Updated anaphylaxis guidelines

Welcome to the Australian Prescriber Podcast. Australian Prescriber: independent, peer-reviewed, and free.

Hello, I'm Jo Cheah, and this is the Australian Prescriber Podcast. Joining me today is Dr Katie Frith, who is a paediatric immunologist, and Katie has written an article on the anaphylaxis guidelines in infants and children. Thank you, Katie, for joining us.

Hey, Jo, thank you for having me.

So, what were the main updates to the anaphylaxis guidelines that have inspired this article?

ASCIA, the peak professional body of immunologists in Australia and New Zealand, updates their anaphylaxis guidelines for health professionals pretty regularly. The main reason for updating it this time was because we had made a decision to reduce the weight threshold for the 0.15 mg adrenaline autoinjector, and also to sort of highlight the importance of position in the management of anaphylaxis for infants.

So this really was an update regarding the management of anaphylaxis in infants and young children. So previously, prior to this update, the 0.15 mg adrenaline injector was only recommended for children weighing 10 kilos and above, but the new guidelines recommend that they can be prescribed now for infants weighing 7.5 kilos and above.

I'm sure that you're aware that in the current product information for these autoinjectors, the weight recommendations in the product information say something a little bit different to ASCIA and our Australian dosing references. So for example, for the 0.15 mg dose, the product information suggests from 15 to 30 kg. So, do you have any comment on whether that will be updated anytime soon?

So, yeah. And that's a common area of confusion amongst parents, pharmacies, schools. Because you're quite right, ASCIA recommendations aren't in keeping with the product information. And the rationale for that is that, it is better to overdose slightly with adrenaline than to underdose. So the risks of a slight increase in dose of IM adrenaline are significantly less than underdosing when managing anaphylaxis.

And that our guidelines to prescribe the 0.15 [mg device] from 7.5 kilos, or we actually recommend the 0.3 mg device for patients weighing 20 kilos and above – not 30, which is what the product information says – are in line with other international allergy organisations such as in Europe, Canada, and America.

As of September 2021, there's going to be three autoinjectors instead of the two that are currently on the market. So can you tell us what this new strength is, and in which patients would we use that new strength in?

It's good to raise awareness of that, because for a long time now we've only had one autoinjector available on the market. But from September, there'll be two brands available: the EpiPen and the Anapen, and both come in a 0.15 and a 0.3 mg device. But the new Anapen will also come in a 0.5 mg device. And we would recommend that this is prescribed for children and adults greater than the age of 12 if their weight was above 50 kilos. Currently, anyone above 20 kilos gets prescribed 0.3 mg device. But now there will be the option to continue giving people above 50 kilos the 0.3 mg device, or to prescribe the 0.5.

So you sit on the ASCIA allergy guideline committee, and so can you tell us a little bit about ASCIA? And for those listening at home, that's the Australasian Society of Clinical Immunology and Allergy.

So ASCIA is, as I've mentioned before, the peak professional body for immunologists in Australia and New Zealand. It was established in 1990, and it's really a very dynamic society that aims to promote high standards in medical training and practice. It promotes a high level of education and training around allergies in particular, and advocates a lot for research into allergies in particular, but also for patients with other immune problems.

And just as a general overview, has there been an increase in allergies, food or otherwise, in children in Australia? And if that was the case, why is that happening?

The million-dollar question. So, yes, definitely we've seen a big increase in rates of food allergy in particular, but an increase in rates also of other types of allergies – so to drugs, and also persistent allergies to venom and other causes. But that hasn't risen as dramatically as food allergies in Australian children.

And that really mirrors what we're seeing in other developed countries and actually starting to see in also developing countries, an increase in food allergies in general, particularly over the last few decades. We're also seeing an increase in fatal anaphylaxis in Australia as well, which is very concerning. And that mirrors that increase in food allergy in general. The million-dollar question, as to why?

There is no one answer. And that's a frustrating thing for us and for parents, obviously, with children with food allergy. I think there's a number of different hypotheses and they probably all play a role. One of the main ones is the dual antigen exposure. So, whether or not early exposure to food allergens through the skin in particular, particularly in children with eczema, so with inflammation there in the skin, is a way that they're sensitised to food allergens before they're introduced to it by mouth.

