γ-Hydroxybutyrate poisoning from toy beads

After confirmation of GHB poisoning in Patient 1 from 1,4-BD detected in Bindeez toy beads, the NSW Poisons Information Centre was notified. The Centre and the NSW Biochemical Genetics Service alerted the NSW Office of Fair Trading about the product. They in turn contacted the company marketing the product to investigate the formulation of the toy beads. When the manufacturer in Hong Kong was contacted, it supplied a list of ingredients in the production of the toy beads; this list did not include 1,4-BD, but did mention the agent 1,5-pentanediol.

Meanwhile, two further samples of Bindeez toy beads were tested at our institution. Both samples tested positive for 1,4-BD. None of the beads tested contained 1,5-pentanediol. With confirmation of similar biochemical analyses from the beads in the second case, the NSW Department of Health and the NSW Office of Fair Trading were further alerted about banning the product. The following day, the NSW Minister for Fair Trading issued an interim ban on the sale of Bindeez products in NSW; other Australian states rapidly followed suit. Further cases of GHB poisoning in Australia came to light during the ensuing days. Staff of the Poisons Information Centre also alerted toxicologists and poisons control centres worldwide where similar products are marketed (eg, Bindeez in the United Kingdom and Aqua Dots in North America) and the potential for GHB poisoning may have existed. With worldwide media coverage and similar cases in North America, an international recall soon followed.

GHB is an endogenously occurring neurotransmitter derived from γ-amino butyric acid (GABA).1 Its known metabolic precursors are 1,4-BD and γ-butyrolactone. A potent sedative and anaesthetic agent, it was initially synthesised in the 1960s.2 GHB and its precursors have recently found notoriety as recreational and club drugs. In 2000, GHB became a banned substance by the United States Drug Enforcement Agency and classified as Schedule 1 by the US Food and Drug Administration.2,3

1,4-BD is a widely available industrial chemical used as a solvent and in the manufacture of some types of plastics and fibres. When ingested, it is metabolised rapidly by alcohol and aldehyde dehydrogenases to GHB.4,5 Hence, the toxicity and clinical features of 1,4-BD poisoning are similar to those of GHB. While 1,4-BD is not a scheduled drug in Australia, it is a category 1 precursor under the Drug Misuse and Trafficking Regulations 2006, which restrict the supply of 1,4-BD (Pharmaceutical Services, NSW Department of Health, personal communication, 12 Nov 2007).

GHB is an agonist at inhibitory GABAB receptors and is excitatory at specific GHB receptors. There is a dose–response relationship in GHB toxicity. Low doses result in vomiting, drowsiness, visual disturbance and disinhibition, while higher-dose effects include confusion, coma, bradycardia and myoclonic (seizure-like) movements.3 Routine urine toxicology screens do not detect GHB in their profile. Specific analysis with gas chromatography–mass spectrometry (GC–MS) or as part of a urine metabolic screen is required. The urine sample from Patient 1 was investigated for possible inherited metabolic diseases, including urinary organic acid analysis by GC–MS.6 This showed a marked increase in GHB (a metabolite seen in succinic semialdehyde dehydrogenase deficiency) but without any increase in 4,5-dihydroxyhexanoate lactone, as would be expected in the inborn error. This pattern strongly suggested an exogenous source of GHB, which was confirmed by the compound being undetectable in a second urine sample taken 3 days later.

Treatment of GHB poisoning is primarily supportive and may involve airway and ventilatory intervention, and atropine for symptomatic bradycardia7 Gastrointestinal decontamination with activated charcoal is not indicated, owing to the rapid absorption of this liquid poison. Additionally, there are no specific antidotes that reliably reverse GHB toxicity.7

Where patients are suspected of ingesting Bindeez toy beads (containing 1,4-BD), they should be observed in the ED for depressed level of consciousness. Patients who remain asymptomatic after 4 hours are unlikely to have ingested enough beads to cause toxicity and can be safely discharged from hospital. Patients developing symptoms should be managed in a similar way to those with GHB intoxication. Moderately intoxicated patients may be managed and observed in the coma position until awake, while patients with airway compromise or respiratory failure may require intubation and mechanical ventilation until toxicity resolves.

The identification of these cases highlights the important role of poisons centres in toxicovigilance and monitoring of potential clusters of poisoning related to new pharmaceuticals and chemical agents. Rapid electronic communication of these cases to worldwide toxicological networks enables health authorities to make a risk assessment of similar toy products overseas. So far, this has resulted in identification of similar suspected cases of GHB poisoning in children and an international withdrawal of the product. Chinese authorities confirmed that toy beads from the Hong Kong manufacturer contained a substance which metabolised to GHB.8

Bindeez bead set

“Make, spray and they stay! Bindeez are magic beads that you use to create colourful and fun designs. Just lay out your design in the special Bindeez tray, then spray them with water and your artwork will magically set in place!” (from an advertisement for the toy).