The Future of Inhalation Anaesthesia.
The administration of Ether in 1846 in Boston is commonly regarded as the hour of birth of modern anaesthesia. Besides “laughing gas” (nitrous oxide), used as excipient gas for volatile anaesthetics, the inhalation anaesthetics Halothane and Enflurane, both being introduced a long time ago, but hardly in use any more, the standard inhalation anaesthetic Isoflurane as well as the new substances Sevoflurane and Desflurane are available today.
In early summer of 2000 the annual Tuebingen Anaesthesia Symposium was held by the Department of Anaesthesiology and Intensive Care Medicine at the Tuebingen University Hospital. At the beginning of a new millennium a look into the future of inhalation anaesthesia was to be ventured. Although volatile anaesthetics have been clinically used for a long time, we know astonishingly little about their exact molecular effective mechanism. According to the accepted working hypothesis of today, Halothane, Enflurane, Isoflurane and Sevoflurane obstruct the spontaneous activity and exitabilty of cortical neurons by increasing the synaptic inhibition in the cortex procured by GABAA receptores. Many findings indicate that, in contrast to this, nitrous oxide and Xenon unfold their anaesthetic properties by blocking NMDA receptores.
The central nervous system (CNS) with its high density of GABAA and NMDA receptores undisputedly is considered as target- and effective organ of volatile anaesthetics. Since a too low as well as an inadequately deep anaesthesia involve high risks for patients, inevitably the question arises, if the CNS function has to be monitored during anaesthesia on a routine basis. An underdosed narcosis may lead to troublesome intraoperative awareness. Risks of an overdosed narcosis basically result from hemodynamic instability; in addition to this, the patient experiences a prolonged phase of recovery and requires more extended care in the recovery room. To estimate the adequate depth of anaesthesia, today anaesthetists monitor hemodynamic and vegetative parameters . Electrophysiological methods, acoustically evoked potentials, crude EEGs, and, derived from the latter, power spectral analyses are being evaluated. At the present, directed neuromonitoring indicates, above all other, an unsufficient depth of anaesthesia. However, a prospective control of anaesthesia depth to prevent vegetative recovery reactions during surgical stress is hardly possible. The experienced anaesthetist and his knowledge of surgical courses is still of major importance.
The more recent volatile anaesthetics Sevoflurane and Desflurane show different physio-chemical properties and a different pharmacokinetic profile than the substances that have been in use so far. This brings up new concepts, but also new risks when applying volatile anaesthetics. Because of the flow's rapid onset and offset, characteristic to both substances, Sevoflurane can be administered to an adult by mask also. Due to its pungent smell, Desflurane is not suitable for mask induction. Both substances allow for a promt ending of anaesthesia, and a quicker recovery of the patient's vigilance. For children, however, a higher rate of restlessness and agitation could be observed. These findings may be explained by an unsufficient analgesia, which effects appear earlier with a quicker recovery from general anaesthesia, and which accordingly has to be treated sooner.
Reports on higher nephrotoxicity of the new substances as well as possible problems concerning their degradation products with the use of carbon dioxide absorbent lead up to some insecurity. Intensive examination, however, could demonstrate that both substances may be utilized without hesitation, not only with the healthy but also with patients suffering from impaired renal function. Only Sevoflurane induced narcoses of extended duration (> 14 MAC hours) tend to occasionally bring about a temporal impairment of the kidney's maximal power of concentration. Concerning degradation products of Sevoflurane in combination with soda lime, Compound B played a certain role in animal experiments. Meanwhile it is clear, however, that for humans there is a larger safety margin, and there is no indication of organspecific toxicity. Even under adverse conditions, the combination of Halothane or Sevoflurane with soda lime leads to a development of carbon monoxide in toxicological negligible concentrations only. There are no risks using absorbents with normal moisture content (14 - 18 % H2O) even when Desflurane is administered.
Speaking about the purchase prize, the new inhalation anaesthetics are more expensive than those substances that have been used upto now. With regard to a lower fresh gas flow as well as other cost factors, such as medical products needed with i. v. anaesthetics, shorter stay at the recovery room, all these compared to the older substances, the utilization of the new substance may be economically advantagous. For a hospital the total economic impact including the costs of anaesthesia will gain an increasing significance in the future. Essentially, this fact is determined by political regulations, which provide that, starting with the year 2003, the settlement of accounts be carried out on the basis of the so called Diagnosis Related Groups (DRGs).
In the past, discussions on the use of “laughing gas” were lead under economical as well as medical aspects. For a long time nitrous oxide was considered to be practically inert and free of side effects. Both assumptions cannot be sustained any longer. Besides various patient related risks and secondary effects, e. g. myelosis at vitamine B 12 deficit, intracranial pressure increase, nausea and vomitting, negative environmental impacts (greenhouse effect) and higher expositions of the anaesthesia personnel have to be taken into account. A task force recruited by the European Academy of Anaesthesiology presently scrutenizes, if and when the use of nitrous oxide is justifiable, or rather, if its use has to be limited if not all together stopped.
Due to its inert gas structure and its properties, Xenon can be looked upon as non-polluting and well tolerated inhalation anaesthetic. Referring to recovery reactions, analgetic potency, cardiovascular stability as well as other factors, Xenon, compared to other inhalation anaesthetics, brings about advantages. Yet more time is needed to work out a comprehensive utility-risk-profile including the relativly high costs of Xenon, in order to define specific indications for the administration of this gas.
The history of modern anaesthesia began with inducing a gaseous anaesthetic. By means of intensive research we have managed to come close to the ideal inhalation anaesthetic. It does not take a prophet to tell that in the future inhalation anaesthetics will keep a strong position within modern anaesthesia.
