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Tadalafil and Acetazolamide Versus Acetazolamide for the Prevention of Severe High-Altitude Illness
Abstract
We report an open-label study comparing tadalafil and acetazolamide (n = 24) versus acetazolamide (n = 27) for prevention of high-altitude illness (HAI) at Mt. Kilimanjaro. Tadalafil group had lower rates of severe HAI compared with controls (4% vs 26%, p = 0.03), mostly because of decreased high-altitude pulmonary edema rates (4% vs 22%, p = 0.06).
... Pretreatment with 10 mg of tadalafil has been shown to protect against HAPE (reducing incidence by 78%) in those who are susceptible by attenuating rises in PAP [117]. Newer research is in agreement with these earlier works demonstrating reductions in the incidence of HAPE with tadalafil [118]. ...
... Sildenafil may be appropriate for AMS and HACE prophylaxis based on its ability to increase cerebral oxygenation [119]. Tadalafil may have the potential to reduce cerebral specific AMS scores; however, it may also increase the potential of headache [110,118,120,121]. Consequently, more research is needed to clarify whether PDE-5 inhibitors can be used to prevent and treat AMS an HACE. ...
Introduction: The physiological responses on exposure to high altitude are relatively well known, but new discoveries are still being made, and novel prevention and treatment strategies may arise. Basic information has changed little since our previous review in this journal 10 years ago, but considerable more detail on standard therapies, and promising new approaches are now available.
Areas covered: Herein, the authors review the role of pharmacological agents in preventing and treating high-altitude illnesses. The authors have drawn on their own experience and that of international experts in this field. The literature search was concluded in March 2018.
Expert opinion: Slow ascent remains the primary prevention strategy, with rapid descent for the management of serious altitude illnesses. Pharmacological agents are particularly helpful when rapid ascent cannot be avoided or when rapid descent is not possible. Acetazolamide remains the drug of choice for prophylaxis of acute mountain sickness. However, evidence indicates that reduced dosage schemes compared to the current recommendations are warranted. Calcium channel blockers and phosphodiesterase inhibitors remain the drugs of choice for the management of high-altitude pulmonary edema. Dexamethasone should be reserved for the treatment of more severe cases of altitude illnesses such as cerebral edema.
... Acclimatization is the most effective prophylaxis, but pharmacological prophylaxis may be more practical, especially in the military population, who often lack time for acclimatization. Aspirin, ibuprofen, acetaminophen, and acetazolamide are all effective for HAH prophylaxis [20][21][22][23][24]. HAH is typically self-limited, but supplemental oxygen rapidly dissipates symptoms [20]. ...
... Treatment consists of descent, oxygen therapy, diuretics, and vasodilators [38,39]. Nifedipine is accepted as the first-line drug for treatment for HAPE, although phosphodiesterase-5 inhibitors may be effective for HAPE treatment and prophylaxis [22,38]. The Indian military has a large highaltitude contingency and has developed simplified criteria for diagnosing HAPE [40]. ...
Purpose of Review
High-altitude combat and medical evacuation pose special challenges to military operations. We aim to summarize the physiologic changes that occur at altitude, as well as review the altitude-related diseases with emphasis on the impact on the military population. Finally, the impact of high-altitude exposure during transportation of combat trauma will be reviewed.
Recent Findings
There is increasing awareness that high-altitude exposure has an impact on mission readiness and could place mission success at risk. High-altitude headache and acute mountain sickness have affected warfighters in both training and combat. Prophylaxis of altitude illness with acetazolamide has been shown to reduce symptoms of altitude exposure; dexamethasone is utilized for the same purpose.
Though not without risk, long-range high-altitude transport of critically ill trauma and medical patients has been found to be safe and effective.
Summary
Hypobaric hypoxia is the primary driving force behind the physiologic effects altitude has on the human body. When combined with the stress of combat and AE, altitude can pose a difficult obstacle when caring for critically ill patients. Awareness of altitude-related disease and its impact when caring for non-altitude-related illness is a crucial component of optimizing healthcare to wounded warriors.
... There are few studies evaluating the effects of tadalafil on healthy athletes [27,[53][54][55]. Many studies have been conducted on subjects with pathologies or who are in conditions of extreme physiological stress [56][57][58][59][60][61][62][63]. Recently, using a similar group of subjects, we have demonstrated that a single dose of tadalafil did not substantially influence performance indicators, during a maximal standardized exercise test in a healthy athlete [27]. ...