There's the hygiene hypothesis that many listeners will be aware of, and that focuses and includes maybe a reduction in microbial diversity. And then there is interest and research around whether or not low vitamin D levels certainly contribute to food allergy. And I suspect that each of these plays a role, because we're certainly seeing an increase in people of all nationalities and backgrounds, and all sort of genetic backgrounds, but Australia seems to be leading the way in an increase in food allergy.

That’s very interesting, because in my role at the hospital, I work in medicines information as well as in clinical trials. So, I've been asked this type of question before, where if you apply goat's milk to the skin, does that sensitise a patient to a goat's milk food allergy? And it's just interesting to hear you actually say that that is one of the theories.

And we do see that there is research to support the fact that yeah, and like food antigen exposure, it's mostly done around peanut that does increase the rate of sensitisation and allergy. And even though there's no evidence to support it, I'm certainly seeing in my own practice an increase in coconut allergy, and it's something we're hoping to study a bit more and there's certainly been a trend to using more coconut oil on the skin. So I do wonder if that plays a role.

Very interesting. Moving on now, I guess, to anaphylaxis in general. So I just wanted to see if you were able to tell us a little bit about anaphylaxis symptoms and then how we would treat it, and moving into intramuscular adrenaline and when that would be appropriate and/or contraindicated.

Anaphylaxis is basically a severe allergic reaction and international definitions vary, which can make it a little bit confusing, but ASCIA defines it as an acute onset illness with typical skin features such as a rash, erythema or with or without angioedema, so with or without swelling. But basically with involvement of the cardiovascular or respiratory symptoms. And some people can have persistent severe gastrointestinal symptoms. They're particularly an issue with allergies to stings or injected drugs, but can be a feature of food allergy as well.

Or the alternative definition is an acute onset of hypotension or bronchospasm, or upper airway obstruction where anaphylaxis is considered possible, even in the absence of a rash. And I think that's really important to highlight that we don't always see those mild to moderate skin symptoms before the onset of respiratory or cardiovascular symptoms. So it's important to be aware of that and when to use adrenaline. So we would have a low threshold for recommending IM adrenaline. It is still the first-line drug of choice for the acute management of anaphylaxis and should always be given early. It is very safe if administered IM, so if in doubt, always err on the side of caution, that's what I tell my patients, and administer early, but we would recommend it for any evidence of cardiovascular involvement.

So in infants and children, often that can present, with little children, it can present with them just becoming pale or floppy or very sleepy, but in older children and adults that may present with dizziness or loss of consciousness, respiratory symptoms, which I see more commonly because that is a more common presentation of paediatric anaphylaxis, would include things like cough, difficulty swallowing, wheeze, which may or may not be audible without a stethoscope, hoarse voice. And if there was persistent cough, and it doesn't have to be a dramatic cough, it's just a little persistent cough that keeps going, or might stop and start but does keep persisting, even one of those signs, we would recommend early use of IM adrenaline into the outer mid-thigh.

Excellent. And just so that everyone's clear, are there any contraindications to using intramuscular adrenaline?

And that's a really good question and really important to highlight that there are no contraindications to IM adrenaline when treating suspected anaphylaxis. We see sometimes people with cardiac conditions, much less obviously in children than compared with the adult community, but looking at big studies that have looked at the use of IM adrenaline, the risk of cardiovascular complications from IM adrenaline is very rare. We don't advocate for the use of IV adrenaline boluses because that's where there are lots of issues and potential side effects with adrenaline toxicity or overdose. And we also don't recommend subcut [subcutaneous] adrenaline because perfusion and absorption is often poor. And so it's always first-line IM.

And also your article, obviously we're talking about the updated anaphylaxis guidelines, but this information is relevant across community settings as well as hospital settings.

Definitely.

Yep. Perfect. And are there any other adjuvant or supportive treatments that can be given when treating anaphylaxis?

Yeah. Firstly, I would say that adrenaline is the first-line drug and always give it early just to highlight that.

But frequently we see that antihistamines are given first and I just wanted to highlight that antihistamines play no role in the management of anaphylaxis. So they can be given after adrenaline, but are really just given as a comfort measure to stop itch and might reduce like facial swelling, but will not help with managing and also won't help prevent anaphylaxis. And I think that's an important thing to point out because I think a lot of people think, well, if I get the antihistamine in early, that might prevent it progressing to anaphylaxis, but that is not true.

