In the second part of his review of mountain sickness, Jeremy Windsor outlines diagnoses and treatment options
The worrying combination of vague symptoms, limited access to tests and the poten tial for other conditions often makes mountain sickness difficult to diagnose. Unfortunately, people with high-altitude illnesses can deteriorate quickly, so it makes good sense to follow the dictum, ‘It’s a high altitude illness until proven otherwise’. In the last issue of SIB(February 2007), I explained how and when high-altitude illness might strike. In this article I will deal with the diagnosis and treatment of the three main illnesses that affect newcomers to altitude. Each begins with a description of a case that I have been involved with, followed by an outline of the treatment options currently avail able. Although fatalities are rare at altitude, healthy people continue to die in mountainous regions from high-altitude illnesses. Early recognition and treatment of these conditions can make an enormous difference.
Acute mountain sickness (AMS)
The Kilimanjaroo party Four teenage members of a Duke of Edinburgh Award expedition were attempting the Marangu route on the Tanzanian mountain, Kilimanjaroo (5,895m). Setting off late from the park entrance (1,600m), the group reached Mandara Hut (2,740m) in just under three hours. After a poor night’s sleep, the next morning all four complained of headache, loss of appetite and tiredness. All were assumed to have AMS and treated with a combination of parac- etamol (1g every six hours) and acetazolamide (125mg every 12 hours). After two days’ rest the group was able to continue and all successfully reached the summit.
The symptoms described by these young men are consistent with a number of conditions: dehydration, exhaustion or even a collective hangover could present in this way! Nevertheless their rapid ascent and their alti tude gained strongly suggested the possi bility of AMS.
In order to avoid the condition, it’s worth following local advice. On Kilimanjaroo guides and porters will greet you with the words, ‘pole, pole’, Swahili for ‘slowly, slowly’. As mentioned in part 1 of this feature, most cases of AMS can be prevented by ascending no more than 400m a day, taking rest days every fourth day and avoiding heavy exercise for at least 24 hours after arrival at a new alti tude. For those who still suffer from AMS, medications such as acetazolamide (Diamox) and the corticosteroid dexamethasone can be taken, either to prevent the onset of symp toms or to manage them once they appear.
Acetazolamide works by encouraging the excretion of bicarbonate in the urine, temporarily correcting the alkaline state that is present in the blood of trekkers and moun taineers at altitude. This change prompts an increase in both the depth and frequency of breathing and an increase in the amount of oxygen delivered to the body’s tissues. Until recently it was not clear what dose of aceta zolamide was appropriate to prevent AMS. However, work by the Nepali high-altitude expert Buddha Basnyat has shown that a dose of 125mg taken twice a day is as effec tive in reducing the incidence of AMS as higher doses of the drug.
In trekkers reaching Lobuche (4,928m) on the Everest Base Camp trek, the incidence of AMS fell from 51% in those taking placebo treatment to 24% (125mg) and 21% (375mg) in those taking acetazolamide(2).
Acetazolamide is also effective in treating the symptoms of AMS once they appear. In the studies done so far, doses of between 250mg and 1,500mg given over 24 hours have been shown to improve AMS symptoms in those who ascend to altitudes of up to 5,500m(3). While the mechanism of action of aceta zolamide is now well understood, little is known about the way dexamethasone works on AMS. Nevertheless, it is a highly effective medication capable of preventing and treating AMS. In 4mg doses taken every six hours, dexamethasone dramatically reduces the severity and incidence of AMS after a rapid ascent to altitudes above 4,000m(4), and an initial dose of 8mg followed by 4mg doses every six hours has been shown to improve symptoms in those who develop AMS on arrival at 4,559m(3).
However effective these drugs are, they are not a panacea. If you develop AMS at alti tude, you are still faced with two important decisions: when should you use the drugs, and perhaps more importantly, when should you descend?
During the 1990s a scoring system was developed to help answer this question. Over the course of a number of meetings at the Canadian ski resort, Lake Louise, experts chose five symptoms and three clinical find ings that, when added together, reflected the severity of an individual’s AMS (see Tables 1a and 1b, above rigth).
Unfortunately this is where the science stops. For a given score of 3, 5 or 10, no one can tell you confidently what is going to happen next. Of course, high scores are very uncomfortable and probably increase your risk of serious complications such as HAPE and HACE. However, a score of 3 (which qualifies for a diagnosis of AMS) can be managed by a combination of rest, fluids and over-the-counter painkillers.
Many experts will try this approach first before making the decision to descend. But if symptoms persist, I would strongly advise descending to a point where they resolve, and a period of rest for 24 hours before climbing again. In these circumstances acetazolamide and dexamethasone may be used. However, their effects may be temporary and the symp toms may return swiftly once you cease the medication. Wherever possible rely upon natural acclimatisation and ascend ‘pole, pole’.