Background: The phosphodiesterase type 5 inhibitor (PDE5I) tadalafil, in addition to its therapeutic role, has shown antioxidant effects in different in vivo models. Supplementation with antioxidants has received interest as a suitable tool for preventing or reducing exercise-related oxidative stress, possibly leading to the improvement of sport performance in athletes. However, the use/abuse of these substances must be evaluated not only within the context of amateur sport, but especially in competitions where elite athletes are more exposed to stressful physical practice. To date, very few human studies have addressed the influence of the administration of PDE5Is on redox balance in subjects with a fitness level comparable to elite athletes; therefore, the aim of this study was to investigate for the first time whether acute ingestion of tadalafil could affect plasma markers related to cellular damage, redox homeostasis, and blood polyamines levels in healthy subjects with an elevated cardiorespiratory fitness level. Methods: Healthy male volunteers (n = 12), with a VO2max range of 40.1–56.0 mL/(kg × min), were administered with a single dose of tadalafil (20 mg). Plasma molecules related to muscle damage and redox-homeostasis, such as creatine kinase (CK), lactate dehydrogenase (LDH), total antioxidant capacity (TAC), reduced/oxidized glutathione ratio (GSH/GSSG), free thiols (FTH), antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)), as well as thiobarbituric acid reactive substances (TBARs), protein carbonyls (PrCAR), and polyamine levels (spermine (Spm) and spermidine (Spd)) were evaluated immediately before and 2, 6 and 24 hours after the acute tadalafil administration. Results: A single tadalafil administration induced an increase in CK and LDH plasma levels 24 after consumption. No effects were observed on redox homeostasis or antioxidant enzyme activities, and neither were they observed on the oxidation target molecules or polyamines levels. Conclusion: Our results show that in subjects with an elevated fitness level, a single administration of tadalafil induced a significant increase in muscle damage target without affecting plasma antioxidant status.
... Além disso, recomenda-se dois dias de aclimatização antes de se envolver em exercício extenuante em altitudes elevadas. (29,30) Vários estudos já demonstraram que a ingestão de líquidos abaixo de 2 litros em 24 horas é um importante fator de risco para o surgimento da cefaleia das alturas. (11,28) Por isso, a hidratação adequada é sugerida como requisito crítico de desempenho em altitude. ...
Objetivo: Esta revisão objetivou investigar o papel da água como fator agravante ou atenuante nas cefaleias. Método: Pesquisou-se a literatura referente ao papel da água nas cefaleias nas principais bases de dados médicas (LiLacs, SciELO, Bireme, Scopus, EBSCO e PubMed). Resultados: A privação de água ocasiona uma inusitada cefaleia denominada cefaleia por privação de água, além de ser um gatilho dos ataques de migrânea. Por outro lado, a ingestão de água é fator de melhora das seguintes cefaleias secundárias: cefaleia pós-punção dural, cefaleia das grandes altitudes e cefaleia da ressaca. Conclusões: A privação de água pode ser considerada um gatilho dos ataques de cefaleia, mas sua ingestão é fator atenuante.
... Kilimanjaro. Both intervention and control groups began study medication on day 3. [25] The carbonic anhydrase inhibitor acetazolamide is the mainstay for the prevention and treatment of acute mountain sickness (AMS) and high-altitude cerebral edema. ...
... Tadalafil once daily was found to improved exercise capacity and reduced time to clinical worsening in patients suffering from pulmonary arterial hypertension (PAH); offering an alternative to Sildenafil as well [21]. Finally, combining tadalafil with acetazolamide, rather than taking acetazolamide alone, can be an even more effective method for the prevention of some conditions [22]. Dosing of sildenafil is less restrictive in cases of compromised renal function. ...
Dihydropyridine calcium channel blockers (CCB) are typically used agents in the clinical management of hypertension. Yet, they have also been utilized in the treatment of various pulmonary disorders with vasoconstriction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been implicated in the development of vasoconstrictive, proinflammatory, and pro-oxidative effects.
A retrospective review was conducted on CCB use in hospitalized patients in search of any difference in outcomes related to specific endpoints: survival to discharge and progression of disease leading to intubation and mechanical ventilation. The electronic medical records for all patients that tested positive for SARS-CoV-2 that were at or above the age of 65 and that expired or survived to discharge from a community hospital in Brooklyn, NY, between the start of the public health crisis due to the viral disease up until April 13, 2020, were included.
Of the 77 patients that were identified, 18 survived until discharge and 59 expired. Seven patients from the expired group were excluded since they died within one day of presentation to the hospital. Five patients were excluded from the expired group since their age was above that of the eldest patient in the survival group (89 years old). With 65 patients left, 24 were found to have been administered either amlodipine or nifedipine (CCB group) and 41 were not (No-CCB group).
Patients treated with a CCB were significantly more likely to survive than those not treated with a CCB: 12 (50%) survived and 12 expired in the CCB group vs. six (14.6%) that survived and 35 (85.4%) that expired in the No-CCB treatment group (P<.01; p=0.0036). CCB patients were also significantly less likely to undergo intubation and mechanical ventilation. Only one patient (4.2%) was intubated in the CCB group whereas 16 (39.0%) were intubated in the No-CCB treatment group (P<.01; p=0.0026).
