John R. H. Archer

Aims: Toxicity in paracetamol overdose with opioid co‐ingestion is poorly understood. We compared outcomes in both paracetamol‐only and paracetamol–opioid overdoses to determine whether toxicity differed significantly between the groups, and to assess the utility of the ratio of measured plasma paracetamol concentration relative to the 4‐hour nomogram‐adjusted level (APAP_pl/APAP_t).Methods: We conducted a retrospective observational study of all patients (n = 1159) presenting to 2 large UK hospitals between 2005 and 2013 with acute single‐dose ingestion paracetamol overdose, with (n = 221) or without (n = 938) opioid co‐ingestion. Adverse outcomes included biomarkers of hepatotoxicity and the need for extended treatment. Several outcomes were assessed in relation to the APAP_pl/APAP_t ratio.Results: Median ingested dose of paracetamol was low in both groups (10 g). Statistical comparison of the median APAP_pl/APAP_t ratios showed a significant difference (0.65 vs. 0.56 for the paracetamol‐only and paracetamol–opioid groups respectively, P = .0329). Although there was a trend towards a lower risk of predefined toxic outcomes with opioid co‐ingestion, statistical analysis did not show a significant difference, with outcomes for the paracetamol‐only and paracetamol–opioid groups including the following: alanine transaminase >2× upper limit of normal, 7.7 vs. 5.7% (P = .6480); alanine transaminase >1000 IU/L, 2.4 vs. 0% (P = .2145); international normalised ratio > 1.3, 8.6 vs. 4.4% (P = .2774); and transfer to tertiary liver unit, 0.2 vs. 0% (P nonsignificant).Conclusion: Our study does not support a change in current clinical practise beyond standard testing at 4 hours or longer post ingestion for mixed low dose paracetamol–opioid overdose.

Following the development of the tramadol crisis currently affecting countries in the Middle East, and Africa, there has been increasing international interest in the regulation of tramadol. This study investigates the misuse of tramadol in patients presenting to emergency departments across Europe. Data from 32 emergency departments in 21 countries were extracted from the Euro‐DEN Plus database for the 4‐year period from 1 January 2014 to 31 December 2017. Of the reported 24,957 emergency department presentations, tramadol misuse was reported in 105 (0.4% presentations). Tramadol misuse was most common in Bratislava (Slovakia; n = 11, 7.5% of all presentations to this centre), Riga (Latvia; n = 4, 4.9%) and Munich (Germany; n = 17, 2.9%). On arrival, 14 (13.3%) of presentations were in coma/Glasgow coma score ≤ 8 and 9 of these had a respiratory rate <12 breaths/min. These presentations potentially pose a significant burden on emergency departments with a large proportion requiring admission to hospital for ongoing care.

Aims To evaluate the long‐term trends of new psychoactive substance (NPS) detection in pooled urine samples collected across a city centre. Methods Pooled urine samples from portable stand‐alone urinals were collected on a monthly basis over 5.5 years (July 2013–December 2018) across a city centre. These were analysed using a high‐performance liquid chromatography system, interfaced to a high‐resolution accurate mass spectrometer. Data were processed against a database containing over 2000 drugs/metabolites including over 800 NPS. Results In total, 44 NPS were detected with variation over time including cathinones (15, 34.1%), synthetic cannabinoids (8, 18.2%) and 21 (47.7%) other NPS. Since the introduction of the UK Psychoactive Substances Act (May 2016) cathinone detection has decreased with minimal detection over the last 4 months of the study. Synthetic cannabinoids were not detected on a regular basis until July 2016 with a subsequent variable detection frequency. There was a consistent, low level detection frequency of all other NPS throughout the study, but which appears to have increased alongside the decrease in cathinone detection. Conclusion Pooled urine analysis of samples taken from portable urinals in a city centre can be used as an effective monitoring tool to determine long‐term trends in the use of NPS. The results of this study demonstrate the impact of the Psychoactive Substances Act and reflect the findings of population surveys and clinical studies. Triangulation of these data with other data sources will enable greater insight into the NPS phenomenon.

The disposition of drugs and their metabolites have been extensively described in the literature, based primarily on the analysis of plasma and urine. However, there are more limited data on their disposition in whole blood, which is often the only specimen available in forensic investigations and cases of driving under the influence of drugs. In this study, we have, for the first time, established pharmacokinetic properties of cocaine (COC) and its metabolites from concurrently collected whole blood and plasma samples, following a single 100 mg dose of cocaine hydrochloride administered via nasal insufflation to seven healthy volunteers. The median C_max of COC and its major metabolites, benzoylecgonine (BZE) and ecgonine methyl ester (EME), were closely related in whole blood and plasma. The median C_max for COC in plasma was 379.7 ng/mL (347.5–517.7) and 344.24 ng/mL (271.6–583.2) in whole blood. The median C_max for BZE in plasma was 441.2 ng/mL (393.6–475. and 371.18 ng/mL (371.1–477.3) in whole blood, EME was 105.5 ng/mL (93.6–151.8) in plasma and 135.5 ng/mL (87.8–183) in whole blood. Calculated medians of the whole blood to plasma ratio of COC (0.76), BZE (0.98) and EME (1.02) of approximately 1, strongly suggesting that the erythrocyte cell wall presents no barrier to COC and its metabolites. Furthermore, whole blood and plasma concentrations of COC were strongly correlated (R² = 0.0914 R = 0.956, p < 0.0001), as was BZE (R² = 0.0932 R = 0.965, p < 0.0001) and EME (R² = 0.0964R = 0.928, p < 0.0001). The minor oxidative metabolite norcocaine (NCOC) was detected in both whole blood and plasma at concentrations between 1 and 5 ng/mL within 60–180 minutes, suggesting that NCOC could be indicator of recent COC administration. Data from this study have shown for the first time that COC and its metabolites BZE and EME are evenly distributed between plasma and whole blood following controlled single‐dose intranasal COC administration.

