Srinivasa Bhattachar

In Response to Risk Determinants of Acute Mountain Sickness by Lawrence and Reid

To the Editor: We recently read with profound interest the article titled “Risk Determinants of Acute Mountain Sickness and Summit Success on a 6-Day Ascent of Mount Kilimanjaro (5895 m)” by Lawrence and Reid. Authors of the present study have reported a lower incidence of acute mountain sickness (AMS) (52.6% with Lake Louise Score Z3) during a 6-day ascent of Mount Kilimanjaro than described in earlier studies on 4and 5-day ascents. This incidence of AMS is seen in spite of the fact that 88% of the trekkers were taking acetazolamide to prevent AMS. Presentation of a detailed evaluation of the temporal profile of acetazolamide intake by the trekkers, such as the location along the ascent route when chemoprophylaxis was initiated and stopped, could have aided understanding of the reasons for the lower incidence of AMS and thus led to a wider future application of the findings of the study. Acetazolamide is known to be effective, ideally if started 1 day before ascent in a dosage of 125 mg twice daily, and it should be continued for 2 to 3 days after target altitude has been achieved. In the present study, to avoid extreme altitude exposure to subjects, trekkers did not spend much time at the summit. The descent of trekkers would have lasted for a few hours, and the expedition doctor would have taken their Lake Louise Score after their return to the base camp (4730 m). This could have added to a recall bias, especially in the background of a possible disturbed sleep during the night of day 5 as all trekkers would have woken early in the morning of day 6 before attempting the summit. As physiologists working in the field of high-altitude medicine, we were interested in knowing the details of physical activity undertaken by the participants during the trek, such as average ascent/descent rate, especially on day 6. Amount of physical activity, rate of ascent, and actual altitude reached are known to affect the incidence of AMS. Also, 1 participant was diagnosed with high altitude pulmonary edema (HAPE) at 2900 m on day 2 and was treated with dexamethasone. We were interested to learn if this patient was experiencing concomitant AMS/high altitude cerebral edema. As per Wilderness Medical Society consensus guidelines, dexamethasone is indicated for prevention of HAPE in a susceptible subject and prevention/treatment of AMS and high altitude cerebral edema. Recommendations on its use for treatment of HAPE has been graded weak with low or very low quality evidence.

Comment on “Soluble Urokinase-Type Plasminogen Activator Receptor Plasma Concentration May Predict Susceptibility to High Altitude Pulmonary Edema”

We read with profound interest the article titled “Soluble Urokinase-Type Plasminogen Activator Receptor Plasma Concentration May Predict Susceptibility to High Altitude Pulmonary Edema” by Hilty et al. [1]. The authors have concluded that soluble urokinase-type plasminogen activator receptor (suPAR) plasma concentration measured before hypoxic exposure may predict susceptibility of a lowlander to high altitude pulmonary edema (HAPE). Despite the fact that inflammation is associated with acute hypoxia exposure in both HAPE and acute mountain sickness (AMS), studying these two high altitude illnesses together in the same cohort in this study seems to be convoluted. AMS and HAPE are known to have pathophysiological processes involving central nervous system and cardiopulmonary systems, respectively, with hypoxia being the common triggering factor [2]. This has also been indirectly acknowledged by the authors, while suggesting that cellular based inflammation does not play a role in the central form of high altitude disease, comprising AMS and high altitude cerebral edema. Moreover, occurrence of HAPEmay not always be associated with AMS [3]. Though the role of inflammation in priming pulmonary endothelium towards hypoxia-related pulmonary edema is well established, the study of the biomarker with respect to AMS is intriguing. Acute hypoxia exposure is associated with sympathetic activation, which results in rise in heart rate (HR) [4]. However, on the contrary as per Table 1 of the study, in dexamethasone prophylaxis group of HAPE susceptible subjects (n = 10), HR was found to decrease from their sea level HR of 74/min to 68/min after hypoxia exposure. As physiologists with experience of working in high altitude physiology, we contemplate if use of dexamethasone in these individuals resulted in these changes. HAPE is a disease known to occur two or more days after exposure to altitudes above 3000m [5]. However, subjects in this study were assessed for HAPE after 24 hours of hypoxia exposure at Margherita Hut (4559m), and an insignificant difference was seen in suPAR levels of HAPE susceptible and nonsusceptible individuals. Subjects were given dexamethasone 24 hours after hypoxia exposure as part of another research project. Otherwise serial measurements of suPAR in clinical overt HAPE subjects, if any, occurring over next 4 days of observation could have helped in establishing suPAR as a possible biomarker for HAPE susceptibility.The outcome of the bigger research project, of which the present work is a part, will definitely be worth a wait, which might mark the end of the pursuit of a well-established biomarker for a potentially fatal but preventable disease like HAPE.