Nifedipine and amlodipine were found to be associated with significantly improved mortality and a decreased risk for intubation and mechanical ventilation in elderly patients hospitalized with COVID-19. Further clinical studies are warranted. Including either nifedipine or amlodipine in medication regimens for elderly patients with hypertension hospitalized for COVID-19 may be considered.
... Headache is a common adverse reaction to phosphodiesterase 5 inhibitors such as tadalafil and sildenafil. However, they can be useful in the treatment of high altitude induced pulmonary edema by reducing pulmonary hypertension [23,24]. ...
Purpose of Review
High altitude headache is a common neurological symptom that is associated with ascent to high altitude. It is classified by the International Classification of Headache Disorders, 3rd Edition (ICHD-3) as a disorder of homeostasis. In this article, we review recent clinical and insights into the pathophysiological mechanisms of high altitude and airplane headache. We also report a second case of post-LASIK myopic shift at high altitude exposure secondary hypoxia. Headache attributed to airplane travel is a severe typically unilateral orbital headache that usually improves after landing. This was a relative recent introduction to the ICHD-3 diagnostic criteria. Headache pain with flight travel has long been known and may have been previously considered as a part of barotrauma. Recent studies have helped identify this as a distinct headache disorder.
Recent Findings
Physiologic, hematological, and biochemical biomarkers have been identified in recent high altitude studies. There have been recent advance in identification of molecular mechanisms underlying neurophysiologic changes secondary to hypoxia. Calcitonin gene–related peptide, a potent vasodilator, has been implicated in migraine pathophysiology. Recent epidemiological studies indicate that the prevalence of airplane headache may be more common than we think in the adult as well at the pediatric population. Simulated flight studies have identified potential biomarkers.
Summary
Although research is limited, there have been advances in both clinical and pathophysiological mechanisms associated with high altitude and airplane headache.
... Fosfódíesterasa-hemlarnir tadalafíl og síldenafíl virðast hafa svipuð áhrif og nífedipín. 59 Með því að hamla fosfódíesterasa verður meira framboð af níturoxíði (NO) í lungnaslagaeðum sem veldur útvíkkun þeirra án þess að hafa áhrif á kerfisblóðþrýsting. Langvirkur beta-viðtakaörvi, salmeteról, hefur verið gefinn í innúðaformi í haerri skömmtum en notaðir eru við meðferð lungnasjúkdóma eins og astma og lungnateppu. ...
Upon reaching a height over 2500 m above seal level symptoms of altitude illness can develop over 1 - 5 days. The risk is mainly -determined by the altitude and rate of ascent and the symptoms vary. Most common are symptoms of acute mountain illness (AMS) but more dangerous high altitude cerebral edema (HACE) and high altitude pulmonary edema (HAPE) can also develop. The causes of AMS, HACE and HAPE are lack of oxygen and insufficient acclimatization, but the presenting form is determined by the responses of the body to the lack of oxygen. The most common symptoms of AMS include headache, fatique and nausea, but insomnia and nausea are also common. The most common symptoms of HAPE are breathlessness and lassitude whereas the cardinal sign of HACE is ataxia, but confusion and loss of consciousness can also develop. In this article all three main forms of altitude illness are reviewed. The emphasis is on preventive measures and treatment but new knowledge on pathogenesis is also addressed.
... Epidemiological studies have been conducted in the Himalayas (Basnyat et al., 2000;Vardy et al., 2006), the Alps (Mairer et al., 2009(Mairer et al., , 2010, the Rocky Mountains (Honigman et al., 1993), Mt. Kilimanjaro (Leshem et al., 2012), and Mt. Fuji (Horiuchi et al., 2016) on the association between the prevalence of AMS and relevant factors. ...
Aims:
We sought to investigate the factors influencing acute mountain sickness (AMS) on Mt. Fuji in Japan, in particular, to assess the effects of sleeping altitude, by means of a questionnaire survey. This study involved 1932 participants who climbed Mt. Fuji, and obtained information regarding sex, age, and whether participants stayed at the mountain lodges. The AMS survey excluded the perceived sleep difficulties assessed with the Lake Louise Scoring (LLS) system for all climbers.
Results:
The overall prevalence of AMS was 31.6% for all participants (LLS score ≥3 with headache, excluding sleep difficulties). A univariate analysis revealed that overnight stay at Mt. Fuji was associated with an increased prevalence of AMS, but that sex and age were not. For overnight lodgers, the mean sleeping altitude in participants with AMS was slightly higher than that in participants without AMS (p < 0.05). Moreover, participants who stayed above 2870 m were more likely to experience AMS than those who stayed below 2815 m (p < 0.001), but sex and age were not significantly associated with the probability of experiencing AMS.
Conclusions:
Staying overnight at a mountain lodge, especially one above 2870 m, may be associated with an increased prevalence of AMS on Mt. Fuji.
