Non-barbiturate drugs for the induction and maintenance of anaesthesia (original) (raw)

Intravenous induction of anaesthesia is now universally accepted, and the gold standard against which all drugs that are used for this purpose must be compared is thiopentone. This is despite early problems that occurred with this agent, which resulted from ignorance of its profound cardiorespiratory depressant effects, particularly when it was used as the sole anaesthetic. Even in more modern times it has been described as ~... perhaps the most dangerous drug available in modern medicine' (Dundee, 1979), yet it remains the most commonly used intravenous anaesthetic. Anaesthetists are fully aware of the properties of thiopentone and probably its most unique feature is its predictability. Indeed, apart from porphyria, it is true to say that there is a safe dose for everyone. Nevertheless, thiopentone has a number of drawbacks, and manufacturers continue to search for new agents. It is highly alkaline and extremely irritant if injected extravascularly or intra-arterially. Cardiorespiratory depression demands judicious use, especially in sick patients and in those with cardiovascular disease. It has no analgesic properties and actually increases sensitivity to somatic pain. Termination of its action is due to redistribution away from the brain, so that cumulation is a major problem on repeat administration and it is unsuitab'le for use by continuous infusion except when given by complicated computer-controlled systems in an exponential fashion. The delayed recovery to 'street' fitness is not acceptable for outpatient anaesthesia. Thiopentone also has a low therapeutic index. A number of non-barbiturate drugs have been introduced in an attempt to overcome the undesirable properties of thiopentone, but some have made only brief appearances. The eugenol derivative propanidid was associated with rapid recovery, but there was an unacceptable incidence of allergic reactions to its sotubilizing agent, Cremophor EL. Steroid anaesthetics have a high therapeutic index, but three have been withdrawn; hydroxydione because of a high incidence of thrombophlebitis, minaxolone as a result of problems related to long-term toxicological testing, and Althesin (alphaxalone/alphadolone), which had been described as approaching the ideal intravenous anaesthetic, because of problems with its vehicle, again Cremophor EL.