Portal de Periódicos da CAPES

Misuse of anaesthetic gases

2016; Wiley; Volume: 71; Issue: 10 Linguagem: Inglês

10.1111/anae.13551

1365-2044

W. F. S. Sellers,

Renal function and acid-base balance

Substances with anaesthetic activity when inhaled are available to the public and are abused. The reasons for such abuse are multiple, but include effects such as dysphoria, intoxication, and hallucinations. Legislation has struggled to catch up with abuse of agents with anaesthetic activity, and this has led to increasing reports in the media. The scale of this abuse and long-term effects are unknown, and this editorial will address some examples of abuse, and include simple in-vitro measurements of volumes, pressures, and oxygen levels, performed by the author using equipment found in anaesthetic rooms. Ether, nitrous oxide (N2O), Norflurane (HFA), chloroform, and trichloro-ethylene may be inhaled to achieve a recreational 'high', and the latter two agents are implicated as sedation agents in robberies and other criminal acts 1, 2 but are not discussed here. Anaesthetists and other health workers are known to abuse anaesthetic agents, by parenteral and inhaled routes; in the USA, 22% of anesthetic departments reported at least one incident of inhaled agent abuse among trainees, nurse anesthetists, and consultants. Mortality rate was high at 8 out of 31 abusers, five deaths were trainees; the ten abusing N2O did not die, and only five of the survivors were able to return to practice 3. Inhaled stupefiants have been ranked in order of popularity of abuse in the USA, namely; gasoline, FreonTM (a chlorofluorocarbon), butane, glue, and N2O 4; abusers of these, other aromatic gases, and even helium are described as 'huffers'. Guidelines for determining inhalant deaths to help Medical Examiners, Coroners and Pathologists are published by an independent US body, the National Inhalant Prevention Coalition 5. Speculating how abusers inhale, in conjunction with measurements, should help to render advice, reduce morbidity, mortality, and increase safety of a pleasure-seeking group of individuals who are unlikely to desist. Ether was inhaled in 'ether frolics' in the Victorian period; it may have been discovered much earlier, by Jabiribn Hayyan in the 8th century, and certainly by Valerius Cordus of Germany in 1540. It is produced by adding sulphuric acid to ethyl alcohol creating 'sweet oil of vitriol'. Ether is an orally ingested drug used by the Lemkos peoples of the Carpathian mountains. Flammable diethyl ether in spray canisters is used to start recalcitrant internal combustion engines. No information is available from Government bodies or found by this author about the scale of ether abuse; ether is very good at starting lawn mowers in the spring (personal observation). Nitrous oxide has been inhaled for recreational purposes since 1799. Deaths from nitrous oxide abuse have been reported 6 (too few to note an increase or decrease), seventeen in England and Wales between the years 2006 to 2012 7, and there were an estimated 700,000 users in England and Wales between the ages of 16 and 59 years in 2013–2014 8. Empty aluminium 8 g cylinders, used to charge whipped cream makers, can be seen littering the outside of clubs and at music festivals. Theft of large N2O cylinders from hospitals occurs, and the Advisory Council on Misuse of Drugs has reported concerns to the Home and Health Secretaries, and gives a comprehensive summary of misuse, theft, cylinder security, and the need for legislation 9. Internal combustion power-boosting N2O cylinder manufacturers pre-empt abuse by adding noxious sulphur dioxide. Nitrous oxide inhalation is addressed, discussed, and worth watching in the 5th of a thirteen chapter series of "Play Safe" drug-use YouTube videos produced by Eddie Einbinder 10. In the 2007 film "The Shooter", actor Mark Wahlberg inhales nitrous oxide from an unshaken 'Mr Whippy' pressurised cream can to unconvincingly render himself unconscious before his late partner's wife removes a bullet from his chest. Whipped cream makers are robust well-sealed aluminium vessels, of similar sizes, and supplied separately are 8 g aluminium pressurised chargers containing N2O, sometimes known as 'whippets' after a US brand name Whip it. A canister is discharged into the chamber without cream. A party balloon is rolled onto the spout, and contents are released with a loud whoosh, filling the balloon. This is removed, sealed with one's fingers, and contents inhaled, standing or supine, with a breath-hold, and/or re-breathing up to 16 times, until the balloon is empty or released. Further chargers into the same cream maker can be added to the same balloon, possibly up to three times, and consecutive charges may be inhaled one after the other. The author performed the following experiment. A nitrous oxide charger (Kayser, Berndorf AG, Vienna, Austria) was discharged into a cream maker (Mosa Corp., Yunlin, Taiwan) 0.25 l, a bicycle tyre gauge (Air tool pro, Specialized UK Ltd., Chessington, Surrey, UK) attached to the spout produced a reading of 30 psi (200 kPa) on release of the gas. Direct inhalation from the spout without a balloon can cause barotrauma. Collecting the nitrous oxide from another charger into an evacuated 2 l anaesthetic reservoir bag, quickly filled and over-expanded it, and by counting 60 ml syringe evacuations until empty, gave a volume of 3.24 l, 2% of which was oxygen. Further charges eliminated oxygen from the cream maker. A filled balloon exerts some positive pressure when inhaled, aiding delivery, but this was not measured. Re-breathing by blowing back into the balloon creates a Valsalva-like manoeuvre. Inhalation of 3.24 l into a 4-l capacity lung could achieve a nitrous oxide concentration of 80%; further inhalations