... There are also a few peri-travel HAI studies in this journal with experimental designs, including one RCT 24 and one non-randomized quasiexperimental trial. 25 Finally, there is also one systematic review on the effectiveness of acetazolamide in the prevention of AMS 26 based on the meta-analysis of seventeen peri-travel RCTs previously published in various journals. Overall, the majority of studies on HAI published in this journal was conducted in the field rather than before or after travel. ...
This Editorial refers to the article by Chan et al. (10.1093/jtm/tav008)
Current travel medicine literature seems to rely heavily on lower quality cross-sectional observational studies1 and descriptive case reports and case series2 for a large part of our body of knowledge. However, the field of travel medicine provides a unique opportunity for conducting good quality research using longitudinal observational (i.e. case control,3 prospective and retrospective cohort4), quasi-experimental5 or experimental study designs.6 Unlike many exposures that lead to various disease or health outcomes in other areas of medicine (e.g. cardiovascular risk factors leading to disease outcomes that take decades to occur), the ecology of travel medicine is naturally designed with a pre-, peri- and post-travel phase occurring over a relatively short period of time (e.g. within weeks, months or a few years). Figure 1 illustrates the various designs that can be used to study various research questions affecting travel medicine practice.
Figure 1.
Main research designs to study travel medicine with examples in the study of acute HAI
Certainly, time and funding are key barriers to publishing applied research for many regular full-time and busy practitioners.7 However, it is not clear why we continue to submit poor quality and underpowered studies8 in greater quantities compared with better quality larger longitudinal studies of travel medicine (Steffen et al .9 speak of such study weakness regarding vaccine preventable diseases). After all, we have that natural advantage of the pre-, peri- and post-exposure sequential periods occurring over a manageable duration that reduces the risk of various selection and information biases such as attrition in cohort studies or recall bias in case control studies.10 There is no good reason for travel medicine to avoid better quality studies; including randomized clinical trials (RCTs) using low-cost measuring tools (e.g. …
*To whom correspondence should be addressed Suite 1024, 710-20 Crowfoot Crescent NW, Calgary, Alberta, Canada T3G 2P6. Email: calgarytraveldoctor{at}gmail.com
... More and more studies were concerned on the prophylaxis and therapy of AMS. [8][9][10][11] Nitric oxide (NO) is a gaseous signaling molecule that participates in a large variety of physiological functions and may have a role in the pathology of altitude illnesses, such as acute mountain sickness (AMS). 12) It plays an important role in people's adaptation to high altitude hypoxia. ...
Nitric oxide (NO) may act as either a pro-oxidant or an antioxidant in biological systems. Previous work has found inhalation of NO improved survival in a high altitude rat model. NO donor isosorbide mononitrate derivants might have a protective effect against hypoxia. We synthesized a series of isosorbide mononitrate derivant compounds to test their anti-hypoxia activities. Normobaric hypoxia and hypobaric hypoxia models were used to study the protective role of NO donor in mice. The results showed isosorbide mononitrate derivants had protective effects in hypoxia mice. Among those compounds, acetyl ferulic isosorbide mononitrate (AFIM) was the most effective. It prolonged the survival time during the normobaric hypoxia test. It decreased malondialdehyde (MDA) and H2O2 in hypobaric hypoxia mice. The antioxidase activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) remained in normal ranges in the AFIM group. As a sign of mitochondrial dysfunction, the activities of ATPase were down regulated in mice under hypobaric hypoxia conditions. AFIM also protected ATPase activities. The protective effects of AFIM might come from a sustained NO supply and the release of acetyl ferulic acid with anti-oxidant activity.
... 62,63 A recently published meta-analysis as well as a clinical trial comparing the effectiveness of tadalafil and acetazolamide versus acetazolamide alone strongly support the effectiveness of acetazolamide at a dose of 250 mg per day as an effective AMS prophylaxis. [64][65][66] Acetazolamide and low-dose sustained-release theophylline both appear to act by increasing central stimulation of respiratory drive, 67,68 and both improve sleep-disordered breathing. There are insufficient data to advocate prevention with hypnotic agents alone or in combination with other drugs. ...
Millions of tourists and climbers visit high altitudes annually. Many unsuspecting and otherwise healthy individuals may get sick when sojourning to these high regions. Acute mountain sickness represents the most common illness, which is usually benign but can rapidly progress to the more severe and potentially fatal forms of high-altitude cerebral edema and high-altitude pulmonary edema.
Data were identified by searches of Medline (1965 to May 2012) and references from relevant articles and books. Studies, reviews, and books specifically pertaining to the epidemiology, prevention, and treatment of high-altitude illnesses in travelers were selected.
This review provides information on geographical aspects, physiology/pathophysiology, clinical features, risk factors, and the prevalence of high-altitude illnesses and also state-of-the art recommendations for prevention and treatment of such illnesses.
Given an increasing number of recreational activities at high and extreme altitudes, the general practitioner and specialist are in higher demand for medical recommendations regarding the prevention and treatment of altitude illness. Despite an ongoing scientific discussion and controversies about the pathophysiological causes of altitude illness, treatment and prevention recommendations are clearer with increased experience over the last two decades.
