The Toxpod

David McCutcheon

December 19, 2018 Tim Scott & Peter Stockham Season 1 Episode 5
The Toxpod
David McCutcheon
Show Notes Transcript

In this episode, Peter chats with Dr David McCutcheon of Royal Perth Hospital about the Western Australian Illicit Substance Evaluation (WISE) project.


McCutcheon, D. et al. An early warning system for emerging drugs of concern in the emergency department: Protocol for the Western Australian Illicit Substance Evaluation (WISE) study. Emergency Medicine Australasia (2018) https://doi.org/10.1111/1742-6723.13185


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The Toxpod is a production of The International Association of Forensic Toxicologists. The opinions expressed by the hosts are their own and do not necessarily reflect the views of TIAFT.

Tim:

Hello and welcome to The Toxpod. I'm Tim Scott. And today we're bringing you another interview that we did at the recent ANZFSS conference in Perth. This time Peter sat down with Dr David McCutcheon, who is an emergency room doctor with some experience dealing with drug affected patients. He's involved at the moment in a very interesting research project with the local forensic toxicology department, but I'll let him tell you about that himself. Hope you enjoy the interview.

Peter:

I'm here with Dr David McCutcheon from Royal Perth Hospital. David, thanks for joining me.

David:

No worries. Great to be with you.

Peter:

So David, can you tell us what inspired you to start up this project?

David:

So I'm a doctor at Royal Perth Hospital Emergency Department and I became interested in novel psychoactive substances when I worked a night shift on New Year's Eve a couple of years ago. And um, we were just hit by these really unusual patients that were coming through the door. We had about 10 or 12 of these patients that came in all from the same dance party. And clearly they'd taken something very odd that we hadn't seen before, they were very, very sweaty, they were agitated and they were flipping around on the trolleys a bit like fish that you've just landed. One of them was flipping around so much, he actually flipped over the rail and out of the trolley and landed up on the floor. Luckily he didn't hurt himself too badly. So yeah, they were, they were quite difficult to control. They were confused and hallucinating and not on the planet that we were on. Big dilated pupils and, and racing hearts. So yeah, we, luckily it was a fairly short lived syndrome that they were experiencing and most of them settled down again within about four hours. Um, a lot of them were discharged home at that point once we'd given them some sedation, uh, or just observed them for a little while. So we suspected they'd all taken pills that they'd thought to be MDMA, but we suspected there was something else going on there. And that's where we really started our collaboration with ChemCentre and the forensic analytical chemists that work there in trying to basically initially find out what, what was in these people's systems at the time. So we hadn't taken proper research samples from them. We asked the hospital pathology laboratory to hold onto some of the hospitals samples initially and then once we had discussed with our clinical toxicologists and also the, the, who introduced us to the scientists at ChemCentre we were able to get the samples down there for analysis. Unfortunately they didn't find anything and we weren't sure why that was, we thought possibly because there's some gel in the tubes that we use for the hospital collection. It might've adsorbed some of the drug. Also the samples were stored at four degrees for up to, I think it was 42 days before they finally got analyzed, by the time I worked at what we were doing. Again, some of these drugs are quite unstable at that temperature, particularly the cathinone drugs. So yeah, we thought it might've been one of those factors or possibly it's a drug that's, that's not part of their screening analysis methodology that they used at that time.

Peter:

So I guess at that point you realized there needed to be a mechanism of some sort to have these types of samples routinely tested to try and identify some of these substances?

Speaker 2:

Yeah, exactly. And then that was the start. That was the New Year's Eve 2013 going into 2014 and in the years following that we really saw an explosion in the use of novel psychoactive substances and that's when we started seeing clusters of cases very unwell. So the big cluster on the gold coast where one person died, there was the cluster in Melbourne on Chapel Street where 20 people became ill and three people died. So and there were scattered deaths at dance parties all through one summer a couple of years ago. That really made us see that this was an urgent problem and appeared to be getting worse. And we really needed some research into what these drugs were, what the effects were on, on people, why people were dying, and uh, all the public health implications associated with that as well.

Peter:

So what sort of toxicological testing is normally done on patients who come into the emergency department?

