Case Report 1490 www.thelancet.com Vol 369 April 28, 2007 Collapse, reported seizure—and an unexpected pill David M Wood, Paul I Dargan, Jennifer Button, David W Holt, Hanna Ovaska, John Ramsey, Alison L Jones In May, 2006, on a Bank Holiday weekend, an 18-year-old woman presented to an inner-city London emergency department. She had been at a nightclub with friends and purchased tablets, which she understood to be Ecstasy or amphetamines, from a dealer. After ingesting five tablets, she collapsed in the nightclub and appeared to have a seizure lasting 10 min. On arrival in the emergency department, she was agitated and had dilated pupils (8 mm), sinus tachycardia (156 bpm), and a blood pressure of 150/51 mm Hg. Her score on the Glasgow coma scale was 15 and she was apyrexial (35·9°C). She had no significant past medical history and was on no regular medication. She was one of seven patients to attend the department that night with a similar presentation. We therefore considered it possible that she had taken a contaminated drug, or a substance not previously sold in the area; and we took a serum sample for analysis, in addition to treating the patient symptomatically with intravenous benzodiazepines (4 mg lorazepam followed by 15 mg diazepam). After 12 h, she was asymptomatic and discharged with advice to avoid recreational drugs. The serum sample was analysed by gas chromatography with mass-spectrometric detection (GCMS); 1-benzylpiperazine was detected at a concentration of 2·5 mg/L. Toxicological screening of the same serum sample did not detect the presence of other piperazines, other drugs, or ethanol. A tablet purchased by the patient (figure) was also analysed, and found to contain 1-benzylpiperazine. 1-benzylpiperazine is one of the piperazine family of drugs, initially developed as veterinary anthelmintic agents in the 1950s. Its chemical structure is similar to that of amphetamine. 1 Piperazines are marketed in the UK, where they are legally available in shops and over the internet, as having similar effects to controlled recreational drugs; pills containing piperazines are known as “pep pills”. 2 No reliable data are available on the consumption of piperazines in the UK, although one manufacturer claims that “over 20 million pills have been consumed in New Zealand with no deaths, or significant lasting injuries”. 2 However, in initial clinical trials of 1-benzylpiperazine, adverse effects similar to those of amphetamines were noted. 3 A prospective study in New Zealand identified adverse effects including nausea, vomiting, tachycardia, hypertension, anxiety, and agitation among 80 patients presenting to emergency departments after 1-benzylpiperazine ingestion. 4 Seizures 4 were reported in 15 (19%), at up to 8 h after ingestion. Three patients had potentially life-threatening recurrent seizures; ingestion of 1-benzylpiperazine by these patients was confirmed by toxicological screening of their urine. Other potentially serious adverse effects included QTc prolongation (QTc duration 430–490 ms in 32 patients) and hyponatraemia (serum sodium concentration 118 mmol/L and serum osmolality 242 mmol/kg) in one patient. Clinicians should be aware of the potential presenting features of piperazine toxicity, particularly because commercially available urine toxicological screening kits for drugs of abuse may not detect piperazines. All patients with strongly suspected or reported ingestion of 1-benzylpiperazine should have an initial baseline ECG, to seek features of cardiotoxicity. They should be observed for up to 8 h after ingestion, because the onset of seizures can be delayed. Initial treatment should be based on the clinical presentation. Further management can require the advice of a clinical toxicologist. References 1 Wikstrom M, Holmgren P, Ahlner J. A2 (N-benzylpiperazine) a new drug of abuse in Sweden. J Anal Toxicol 2004; 28: 67–70. 2 Spiritualhigh.co.uk – Staying Safe on PEP Pills. http://www. spiritualhigh.co.uk/information/drug-harm-minimisation-and-legal- highs/staying-safe-on-pep-pills/3-7-7-19 (accessed April 2, 2007). 3 Bye C, Munro-Faure AD, Peck AW, Young PA. A comparison of the effects of 1-benzylpiperazine and dexamphetamine on human performance tests. Eur J Clin Pharmacol 1973; 6: 163–69. 4 Gee P, Richardson S, Woltersdorf W, Moore G. Toxic effects of BZP-based herbal party pills in humans: a prospective study in Christchurch, New Zealand. N Z Med J 2005; J 118: U1784. Lancet 2007; 369: 1490 Department of Clinical Toxicology, Guy’s and St Thomas’ Poisons Unit, London SE14 5ER, UK (D M Wood MD, P I Dargan FRCPE, H Ovaska MD); Analytical Unit (J Button MSc, Prof D W Holt FRCPath) and TICTAC Communications Ltd (J Ramsey), St George’s University of London, London SW17 0RE, UK; and Faculty of Health, University of Newcastle, NSW 2308, Australia (Prof A L Jones MD) Correspondence to: Dr David Wood David.wood@gstt.nhs.uk CH 2 NH 2 CH 3 CH CH 2 N N H A B 1-benzylpiperazine Amphetamine Figure: 1-benzylpiperazine (A) One of the tablets purchased by the patient. (B) 1-benzylpiperazine and amphetamine.