Mountain climbing is associated with many risky, life-threatening situations. One of the most common attacking diseases at altitudes above 2500 m is altitude disease (HAI). This disease consists of: acute alpine disease, cerebral oedema and pulmonary oedema at altitude. The best way to prevent altitude diseases is by means of alcomatisation and slow increase in altitude. Climbers should follow the principle "climb high, sleep low". Sometimes, however, time or inability to descend do not allow for acclimatization. In such conditions, it is necessary to use pharmaceuticals that prevent the occurrence of an illness of altitude. The following article discusses research on the most commonly used drug in the prevention of acute mountain disease - acetazolamide. This drug was first used in the 60s of the XX century, demonstrating its effectiveness in the prevention of mountain disease. Since then, it has been the subject of many studies.
Introduction
Phosphodiesterase type 5 (PDE5) hydrolyses cyclic guanylate monophosphate specifically to 5′ guanylate monophosphate, promoting corporeal vascular relaxation and penile erection in response to sexual stimulation. Oral PDE5 inhibitors (PDE5-Is) have afforded effective and well-tolerated treatment for erectile dysfunction. In addition, PDE5-Is have stimulated academic and clinical interest for their potential benefits in diverse non-sexual applications.
Aim
To highlight possible potential non-sexual implications of PDE5-Is.
Methods
A systematic review was conducted until January 2016 based on a search of all relevant articles in Medline Medical Subject Heading, Scopus, Cochrane Library, EMBASE, and CINAHL databases without language restriction. Key words used to assess outcome and estimates for the relevant associations were PDE5 inhibitors, sildenafil, tadalafil, vardenafil, and avanafil.
Main Outcome Measures
Different non-sexual implications for PDE5-Is.
Results
PDE5-Is demonstrated beneficial effects in different medical applications with possible widespread implications for cardiovascular, pulmonary, cutaneous, gastrointestinal, urogenital, cellular, musculoskeletal, neurologic, and reproductive disorders. However, most applications were carried out experimentally in preclinical studies of off-label indications.
Conclusion
PDE5-Is are a conceptually attractive therapeutic class of agents with pleiotropic effects. Exploring PDE5-Is for their possible implications seems to be valuable in different medical disorders. However, well-designed clinical trials are needed before these agents can be recommended for selected applications.
Mostafa T. Non-Sexual Implications of Phosphodiesterase Type 5 Inhibitors. Sex Med Rev 2017;5:170–199.
High-altitude headache is one of many neurological symptoms associated with the ascent to high altitudes. Cellular hypoxia due to decreased barometric pressure seems to be the common final pathway for headache as altitude increases. Susceptibility to high-altitude headache depends on genetic factors, history of migraine, and acclimatization, but symptoms of acute mountain sickness are universal at very high altitudes. This review summarizes the pathophysiology of acute mountain sickness and high-altitude headache as well as the evidence for treatment and prevention with different drugs and devices which may be useful for regular and novice mountaineers. This includes an examination of other headache disorders which may mimic high-altitude headache.
High-altitude pulmonary edema (HAPE) is a lethal, noncardiogenic form of pulmonary edema that afflicts susceptible individuals after rapid ascent to high altitude above 2,500 m. Prevention of HAPE is achieved most effectively by gradual ascent allowing time for proper acclimatization. Certain prophylactic medications may further reduce the risk of ascending to high altitude in individuals with a prior history of HAPE. The most effective and reliable treatment of HAPE is immediate descent and administration of supplemental oxygen.
High altitude headache (HAH) has been defined by the International Headache Society as a headache that appears within 24 hours after ascent to 2,500 m or higher [1••]. The headache can appear in isolation or as part of acute mountain sickness (AMS), which has more dramatic symptoms than the headache alone. If symptoms are ignored, more serious conditions such as high altitude cerebral edema (HACE), high altitude pulmonary edema (HAPE), or even death may ensue. While there is no definitive understanding of the underlying pathophysiologic mechanism, it is speculated that HAH occurs from the combination of hypoxemia-induced intracranial vasodilation and subsequent cerebral edema. There are a number of preventive measures that can be adopted prior to ascending, including acclimatization and various medications. A variety of pharmacological interventions are also available to clinicians to treat this extremely widespread condition.
