Management of acute hyperkalaemia: evidence, practice and pitfalls

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Hello, and welcome to the Australian Prescriber Podcast. I'm Jo Cheah, a hospital pharmacist in Melbourne and your host for this episode. Today, I have the pleasure of interviewing Samuel Ford, clinical pharmacist at Royal Brisbane and Women's Hospital and PhD candidate at the University of Queensland in Brisbane. Sam co-authored an article with Anna Zipf and Julian Williams called Management of acute hyperkalaemia: evidence, practice and pitfalls in Australian Prescriber. Welcome to the podcast, Sam. Thanks for being here.

Thanks for having me, Jo.

So Sam, what does acute hyperkalaemia look like?

I suppose the tricky thing is that it doesn't necessarily look like anything in particular. It could be quite a general or vague presentation. In my line of work in the emergency department, people might present with muscle weakness or some nausea, but it's often not until we get some early blood chemistry that we identify hyperkalaemia.

And where would you normally come across these patients? For example, are they presenting at the GP or coming into the emergency department?

Yeah, I think you can come across hyperkalaemia in a lot of areas of practise. Certainly, we get referrals in the ED [Emergency Department] from GPs[General Practitioners] or from clinics who've looked at some chemistry that they've ordered maybe the day before and sent them in due to a potassium level that's too high. And certainly, we see a lot of people presenting with hyperkalaemia at my hospital as we are a renal and dialysis centre.

So for example, would patients present symptomatically or, like you said, more so from a routine serum analysis that they'd had the day before?

Yeah, most commonly, it's found when we do routine blood chemistry in the emergency department. And yeah, there might be some indicators that the patient's at risk of hyperkalaemia, and that might be on an ECG [electrocardiogram], which we can talk about in a moment, or that your pre-test suspicion is quite high due to comorbidities like chronic kidney disease.

Yeah. And what are you most concerned about if it was left untreated?

So the biggest risk with hyperkalaemia is progression to unstable arrhythmias, and it's all about cardiac risk. So as the severity of hyperkalaemia increases, the risk of significant bradycardias, QRS widening, and ventricular arrhythmias like ventricular tachycardia do become more of a concern.

You did mention, for example, at your hospital, there's renal dialysis, so I'm assuming those people are at risk. What other groups of patients are most at risk of acute hyperkalaemia?

Yeah, so our patients that are on haemodialysis for chronic kidney disease are definitely overrepresented in this space. And commonly, we'll see patients who might have missed a dialysis session or perhaps had a shorter than normal dialysis session recently, and they might present with hyperkalaemia. Other patients who are not on dialysis but have some degree of renal impairment may also develop hyperkalaemia, particularly if they have some other trigger like an acute viral illness where they've got some vomiting and diarrhoea and they've got a bit of an acute kidney injury on top of medicines that might predispose you to hyperkalaemia. And there's a table in our article, but commonly, some of these are things like renin-angiotensin inhibitors and antibiotics like trimethoprim.

You mentioned, for example, there could be a viral illness. Are there any other triggers that we should be aware of?

Other triggers are sort of more long-term things like poor glycaemic control can increase your risk of hyperkalaemia and things like chronic constipation, particularly in our patients with chronic kidney disease who rely on faecal excretion of potassium.

So once the patient has presented and you suspect acute hyperkalaemia, what are your first steps in diagnosing them?

Yeah, so obviously, I work with my medical colleagues for the diagnosis side of things, but the things the team as a whole are thinking about is in the first instance, is this a true hyperkalaemia? And it's important to understand where that values come from. We commonly use point of care blood gas testing in the emergency department, which is a really fantastic tool because it gives you rapid access to information about blood chemistry. But importantly, it doesn't give you an indication about pseudohyperkalaemia. And so, that's where there may be haemolysis where you've got cell rupture and potassium coming out of the cell caused by a difficult venous draw, for example, or other causes like very high white blood cell counts or very high platelets, which can give you a pseudohyperkalaemia.

So the first step is to confirm that it's definitely a hyperkalaemia. If you are using a blood gas result, you want to marry that against your pretest probability. Ask yourself, "Does this patient have risk factors? Are they a patient with chronic kidney disease," for example. If you're happy that it is a hyperkalaemia, the next step is certainly an ECG. ECG is really helpful in terms of risk stratification. So the ECG combined with the absolute serum or plasma level of potassium give you an idea about how high risk this patient is.

And what sort of ECG changes are you looking for?

Yeah, it's good to touch on this because I think I was certainly taught and a lot of people are aware that hyperkalaemia causes peaked T waves, and this is certainly the most common ECG change, but it's the one that's least correlated with clinical outcomes, certainly least correlated with bad clinical outcomes. ECG changes that we're more worried about are things like QRS widening and junctional rhythms like bradycardia, for example.

