Should I Use Diamox to Prevent Acute Mountain Sickness When Climbing?

April and May is the time for trekkers in the Himalayas. I ventured off to Everest Base Camp, during prep there were many discussions about whether climbers should take Acetazolamide / Diamox. So what’s the science, and what did I do?

Should I Use Diamox to Prevent Acute Mountain Sickness When Climbing?

So, first things first, before we start trying to prevent a problem, we need to know about the issue. What is acute mountain sickness and perhaps more importantly is it something climbers really need to care about?

Given by the number of warning signs in the various villages and settlements that I’ve seen on the way up to Everest Base Camp…

Yup, caring about AMS is probably one of those things which would be, what’s the word? Sensible!

Particularly so as the Golden Rule which is reinforced at every medical station, by every expedition medic and every mountain guide worth their wage is very simple: Any medical issue is Acute Mountain Sickness until proven otherwise

Any medical issue is Acute Mountain Sickness until proven otherwise

What is Acute Mountain Sickness

Erm… That is. On my first summiting of Mt Kilimanjaro! So other than me looking as sick as a dog what is actually going on with AMS?

Acute sickness or Altitude Mountain Sickness as it is sometimes known as a syndrome which may affect climbers above 2500m. Not everyone is going to develop AMS, but likelihood rises along with the height of the peak you are aiming for. I’ve heard some people say you are not going to be looking down on the clouds, then you are really not at risk.

This is, with the kindest tone – rubbish. Although I can see where that thought process has come from, even on Ben Nevis, the highest point in the UK, you can end up looking down at the fluffy stuff, but at 1344m AMS isnt a worry.

Acute Moutain Sickness is when we are talking about high mountains. We know that about 1 in 10 climbers will be affected when they reach 3500m, but ramps quite dramatically, by 4500m altitude 3 out of 4 climbers will be affected.

AMS is thought to occur as a result of high pressures in the brain, resulting in poor oxygenation of its tissues. The brain kind of has this thing about needing oxygen, it tends to get a little grumpy without it, resulting in the symptoms that can be observed in AMS:

• Headache and one of the following:
  • Dizziness,
  • Nausea,
  • Tiredness,
  • Lost appetite,
  • Shortness of breath,
  • Insomnia.

Again here is me, proving the point on Mt Kilimanjaro – been doing very well on the walk until arriving at Barafu Hut camp, at 4645m, and what do you know, by evening I could tick off all six symptoms!

HOWEVER none of those symptoms on their own is massively worrying, basically, AMS is a really unpleasant hangover. So why is there such a stress about it? For one, when climbing, you ARE in a dangerous region, and being dizzy, tired, not eating, will increase your risks of having an accident, which could result in an expensive taxi ride home

When on the mountain, ANYTHING is AMS until proven otherwise. If a climber had fallen and broken their arm, that is AMS until proven otherwise – did they fall and break the arm as a result of being dizzy from AMS? Thing begin to make sense

But AMS, is only the start of the story, this can take a turn for the worse and progress to a condition called High Altitude Cerebral Oedema, which is a life-threatening condition with a more severe symptom list

• Severe headache,
• Confusion,
• Vomiting,
• Loss of balance

All symptoms which on their own can be quite dangerous when climbing, regardless of the fact that your brain is now getting squeezed by fluid building up inside your head

What Causes AMS?

AMS happens because the air is thin, ie. less oxygen going in per breath than normal, leading to climbers breathing harder than normal. The percentage of oxygen in the air remains constant – 21%, but it is the partial pressure of oxygen which falls. Pretty much in a straight line as you climb. So if we say that at sea level the atmospheric pressure is 100%, by 5500m above sea level (Everest base camp) you’ll be getting 50% less oxygen per breath. Which you see as a decrease in oxygen saturation in the blood.

On the Garmin Fenix 5 Plus above, you can see in the upper RIGHT that we’re at 4880m, and on the Masimo Mightysats probe, the amount of oxygen in my blood is down from the normal, healthy 98-100%, to a slightly unpleasant 86%

Surely the answer is the same as when you are running? You need more oxygen, so you breathe harder. Makes sense. But in that situation, your muscles are having to work hard (assuming you aren’t slacking on your run) and producing additional carbon dioxide, the waste gas of metabolism.

But when you are walking along at altitude, you are breathing harder, due to lower atmospheric pressure, breathing out lots of CO2 as well, so where is the issue?

Initially getting in more oxygen in and getting more CO2 out sounds like a benefit for someone during a trek, however, this is the start of the AMS issues. When CO2 is dissolved in the bloodstream, the blood is slightly acidic, which is normal, it is how our cells and enzymes within them are optimised to function. When we breathe off too much CO2 as a result of trying to get in more oxygen, (and there isnt the same metabolic respiration going on as when you run) there isn’t the normal amount of CO2 in the blood to remain the same pH anymore. As a result, the climbers blood becomes slightly more alkaline than normal, in what is termed a respiratory alkalosis.