Although it is best to prevent acute mountain sickness (AMS) 1 by gradual ascent without using any drugs, this may not always be an option in many settings. Rescuers may need to go up rapidly to high altitudes; or logistically, owing to a lack of camp site, it may not be possible for trekkers and climbers to spend the night at an optimal altitude. Furthermore, airports in places like Lhasa, Tibet (3,490 m) and La Paz, Bolivia (4,058 m) may cause travelers to arrive at high altitude without the ability to acclimatize en route. Some people who are predisposed to AMS may be protected by taking a prophylactic drug while ascending high altitudes. Many, such as pilgrims, often disregard strongly delivered advice about gradual ascent in their single‐minded determination to ascend the sacred site. 2 In addition, there is a fast‐growing population of climbers in pursuit of a summit who are being advised by physicians to use prophylactic medicine to both improve performance and achieve summit success. Poor knowledge and lack of awareness of side effects may lead to widespread misuse of drugs. Finally, sudden military deployment to high altitude regions of the world, such as the Hindu Kush mountains in Afghanistan, may necessitate drug prophylaxis for the prevention of AMS. Two articles 3,4in the present issue deal with the use of acetazolamide at high altitude in the …
Corresponding Author: Buddha Basnyat, MD, MSc, FACP, FRCP (E), Nepal International Clinic, Lal Durbar Marg, GPO Box 3596, Kathmandu, Nepal. E‐mail: rishibas{at}wlink.com.np
The aim of this study was to evaluate the prevalence of acute mountain sickness (AMS) among trekkers on Mount Kilimanjaro during the winter season of 2006-2007. A A total of 130 Finnish trekkers at Marungu route were asked to complete daily a Lake Louise self-report and clinical assessment score questionnaire with the help of a trainee Finnish guide during their trek to Kilimanjaro. A Lake Louise questionnaire score>or=3 indicated AMS. Altogether 112 mountaineers or travelers [54 men, 58 women, mean age 51+/-10 (SD) years] were studied. Fifty-nine travelers (53%) reached Gillman's Point or Uhuru Peak. The incidence of AMS among Finnish Kilimanjaro trekkers was 75%. The most common high altitude symptoms were headache, followed by sleeping problems and fatigue or weakness. The incidence of AMS is high among trekkers climbing Mount Kilimanjaro.The main reason for this seems to be rapid ascent. Kilimanjaro treks normally have a fixed timetable, and for commercial reasons there is little opportunity to spend extra days for acclimatization in the camps. Some contributing factors are preventable, so we recommend an educational program for all the trekking agencies that guide on this peak and, in particular, the Tanzania-based guiding agencies, which, typically, are driving these very fast ascent rates.
High-altitude pulmonary edema (HAPE) is caused by exaggerated hypoxic pulmonary vasoconstriction associated with decreased bioavailability of nitric oxide in the lungs and by impaired reabsorption of alveolar fluid.
To investigate whether dexamethasone or tadalafil reduces the incidence of HAPE and acute mountain sickness (AMS) in adults with a history of HAPE.
Randomized, double-blind, placebo-controlled study performed in summer 2003.
Ascent from 490 m within 24 hours and stay for 2 nights at 4559 m.
29 adults with previous HAPE.
Prophylactic tadalafil (10 mg), dexamethasone (8 mg), or placebo twice daily during ascent and stay at 4559 m.
Chest radiography was used to diagnose HAPE. A Lake Louise score greater than 4 defined AMS. Systolic pulmonary artery pressure was measured by using Doppler echocardiography, and nasal potentials were measured as a surrogate marker of alveolar sodium transport.
Two participants who received tadalafil developed severe AMS on arrival at 4559 m and withdrew from the study; they did not have HAPE at that time. High-altitude pulmonary edema developed in 7 of 9 participants receiving placebo and 1 of the remaining 8 participants receiving tadalafil but in none of the 10 participants receiving dexamethasone (P = 0.007 for tadalafil vs. placebo; P < 0.001 for dexamethasone vs. placebo). Eight of 9 participants receiving placebo, 7 of 10 receiving tadalafil, and 3 of 10 receiving dexamethasone had AMS (P = 1.0 for tadalafil vs. placebo; P = 0.020 for dexamethasone vs. placebo). At high altitude, systolic pulmonary artery pressure increased less in participants receiving dexamethasone (16 mm Hg [95% CI, 9 to 23 mm Hg]) and tadalafil (13 mm Hg [CI, 6 to 20 mm Hg]) than in those receiving placebo (28 mm Hg [CI, 20 to 36 mm Hg]) (P = 0.005 for tadalafil vs. placebo; P = 0.012 for dexamethasone vs. placebo). No statistically significant difference between groups was found in change in nasal potentials and expression of leukocyte sodium transport protein messenger RNA.
The study involved a small sample of adults with a history of HAPE.
Both dexamethasone and tadalafil decrease systolic pulmonary artery pressure and may reduce the incidence of HAPE in adults with a history of HAPE. Dexamethasone prophylaxis may also reduce the incidence of AMS in these adults. ClinicalTrials.gov identifier: NCT00274430.
