Desflurane

More than 150 years ago William Morton successfully used diethyl ether as general anaesthesia. Advances in anaesthesia have made many new surgical techniques possible, and mortality directly attributable to anaesthesia is now rare. Most recent advances have contributed to an important decrease in morbidity from anaesthesia and to an increase in quality of perioperative management.

Methods

Although anaesthesia encompasses intensive care medicine and chronic pain management, our review is limited to advances in anaesthesia for surgery and obstetrics. We discuss topics that we believe, after canvassing our colleagues, to be the most topical in recent international literature on anaesthesia. Although some of the developments have a long history, they are all recent additions to clinical practice.

Inhalational anaesthesia

Volatile anaesthetics remain the commonest agents for maintenance of anaesthesia but since the introduction of sodium thiopentone, intravenous agents have been used for induction. Induction with volatile agents is often slow, stormy, and unpleasant for the patient Volatile agents that possessed acceptable induction characteristics lost favour because of their side effects, but the new agent sevoflurane has, to a great extent, improved their popularity.[1]

Sevoflurane

Although first synthesised in the late 1960s, sevoflurane has only recently been available for general use. Sevoflurane is a methylpropyl ether which, because of its high insolubility--it is more than three times less soluble in blood than halothane--produces both rapid induction and recovery characteristics and easy control of anaesthetic depth.[2] Sevoflurane's low solubility enables a faster onset of anaesthesia because the partial pressure of the gas in the brain increases more rapidly than it does with the older agents. Similarly, when administration of sevoflurane ceases, the fall in partial pressure of the gas in the brain is equally rapid, and therefore recovery from anaesthesia is also faster than with the older agents. Importantly, sevoflurane does not irritate the airways and is therefore associated with a rapid and pleasant induction. Induction with sevoflurane is becoming extremely popular, especially in children, but maintenance with sevoflurane is less popular owing to its expense and a potentially nephrotoxic metabolite, compound A, which may accumulate during closed circuit anaesthesia with low gas flows. Considerable debate about the significance of sevoflurane in maintenance is ongoing, but its use in low flow circuits has been restricted in the United States.[3]

Desflurane

Desflurane was also developed in the 1960s and has been only recently introduced into clinical practice.[4] Although desflurane has similar physical properties to sevoflurane it is irritant to the airway and, when used in children, 50% may develop signs of laryngospasm.[5] When used for maintenance, however, desflurane allows precise control of depth of anaesthesia[6] and very rapid recovery.[7] As desflurane can be used safely at low gas flows, thus allowing costs to be kept down,[8] these characteristics can be exploited.

Xenon

Xenon is an inert gas with anaesthetic properties but until recently its cost has been prohibitive. It is extremely insoluble in plasma and thus exhibits an even faster onset of action and recovery than any volatile agent.[9] It is not sufficiently potent to be used alone in most patients, however, but may replace nitrous oxide as a supplement to general anaesthesia in the future; it has analgesic properties, is less soluble, and is not a greenhouse gas (unlike nitrous oxide).[10]

Intravenous anaesthesia

Total intravenous anaesthesia

Propofol

Since the introduction of propofol in 1984 no new intravenous anaesthetic agents have been introduced. Significant advances have been made, however, in the methods of administration of propofol for induction and maintenance of anaesthesia without the use of volatile agents, termed total intravenous anaesthesia. Exponents of this technique claim excellent recovery characteristics and a low incidence of postoperative nausea and vomiting, with the avoidance of potentially harmful pollution of the surgical environment.[11] A major disadvantage of propofol has been the difficulty of achieving the desired plasma concentration by manual control of the infusion rate since to maintain this concentration accurately the infusion rate must be adjusted frequently. In practice the resulting plasma concentration can vary erratically causing haemodynamic instability or light anaesthesia.

Target controlled infusion

Target controlled infusion systems allow the anaesthetist to set a desired plasma concentration, which the software inside the pump produces rapidly but safely by controlling the infusion rate according to complex but standard pharmacokinetic equations.[12 13] Changes may still be required according to clinical signs, but the technique enables changes in rate to reflect factors such as patient characteristics, previous administration of propofol, and duration of infusion (fig 1).

[Fig 1 ILLUSTRATION OMITTED]

If a reliable monitor of anaesthetic depth becomes available it will be possible to "dose the loop" and provide virtually automatic anaesthesia by feedback control of a target controlled infusion system. Much research has focused on this, with the aim of producing a machine that will reliably indicate whether a paralysed patient is anaesthetised. Unfortunately, autonomic clinical signs do not always detect an aware patient especially in the presence of drugs that affect these signs, such as [Beta] blockers. Recent work has concentrated on measurements derived from an electroencephalogram, but most of these are unreliable or too complex for practical use. The auditory evoked potential index--a single numerical variable derived from the auditory evoked potential--was found to show consistent changes that may reliably detect awareness.[15 16] Prototype closed loop systems, using the auditory evoked potential index to control propofol given by target controlled infusion, have been described.[17]

Remifentanil

Remifentanil is a new potent synthetic opioid ideally suited for infusion (often with a target controlled infusion system) during anaesthesia. Unlike other opioids, remifentanil contains a methyl ester in its structure, which allows rapid extrahepatic non-saturable metabolism by non-specific esterases in blood and tissues.[18] Most significantly, the terminal half life of remifentanil is less than 10 minutes and, unlike all other opioids, this is not affected by duration of infusion (fig 2).[19] Remifentanil's place in anaesthesia has yet to be fully determined. Critics point out the lack of postoperative analgesia with remifentanil, but it is already widely used during neuroanaesthesia and is likely to represent a significant advance in several other areas such as cardiac and cardiovascular anaesthesia.