And if the patient's presented and you've done the first steps to diagnose and potentially have started treating, which we can chat about in a moment, how often are you then repeating blood gas or blood tests or ECG monitoring?

Yeah, so I guess it does depend on their risk stratification and what treatments you're using. For the patient cohort we're speaking about in this article, we'd really want to be testing serum potassium within 1 to 2 hours again after treatment and then again, 2 to 4 hours later to monitor for rebound potassium as it shifts back out of the cell, which we'll talk about in a moment, and then measuring potassium again after about 24 hours. ECGs can be taken around a similar time to the potassium monitoring.

And just for my knowledge, would most of this be happening in an emergency department or would they be transferred to a ward for that 24-hour monitoring once they've presented?

A lot of the time, the initial treatment for hyperkalaemia is conducted in the emergency department over the first few hours. Some of our patients who are on chronic haemodialysis, ultimately, that's the fix. And so, if there is a dialysis chair or bed available, they may go to dialysis quite quickly. But as you can understand, there's often delays with our hospitals, and so they may be with us in the emergency department for some hours.

Yeah, good to know. So in terms of treatment, the article has an excellent summary of what treatments to use and the goals of the treatments. I would refer our listeners to Box 3 in the article, but for the purpose of this interview, could you provide a brief overview of the treatments used and the goals of each?

Yeah, definitely. In terms of acute treatment of hyperkalaemia, there's really 3 stages. The first one is all about cardiac protection. We use calcium to keep the heart safe, and traditionally, this was thought that it somehow stabilised the cardiac membrane, but more recent evidence from some animal work has shown that it's really more about allowing the continued propagation of action potentials for the heart. Hyperkalaemia inactivates those fast sodium channels that are really important for action potentials and conduction of heart activity. And we think now that calcium administration allows for the uptake of calcium through these L-type calcium channels to counteract the inactivated sodium channels. So we use calcium, and most commonly, it's calcium gluconate, which is a product that contains 2.2 mmol per 10 mL vial. And we would use 30 mL now, which is a greater volume than we've used historically. And it's important to distinguish this from calcium chloride, which is a more concentrated product that we reserve for situations where it's more time critical like the peri-arrest setting.

So calcium gives us about half an hour to an hour of cardiac protection, and this time is where we really want to be implementing some other strategies. And step 2 of treatment is to shift potassium into the cell, lowering that extracellular concentration that is causing the danger. Mainstay of treatment for shifting potassium is still insulin and dextrose therapy. Insulin moves potassium into the cell via the sodium-potassium ATPase, and we co-administer with dextrose or glucose to prevent hypoglycaemia. We also use [nebulised] salbutamol, which also shifts potassium into the cell, and we know that this is additive in efficacy to insulin dextrose. We also think that it might slightly lower the risk of hypoglycaemia associated with insulin therapy as well.

The last treatment for shifting potassium is sodium bicarbonate, but this has really fallen out of favour. We don't really think this has much of a role in acute hyperkalaemia management now. The exception, however, is for patients with significant metabolic acidosis. And in that case, it is a good treatment option, but important to distinguish that from other types of acidosis like diabetic ketoacidosis and lactic acidosis where we wouldn't want to be reaching for sodium bicarbonate. These are sort of temporary measures that we've done so far. So step 3 is really about removing total body potassium, and we can do this a number of ways. Obviously, most commonly, it's dialysis for our patients with severe chronic kidney disease. We can also rely on patient's residual kidney function for those that still have kidney function. We can give them supportive cares and time to excrete that potassium. And there is also potassium binders, but these are very, very slow to act and do come with their own downside. So they have less of a role in the immediate acute phase for hyperkalaemia.

Interestingly, the article mentioned a couple of new binders that I hadn't heard about. What are your thoughts on those?

Yeah, so these newer binders seem to have promise as their onset of action is quite a lot faster. So that's products like Sodium Zirconium Cyclosilicate. And although they did seem to have promise, the evidence so far suggests that they probably don't add much, if any, benefit on top of standard of care to our current acute hyperkalaemia management. Where they do seem to have promise though is when they're taken more chronically and they seem to allow for the continuation of drugs like renin-angiotensin inhibitors in patients with renal disease who would otherwise not be able to tolerate them due to the risk of hyperkalaemia.

Are there any risks associated with the treatments that you mentioned that you'd like to highlight?

