Australian biters and stingers: the latest on antivenoms with Professor Geoff Isbister

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

Hi, I'm Dr Justin Coleman, a GP from Brisbane, and with me I have Professor Geoff Isbister, a clinical toxicologist from the University of Newcastle. Welcome Geoff.

Hi, how's it going?

Very well. Geoff, you seem to have developed a passion for little critters that sting, bite and quite frankly have the potential to make our lives a misery. What is this strange attraction you have to things that send most of us running for the door or for a hearty broomstick?

To be honest I don’t have a good answer. I mean a lot of people would say ‘Oh, did I grow up collecting snakes or spiders?’, and I certainly don't go anywhere near snakes. I think my interest came from the fact that bites and stings can cause systemic effects from all systems, you know, I'm not a specialist in one yet the whole range of things which makes it far more interesting.

You should have been a general practitioner Geoff. You've developed quite a rep as a myth buster over the years so I thought we'd start with spiders and work our way up in size or if you prefer work our way down in number of legs and the first I heard of your work was when you debunked the myth that those mysterious necrotic skin ulcers are due to the bite of a whitetail spider. What happened there?

So spiders have been blamed for many things and I mean towards the end of my research on that I discovered even the Great Plague was blamed on spiders and I think it's a fear of this eight-legged creature. And also when people see a doctor they, if they've got something wrong with them, often they want a reason for it, an external cause, and spiders were a great thing for it. And in Australia in the early 80s people started developing different varied necrotic ulcers and they were blamed on the whitetail spider and that was really because someone went back to a house where these people were and found whitetail spiders in the house. The problem is is that in eastern and southern Australia every second house there's a whitetail spider in it. And from then this myth just grew. So when I started doing my research I worked in Sydney, I wasn't near the coast, and I wanted to do bites and stings, so there was no snakes, there was no marine things, so I thought oh well all I can do is spiders, so I started just taking calls from the Poisons Centre where we got definite cases and over a two-year period I collected people who had been bitten by a spider who’d collected it, they then posted it to me. I became very unpopular at the hospital I was working at as we had all these spiders arriving in the mail.

And with all the Australia Post posties I would imagine wouldn't have been too happy.

Well yeah, that's right. I found out after I did it that it's not actually illegal to send spiders. It's illegal to send snakes, bees and scorpions by post but so I was ok with spiders. And then what I essentially did was a study, so here's a definite bite, I got an arachnologist at the Australian Museum, Mike Gray, identified all of these spiders I collected, and we just correlated definite bites with definite clinical effects. And of the 130 whitetail spider bites we had a whole lot of people with a bit of pain, red spot, and nothing more than that, so it didn't cause these necrotic ulcers. In a reverse study we had people being referred to us because at that stage I was working in the Toxicology Unit, we got ulcers referred to us, and in every single case we could find another cause, and I learned a lot about weird infections and dermatological things I'd never heard of that can cause ulcers.

I was so hoping you would tell me the reverse study was having people deliberately bitten by whitetail spiders but perhaps that research is in the future. You then tackled that great Aussie icon the redback on the toilet seat and magnificently named your work the Redback Anti-venom Evaluation study or RAVE which for me conjured up images of what toxicologists get up to after hours in the lab, and this study compared different delivery mechanisms for redback spider anti-venom, and what did you find there?

So I can't take credit for RAVE. That was one of the other investigators, I'm not very good at acronyms. Great acronym. So what we did is we looked at intramuscular versus intravenous because we found that people weren't responding that well, there were case reports, give IM then gave IV and they got dramatically better. So we compared them in a randomised controlled trial and showed that they were the same despite really wanting IV to be better because yeah that made sense. Problem with that was is that we showed they were either both equally effective or equally ineffective is what we then became concerned about because we measured anti-venom in patients and when you gave it IV you could detect it in blood but not when you gave it intramuscularly. So that gave us clinical equipoise and the ethical ability to do the placebo randomised control trial which we finished and was published more recently and showed that anti-venom is no better than just pain relief alone for redback spider bites.