David:

So a lot of people would be surprised to hear that we do almost no toxicological testing in emergency. Uh, we have a breath alcohol analyzer that we use, if a patient's compliant enough. Other than that, we do do blood alcohol levels fairly regularly, but urine toxicology screens we really don't tend to use because you do get false readings on them, but also they don't really change what we do. So there's only in medicine, often there's no point doing a test if it's not going to change your treatment or the outcome. So most of these cases of toxicity are managed with what we call supportive care, which is just looking after the patient's needs as they appear, controlling abnormalities, so if they're agitated, we give them sedation, if they're hot, we cool them down. If they're dehydrated, we give them fluids. If their bladder is distended because they can't pee, we'll put a catheter in. All that sort of stuff, which just makes people feel better, relieves their symptoms, and we just wait until the drug wears off so that that would generally be our approach to the poisoned patient that's taken illicit drugs. We rarely do do urine drug screens if we're querying a diagnosis, say of whether someone might be intoxicated with drugs or whether they might have a mental health disorder. So often that's requested by our psychiatry team rather than by the emergency doctors. We often get people coming in demanding blood tests or urine tests after they say their drink has been spiked and we, uh, there was a study recently showing that almost none of the patients that claim their drink has been spiked, had anything in their system other than alcohol. So we even don't perform that testing anymore either.

Peter:

Yeah. There's been a few studies like that, I think. So when a psychotic patient who might be violent comes into a hospital, what sort of impact does it have on the emergency department?

David:

It's very difficult because we're often overcrowded as it is due to hospital beds being full with medical patients, particularly this time of year, the winter, spring flu season. So we're often dealing with a situation where we've got patients on the ramp as we call it, which is patients on ambulance stretchers out the front of our emergency department that can't even get inside. We usually get some pre-hospital notification but not always of a violent patient approaching us. And then we really have to prepare. So some patients are too unwell to bring into the emergency department to sedate. So then we might use a little area just inside the front door, um, to, to restrain them and give them sedation. Otherwise we tend to try and move them into a medical assessment cubicle where we can do things in the safest way possible. It involves lots of people, so we would usually have three security guards, there may be police that have come in with the patient as well. There will be several nurses, uh, at least one doctor to put in the intravenous line and, and administer the drugs. So yeah, it, it can be quite disruptive to the emergency department and then we, we have to make sure that patient's managed in a safe manner as well. And so we hook them up to all sorts of monitoring to make sure their oxygen level's okay and they're not blocking the airway, they're managed on their side, we take care of their pressure care and all that sort of stuff as well.

Peter:

In a situation where there are multiple intoxications, say from a cluster of intoxications, It's virtually impossible to treat all those patients at one hospital, I would imagine.

David:

Yeah. So if you imagine an emergency department that's already quite full, if a, if a large number of patients came in at once, it would be very difficult to manage them all if they all had that same need. The worst case would be that they're coming by private transport all at once, or the event is within walking distance from the emergency department. That would be very difficult for us to manage. So really we, we could only manage several patients that are highly agitated at any one time. Other than that, we're, we'd be looking at what we call a disaster situation, which is defined by our needs, uh, in excess of our resources and we're going to have to manage patients one at a time or we're going to have to divert them to other hospitals so they can all be managed safely. And we had a recent case of that where we had nine backpackers all overdose all at the same time on what ended up being hyoscine, a travel sickness medication, but we at the time thought it was likely to be an NPS. They came in with highly agitated and confused with dilated pupils and overheating and looked very much like it could have been any type of stimulant or NPS. So the initial plan was to bring them all to our hospital at the same time, but the doctors that were in charge very wisely negotiated with the other hospitals and they were split between different places and that's a safer way of managing a situation like that.

Peter:

So how does the project actually work from your end?

David:

Basically it's, it's fairly simple in what we do. If a patient comes into our emergency department and the treating doctor feels that they're currently intoxicated with a stimulant, hallucinogenic or cannabinoid drug, they can be enrolled into the study. If they're already having blood tests done or a cannula put in for their normal clinical treatment, an extra blood sample is taken and de identified and frozen onsite in our emergency research lab, which we're very lucky to have at Royal Perth Hospital and then we collect clinical data about the patient which is then matched to that sample, but de identified from the, the patient details.

Peter:

Why is the de identification process so important?

