The Wellington Coroner, Mr Garry L Evans, recently investigated and reported on the deaths of six young New Zealanders due to butane inhalation (Decisions 86-91/05, 26 September 2005). These deaths occurred between January 2003 and April 2004 in people aged 15–27 years. The reports are compelling reading and strong recommendations are made about the management of drug abuse in New Zealand. These reports had widespread attention in the national media. The following is a brief overview of the clinical pharmacology of abused inhalants, in particular the properties and actions of butane.

The lifetime prevalence of inhalant abuse in New Zealanders is about 2%.1 The most commonly abused inhalants are solvents from adhesives, fuels, aerosol propellants, and nitrous oxide. Most abusers are adolescents and there is a high risk of death compared to other drug abuse.2

Abused inhalants can be loosely grouped into three groups on the basis of their pharmacological and behavioural effects.3 The first two groups are the volatile alkyl nitrites and nitrous oxide. The prototypic volatile alkyl nitrite is amyl nitrite. The basis for use and abuse of the alkyl nitrites is their vasodilatory and smooth muscle relaxant effects. Nitrous oxide is a widely used gaseous anaesthetic that is also used commercially as an aerosol (e.g. in whipped cream). Nitrous oxide has a pattern of effects that include stimulant, depressant, and hallucinogenic effects. However the exact mechanism of action on the central nervous system (CNS) is poorly understood.

The third group includes volatile solvents, fuels, and anaesthetics. Volatile substances have long being used in anaesthesia and also have a long history of abuse. Notable abusers in Victorian England included Coleridge, Southey, and Wedgwood. Anaesthetic agents have evolved from ether, to halogenated alkanes (e.g. halothane), and to the currently used halogenated ethers (e.g. sevoflurane). While the mechanisms of action of volatile substances are similar, these halogenated gases appear to have additional gaba enhancing activity, which provides advantages for anaesthesia.4

The mechanism of action of volatile substances remains poorly understood and their range of effects is much greater than can be elicited by specific molecular targets.5 Volatile substances are rapidly absorbed from the lungs and spread throughout the CNS affecting the properties of lipid membranes. The changes in cell membranes affect multiple cell-signalling processes.

A generalisation that is usually valid is the Meyer-Overton rule Potency of inhalational agents correlate directly with their lipid solubility. In anaesthesia potency is often defined by the minimum alveolar concentration required to produce an effect. The magnitude of effect is dependent on both dose and potency.

The acute affect of volatile substance abuse is characterised by rapid onset of intoxication and rapid recovery.6 Intentional abuse can cause the desired effects of euphoria and disinhibition, and the undesired effects of nausea, vomiting, dizziness, ataxia and cough. Higher doses can cause drowsiness, coma, respiratory depression and seizures.7 Pulmonary aspiration of stomach contents, and pneumonitis can occur. Cardiac arrhythmias are often implicated in fatalities.8

The chronic effects of volatile substance abuse have been characterised particularly for toluene, the solvent of “glue sniffing”. 9 Long-term use can cause permanent cerebellar and cortical damage and chemical pneumonitis is relatively common. In addition, hepatitis, bone marrow suppression, and renal failure have all been reported. Substance-abuse during pregnancy is a particular risk given the age of the abusing population, with toluene abuse during pregnancy being consistently associated with foetal malformations.

Butane, also known as liquid petroleum gas (LPG), is widely used as a propellant in aerosols and as a fuel for LPG appliances and cigarette lighters. It is a colourless, flammable gas with a boiling point of –0.5°C. The butane causing the Wellington fatalities came from a range of sources, including air freshener, lighter fluid, a gas heater, a gas element, and butane canisters for camp stoves (x2). Butane’s relatively high volatility, with rapid evaporation from compressed liquid, permits high dose rates. It is also highly lipid soluble (logP 2.81) and thus potent. The combination of a high dose and potency facilitated lethal toxicity in these six young New Zealanders.

Author information: Matthew P Doogue, Clinical Pharmacology Registrar; Murray L Barclay, Clinical Pharmacologist; Department of Clinical Pharmacology, Canterbury District Health Board, Christchurch

Correspondence: Matt Doogue, Department of Clinical Pharmacology, Christchurch Hospital, Private Bag 4710, Christchurch. Fax: (03) 364 1003; email matthewd@cdhb.govt.nz