Risk of high altitude pulmonary edema and telomere length

We read with profound interest the article entitled ‘Telomere length‐ related gene ACYP2 polymorphism is associated with the risk of HAPE in Chinese Han population’ by He et al., which reports a significant association between two single nucleotide polymorphisms (SNPs), rs12615793 and rs11896604, and a decreased risk of high altitude pulmonary edema (HAPE). A total of 568 Han Chinese lowlanders (265 HAPE patients and 303 healthy controls) from Northwest China were included in the study group. It was noted that HAPE was diagnosed on the basis of standard criteria, which included patient interviews such as cough, dyspnea and cyanosis at rest, as well as imaging examinations such as X‐ray, computed tomography or magnetic resonance imaging of the chest. All HAPE cases were found to have confirmed radiological findings suggestive of HAPE. Clinically, HAPE is diagnosed by the presence of at least two symptoms (dyspnea at rest, cough, weakness or decreased exercise performance, chest tightness or congestion) or at least two signs (rales or wheezing in at least one lung field, central cyanosis, tachypnea, tachycardia) in the setting of a recent gain in altitude. It would have been appropriate for He et al. to have also included other important parameters (e.g. heart rate and respiratory rate) required for the diagnosis of HAPE so that their results could be compared with other genetic studies carried out on HAPE. He et al. reported that none of the subjects of control group (who had same ascent rate and altitude as achieved by the HAPE cases) developed signs and symptoms of HAPE within 7 days of exposure to high altitude. The basis of choosing a ‘7‐day’ period of observation for the control group is not clear because HAPE is known to occur mostly 2–4 days after reaching an altitude of 3000 m or more. It would also have been appropriate for the timing of appearance of the symptoms of HAPE to have been included in their study. HAPE is classified into various grades, varying from mild to severe, based on clinical profile, X‐ray findings and objective criteria such as heart rate and respiratory rate. Although not within the scope of the

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.

Delayed-onset high-altitude pulmonary edema

A 28-year-old male with no co-morbid illness was admitted to our hospital (located at a height of ∼11,500 ft) with complaints of breathlessness and cough associated with pinkish sputum. He denied history of fever and chest pain. He was inducted to high-altitude area (height ∼11,500 ft) 4 months back. General examination revealed the following: temperature 98°F, blood pressure 106/82 mm Hg, pulse rate 106/min, respiratory rate 24/min, and oxygen saturation 64% at room air and 96% on oxygen inhalation. Chest auscultation revealed bilateral diffuse crepts. Arterial blood gas analysis on room air suggested severe type-I respiratory failure (pH: 7.443, PaO2: 28.1, PaCO2: 33.0). Electrocardiogram showed no significant abnormality. Chest radiograph showed bilateral diffuse confluent alveolar opacities [Figure 1]. Hematological investigation revealed hemoglobin of 13.4 g/dl and total leukocyte count of 15,400/cm3 with neutrophil predominance (81%). Based on clinical and radiological parameters, he was diagnosed to have high-altitude pulmonary edema (HAPE). Detailed history disclosed that he had features of upper respiratory tract infection 1 week back and over-exerted on the day of admission, which could be the risk factors for HAPE in this individual after prolonged stay in a high-altitude area. He was managed with bed rest and high-fl ow oxygen inhalation to which he responded well clinically as well as radiologically as was evident in repeat chest radiograph done after 36 h [Figure 2].

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.

Management of HAPE with bed rest and supplemental oxygen in hospital setting at high altitude (11,500 ft): A review of 43 cases

Objectives: To evaluate the safety and efficacy of treating high-altitude pulmonary edema (HAPE) by bed rest and supplemental oxygen in hospital setting at high altitude. Materials and Methods: In a prospective case series, all patients who were diagnosed clinically with HAPE on admission to our hospital located at a height of 11,500 ft were evaluated and managed with bed rest and oxygen supplementation. Results: A total of 43 patients of HAPE with mean age of 31 years (range 20–48 years) were admitted to our hospital. Infections followed by unaccustomed physical exertion were the predominant risk factors. 95.35% of the patients improved successfully with oxygen and bed rest alone with mean hospital stay of 2.67 ± 1.06 (1–6 days). Two patients (4.65%) required nifedipine and evacuation to lower altitude. Of this, one patient suffering from concomitant viral infection expired 4 days after evacuation to near sea level. Conclusion: Majority of the patients with HAPE where medical facilities are available can be safely treated with bed rest and oxygen supplementation at moderate high altitude without descent.