Background: High-altitude pulmonary edema (HAPE) is caused by exaggerated hypoxic pulmonary vasoconstriction associated with decreased bioavailability of nitric oxide in the lungs and by impaired reabsorption of alveolar fluid. Objective: To investigate whether dexamethasone or tadalafil reduces the incidence of HAPE and acute mountain sickness (AMS) in adults with a history of HAPE. Design: Randomized, double-blind, placebo-controlled study performed in summer 2003. Setting: Ascent from 490 m within 24 hours and stay for 2 nights at 4559 m. Patients: 29 adults with previous HAPE. Intervention: Prophylactic tadalafil (10 mg), dexamethasone (8 mg), or placebo twice daily during ascent and stay at 4559 m. Measurements: Chest radiography was used to diagnose HAPE. A Lake Louise score greater than 4 defined AMS. Systolic pulmonary artery pressure was measured by using Doppler echocardiography, and nasal potentials were measured as a surrogate marker of alveolar sodium transport. Results: Two participants who received tadalafil developed severe AMS on arrival at 4559 m and withdrew from the study; they did not have HAPE at that time. High-altitude pulmonary edema developed in 7 of 9 participants receiving placebo and 1 of the remaining 8 participants receiving tadalafil but in none of the 10 participants receiving dexamethasone (P = 0.007 for tadalafil vs. placebo; P < 0.001 for dexamethasone vs. placebo). Eight of 9 participants receiving placebo, 7 of 10 receiving tadalafil, and 3 of 10 receiving dexamethasone had AMS (P = 1.0 for tadalafil vs. placebo; P = 0.020 for dexamethasone vs. placebo). At high altitude, systolic pulmonary artery pressure increased less in participants receiving dexamethasone (16 mm Hg [95% Cl, 9 to 23 mm Hg]) and tadalafil (13 mm Hg [Cl, 6 to 20 mm Hg]) than in those receiving placebo (28 mm Hg [Cl, 20 to 36 mm Hg]) (P = 0.005 for tadalafil vs. placebo; P = 0.012 for dexamethasone vs. placebo). No statistically significant difference between groups was found in change in nasal potentials and expression of leukocyte sodium transport protein messenger RNA. Limitations: The study involved a small sample of adults with a history of HAPE. Conclusions: Both dexamethasone and tadalafil decrease systolic pulmonary artery pressure and may reduce the incidence of HAPE in adults with a history of HAPE. Dexamethasone prophylaxis may also reduce the incidence of AMS in these adults.
The incidence of acute mountain sickness can be reduced by ascending slowly to altitude. We compared a recommended ascent rate with those offered by commercial companies to three of the most popular high-altitude destinations in the world. While the majority complied with the recommended ascent rate, ascents on Kilimanjaro did not.
To determine the incidence of acute mountain sickness (AMS), the frequency of summiting success, and the factors that affect these in trekkers on Kilimanjaro, one of the world's most summitted high-altitude peaks.
The study group comprised 312 trekkers attempting Mt Kilimanjaro summit by the Marango Route. Trekkers ascended over 4 or 5 days along a fixed ascent profile, stopping at 3 huts on ascent (2700 m, 3700 m, and 4700 m) before attempting the summit. Researchers were stationed at each hut for 16 days. Each night we measured heart rate, respiratory rate, blood pressure, oxygen saturation, and Lake Louise Score. We recorded the highest altitude that trekkers reached on the mountain.
Of 181 complete sets of data, 111 (61%) trekkers reached the summit, and 139 (77%) developed AMS. Physiological results were not related to summit success. The incidence of AMS and summiting success were similar in those on the 4- or 5-day route. Trekkers on the 5-day route who used acetazolamide were less likely to develop AMS and more likely to summit than were those not taking acetazolamide (P = <.05); this difference was not present with trekkers on the 4-day route.
The risk of developing AMS is high on Mt Kilimanjaro. Although taking an extra day to acclimatize with the use of acetazolamide did provide some protection against AMS, ideally trekkers need a more gradual route profile for climbing this mountain.
Trekking in Nepal is a popular adventure travel activity involving more than 80,000 people of all ages annually. This study focuses on the demographic characteristics and clinical course of altitude illness patients evacuated to Kathmandu and estimates the rates of evacuation in different regions of Nepal.
During the years 1999 to 2006, all patients who presented with altitude illness to the CIWEC clinic in Kathmandu were evaluated and included in the study if the final diagnosis was compatible with high-altitude cerebral edema (HACE), high-altitude pulmonary edema (HAPE), or acute mountain sickness (AMS). Altitude illness-related deaths were reported according to death certificates issued by selected embassies in Kathmandu.
A total of 406 patients were evaluated, among them 327 retrospectively and 79 prospectively. HACE was diagnosed in 21%, HAPE in 34%, combined HAPE and HACE in 27%, and AMS in 18%. Mean patient age was older than trekker controls (44 +/- 13.5 vs 38.6 +/- 13.9 y, p < 0.0001). Everest region trekkers were more likely to be evacuated for altitude illness than trekkers in other regions. The estimated incidence of altitude illness-related death was 7.7/100,000 trekkers. Most altitude illness symptoms resolved completely within 2 days of evacuation.
