Methoxyflurane : inspiration of the old to breathe life into the new

Abstract

The history of modern anaesthesia – from “...no humbug!” to HFNO – has a remarkably short span for the degree of scientific advancement and technological complexity we currently enjoy. Indeed, the data-saturated clinical and research environments within the speciality may lead us to presume that development of new therapies is continuously accelerating. Remove the electronics, however, and examination of the therapeutics at our disposal reveals a different story. Using inhaled agents as an example: Scientific descriptions of the use of ether and diethyl ether in the 1500s are available. Priestley’s ‘airs’ of oxygen and nitrous oxide date from the late 1700s, although it was a century later by the time anyone suggested that administering the nitrous oxide with oxygen was perhaps a safer plan. Morton’s 1846 Etherdome demonstration of effective operative anaesthesia in humans precipitated a gust of inhalational invention that also saw chloroform becoming commonplace, but it was only in the 1920s that volatile anaesthesia using ethylene and cyclopropane began to resemble anything like modern delivery methods. The explosive potential of early agents holds an ironic twist for the discovery/development of the halogenated/fluorinated volatiles, which stemmed from the field of chemistry advanced to support the Manhattan Project. Steadily, the names of agents familiar to those practising anaesthesia today emerged: halothane (in clinical use from 1956), methoxyflurane (1960), enflurane (1966), isoflurane (1972), and then a two-decade hiatus before the introduction of desflurane (1992) and sevoflurane (1994). While the latter may feel recent, it is sobering to consider that we are now reaching the point at which our “newest” inhalational agents were introduced before our registrars were born. (Xenon has been excluded from this discussion, as it is still not, nor is it likely to be, in regular clinical use).