALYSIS: Analysis was done using SPSS 17.0. RESULTS: A total of 47 patients of HAPE were recruited to the study with daily ONSD recording of both eyes during the admission period. The mean ONSD of the left eye was 4.60 (standard deviation [SD] = 0.71) whereas the mean ONSD of right eye 4.59 (SD = 0.72). The ONSD of the right eye and left eye was strongly correlated (correlation coefficient = 0.98 with P < 0.0001). The mean difference in the ONSD of both eyes (right-left) was -0.0044 (SD = 0.11) which was not statistically significant (P = 0.533). CONCLUSION: Our results suggest that the difference in ONSD of both eyes is not statistically significant in disease or health. This study also suggests that the ONSD of either eye can be predicted by the other eye recordings. Based on these findings, it can be suggested that during ocular USG for routine bedside/research purposes it is sufficient to measure ONSD of any of the one eye to save time and avoid discomfort to the patient.

Acute mountain sickness amongst tourists to Lhasa.

Acute mountain sickness is the commonest acute high altitude illness occurring at high altitude. Its prevalence is dependent on the ascent rate, altitude achieved, physical effort required to reach the target altitude and pharmacological intervention undertaken by the tourists visiting high altitude areas. This Letter to the Editor is an endeavour to re-emphasise the importance of all these factors affecting the prevalence of acute mountain sickness.

Managing High-Altitude Pulmonary Edema with Oxygen Alone: Results of a Randomized Controlled Trial.

Yanamandra, Uday, Velu Nair, Surinderpal Singh, Amul Gupta, Deepak Mulajkar, Sushma Yanamandra, Konchok Norgais, Ruchira Mukherjee, Vikrant Singh, Srinivasa A. Bhattachar, Sagarika Patyal, and Rajan Grewal. High-altitude pulmonary edema management: Is anything other than oxygen required? Results of a randomized controlled trial. High Alt Med Biol. 17:294-299, 2016.-Treatment strategies for management of high-altitude pulmonary edema (HAPE) are mainly based on the observational studies with only two randomized controlled trials, thus the practice is very heterogeneous and individualized as per the choice of treating physician. To compare the response to different modalities of therapy in patients with HAPE in a randomized controlled manner. We conducted an open-label, randomized noninferiority trial to compare three modalities of therapy (Therapy 1: supplemental O2 with oral dexamethasone 8 mg q8 hours [n = 42], Therapy 2: supplemental O2 with sustained release oral nifedipine 20 mg q8 hours [n = 41], and Therapy 3: only supplemental O2 [n = 50]). Bed rest was mandated in all patients. The study was conducted in a cohort of previously healthy young lowlander males at an altitude of 3500 m. Baseline characteristics of the patients were comparable in the study arms. Complete response was defined as clinical and radiological resolution of features of HAPE, no oxygen dependency, a normal 6-minute walk test (6MWT) on 2 consecutive days, and normal two-dimensional echocardiography. Results were compared by analysis of variance using SPSS version 16.0. There was no statistical difference in duration of therapy to complete response between the three groups (Therapy 1: 8.1 ± 4.0 days, Therapy 2: 6.7 ± 3.9 days, Therapy 3: 6.8 ± 3.2 days; p = 0.15). There were no deaths in any of the groups. We conclude that oxygen and bed rest alone are adequate therapy for HAPE and that adjuvant pharmacotherapy with either dexamethasone or nifedipine does not hasten recovery.

Pulmonary Embolism in Young Natives of High Altitude.

Thrombotic events are relatively common in high altitude areas and known to occur in young soldiers working at high altitude without usual risk factors associated with thrombosis at sea-level. However, till now, cases with thrombotic events were reported only in lowlanders staying at high altitude. These two cases of pulmonary embolism demonstrate that thrombotic events can occur in highlanders after a prolonged stay at the extreme altitude.