You're doing magnificently well for this natural sceptic. Two out of two so far. Let me ask you a quick true or false, Geoff, to keep you on your toes. If you get bitten by a radioactive spider can you learn to climb up the outside of buildings?

I've never tried it, I don't know the answer to that, but I think the answer’s probably false in the real world unless you're watching Spider-man.

Okay, I wouldn't want to be part of that trial I guess, I wouldn't ever need to use the stairs again, but it could be a bit dangerous. While we're still at the eight-leg level of this conversation let's talk about scorpions. Are bites common in Australia from scorpions and if so how does treatment differ from spider bites?

I would say they're uncommon to rare. They certainly occur. When I started doing a study I was surprised that we even had scorpions. There are lots and lots of scorpions in Australia if you know how to look for them, but not as many stings, so I think over about a two-year period at the Poisons Centre we got about 100 cases, and essentially they cause pain, probably a lot more pain than a spider bite, but really it lasts four to six hours and then it goes. Most importantly we don't have scorpions that cause severe systemic toxicity and, worldwide, scorpions after snakes are the largest cause of severe morbidity and mortality from bites and stings.

Thank you. I'm talking to Geoff isbister, a two-legged clinical toxicologist from Newcastle. Onto snakes now and much of your research has actually resulted in less anti-venom being used rather than more, and I'm guessing that milking a snake’s fangs is considerably more fraught than milking a cow, but there was one point in time where we used to continually deliver anti-venom over the course of treating a snakebite and we went through our anti-venom stocks at a great rate and probably harmed patients in the process, but you're a part of changing that?

I mean when I trained that was what you did. You keep doing blood tests in particular coagulation studies and every time they're abnormal you gave more anti-venom because if they weren't better than clearly you needed to give more treatment. What we've shown since then, and I mean you look back and think it's completely obvious, the type of coagulopathy which we call venom-induced consumptive coagulopathy in most snake bites in Australia, and it's probably 80% of what we're dealing with with Australian snake bite, is a consumptive coagulopathy, so it's a factor deficiency, it's like someone with haemophilia. So even if you give anti-venom and stopped the toxin doing its damage which it does very rapidly, it's not going to get better until you make more factors, your liver synthesises more factors, it doesn't matter how much anti-venom you give you aren't going to get more factors until you just wait that time. So what it really is about and we knew this from neurotoxicity as well is that many of the effects of snakes are irreversible so giving anti-venom once the effects have occurred isn't going to make the patient better. It'll stop them or prevent them getting worse, so now our focus is really on giving anti-venom early to stop things happening and more importantly the neurotoxicity and myotoxicity or rhabdomyolysis.

Okay so if we have to give it early, so the patient comes in with a leg trussed up like a turkey after their first aid for snakebite, and we want to know whether they've been envenomated as opposed to just bitten how accurate is our clinical history and examination versus clotting tests, that's presumably aPTT, INR, versus any other test?

Answering your exact question of how accurate is clinical history versus the laboratory, the laboratory is 100% accurate because if you've got venom-induced consumptive coagulopathy it's defined by having, you know, completely abnormal so an unrecordable INR and aPTT. However that doesn't help, that tells you the patient's got it. The question you really want to ask is, is the clinical history early on, can we make the decision then because that's when we need to give the anti-venom, we don't want a blood test that tells us well it's too late, you've already got those effect. Creatine kinase (CK) is another thing, is that once that goes up well you know you've got muscle damage, so you can be sure that it's there but it doesn't help you with the anti-venom. So now we are really moving to that initial period in the first, you know, even two hours and if patients do have clinical symptoms, so if they've got headache, nausea, vomiting, certainly myself and encouraging people more to think well that really means that they've got venom in their system and if you give anti-venom now it's going to be the most effective that it can be so that later on when you do those blood tests hopefully they're not going to be abnormal.

