Clinical record
A cluster of 10 patients presented during the night of 31 December 2013 to the emergency department of Royal Perth Hospital with states of agitated delirium or exhibiting unusual behaviour. Eight of the patients had attended an open-air dance party in the city close to the hospital, and nine had arrived by ambulance. All except one admitted to taking non-prescription drugs in tablet form, most believing they were consuming ecstasy (3,4-methylenedioxymethamphetamine, MDMA) in the form of blue or grey pills, in several cases imprinted with a lightning bolt. Media warnings had already been issued in response to similar cases involving acute psychosis reported by another metropolitan emergency department (Fremantle Hospital).1,2
The median age of the patients in our cluster was 20 years (interquartile range [IQR], 18–22 years). The median initial heart rate was 115 beats per minute (IQR, 84–155 beats per minute). Four patients were febrile (temperature ≥ 37°C) but only one had a temperature greater than 38°C. All patients had dilated pupils (median width, 6 mm [IQR, 5–7 mm]). Five patients required intravenous sedation, and in two cases more than 50 mg diazepam was required.
The patients had posed a significant risk to themselves before attending the emergency department: one had been found collapsed on the dance floor, another had wandered through vehicular traffic, and a third had fallen after climbing an 11 metre-high lighting rig.
The clinical syndrome included a state of agitated delirium, with labile mood, tachycardia, dilated pupils, sweating and, in several patients, involuntary movements. Clonus was present in only one case. One patient tried several times to hit staff members, while another spat at them. The most severely affected patient developed status epilepticus, and required intubation and admission to the intensive care unit. After recovery, he stated it was only the second time he had used non-prescription drugs.
The cluster of patients had a significant impact on emergency department resources. They comprised 10 of the 83 patients who presented to the department in the 7-hour period between 19:55 and 02:55. Many required intensive nursing care and intravenous sedation. One patient flipped over the safety railing of his trolley and landed on his head, but was not significantly injured. The median hospital length of stay was 5.4 hours (IQR, 3.0–11.9 hours).
Emergency treatment of the patients followed standard procedures for a sympathomimetic syndrome,3 and included oral or intravenous administration of benzodiazepines and fluids, observation and, in one case, intubation and cooling for status epilepticus. In patients for whom benzodiazepines were indicated, unusually large doses were needed to achieve adequate sedation.
Blood samples were taken from nine of the patients when intravenous cannulae were inserted as part of routine clinical care. Retrospective analysis of stored plasma samples using liquid chromatography–mass spectrometry was undertaken 40 days later by ChemCentre forensic laboratories (Perth, WA) to attempt to identify the substances responsible for the patients' symptoms. Results were compared with a large library of conventional and novel recreational drugs.
No novel synthetic agents were identified, but methamphetamine was detected in samples from two patients. The clinical syndrome observed and the absence of evidence for conventional drugs of misuse in all but two of the samples aroused suspicions of unidentified synthetic drugs. As analysis of drugs recently seized by police indicated that many “ecstasy tablets” contained high amounts of caffeine, caffeine levels were assessed in our samples, but were found to be uniformly low. Most of the tablets taken by the patients had been marketed as ecstasy, but no MDMA was detected in any of the plasma samples. Interestingly, lactate levels were elevated in all patients (median concentration, 3.1 mmol/L; IQR, 2.5–3.8 mmol/L), and all samples but one contained high levels of ethanol (median concentration, 180 mg/100 mL; IQR, 140–220 mg/100 mL).
Discussion
The continued emergence of novel synthetic recreational drugs is a growing problem in many countries, and the short- and long-term effects of these compounds are poorly understood. There have been recent deaths in Australia linked with such substances.4 Little reliable information is readily available to inform either users or clinicians.
There are several possible technical reasons why new synthetic drugs were not detected in our patients' plasma samples. These could include adsorption of the drug by gel in the collecting tube5 and instability of the drug at room temperature or when refrigerated at 4°C.6-7 These problems may have been compounded by the 40-day delay between collection and analysis.
Ongoing research into new synthetic drugs is needed to identify which harmful substances are currently circulating in the community and to inform potential users of their harms. Public warnings about clusters of cases, if deemed appropriate, should be issued on the basis of clinical presentations rather than of definitive analyses, given the time delay involved in performing these. The optimal treatment of patients is unknown and will vary according to the compound ingested. Future research should also consider the most appropriate methods for collecting samples to optimise analysis outcomes, including the temperature at which samples should be stored to preserve the chemicals of interest.
Public health warnings about a dangerous batch of “ecstasy” tablets had been issued to the media earlier in the day on which our patients had taken their pills,1,2 but the effectiveness of these messages is unknown. Most of our patients erroneously thought they had taken MDMA, and all had consumed only a small number of tablets. Media reports often mention the dangers of an “overdose”, implying the consumption of many tablets, which could mislead users into believing that one or two tablets (of an unknown substance) are safe. Public health messages should consider the need to communicate risk effectively, but there may also be unintended adverse consequences. These include encouraging experimentation by alerting naive or non-consumers to potential new drugs.
Lessons from practice
- The use of novel synthetic drugs is an increasing problem.
- There is little reliable information to inform users or clinicians about these drugs.
- The optimal use of the media to warn potential users is yet to be defined.