Altitude illness that results in evacuation occurs more commonly among trekkers in the Everest region and among older trekkers. The outcome of all persons evacuated for altitude illness was uniformly good, and the rate of recovery was rapid. However, the incidence of altitude illness-related death continued to rise over past decade.
Pulmonary function abnormalities after exercise are suggestive of pulmonary edema; however, radiographic evidence is lacking. Well-trained cyclists were studied to determine whether there is radiographic evidence of pulmonary edema after endurance exercise (cycling distance 5.3-131.5 km) at altitude. Chest radiographs obtained before exercise were coded for later interpretation. Films obtained after exercise were coded with a different number. A total of 74 sets of posteroanterior and lateral films were analyzed by three radiologists for signs of pulmonary edema. Radiographic changes were graded on a three-point scale. An edema score was calculated by summing the score for each individual radiographic finding for each radiologist and an overall edema score representing the mean scores from all three radiologists. The overall edema score increased from 0.8 +/- 1.2 before exercise to 1.8 +/- 1.6 after exercise (P < 0.01). These results suggest that, after prolonged high-intensity exercise at moderate altitude, there is radiographic evidence of early pulmonary edema in some cyclists.
To examine the effects of extreme altitude mountaineering on glycaemic control in Type 1 diabetes, and to establish whether diabetes predisposes to acute mountain sickness (AMS).
Fifteen people with Type 1 diabetes and 22 nondiabetic controls were studied during the Diabetes Federation of Ireland Expedition to Kilimanjaro. Daily insulin requirements, blood glucose estimations and hypoglycaemic attacks were recorded in diaries by the people with diabetes. The performance of blood glucose meters at altitude was assessed using standard glucose solutions. Symptoms of acute mountain sickness were recorded daily by people with diabetes and by the nondiabetic controls using the Lake Louise Scoring Charts. The expedition medical team recorded the incidence of complications of altitude and of diabetes. The final height attained for each individual was recorded by the expedition medical team and verified by the expedition guides.
The final altitude ascended was lower in the diabetic than the nondiabetic group (5187 +/- 514 vs. 5654 +/- 307 m, P = 0.001). The mean daily insulin dose was reduced from 67.1 +/- 28.3-32.9 +/- 11.8 units (P < 0.001), but only 50% of recorded blood glucose readings were within the target range of 6-14 mmol/L. There were few hypoglycaemic attacks after the first two days of climbing. Both blood glucose meters tested showed readings as low as 60% of standard glucose concentrations at high altitude and low temperatures. The Lake Louise questionnaires showed that symptoms of AMS occurred equally in the diabetic and nondiabetic groups. There were two episodes of mild diabetic ketoacidosis; two of the diabetic group and three of the nondiabetic group developed retinal haemorrhages.
People with Type 1 diabetes can participate in extreme altitude mountaineering. However, there are significant risks associated with this activity, including hypoglycaemia, ketoacidosis and retinal haemorrhage, with the additional difficulties in assessing glycaemic control due to meter inaccuracy at high altitude. People with Type 1 diabetes must be carefully counselled before attempting extreme altitude mountaineering.
Acute mountain sickness (AMS) may be an early stage of high altitude cerebral edema. If so, AMS could result from an alteration of dynamic autoregulation of cerebral blood flow resulting in overperfusion of capillaries and vasogenic cerebral edema.
We measured middle cerebral artery blood flow velocity (Vmca) by transcranial Doppler and arterial blood pressure by finger plethysmography at 490 m and 20 hours after arrival at 4559 m in 35 volunteers who had been randomized to tadalafil, dexamethasone, or placebo in a study on the pharmacological prevention of high altitude pulmonary edema. A dynamic cerebral autoregulation index (ARI) was calculated from continuous recordings of Vmca and blood pressure during transiently induced hypotension.
Altitude was associated with an increase in a cerebral-sensible AMS (AMS-C) score (P<0.001) and with a decrease in arterial oxygen saturation (Sao2), whereas average Vmca or ARI did not change. However, at altitude, the subjects with the lowest ARI combined with the lowest Sao2 presented with the highest AMS-C score (P<0.03). In addition, a stepwise multiple linear regression analysis on arterial Pco2, Sao2, and baseline or altitude ARI identified altitude ARI as the only significant predictor of the AMS-C score (P=0.01). The AMS-C score was lower in dexamethasone-treated subjects compared with high altitude pulmonary edema-susceptible untreated subjects. Neither tadalafil nor dexamethasone had any significant effect on Vmca or ARI.
High altitude hypoxia is associated with impairment in the regulation of the cerebral circulation that might play a role in AMS pathogenesis.
Deaths due to high altitude illness among tourists climbing Mt Kilimanjaro. Proceedings of the 2004 South African Travel Medicine Society
- M Hauser
- A Mueller
- B Swai
Hauser M, Mueller A, Swai B, et al. Deaths due to high altitude illness among tourists climbing Mt Kilimanjaro. Proceedings of the 2004 South African Travel Medicine Society; 2004; Cape Town, South Africa.