Very interesting, thanks Geoff. Look we've done eight legs and we've done no legs but let's finish off with things that look like they probably have lots of legs but you're probably going to tell me they don't have any which is jellyfish and blue bottles and other submerged terrors of the shallows. You published some wonderfully pragmatic research in the MJA a decade ago called a randomised controlled trial of hot water (45 degrees) immersion versus icepacks for pain relief in blue bottle stings, so which one – the kettle or the freezer – and what have you done since with other jellyfish?

All the hard work was actually done by the emergency registrar who did this research project. He was the one who sat on the beach and collected these patients.

That’s what registrars are for.

Well, yeah, they did the hard work. I said I'd be a great study to do, but yeah. So we had to get council permission, we could only do it on Sundays when the volunteer lifesavers were there. We recruited I mean almost 100 patients. We recruited a third of them in one day because as you know the blue bottles come, everyone gets stung and then you sit on the beach for the next three weeks doing nothing. So from that point of view it was it was a difficult study. The other thing I liked about it is we showed that a treatment worked because I think one of my colleagues here calls me Dr TN – therapeutic nihilist – because as you can see prove anti-venom doesn't work, prove this doesn't work, use less dose, at least with the blue bottles we showed that hot water was clearly more effective than ice packs, so 20 minutes of either immersing a limb or even a shower if you can't do immersion will treat the pain of blue bottle stings in 90% of patients compared to what appeared to be more of a placebo effect with ice packs.

Okay is that presumably because the toxin is designed for use in sea water and you do something to the proteins or something when you heat it up?

yeah that's exactly right, so there's in vitro studies that have shown if you heat the toxins up above 45 degrees the proteins degrade and so therefore they won't work. The problem is is that you've got a very narrow range there because if you go over 50 and you expose someone for up to an hour then you'll actually get a superficial burn which has been what's made it harder to put this study into practice because you need your supply that does exactly the 45 degrees.

Okay and you've recently extended that to box jellyfish? What's the story there?

So we looked at box jellyfish but we looked at it in the emergency department at Royal Darwin Hospital and we showed there was no difference between the hot water and ice packs and that was an unusual finding and I think the difference was is those patients were being treated after they'd been picked up from where they'd been stung by ambulance, come to the emergency department and there was quite a delay and we think that that's why it wasn't as effective. You've waited too long whereas off the beach with blue bottle stings you know people were getting treated within you know five minutes of their sting. The one thing is we think that you need to give it earlier for box jellyfish stings, much more difficult study to do in the future, but in terms of emergency like in the hospital management clearly hot water was no more effective than ice packs, ice packs are easier to use, so even though it's probably a placebo effect and that's still the current recommendation for it.

Very interesting. I take it we save the vinegar for the fish and chips still?

Vinegar’s different although it has become a bit controversial in the last few years. Vinegar is designed to essentially stop nematocysts, more toxin, getting in. So it's not about pain, as you can imagine if you've got a sting and you pour vinegar over it, it will make the pain much worse. It's about stopping, for box jellyfish, severe life-threatening envenoming so it's definitely not recommended for blue bottles because it'll just make the pain worse, it’s recommended for jellyfish where you're trying to stop systemic envenoming.

Very interesting, that's all we've got time for so thank you very much Dr Geoff Isbister and thanks for spending your time educating us at Australian Prescriber. I'm Dr Justin Coleman and you'll hear again from me soon.

Thanks.

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Over the years Geoff Isbister has written articles on spiders, snakes and stinging thingies available online at nps.org.au/australian-prescriber and like our whole journal it won't cost you a brass Razoo. Subscribe and we'll deliver ourselves straight to your inbox or follow us on twitter @AustPrescriber. The guest’s views are his own not NPS's and i just make up things as I go. I also host the GP Sceptics podcast series. Google GP Sceptics or my name. I'm Dr Justin Coleman, thanks for listening to another Australian Prescriber Podcast.