We sometimes use salbutamol either nebulised or via a spacer after adrenaline, if there's persistent wheeze, particularly in a person who's got underlying asthma. We will sometimes give steroids, although the role for steroids in the management of anaphylaxis is sort of limited evidence for its support, but it is sometimes given if a person has a history of reactive airways disease such as asthma. And it is sometimes given as people try to prevent biphasic reactions. But as I say, the evidence for use in either is scant. And fluids need to be considered if a patient is hypotensive. So they're the main adjuncts.

And in regards to the very interesting point and important point about not using antihistamines to prevent a reaction, is that just because the pathophysiology of the anaphylactic reaction occurring is not reliant on the histaminergic pathway?

Yeah, no you're right, Jo, because there's a lot of mediators released and histamine isn't the only one triggering the anaphylactic reaction. Whereas adrenaline will obviously act on… it’s sort of a non-selective agonist of all our adrenergic receptors, so will work to reduce mucosal oedema, it'll help dilate the airways and help vasoconstriction as well as cardiac contractility. So really has a sort of systemic effect in managing all the symptoms of anaphylaxis.

Another big highlight of the update, as you mentioned, right at the start of the interview, was about the positioning of the patient. So can you talk to us about why positioning of the patient is important and what can happen if the correct positioning is not used?

Okay. And I think that is again, another really important issue. And one we wanted to highlight with this article. We know from reviews, looking at fatal anaphylaxis in Australia, that the upright posture either standing or sitting, even after receiving adrenaline, has been associated with an increased risk of fatal anaphylaxis and that's due to reduced blood flow to the heart and brain. So we would definitely recommend people lie supine, or if they're vomiting, they can lie in the recovery position. And that's also the recommended position for pregnant people experiencing anaphylaxis. For children and young infants we would also recommend holding them in the parent's arms, but holding them horizontally, not up and over the shoulder as it is often done.

And I think it's also important to say that some people who are experiencing anaphylaxis are experiencing difficulty breathing and so might feel better in a sitting position and they can be allowed to sit, but they shouldn't be sitting in a chair. They should be sitting with their legs extended out in front of them. And all of these are measures to try and increase blood flow to the heart, improve venous return and reduce the risk of fatal anaphylaxis. And I think maintaining that posture, it's very hard because how long do you keep them in this recovery position or prevent them from standing or walking? We would say there's no good evidence to support it. But from clinical experience and expert opinion, we would say for at least an hour after adrenaline and resolution of all symptoms, and if two or more doses of adrenaline have been given, we would recommend for at least four hours.

So that means being stretchered or wheelchaired to the ambulance. That means if you need to go to the bathroom while you're in ED using a trolley or a wheelchair, because we have seen patients where they're feeling a lot better, they walk to the bathroom and then collapse.

And for those listening, if you're more visual, if you refer to the article, there's actually diagrams of what these positions look like in different types of patients. So infants, children, and even up to adults and pregnant people.

And they're the same infographics that we've put on the ASCIA action plans, which are actually about to be updated again, which I think is helpful as a visual reminder.

To summarise the interview, do you have a couple of main points that you'd like to share with the audience?

So I'd just like to say that anaphylaxis can be really unpredictable and initial symptoms may seem really mild so it's often under-recognised. Always treat with adrenaline and adrenaline early. And if in doubt, err on the side of caution, and just that position is really important. So sitting and standing significantly increases the risk of an adverse outcome. So supine or sitting with the legs extended is important.

And lastly, it sort of just came to me then, with the introduction of Anapen later this year, are the administration instructions the same or...

No, it's slightly different. They're both autoinjectors, but they are slightly different. So ASCIA will be producing information and videos on how to use the Anapen. And we will also be producing updated and anaphylaxis action plans. There'll be one for EpiPen and one for Anapen because they do vary slightly.

Good to know and looking forward to seeing those resources become available. That is all the time we have for today's episode. I'm so thankful for Dr Katie Frith for joining me.

Thank you so much, Jo. It's been great.

[Music]

The views of the hosts and the guests on the podcast are their own and may not represent Australian Prescriber or NPS MedicineWise. I'm Jo Cheah. Thanks again for listening to the Australian Prescriber Podcast.