and exhalations into a balloon of nitrous oxide will lead to hypoxia and carbon dioxide retention, especially if there are up to sixteen respiratory cycles from the 3.24 l reservoir. Three discharges into a strong balloon could produce a 10.72 l (3 × 3.24 l) reservoir. A 'Fink' effect of diffusion hypoxia 11 will occur when the gas is exhaled. Pneumothorax has been described 7, and nitrous oxide increases the size of an existing air space. Astute abusers realise that a short period of acute pain relief is possible, for instance when defecating through haemorrhoids or an anal fissure. In the past, 100% nitrous oxide from dental anaesthetic machines was possible (and used) by turning a knob to 'dial up' that proportion. Inhalational acute pain relief of a safer nature is possible with a PenthroxR (MEGA, Cromer, NSW, Australia) inhaler (a kazoo-like device) which comes with a small vial of methoxyflurane; this anaesthetic agent has re-surfaced for medical use in the UK, having been kazoo-ed (but not reportedly abused), for years in Australia. The hydrofluoroalkane (HFA) norflurane, formula CFH2CF3, was thought to be as inert pharmacologically as chlorofluorocarbons, and therefore not fully investigated. It is an inhalational anaesthetic agent of intermediate potency 12, propels drugs in most pressurised metered-dose asthma inhalers (pMDI), and is a water pipe freezer, air-conditioning, and refrigerator liquid. There are no Home Office statistics concerning abuse of pMDIs 13 and industrial HFAs which may well have replaced Freon as an agent of abuse. Norflurane, or 1,1,1,2-tetrafluoroethane (the same agent), and apaflurane, HFA227ea, are pMDI propellants which replaced CFCs in the late 1990s. Norflurane is a non-flammable anaesthetic agent with a boiling point of minus 26.5 °C; anaesthesia was studied only in animals, it required 50% in oxygen and was safe 12. Hydrofluoroalkane propellants (HFA 227ea has no anaesthetic activity) interfere with older anaesthetic vapour monitors 14. Hydrofluoroalkane 134a was subjected to toxicology studies before the change to chlorofluorocarbons up to only 0.8% in air; researchers neglected their chemistry and literature homework, and failed to link the anaesthetic publication describing 1,1,1,2-tetrafluoroethane to the structure of HFA134a. Inhaled anaesthetic agents relax smooth muscle as do all other hydro-fluorocarbons, also found in bitumenous products (e.g. road tar), and were used for asthma relief in the form of creosote, burnt in a Creosoline lamp and inhaled 15. Changes in bronchial caliber in healthy volunteer HFA studies using respiratory function testing were not measured, after the agent had been exhaled 16, 17. A finding in a study assessing safety and suitability of HFA134a as a flame retardant led twice to abandonment of inhalation in volunteer #5 breathing 0.4% and later 0.2% in air, because of a rise in pulse rate and hypertension 18. It is possible that HFA134a (similar to halothane, but without bromine and chlorine) and HFA227ea will trigger malignant hyperpyrexia. It is serendipitous that current asthma pMDIs use propellants that relax smooth muscle, but as yet there is no in vivo or vitro research to quantify the effect of HFAs on bronchi, vasculature, uterus, and gut. Pressurised metered-dose asthma inhalers may be abused for propellant or beta-1 and -2 agonist stimulation effects. In the times of CFC propellants, and because steroid inhalers were not abused, salbutamol was thought to provide 'stimulation' from beta1 and 2-agonist effects 19. To treat acute severe asthma, when single puffs of salbutamol are obviously ineffective, it is suggested that the user should actuate a well-shaken large pMDI 10 to 12 times into a 1 l or more holding vessel such as an empty soft drink bottle, or into proprietary non-valved asthma holding chambers, to inhale and breath hold, or re-breathe the contents hoping for relief before professional help arrives if out-of-hospital 20. The partial pressure effect of HFA134a gas reduces inhaled oxygen levels. 'Huffers' probably use multiple pMDI discharges into closed vessels from which the product is inhaled. The same measurement and collection system as for N2O was used, with pMDIs placed inside a subsequently sealed and evacuated 2 l anaesthetic reservoir bag, discharged until the bag was full, volume measured, then divided by the number of puffs. Small salbutamol (SalamolR; TEVA, Castleford, West Yorks, UK) pMDIs produce 7 ml of HFA134a propellant per actuation, large ones (VentolinR; GSK, Brentford, Middlesex, UK) produce 16 ml; both deliver 100 μg of salbutamol powder and 1% ethanol; 99% of discharged material is propellant. The filled bag contained no oxygen. When discharging until empty, it was found that 220 full propellant volumes are available from both small and large salbutamol x 200 dose pMDIs, which are effectively mini vapourisers; cooling occurs on evaporation. Breathing in ten 'puffs' with air in one inhalation will deliver 160 ml of HFA134a and 1600 mcg of salbutamol and is a known alternative to oxygen-delivered jet nebulised salbutamol for acute asthma attacks. In vitro, oxygen levels in valved holding chambers falls because of a partial pressure effect of HFA gas, 21% to 11% in the smallest (126 ml volume), and 21% to 17% in the largest chamber (788 ml volume) 21. Professional endurance athletes (and patients with severe wheeze) who require acute relief from their asthma symptoms are better off using the larger of the salbutamol inhalers. Recent legislation may change availability; advice to users of these agents, apart from to desist, would be to arrange a designated, sober, and alert companion with skills in cardiopulmonary resuscitation to be by one's side. No external funding or competing interests declared.