The big one we focus on in the article is, of course, the risk of hypoglycaemia associated with insulin dextrose therapy, and this is probably more common than some of your listeners would appreciate. The literature tells us that it's about 1 in 5 patients become hypoglycaemia, and certainly, our local work has shown that it's as high as 1 in 4 patients. And so, the newer guidelines really focus on trying to address this risk, both in terms of recognising risk factors, so patients with renal disease, patients who are lower body weight, and really importantly, patients with a pre-treatment blood glucose of less than 7 mmol/L are really at risk of hypoglycaemia. And so counterintuitively, perhaps it's our non-diabetics who we really need to be doing BGL monitoring the most.

Our article suggests what the UKKA [UK Kidney Association] guidelines also suggest, and that's if we do identify patients who are at risk of hypoglycaemia, we want to be thinking about giving them an additional glucose infusion post that initial insulin and glucose bolus. And certainly, for our patients with end-stage renal disease, we can also think about giving a lower dose of insulin, 5 units compared to 10. There is some evidence that shows that perhaps this is just as efficacious while lowering the risk of hypoglycaemia in that cohort.

Very interesting. And I'll just highlight that all the doses that you've mentioned, they're in the article, so our listeners don't have to memorise them. You have mentioned some recent changes in evidence and guidelines. Were there any others that were important to mention today?

Yeah, I think we sort of touched on them, but just to recap, the calcium dosing has changed. Traditionally, it was 10 mL of calcium gluconate, but there's a bit of clinical research now to suggest that 10 mL is almost never sufficient to be able to cause any ECG resolution. So we really want to be using 30 mL of calcium gluconate now in the first instance; or in the peri-arrest setting, 10 mL of calcium chloride. The other change is really focusing on that risk of hypoglycaemia with insulin-dextrose therapy and considering an additional glucose infusion or perhaps a slightly lower dose of insulin. We do have those newer potassium binders, but their role is probably more in the chronic space than in the acute care phase. And there's also some changes around preventative management. I think in the past, there was more of a focus put on dietary restriction, and guidelines are really moving away from that because of the risk of malnutrition and also a bit of a signal that it may increase cardiovascular risk if we have very extreme low potassium dietary recommendations.

So now, the recommendations are really about managing glycaemic control, preventing constipation, and creating some sensible sick day plans for appropriate patients. So, these are patients who are perhaps on renin-angiotensin inhibitors and giving them a bit of a plan about what to do if they do become unwell like with a vomiting or diarrhoea illness. And this might be withholding those medicines for a couple of days just to reduce their risk of hyperkalaemia.

Thanks, Sam. And what role do pharmacists play in treating and managing acute hyperkalaemia?

I think the role pharmacists play in this space is similar to other areas of medicine. I'd like to think that we advocate for efficacious and evidence-based use of medicines as well as medication safety. So I guess in the context of hyperkalaemia, it's making sure that we get that calcium gluconate dose correct in the first instance and also helping the team recognise those risk factors and perhaps suggesting a slightly altered insulin-dextrose regimen for certain patients and advocating for [nebulised] salbutamol as add-on therapy, its additive efficacy and perhaps even lowers the risk of hyperglycaemia.

And there's some value that pharmacists can add in terms of when do patients restart their medications that affect potassium?

Yeah, this is good to touch on because I think one of the risks that's perhaps underappreciated is these patients get some of these medicines like ACE [angiotensin-converting enzyme] inhibitors or angiotensin II receptor blockers appropriately withheld in the short term, but the risk is that they don't get restarted appropriately. And so, I guess this is another role for the pharmacist as well as the rest of the team is to have a plan for restarting these things. The general advice is that once a patient's kidney function recovers, if indeed they did have an acute kidney injury and their potassium falls below about 5.5 mmol/L, we can look at reintroducing these things one at a time with appropriate monitoring. So, reintroducing the ACE inhibitor and reintroducing the spironolactone if they happen to be on that, for example.

Yeah, that's great. Thanks for summarising all of that, Sam. Are there any other take-home messages that you had for our listeners?

I think the take-home message is that hyperkalaemia care needs to be personalised, both in terms of risk assessment and in terms of diagnosis in the beginning, making sure we're considering whether it is a true hyperkalaemia and not a pseudohyperkalaemia if we're looking off a blood gas and then also individualising care to those patient risk factors that we've talked about in the podcast.

Fantastic. It's been really enjoyable to have a chat with you today, Sam. Thank you so much.

Yeah. Thanks, Jo. It was a pleasure.

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The full article is available on the Australian Prescriber website. The views of the hosts and guests on the podcast are their own and may not represent Australian Prescriber or Therapeutic Guidelines. Samuel Ford has received funding from the Emergency Medicine Foundation Leading Edge Grant to support a clinical trial related to hyperkalaemia management. He has received scholarships to support his PhD studies from the University of Queensland and the Dr Jian Zhou Memorial Scholarship Fund. I'm Joe Cheah and thanks for joining us on the Australian Prescriber Podcast.

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