You can try it now actually. Breathe really rapidly for about 30 secs and you’ll feel a little light headed and your fingers might tingle. You’ve just blown off a load of CO2 – more than you are generating assuming you are sat down reading this. In doing so have caused your own mini respiratory alkalosis.

Climbers will experience this effect if they ascend too quickly due to lower levels of oxygen than they are used to normally, as your body doesn’t have chance to adjust it’s systems so you are not breathing off too much carbon dioxide.

You get a wide range of people, from age, from technical ability, from fitness, and also medical comorbidities on treks. Just on age alone, my Everest Basecamp trek had a group age range from people in their 20’s to their 60’s!

• 

• 

• 

This is important as the extremes of age, children and the elderly are more at risk of AMS. But these are fixed variables, things you can’t change. What risk factors for AMS are modifiable?

Acute Mountain Sickness Risk Factors

• Alcohol consumption – it’s strongly advised people avoid alcohol on the ascent, but there isn’t thought to be a risk on the descent
• Smoking
• Benzodiazepine use
• Sleeping tablet use (it is harder to sleep the higher up you climb)
• Strenuous exercise (Running and pushing your pace rather than a slow walk up hill)
• Rapid ascent – high risk is considered having ascended> 3500 m in a day (That can mean using a helicopter to quickly ascend for example, doesn’t just mean walking)
• Previous AMS – Having had a condition once, by it’s very nature means you are at risk again

When climbing, the two mantras of “slowly slowly” (kind of self-explanatory,) and “climb high, and sleep low” dominate. Whilst it is considered safe to ascend approximately 500m in a day, “climb high-sleep low” involves ascending more than 500m, exposing the body to lower oxygen levels, but then descending down to spend the night at a lower level, thus helping the body to adapt and aclimatise.

Climbing high and sleeping low is also applied on rest acclimatisation days where a circular route is used simply to gain altitude and then return to the lodge/camp. Again with the focus or reducing the chance of AMS. Such rest days can actually be really enjoyable especially if it turns out that there is an EPIC Himalayan bakery one valley over 😊

• 

• 

• 

• 

• 

• 

Although if you do go mountain cake shopping, it is always polite to bring some back to those who might have stayed to rest at camp. This was Martina, our cake barer who decided she’d carry a 12 person sized apple pie across a valley and up and down a mountainside to the people who’d remained in camp having a full rest day

Such flat out rest days alone can vital to preventing the onset of AMS, as you’ll still be acclimatising, whilst not exerting yourself. But if someone is really feeling the trek during a rest stage they probably need to be starting Diamox / Acetazolamide for the rest of their climb. The reason for this that AMS can be the herald of two nastier conditions, High Altitude Pulmonary Oedema and High Altitude Cerebral Oedema

High Altitude Pulmonary Oedema – HAPE

Ok, first things first the Americans spell oedema incorrectly 😜 and drop the “O”. The one advantage of this, is that it means we get a nice mnemonic for High Altitude Pulmonary edema – HAPE. The same is also true for High Altitude Cerebral edema so becoming HACE.

Earlier we spoke about AMS increasing fluid leakage from blood vessels. That is exactly what is happening here, but now the fluid is leaking into the lungs, and in the case of HACE, putting pressure on the brain

High Altitude Cerebral Oedema – HAPE

Ok, this is the severe stuff – essentially severe AMS. This is where people die.  The symptoms alone should suggested something is wrong. Those being:

• Confusion
• Loss of balance (Ataxia)
• Visual symptoms
• Difficulty walking

HACE is so dangerous, as anyone who has developed this form of severe AMS will have micro-haemorrhages, small bleeds on the brain. So even though you may descend rapidly and the symptoms recover, there is always the chance of some lasting effects. One of my friends who has had one episode of HACE swears that the condition has had a lasting effect on his memory

Preventing Acute Mountain Sickness

Ways of preventing AMS, are largely related to the risk factors. There are things which we know WON‘T help prevent AMS, but are sometimes suggested. So let’s get rid of the red herrings first:

• Coca leaves
• Pre-acclimatisation tents
• Vitamin tablets
• Aspirin
• Low iron levels / anaemia
• Sumatriptan (migraine relief medication)
• Garlic (vampires not really something to worry about at altitude either)

Current research suggests that the following things may reduce chances of developing AMS:

• Rest day every 3 to 4 days
• Using dialogues before you start the ascent
• Maximum of 500 m a day ascent
• Ginkgo bilboa, although there is no definitive evidence for this
• Ibuprofen
• Iron supplements – weak evidence
• Steroids (Dexamethasone) but now we are talking about special forces army stuff.
• Diamox – which will bring us nicely to the question:

What is Diamox / Acetazolamide?