Both AMS medications have a number of side effects (see Table 2, below right). The catalogue of possible side-effects, together with the popularity of ‘natural reme dies’, has led to the increasing use of ‘herbal’ treatments such as ginkgo biloba in AMS. But trials with gingko biloba have shown that, despite its popularity, it is of no or little benefit in preventing or treating AMS(6). With aceta zolamide and dexamethasone now firmly established as safe and effective treatments, the use of alternatives is best avoided.
High-altitude pulmonary oedema
Aconcagua descent On descending from the summit of the Argentinean mountain Cerro Aconcagua (6,962m), a young female climber became increasingly tired and breathless. On arriving back at Camp 2 (5,700m) she began to cough up blood-stained sputum and complained of pain in her chest. On examination at rest she was found to have a respiratory rate of 44, a heart rate of 142 and an arterial oxygen saturation of 65%. A diagnosis of HAPE was made and 20mg of nifedipine SR given. With her friends carrying her equipment, she was able to descend to Plaza Argentina Base Camp (4,200m). The next morning she was evacuated by helicopter to the local hospital. After two days of treatment she was given the ‘all clear’ and discharged home.
In recent years, AMS sufferers in general have benefited from a large number of exper iments and drug trials. But when it comes to HAPE, the victims have to rely upon a much smaller body of evidence for their treatment. This is largely the result of two factors: only small numbers of HAPE victims have been available to researchers; and the life-threat ening nature of the disease has made it diffi cult to justify the use of unproven medications.
In order to overcome these factors, a number of researchers have identified indi viduals who are either resistant to HAPE or have been previously diagnosed with the condition. Many of these have subsequently been selected to undertake experiments at the Campana Regina Margherita high alti tude research facility in the Swiss Alps.
Situated at 4,559m, the facility is home to doctors and researchers throughout the summer months and provides comprehen sive medical treatment for those who fall ill. Importantly, rapid descent to lower altitudes can be undertaken either on foot or by a rescue helicopter that lands nearby. Researchers from the University of Heidelberg, led by Peter Bärtsch and Marco Maggiorini, were the first to show that nifedipine 20mg, a calcium channel blocker, can successfully prevent and treat HAPE episodes in HAPE-susceptible volunteers who ascended to the facility.
Nifedipine works by relaxing the layers of smooth muscle that surround arteries and subsequently reduces blood pressure. In those suffering from HAPE, pressure in the pulmonary arteries rises dramatically, causing damage to the fragile alveolar-capil lary membrane and the accumulation of fluid in the alveoli. By reducing pulmonary artery pressure, nifedipine decreases the inci dence of HAPE from 63% to 10% in HAPE susceptible volunteers(7).
More recently, experiments at the Campana Regina Margherita have shown that the increase in pulmonary artery pres sure seen in HAPE may be directly connected to the sharp fall in nitric oxide production that is commonly seen in HAPE susceptible volunteers. At high altitude, levels of nitric oxide fall in all of us; however, in those with HAPE, this process is exagger- ated. Treating HAPE victims with nitric oxide gas (a dose of 40 parts per million) rapidly reduces pulmonary artery pressure and improves oxygen delivery to the tissues.
Although bottled nitric oxide gas is not a practical option on a mountainside, an unlikely alternative is available: Viagra. Sildenafil (Viagra) and other phosphodiesterase-5 inhibitors prevent the breakdown of nitric oxide and cause a marked rise in nitric oxide concentrations in the lungs. Sildenafil (40mg every eight hours) reduces pulmonary artery pressures and increases arterial oxygen satu ration in healthy volunteers taken to 4,350m(8). Tadalafil (10mg every 12 hours) reduces the incidence of HAPE from 74% to 10% in HAPE-susceptible volunteers who ascend to the research facility in less than 24 hours(9).
Although nifedipine and phosphodi- esterase-5 inhibitors lower pulmonary artery pressure and reduce damage to the alveolar capillary membrane, neither has a signifi cant effect upon the fluid that collects in the damaged lung. In HAPE-susceptible volun- teers, exposure to altitude is associated with a marked reduction in the concentration and activity of apical membrane sodium chan- nels (ENaC). These channels are largely responsible for clearing fluid from the alveoli, and, when damaged, contribute to the forma- tion of HAPE. At altitude, ENaC activity can be increased by the use of long-acting beta-2 agonists such as salmeterol, which are used in the treatment of asthma. Given via an inhaler (125mcg every 12 hours), salmeterol has been shown to decrease the incidence of HAPE from 74% to 33% in HAPE-susceptible volunteers.
These results are highly encouraging. Agents such as tadalafil and salmeterol are safe, practical and, above all, effective in preventing HAPE. What we do not know is how well they work to treat HAPE once it has developed at altitude. Until further trials have been under- taken, the use of these drugs alongside conven- tional treatments remains speculative.