- Future storage and analysis of substances should take into account their potential instability and low plasma concentrations.
David G.E.Caldicott
The management of multiple simultaneous presentations of a presumed illicit drug aetiology is frequently challenging 1. It also offers the opportunity to characterize the agent involved and its effects on a de facto series of patients. Classical approaches to this scenario appropriately focus on the treatment of patients, but in such a rapidly evolving market, one or two extra steps can help to characterise the specific agents involved, and undermine the false sense of security surrounding the novel psychotropic substance (NPS) / ‘legal high’ market.
The NPS market has evolved to bypass traditional prohibition approaches to more ‘classic’ illicit market, and for clinicians to have an impact on the harms associated with this NPS market, we must be prepared to be every bit as nimble as the market itself, even to the extent of involving consumers themselves in identifying products responsible for mass intoxication.
An example of such a nimble intervention is ‘drug checking’, an evolution of the intervention previously known as ‘pill testing”. Early Australian work demonstrated its utility in identifying novel products long before law enforcement and customs1, and well-before the formal recognition of the nascent ‘legal high market’. Modern programs in Europe use state-of-the-art HPLC (high performance liquid chromatography) or GCMS (gas chromatography / mass spectrometry), and even have a code of best practice2. In November 2005, the AMA itself passed a resolution calling for a medically supervised trial of pill testing methodology in Australia. A decade later, this very sensible recommendation is still ignored. As well as in situ testing at points of consumption, we have developed hybrid models which provide the facility for patients (and their proxies) to submit native product for analysis3. In the circumstances described in McCutcheon, we would be fairly certain of our ability to acquire native product for sanctioned formal analysis, prior to destruction.
Our experience with consumers5, and consumers overseas, suggest that they respond by moderating intake when faced with factual information that is not overly burdened with moral messages. Interventions such as ‘drug checking’ not only permit us to access and influence consumers, but also expedite our acquisition of knowledge of the dizzying array of products currently on the market. We mustn’t underestimate the value of that information as a currency to the consumer, and its potential utility to clinicians and toxicologists globally.
1) McCutcheon DS, Oosthuizen FJ, Hoggett KA, Fatovich DM. A bolt out of the blue:
the night of the blue pills. Med J Aust. 2015 Jun 1;202(10):543
2) Camilleri AM, Caldicott D. Underground pill testing, down under. Forensic Sci. Int. 2005 Jun 30;151(1):53-8.
3) http://www.emcdda.europa.eu/attachements.cfm/att_231074_EN_INT15_NEWIP_Drug%20checking_standards-final_20.12-A4.pdf
4) For further information see www.wedinos.org/ and http://actinos.org/
5) Johnston, Jennifer, Monica J. Barratt, Craig L. Fry, Stuart Kinner, Mark Stoové, Louisa Degenhardt, Jessica George, Rebecca Jenkinson, Matthew Dunn, and Raimondo Bruno. "A survey of regular ecstasy users’ knowledge and practices around determining pill content and purity: Implications for policy and practice." International Journal of Drug Policy 17, no. 6 (2006): 464-472.
Competing Interests: No relevant disclosures
Assoc Prof David G.E.Caldicott
Calvary Public Hospital / Australian National University
Monica JBarratt
These presentations may have been avoided if they had occurred in a setting with an integrated drug checking service. In many European countries(2), health workers collect anonymous samples of illicit substances from consumers in collaboration with nightlife promoters, welfare and law enforcement officers. Results of on-site testing are compared against a comprehensive database of psychoactive substances, and festival organisers permit announcements regarding emerging hazards to persuade patrons to exercise further caution. In McCutcheon et al.’s case series, an alert at the festival that ‘blue lightning bolts’ were being mis-sold as MDMA may have helped avert further use.
The discovery of the content of these pills may have assisted in clinical management. Drug checking has an important role to play in the public health and clinical response to the rapidly increasing number of new psychoactive substances (with more than 100 new substances reported globally in 2014(3)). In the Netherlands, for example, anonymous testing is incorporated into the monitoring system to detect and respond to the emergence of new harmful substances(4).
Young people will continue to use psychoactive substances – illicit and licit – and most will not develop substance use disorders. To help keep young people as safe as possible, Australia should trial, develop and implement an integrated drug checking and monitoring system drawing on the vast European experience.
References
1. McCutcheon DS, Oosthuizen FJ, Hoggett KA, Fatovich DM. A bolt out of the blue: the night of the blue pills. Med J Aust. 2015;202(10):543.
2. Nightlife Empowerment & Well-Being Implementation Project. Drug Checking Service Good Practice Standards. Funded by the Health Programme of the European Union. Lisbon: European Monitoring Centre for Drugs and Drug Addiction, 2013.
3. United Nations Office on Drugs and Crime. 2015 World Drug Report. Vienna: United Nations, 2015.
4. Brunt TM, Niesink RJM. The Drug Information and Monitoring System (DIMS) in the Netherlands: Implementation, results, and international comparison. Drug Testing and Analysis. 2011;3(9):621-34.
Competing Interests: No relevant disclosures
Dr Monica JBarratt
NHMRC Research Fellow, Drug Policy Modelling Program, National Drug and Alcohol Research Centre, UNSW Australia; Adjunct, National Drug Research Institute, Curtin University; Visiting, Centre for Population Health, Burnet Institute