FACEMs lead project to demystify psychoactive substances

Professor Daniel Fatovich would tell you the only thing more confusing than a Blue Mitsubishi in the 1990s was a Red Mitsubishi, and not because of anything that resembled a car.

“We had a young person come in who’d taken a pill called the ‘Blue Mitsubishi,’” the WA-based emergency physician and researcher explains. “I had no idea what a ‘Blue Mitsubishi’ was.”

With no information available on the substance to inform treatment, and no blood tests that could detect or identify its contents, Prof Fatovich realised the “huge knowledge gap” on the substance required more investigation.

An hour or two later, the scale of the issue Prof Fatovich was observing became more apparent when another young person showed up to the Royal Perth Hospital (RPH) emergency department (ED) having taken a different illicit substance.

“They’d taken a ‘Red Mitsubishi’, and we all thought, ‘Oh no! The ‘Red Mitsubishi’ has got to be worse than the ‘Blue Mitsubishi!’”

Once again, there was no data and no knowledge on the substance, and no way to know how to treat the patient beyond the surface-level symptoms they were displaying.

“That’s where it first struck me. ‘Gee, there’s so much we don’t know about illicit drugs and what people are taking.’”

Professor Daniel Fatovich, pictured above.

More than two decades later, Prof Fatovich and fellow emergency physician and clinical toxicologist Dr Jessamine Soderstrom co-ordinate and manage the Emerging Drugs Network of Australia (EDNA).

EDNA addresses the knowledge gap in understanding illicit substances by encouraging clinicians, toxicologists and forensic laboratories to share expertise and knowledge on novel psychoactive substances; engage with public health and; ultimately, promote research-driven excellence to advance patient care.

While intoxicated patients in EDs are more commonly found to be experiencing the effects of alcohol poisoning, the Australian Institute of Health and Welfare (AIHW) reports illicit substance consumption is an increasingly regular social occurrence.

In 2019, the AIHW reported an estimated 3.4 million Australians used an illicit substance in the preceding 12 months. The same report also stated that, although drug-related presentations were directly responsible for a little over 1% of hospitalisations in 2020-21, the rate of the total burden of disease and injury related to illicit drug use has gone up by 35% between 2003 and 2018. Prof Fatovich’s own research also confirms that current coding systems significantly under-report illicit drug harms in EDs.

According to Dr Soderstrom, EDNA aims to clarify both what is causing the patient’s symptoms and the best way to subsequently treat them, rather than relying solely on surface level clinical observation.

“It is simply not good enough for us to treat recreational drug use differently than we treat other illnesses,” she says. “If someone has a temperature, you wouldn’t just go, ‘Oh, yeah, they’ve got an infection’ without looking for the source. With recreational drug use, that’s what we do – we just treat the symptoms. It doesn’t really matter what it is that they’ve taken.”

While Prof Fatovich’s observation on the knowledge gap for illicit substances pre-dates EDNA by decades, the project’s steps towards reality, and Dr Soderstrom’s involvement, began with a cluster of lightning bolt-marked blue and grey pills circulating around Perth on New Year’s Eve, 2013

“Every Christmas and New Year, there’s always a cluster of some funky drugs,” Dr Soderstrom explains. “We never know what it is – there has not been the capacity within the health system to be able to identify these drugs.”

““It is simply not good enough for us to treat recreational drug use differently than we treat other illnesses.””

Ten patients arrived in RPH presenting with a variety of symptoms ranging from an elevated heart rate through to what was described as “a state of agitated delirium”, each having taken the pill under the impression it was ecstasy.

One of the 10 patients had arrived after attempting, and failing, to ascend an 11-metre-high lighting rig, while another presented after attempting to walk through moving traffic.

Testing of the patient samples revealed that not only was MDMA not found, but that the only known substance found in two of the 10 samples was methamphetamine.

“Long story short, those samples were useless,” Prof Fatovich says.

“When you collect blood samples for illicit drugs, a lot of them are very unstable at room temperature, so basically it deteriorates and you could do the analysis and find nothing, when obviously something was there.”

While the experience sharpened the sample collection methods of the RPH ED, it also ignited a broader discussion of what was required to understand the complexity of patient presentations involving illicit substances.

As a result, another FACEM at RPH, Dr David McCutcheon, led the Western Australian Illicit Substance Evaluation (WISE) study, which investigated the potential for an “early warning system” for new and novel psychoactive substances (NPS) appearing in the ED.

Dr Jessamine Soderstrom, pictured above.

While Dr McCutcheon was the recipient of ACEM’s Al Spilman Early Career Researcher Grant in 2018 for his work, several other FACEMs, including Dr Soderstrom and Prof Fatovich, were all co-authors on the report.

“It was really a pilot project to work out what it is that people were taking, the impact on the ED and whether it was a useful project,” Dr Soderstrom says. “When the project started going, all of the added benefits became quite astounding, to be honest, and it’s just grown from there.”

The value of the project became apparent one Christmas Eve – “It’s always Christmas,” Dr Soderstrom says – when several young people ended up on breathing machines after presenting under the influence of what was presumed to be MDMA.

Friends of one of the people in hospital brought along a bag containing the pills the young man had taken, and before turning it over to the police, Dr Soderstrom was able to secure a sample for analysis, immediately sending it to the testing lab.