High-altitude cerebral oedema On top of Cho Oyu
From the summit of the Tibetan giant Cho Oyu (8,201m), a team of British moun taineers spotted a lone figure moving slowly and unsteadily towards them. Realising he was in difficulty, they descended quickly and found him lying face down in the snow. On closer inspection they discovered he had lost his gloves and sunglasses, and was so confused he was unable to answer simple questions. A diagnosis of HACE was made and an injection of dexamethasone 8mg administered. Eventually he was helped down to Camp 3 (7,400m), where he was met by his team mates. On returning to Advanced Base Camp (5,650m) three days later, he was found to have no memory of the incident. Despite making a full recovery from HACE, he eventually lost four fingers from frostbite.
Those suffering from HAPE and HACE are balanced on a knife- dge: without prompt treatment, victims can quickly deteriorate and sometimes die. Although dexamethasone and acetazolamide are commonly used to treat HACE, the main priority is to descend.
On the Nepali side of Mt Everest, Base Camp is situated at 5,400m. At this altitude the atmospheric pressure is 50% of its sea level value. As Table 3 shows, a fall in atmos pheric pressure results in a similar reduction in the amount of oxygen that is available. By descending rapidly, both the atmospheric pressure and availability of oxygen quickly rise and life- threatening symptoms resolve.
Many of those stricken with HAPE or HACE are often unable to walk and need to be carried down or rescued by helicopter. At Everest Base Camp this can lead to consid erable delays. In the meantime two thera- peutic options are available that increase the amount of oxygen available and simulate a temporary ‘descent’:
Supplemental oxygen:breathing supple mental oxygen from either a face mask or nasal prongs increases the fraction of inspired oxygen (FiO2) available and the amount of oxygen delivered to the body’s tissues. At present a number of ‘open’ oxygen systems are available for high altitude use, based on the ‘Hudson mask’ design commonly seen in hospitals and in the homes of those who require supplemental oxygen. On the moun- tainside, these devices allow HAPE or HACE victims to breathe a mixture of pure oxygen and air from the atmosphere. Depending upon the chosen flow rate (normally 2 to 4 l/min) and the breathing pattern of the sufferer, the ‘open system’ can increase the FiO2 to values of between 25% and 35%.
Portable Hyperbaric Chamber: commonly known as the ‘Gamow bag’, these devices consist of a rigid, cylindrical air-tight tube and a foot pump. Victims are zipped inside the chamber and air is pumped in. Unlike supplemental oxygen, which increases the FiO2, the Gamow Bag increases the baro metric pressure inside the chamber. The results are the same: an increase in the pres sure of inspired oxygen and a ‘reduction’ in the altitude to which the victim is exposed.
The benefits that can be gained from supplemental oxygen and portable hyper- baric chambers tend to disappear within a few hours once the patient is removed from the oxygen-rich environment. In cases of life threatening high-altitude illness, the only definitive cure is descent.
Although AMS, HAPE and HACE can be avoided by ascending slowly and minimising heavy exercise, high-altitude illnesses can still occur. It is therefore vital to be able to recog nise their signs and symptoms and be aware of the treatment options available. Assume high-altitude illness until proven otherwise!
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2Basnyat, B et al (2006) ‘Acetazolamide 125mg BD is not significantly different from 375mg BD in the prevention of acute mountain sickness: the prophylactic acetazolamide dosage comparison for efficacy (PACE) trial’. High Alt. Med. Biol. Spring;7(1):17-27.
3Bärtsch, P and Roach, RC (2001) ‘Acute mountain sickness and high altitude cerebral oedema’. In: High altitude – An Exploration of Human Adaptation. Eds: Hornbein TF, Schoene, RB. New York: Marcel Dekker. p731-76.
4Bernhard WN et al (1998) ‘Acetazolamide plus low-dose dexamethasone is better than acetazolamide alone to ameliorate symptoms of acute mountain sickness’. Aviat. Space Environ. Med. Sep;69(9):883-6.
5Roach RC et al (1993) ‘The Lake Louise acute mountain sickness scoring system’. In: Hypoxia and Mountain Medicine. Eds: JR Sutton, CS Houston and G Coates. Burlington: Queen City Printers, p 272-4.
6Bartsch, P et al (2004) ‘Acute mountain sickness: controversies and advances’. High Alt. Med. Biol. Summer;5(2):110-124.
7 Maggiorini, M (2006) ‘High altitude-induced pulmonary oedema’.Cardiovasc. Res.Oct 1;72(1):41- 50.
8Richalet J-P et al (2005) ‘Sildenafil inhibits altitude-induced hypoxaemia and pulmonary hypertension’. Am. J Respir. Crit. Care Med.Feb 1;171(3):275-81.
9Maggiorini, M et al (2006) ‘Both tadalafil and dexamethasone may reduce the incidence of high altitude pulmonary oedema: a randomized trial’. Ann. Intern. Med. Oct 3;145(7):497-506.
10 Sartori C et al (2002) ‘ Salmeterol for the prevention of high altitude pulmonary oedema’. New Engl. J Med.346:1631-6.