Acetazolamide is a ‘water tablet’ sold under the brand name ‘Diamox’. Diamox is prescribed commonly for glaucoma, and for the treatment of epilepsy. Diamox is also used, in the UK, off license for acute mountain sickness prophylaxis.

Let’s just unpack that a moment. An off licensed medication is one where the manufacturer hasn’t applied for a license that medication to be used to treat a certain condition. Perhaps, more importantly, that means there will not have been specific clinical trials focused on that particular use case. There has however been quite a bit of “aftermarket research” in the case of Diamox, as we’ll discuss.

Diamox targets the kidneys in order to reduce the risk of AMS but how does it work? Here comes the science bit!

The kidneys are an important organ for controlling the pH of the blood. As we’ve seen above, altitude tends to raise the pH of the blood due to additional loss of CO2 as you breathe harder. The kidneys contain an enzyme called carbonic anhydrase which allows the body to bind CO2 in the blood, as carbonic acid. The result of this is that the blood becomes more acidic, a lower pH, so immediately you can see it will be harder for someone raise their blood pH by “blowing off” their carbon dioxide. There is an additional, arguably more important, benefit that at altitude this results in better oxygenation of the blood. Now we could get into oxygen dissociation charts to explain why, and look at all biochemistry of the partial pressures of oxygen, but I honestly think that would be overdoing it here!

Are there any problems with Diamox?

So what is the downside? Well, Diamox / Acetazolamide has a couple of side effects, which are directly related to its mechanism of action – blood vessel dilation. When you are exercising blood vessels dilate, and the target tissue gets more blood. As Diamox causes blood vessel dilation generally, everywhere gets more blood.

• More blood flows into the kidneys, producing, in turn, polyuria (needing the loo more frequently),
• The body responds to this with polydipsia (making you drink more as you feel thirsty).
• Paraesthesia (tingling in the hands and feet),
• Nausea, headache, and dizziness, are also all common side effects, again related to how the blood is pumping around the body

Diamox also lowers your blood pressure a bit, by causing the blood vessels to relax, which again increases the amount of blood (and therefore oxygen) that gets to your brain. Therefore counteracting the effects of Acute Mountain Sickness.

Well, that is the theory anyway! As for any hard rigorous studies into Diamox, things seem a little muddier…

A bunch of studies have been done to try and work out exactly how the drug works with AMS. Most of these have failed. But those studies have found that Diamox significantly decreases the incidence of AMS. In fact one trial found that Diamox reduced the risk of AMS development by 54.7%! (Only 11% of people in the study developed AMS, in contrast to the 24.3% of people on the placebo who did develop AMS).

FINE. So we know that Diamox / Acetazolamide does prevent AMS, and we think we understand why it works, so what did I do?

Why I took Diamox before climbing

Now, not every person who goes up a mountain will get AMS, the number of patients needed to treat (NNT) with Diamox to prevent one case of AMS is 5. Meaning that of five climbers who take Diamox, four of them would get no benefit in terms of preventing AMS. In terms of straight forward pharmacology, many patients take daily medications, for life, with much higher NNT’s

Personally, there wasn’t any chance of me NOT taking Diamox when off to Everest Base Camp. The simple reason being that I didn’t take it when I climbed Mt Kilimanjaro. The swathes of vomit I left near the summit attest to the fact that I was not a very well chap, and really need to look to prevent AMS in future. If you’v had AMS in the past, there is a strong chance you’ll get it again

It used to be recommended that patients take high dose Diamox, 500mg daily. However, more recent trials found that 250mg daily (split into 125mg doses, once in the morning and once in the evening) produces the same protection from AMS as 500mg. The current consensus is that 125mg twice daily should be the recommended dose, as it gives the same protection and will likely generate fewer side effects.

Conclusion – is Diamox worth taking?

The side effects of Acetazolamide are clinically mild, yet the benefits potentially considerable with a major reduction in the incidence of a potentially deadly AMS. My opinion – take the drugs. Put up with the tingly hands. Climb less than 500m a day. Don’t die for your holiday! Take acetazolamide to prevent acute mountain sickness if you’ve any doubt

But that is my opinion, from my experiences. People should absolutely make their own decisions about the medications they take. That is as true back home in GP land, as much as it is on the mountainside.

References used in this post:

• Vardy et al, 2006
• Roach and Hackett 2001
• Wu, 2012
• Nieto Estrada VH, et al 2017
• Peacock A, BMJ, 1998
• Alizadeh et al, 2012