“It was a combination of a novel hallucinogen, as well as 5-NBOMBe and flouro - amphetamine,” she explains. “Whenever you fluorinate – which means you add a fluoride compound to an amphetamine group – it makes it a lot more potent; you add two different types of stimulant drugs [the LSD and fluorinated amphetamine] together it just makes the toxicity that much worse.”

While these drug testing initiatives wouldn’t affect the medical outcomes for the people who had already taken the substances, it did allow the RPH ED to collaborate with WA Police and issue a media alert about the visual presentation and content of the substance, potentially saving lives.

The experience left Dr Soderstrom with some lingering observations. “What it made me realise is that we did not have a systematic way of detecting what it is that people had taken, and also, how do we then message? How do we let the public know what is out there and what is actually causing harm?”

Other logistical challenges arose throughout WISE, which was only based at one, albeit central, Perth hospital.

It became especially evident during a cluster involving patients who had consumed what was thought to be cocaine but in fact was a batch of motion sickness medication.

With seven patients scattered across hospitals around the metropolitan area, the collection of samples for analysis was especially challenging. 

“There was no co-ordinated way of getting the bloods,” Dr Soderstrom says. “It was a complete palaver trying to find the blood sample from this hospital and that hospital and get them all co-ordinated to send to the ChemCentre [the forensic pathology lab working with WISE].”

Such instances, along with the recognition that other labs and emergency departments were undertaking similar investigations across the country, meant the need for a nationally organised approach to investigating new psychoactive substances became impossible to ignore.

“It was really the learnings from the WISE project that then got us thinking, ‘You know what? There’s a better way of doing this,’” Dr Soderstrom observes.

The Emerging Drugs Network of Australia team, pictured above. From left: Dr Courtney Weber (EDNA Data Manager), Dr Jess Soderstrom, Prof Daniel Fatovich. (Absent: Dr Jen Smith, Research Fellow). Photographer: Brydon Dunstan, Medical Multimedia, Royal Perth Hospital.

Enter EDNA, which takes the lessons from the WISE project and adds adaptations and processes for a national context, ensuring information and lessons from EDs across the country are shared to create objective baseline data, improving patient care and minimising harm.

EDNA, which is still in its initial five-year phase (2021-2025), has received significant cross-jurisdictional state and federal funding, including a National Health and Medical Research Council (NHMRC) Ideas grant valued at $3.7 million – the highest amount received in its funding round.

While the process of ED observation, sample collection and testing remained similar to the processes established for the WISE project, the difference is that the information is now entered into a registry that can be accessed nationally.

Six states and territories are involved across the country – NSW, Victoria, Queensland, SA, WA and Tasmania – with a major tertiary hospital and forensic laboratory in each of these jurisdictions acting as “sentinel” locations to monitor illicit and emerging drugs.

While blood samples are collected and put into storage as quickly as possible after a patient presents to an ED, other information about the patient – particularly details about their clinical presentation – can take up to a month to collect and store.

““People have been crying out for years to address this knowledge gap, and basically, we’re actually doing it, we’re addressing the knowledge gap.””

Patients are nominated as potential subjects if they have severe or unusual symptoms, based on whether their symptoms match those linked to stimulant, hallucinogenic or opioid poisoning and/or they belong to a possible larger group of poisonings. Intravenous or blood sampling must also be a normal part of their treatment, and the patients themselves are de-identified when their information enters the registry.

Prof Fatovich considers the new knowledge emerging from EDNA’s multi-disciplinarity and collaborative focus a personal highlight of his time managing the project.

“When I chair the national steering committee meeting [for EDNA], we’ve got a big TV screen, and there’s 30, 35, 40 little heads on the screen, from all around the country. Yes, there are emergency physicians on there, but there’s a whole lot of other disciplines as well – the engagement from so many different people from so many different backgrounds is incredibly satisfying,” he says.

“People have been crying out for years to address this knowledge gap, and basically, we’re actually doing it, we’re addressing the knowledge gap.”

Going forward, the ongoing aim is to continue expanding the project’s reach, according to Dr Soderstrom.

“Our aim is to build capacity, and to continue to work with the health department[s], with objective data, to work out how we can actually reduce harm,” adding that she also has an eye on the project’s long-term future outside of her and Prof Fatovich’s stewardship.

“This project has to be bigger than a person, it has to be bigger than me and Danny.”

Nevertheless, while the project continues to expand and define its long-term future, Prof Fatovich laughs when asked if he thought he’d ever be co-ordinating a multi-disciplinary research project addressing illicit substance use when completing his medical training.

““That’s the whole point about this: It’s all eminently preventable.””

“When you first start out as a doctor, I don’t think you think of anything like that. I think you’re just happy to be a doctor, to be treating some patients and sometimes actually knowing what you were doing.”

However, the further his career has progressed, the more the idea of contributing to a better health system has entered his mind.

He says, “You think of ways of how you can make the system better and I don’t think I deliberately set out to make the system better through this idea, but I think that’s what’s going to eventuate. We need to be a learning health system.”

Dr Soderstrom, who shares similar sentiments, notes that a better process of reporting and researching for illicit substances is well overdue, and the consequences of the recent past are too dire to repeat.

“When you have spoken to families of those young people who have died at music festivals, it is heartbreaking and they didn’t need to die,” she says.

“That’s the whole point about this: It’s all imminently preventable.”