David:

It's an observational study, so we're not changing our treatment of the patient in any way, but the risk to the patient from being involved in a study like this is, say if the police or a judge subpoenaed our research records, they may reveal if they're identifiable, that a patient is linked to a positive drug test and that might have implications for them if they're involved in some sort of other activity that's of interest to the police. So as part of our negotiations with the ethics committee in designing the study, we developed a permanent de identification process that, where the link between the patient ID and their study ID is permanently destroyed. The way we do that is with a delayed time window in place, which allows us to collect quite high quality clinical data. So what we do is we have a patient sticker which we place on a piece of paper which has the study ID and that's filed securely in a, in a file. The reason we don't do anything electronic is electronic databases can always be backed up and accessed later even if things are deleted. So we consider anything we put on a computer to be potentially permanent. So it's just on a piece of paper and that gives us time for the research staff back of house to get blood result information to find out what's happened to the patient in terms of whether they go to ICU, or whether they have renal failure or they're put on a ventilator or whatever types of special treatment they may need. And then once at 10 days, 10 business day period after hospital discharge has passed or earlier, if we are able to get all the information before that, then that piece of paper is shredded and then the link to the patient ID is destroyed forever, but the sample with the drugs, by name and by concentration will still be able to be linked to that clinical data under that study ID.

Peter:

This post-admission information is very important in a study like this because you can link back to the physiological changes and effects of any new drug that may come out.

David:

Yeah, well that's the whole reason we're doing this study is to identify the drugs that people are taking. That's one part of it, but also we want to learn about these novel psychoactive substances and what they do and which ones are dangerous and which ones are less dangerous and that information is going to be really useful to people who might think about using these drugs, but also to the doctors who would like to treat them and to health authorities and government authorities in managing the, and understanding the use of drugs across Australia.

Peter:

Is it possible to get a faster turnaround on the tox results? For example, if there's a group of overdoses on the weekend that might come from the same source?

David:

Yeah, so we've done that twice now. Um, it's kind of a, a rapid early warning system, you could call it. On one occasion on Christmas Eve, we had two patients come in very unwell after taking a novel psychoactive substance. We were able to rapidly deidentify them and collect the clinical data and send the samples to ChemCentre for urgent analysis, which they did over the holiday period. And within 48 hours they were able to do a media release with the police who were able to, they also had a capsule of the, the NPS substance that they could show a picture of. They were able to describe that two people had been really unwell, they were able to name the drug involved. Um, and this all occurred while the drug's still in circulation in that festive period. So presumably this for, for discretionary drug users who only take their drugs for, um, you know, irregularly, that might actually reduce their use and could potentially be lifesaving.

Peter:

Yeah. It could change someone's mind and then you have potentially saved a life. So it's very important this information gets back to the community.

David:

Yeah. There's public health interventions are quite interesting because certain types of drugs you may have the opposite effect to what you would like. For example, if you put a public health warning out that there's a particularly strong batch of heroin in a particular area, drug users who are addicted drug users, who are compulsive users, may seek out that heroin because they think it will give them a stronger hit. So you could actually potentially cause harm by a public health announcement like that. So it really is best suited to those party type drugs where people take them occasionally on weekends or on festivals, for example.

Peter:

What types of sources are there now to provide information on NPS to communities?

David:

Yeah. So there's, there's several sources, and I'm not privy to all of these, but certainly the police are able to access coronial information and drug analysis. There's also police seizures of drugs which are analyzed for content and what they find, I believe they also do monitoring of, of Internet forums where people discuss drugs and what they're going to take. And there's a, we had a talk today on wastewater analysis and, and that takes place in various different cities to give an overall picture of what drugs are currently being used. The problem with NPS drugs is they're, there's sometimes very high potency drugs which are present in low quantities and when you combine that with a, a low incidence of use in the population, they can be quite hard to detect in wastewater. So that does fall down with these type of drugs in it. It's, it may not be the best way to try and work out when or where people are using them.

Peter:

That's right. And the wastewater analysis, as I understand it, is sampled over a long time, so they may just be a period of a few days when a particular substance is used. And that'll make it difficult to detect it in waste water.

David:

Yeah. I think until you have a drug that's in very common use such as methamphetamine, then obviously it's quite useful to give an overall picture of use, but yeah, for uncommon drugs or, or low potency drugs or unstable drugs as well is the other problem. As we were talking about earlier, cathinone drugs can be quite unstable at room temperature. And so it, it may be that the trace has disappeared by the time you analyze the drugs.

Peter:

And you're collaborating on this project with ChemCentre Western Australia, which is a highly advanced forensic tox lab. Was there much interaction between the hospitals and the laboratory before the project started?

David:

No, it's really it, it was really a case series that sparked off the collaboration and we, we, uh, we all have a passion for advancing knowledge in this area and it's, um, it's really been an incredibly useful collaboration that we have. I think for a project like this to be successful, you really need close collaboration with the clinical staff who can obtain the blood samples and the clinical information and the analytical chemists who can actually provide the high level complex analysis that is required for these samples. And so we were involved in designing the study together and the methodology and uh, we, we meet regularly as part of the steering committee to work out where the study's going. So it, it really is quite a successful collaboration we have going.