Objective: The aim of this study was to establish a management protocol for body stuffers presenting to the emergency department. Methods: This is a retrospective observational case series of patients presenting to the emergency department of a large inner-city hospital as ‘body stuffers’ during the period between 1 January 2006 and 31 October 2011, irrespective of the type of drug ingested. We reviewed demographic data, ingestion characteristics, clinical progress and outcome. Results: A total of 126 patients were included in the study, with a mean age of 31±8.10 years (range 15–58 years), among whom 106 were male (84%). Drugs ingested were as follows: heroin (n=61, 48%), cocaine (n=58, 46%), other drugs (n=20, 16%) and unknown (n=10, 8%). Of the patients, 23 (18%) ingested more than one drug. At presentation, 96 had features of drug toxicity. The presence of depressant drug toxidrome was more commonly observed among heroin users, but stimulant drug toxidromes were seen across all groups. Of the patients, 12 developed changes in clinical state, with a mean time to development of symptoms of 2 h 50 min±1 h 39 min (range from 1 h 0 min to 5 h 36 min). Abdominal radiography showed the presence of foreign bodies in 8% of the tests performed, and packets were recovered from one patient who underwent gut decontamination. Conclusion: Patients developed new or worsening features of drug toxicity within 6 h of presentation. Toxidromes observed are often not drug/class specific, and treatment including gut decontamination and radiography do not aid in expediting discharge. We propose an observation period of 6 h from the time of admission as the time required if the patient is asymptomatic or there is resolution of presenting signs and symptoms.

Context. There is increasing interest in the analysis of waste water at sewage treatment plants to monitor recreational drug use. This technique is limited for novel psychoactive substances (NPS) due to limited knowledge on their human and bacterial metabolism and stability in waste water. Small studies have reported the detection of NPS using pooled anonymous urine samples, which eliminates some of these potential confounders. Objective. To determine patterns of recreational drug, including NPS, use by confirming their presence in analysis of pooled urine from portable street urinals across a wide geographical area in central London over a 6-month period. Materials and methods. Pooled anonymous urine samples were collected from 12 four-bay stand-alone portable urinals distributed once a month across central London for six consecutive months. Samples were analysed using high-performance liquid chromatography coupled to high-resolution accurate mass spectrometry (LC-HRAM-MS); acquired data were processed against target compound databases. Results. With regards to Classical Recreational Drugs, there was consistency of detection of cathine, cocaine, morphine, MDMA over the 6 months, with variability of detection of amphetamine, ketamine and cannabis. With regards to NPS, a total of 13 NPS were detected during the six months. Mephedrone and methylhexaneamine were detected consistently each month. Other commonly detected NPS included methiopropamine (5 months), pipradrol (4 months), cathinone (4 months), 5-(2-aminopropyl)benzofuran (3 months) and 4-methyethcathinone (3 months). Of note, methoxetamine and the synthetic cannabinoid receptor agonists were not detected in any samples. Discussion. Previous studies using the same method detected three and five NPS in a nightclub and pissoir setting, respectively, on a single night. The longer sampling time of 6 months has allowed detection of 13 NPS. Of note, mephedrone showed the least month-to-month variation in detection over the 6-month sampling period. With regards to classical recreational drugs, those detected were consistent with use-data from UK population surveys. The only exception is amphetamine which these surveys have shown a steady decline in use since 1996 but our study showed some variation in the frequency of its detection. However, the sampling period was too short and a longer study is needed to detect the trend in decreasing use. Conclusion. This study demonstrates that analysis of anonymous pooled urine samples from stand-alone urinals can be used to detect and monitor trends in the use of classical recreational drugs and NPS in a large city centre over time. This technique has the potential to be a novel key indicator alongside other existing indicators to provide a more robust picture of the use of recreational drugs including NPS.

Background: The epidemiology on recreational drug use is based on self-reported user surveys. The scope of this is limited as users are often not aware of exactly what drug(s) they are using. Waste water (sewage plant) analysis has been used to identify “regional” recreational drug use but is limited by a lack of understanding of the metabolism and stability of novel recreational drugs. Aims: The feasibility of collecting pooled urine samples from a sub-population attending a night-club using a portal urinal to confirm the classical and novel recreational drugs being used. Design and Methods: Urine samples were collected from a nightclub over one weekend for analysis by various chromatographic techniques involving mass spectrometry. Results: Classical recreational drugs and novel psychoactive substance, including mephedrone, 3-trifluoromethylphenylpiperazine and 2-aminoindane were found. Parent drug/metabolites were also detected for amphetamine, cocaine, ketamine, MDMA, mephedrone and 3-trifluoromethylphenylpiperazine. Conclusion: Anonymous pooled urine samples from within a nightclub can be used to confirm the actual drugs being used by some individuals within this sub-population. Metabolite detection indicates drugs were being used and not simply discarded into the urinal. This methodology could be used to monitor recreational drug trend in other environments, e.g. schools, geographical regions/areas and compare drug use over time.