ROCK2 and MYLK variants and high-altitude pulmonary edema

© 2016 Sikri and Bhattachar. This work is published by Dove Medical Press Limited, and licensed under a Creative Commons Attribution License. The full terms of the License are available at http://creativecommons.org/licenses/by/4.0/. The license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Acute mountain sickness and duration of pre-exposure to high altitude.

We recently read the article ‘Short-term high-altitude pre-exposure improves neurobehavioral ability’ by Guo et al. [1] with profound interest. In this field study with a large sample size, the authors have showed that a short-term pre-exposure (4 days) at 3700 m elicits a greater effect compared with a long-term pre-exposure (3-month) in improving human neurobehavioral parameters, including mood states and cognitive performance, and reducing acute mountain sickness (AMS) at an altitude of 4400 m. The authors evaluated mood states, cognitive performance, and AMS at 400, 3700 m (on the 4th day of the exposure), and 4400 m (on the 10th day of exposure) in participants.

Chemokines in High Altitude Pulmonary Edema.

To the Editor We read the article titled ‘‘Hypoxia-induced inflammatory chemokines in subjects with a history of high-altitude pulmonary edema’’ by Mishra et al. [1] with profound interest. Indeed hypoxia exposure whether, in vitro or in vivo, is associated with rise in inflammatory markers. However, in the previous studies, as also quoted in the article by the authors, the duration of hypoxia exposure varied from 16 to 72 h [2–5] On the contrary, in the present study duration of simulated hypoxia of 4500 m was only 30 min. It remains obscure that those changes seen in the chemokines are actually the result of hypoxia induced inflammation or otherwise. The baseline values of all chemokines (MIP-1a, MCP-1 and IL-8) in HAPE-S group were found to be higher compared to control group. It would be nice to know if any inclusion/exclusion criteria were applied for selection of subjects to control for confounders like presence of common infections or bronchial asthma which might contribute to higher levels of chemokines [6]. There was considerable variation in the values of chemokines among subjects of HAPE-S group. We would like to know if data regarding time elapsed since previous episode of HAPE was collected, which might possibly explain the variation in baseline and exposure values of chemokines in the HAPE-S group. Authors of the present study have compared SpO2 levels in subjects susceptible and resistant to high pulmonary edema (HAPE) but have inadvertently missed out the comparison of respiratory rate (RR) and heart rate (HR) in them. Differences in these two parameters among participants of the two groups would have clarified variations of compensatory mechanisms in response to hypoxia among the HAPES group compared to control group. Thus reporting of RR and HR could have elucidated further the findings of this study as tachypnoea and tachycardia are two important signs which form the diagnostic criteria for HAPE [7]. In HA medicine, HAPE is not considered a severe form of acute mountain sickness (AMS) as mentioned by the authors. HAPE and AMS are two distinguished forms of high altitude illnesses with hypoxia as a common causative agent. HAPE can also occur without any symptoms of AMS [8]. Also, HAPE is not limited to only genetically susceptible individuals as they are the ones who report their illness earlier than the general population. Essentially all healthy people are vulnerable to HAPE [9]. In fact during Operation Everest II, after a rapid ascent to 6100 m in a chamber all the seven participants developed HAPE [10]. Occurrence of overt or clinical form of HAPE is dependent on quantum of hypoxia exposure (altitude achieved), rate of ascent, duration of hypoxia exposure and amount of physical activity undertaken at that altitude by the individual [9].Therefore, assuming that an individual resistant to HAPE at 3400 m will not suffer from it at 4500 m seems to be an anomaly. Possibly, results of the present study could have been very interesting if chemokine levels were studied in these individuals after exposure to simulated hypoxia equivalent to 3400 m for a longer duration (like 24 h) as clinical HAPE is known to occur after an exposure to hypoxia of 2 or more days after an ascent to altitudes above 3000 m [11]. This comment refers to the article available at doi:10.1007/s12291015-0491-3.