Peter:

You're gathering a lot of useful information through the project. How are you going to release this information?

David:

Yeah, well it's, it's being released in a few different ways at the moment. For starters, we've just had our methodology paper accepted for publication, so that's in the emergency medicine literature. Uh, so in the next couple of months that, that should come out in emergency medicine Australasia, but that's, that's gonna, that's got quite a lot of detailed information about the study methodology, the laboratory methodology and it's also got in the supplementary material, our entire case report form for data collection as well. So that will certainly enable other people to do similar work to us if they, if they want to establish projects or I know there's other projects running in different cities like in Adelaide that you're involved with. In terms of releasing results, we've, we have made these media releases about clusters of cases and we've been speaking at toxicology and emergency medicine conferences about some of the more interesting cases out of the study, but we will be releasing some scientific publications regarding methamphetamine levels and regarding some of these larger case series and probably some overall information just about the prevalence of NPS in the samples that we're detecting. So there has been a lot of media interest in certainly in Perth about some of our work, particularly when there's clusters of cases come in. So I think given that there's always a bit of profile and interest around these cases, there's, there's going to be continual opportunities to give public health messages and to give some of the results of the study. And that's important because one of our aims is to provide information to people who might use these drugs and so the media is going to be important part of that.

Peter:

So the project's been going for a couple of years now and from your presentation earlier today, it was obvious, there has been a high prevalence of methamphet cases. Can you tell us about the spread of results and any conclusions you can draw from those results?

David:

Uh, our analysis is very preliminary at the moment, and, and definitely mostly qualitative, but we've certainly seen the majority of cases that we enrol do contained methamphetamine. So we've got preliminary analysis on the first 347 cases and 229 of those were methamphetamine. But we found a lot of novel psychoactive substances as well. And in patients that had methamphetamine intoxication, who had another drug detected, almost half of those were NPS drugs, so they are certainly out there probably a little more than than people would think. The most important NPS we detected was actually a combination of two drugs, 25C-NBOMe and 4-fluoroamphetamine. And we have a case series of 16 cases of, of that particular combination. Uh, so we suspect given that the drugs are both present in all of these samples, there's probably a fairly high level importation of, of that combination that's been then distributed. We believe there are cases in other cities with that same combination as well that have caused fatalities and clusters of, of patients becoming unwell. So that certainly is, has been shown to be quite a bad combination of drugs. Toxicology research is quite muddy, so we don't know if it's the NBOMe or if it's the 4-fluoroamphet or if it's the combination of them that that causes the toxic effects.

Peter:

What about other traditional drugs like cocaine?

David:

Cocaine, I don't have the results in front of me, I'm sorry, so I can't give you the exact numbers, but we did find some cases of cocaine or the metabolites and in four of those cases we found levamisole as well, which has been associated with some quite significant health problems, so it's often cut with cocaine, particularly in the US, but it can cause toxicity including bone marrow failure and it can cause necrosis of the skin, which is death of the skin. So it's a little worrying to see that that's present in the cocaine samples that we have in in Western Australia.

Peter:

Sometimes we see cutting agents like that in tox samples and we don't think a lot of them because they're not psychoactive, but you can't forget they can have serious health effects as well.

David:

Oh, absolutely. Yeah.

Peter:

I've often wondered with these patients that come into the hospital in a psychotic state, do they remember that psychotic episode afterwards or are they too ill to remember it?

David:

Yeah that's an interesting question. Some of them do and some of them don't and I, we don't always ask them specifically about it, but yeah, a lot of them when they wake up in the morning don't pay much, don't give much reference to how they were the night before. So I suspect there is some amnesia about what's, what's happened when they've been in that state, but some of them do, do remember certainly aspects of it. And they tend to present in a certain way, so, we unfortunately have a lot of experience at Royal Perth Hospital, particularly of seeing these patients. We get several every day coming in a highly agitated state and they, they have this combination of, of agitation which is mixed with a bit of aggression, but also this paranoia and unusual ideas often about people watching them or listening to them or that people are out to get them. And that seems to be a pretty common thought disorder that they present with. In addition to the agitation and the, and the aggression.

Peter:

One of your colleagues told me today about a patient who thought they were being chased by Godzilla. So you'd probably be glad to forget that the next day.

David:

Yeah, well some of their hallucinations are quite terrifying for them and the interesting ones is where they come in paranoid that they're being chased or hunted down by organized crime gangs and you never know that might be true or that might be delusional. So we're never entirely sure about those ones. But there, there are certainly people that are scared they're being chased by monsters or, or Godzilla. We always escalate our, our intervention to the minimum necessary and progress from there. So if someone's willing to take a, a tablet or some sedation by mouth, we always offer that first. Um, and that can certainly take the edge off things even if we do need to put a drip in and give some sedation through the IV. So yeah, so sometimes we do have to restrain them because they're completely uncooperative and then put a, give them sedation through the drip.

Peter:

So what types of drugs do you commonly use in the emergency department to sedate someone who presents with psychosis?

David:

We tend to use a combination of drugs and the most common, a common combination would be midazolam and droperidol. So midazolam's a benzodiazepine agent that has a reasonably quick onset of action, although it doesn't last for very long. We use that to gain quicker control of the patient and have them settled down more quickly. But we also give droperidol which is an antipsychotic agent that helps with some of the, uh, the delusions and paranoia type symptoms they have, but it's also quite deeply sedating itself as well. And that combination seems to be the most effective for us. If we just use midazolam by itself, it wears off and they, they reemerge and, and are just as angry as when before we put them to sleep, except there's often just one nurse at the end of the bed rather than the whole team ready. So that's not a good outcome for us. So we'd rather they, they sleep for a bit longer until some of this psychosis wears off and they're a bit more manageable.

Peter:

We haven't really discussed SynCanns yet. Can you tell us about the kinds of symptoms that are exhibited by patients who have taken a synthetic cannabinoid?

David:

So synthetic cannabinoids are a very interesting group of drugs because they have such a varied, varied effect on people. Some of them are similar to, to natural cannabis in producing that kind of sedated type appearance, but some of them really are the total opposite. We see people come in with dilated pupils having seizures, uh, with a rapid heart rate and tense and it's almost like a, an amphetamine like syndrome that we see from them. Others are deeply, deeply sedating and people become almost comatose, and I think they're such complex molecules, much more so than the simple molecules like methamphetamine, and there's lots of different aspects to the molecules that can have different effects. So yeah, they're, they're, very varied drugs. The interesting thing about our study is that we've hardly seen any of them and that's due to a legislative change which basically banned all novel psychoactive substances, in fact, all psychoactive substances in Western Australia a couple of years ago. And since then they're very, very uncommon. We were seeing them very regularly before that.

Peter:

It's great to see a melding of expertise from the analytical side and the clinical side.

David:

Yeah, it's, it's worked so well in this case and um, you know, I think it would be great if, if similar collaborations around the country spring up because there's, there's significant regional variations in drug use and having one site in Perth which is quite isolated from the other parts of Australia that are more interconnected. It would be better to have Sydney and Melbourne and Adelaide and Brisbane sites like that where, you know, the, we'd get a, probably a, a more realistic picture. For example, we don't see GHB, we almost never see GHB over in Western Australia, but it's very common in South Australia and Victoria.

Peter:

That's very interesting when you mentioned that earlier today.

David:

Yeah, I don't know why that is. Um, it's not particularly difficult to import or get hold of, but it's just not in common use and with drug use we find that there are trends that don't have a logical explanation. People just, local drugs become fashionable I guess, and um, that, that fashion declines again. As we're seeing with methamphetamine, the use in Australia is actually declining at the moment. It's becoming less trendy and less fashionable for people to start using it. The problem is the people that are using it find it very difficult to stop. So I don't think we're gonna see a huge decrease in, in numbers of dependent methamphetamine users for a little while. But um, yeah, that trend will, will gradually fall away and another drug will take its place. And that's why a network of sites doing research like we're doing in Perth, will hopefully pick up as early as possible the next trend and the next drug because we are always behind when we're trying to work out how to manage these things. And we want to be as ahead of the game as possible.

Peter:

Well thanks David for telling us about your innovative project and thanks for joining us on The Toxpod.

Tim:

I found that interview really interesting. It's great, as Peter said, when you get the clinical side of toxicology coming together with the analytical side, which is exactly what happens at FACTA conferences. FACTA is on in June 2019. You can check out all the details at facta2019.com.au. Three days of clinical and forensic toxicology. Hope to see you there. And if you want to contact us at The Toxpod, you can send us an email at thetoxpod@sa.gov.au. Thanks for listening and we'll see you next time.