[Fig 2 ILLUSTRATION OMITTED]

Local anaesthetics

Bupivacaine

Bupivacaine is the most frequently used local anaesthetic for perioperative and postoperative pain relief in many countries. Onset of anaesthesia is rapid (within minutes), but the duration of action is comparatively long, sometimes lasting for several hours depending on the dose given and route of administration. In common with all local anaesthetics, bupivacaine can cause severe central nervous system and cardiovascular toxicity if given intravenously by mistake or if used in excessive doses by other routes.[20 21]

The bupivacaine molecule exhibits stereoisomerism, and recent studies comparing the two enantiomers have shown that R(+)-bupivacaine is 3-4 times more likely to cause cardiovascular toxicity than S(-)-bupivacaine in rabbit hearts.[22] Studies in sheep have shown a higher threshold for convulsions with the S(-) form.[23] Less cardiovascular disturbance has also been shown in humans with the S(-) form.[24] This improved safety profile is not at the expense of efficacy as S(-)-bupivacaine has been shown to be at least as good as racemic RS-bupivacaine when used either extradurally or for brachial plexus block.[25 26] Bupivacaine is likely to be generally available shortly and probably represents a significant advance in safety.

Ropivacaine

Ropivacaine is a new local anaesthetic with a structure similar to bupivacaine, but prepared only as the pure S(-) isomer.[27] The sensory anaesthesia produced is similar to that of bupivacaine but its central nervous system and cardiovascular toxicity profile in humans is superior to that of RS-bupivacaine.[28] During the course of clinical trials some patients have received accidental large intravenous doses of ropivacaine, but none has suffered harmful systemic toxicity.[29] In addition, it has been claimed that ropivacaine produces greater sensory motor separation when used by the epidural route,[30] allowing good analgesia with less intense motor block than bupivacaine.

Mobile epidurals

A recent advance in obstetric anaesthesia has been the introduction of mobile epidurals.[31] To produce adequate analgesia, traditional epidurals require the use of local anesthetics in concentrations that may produce significant motor neuronal blockade and consequent immobility. In contrast, mobile techniques usually depend on the epidural administration of a mixture of very low concentration local anaesthetic together with an opioid such as fentanyl. The lower concentration of local anaesthetic minimises motor block, whereas the opioid acts at opiate receptors in the central nervous system to enhance analgesia. The preserved mobility is often sufficient to allow walking, free of pain, which is popular with women in labour. [32] It has been suggested that the immobility and loss of muscle tone produced by traditional epidurals may delay progress in labour and cause increased rates of instrumental delivery and caesarian sections, a view supported by a recent comprehensive systematic review.[33] Large randomised multicentre studies are in progress to compare mobile epidurals with conventional epidurals in this respect. Mobile epidurals are currently rarely available outside large centres, partly because medical and midwifery staff require training. If beneficial effects on the numbers of normal deliveries are shown, however, we can expect mobile epidurals to become quickly more common.

Similar low concentration local anaesthetic-opioid mixtures have recently been used in epidurals for postoperative pain management, allowing improved and earlier mobilisation and greater patient satisfaction. Despite these benefits, the use of this technique is also limited because provision of an epidural service on general surgical wards requires support from an acute pain team.

Postoperative emesis

Postoperative nausea and vomiting remains a significant morbidity problem after general anaesthesia and the [5-HT.sub.3] antagonists have been shown to be at least as effective as standard antiemetics but with an improved side effect profile. [34 35] Postoperative nausea and vomiting remains a problem, however, and ongoing studies are investigating the efficacy of combination therapy (antagonising more than one receptor type) and the activity of the new neurokinin type 1 receptor antagonists. Preliminary studies of neurokinin type 1 receptor antagonists show promise. [36]

Equipment

Laryngeal mask airway

One of the most significant advances in anaesthesia in recent years has been the laryngeal mask airway. This device can be inserted blindly (without a laryngoscope), leaves the anaesthetist's hands free, and produces a close enough seal around the laryngeal inlet to allow spontaneous or, with certain provisos, positive pressure ventilation. Because of its simplicity of use, it is rare not to anaesthetise at least one patient on an operating list with a laryngeal mask airway. Since its introduction, anaesthetists have devised ways of using the laryngeal mask airway to facilitate tracheal intubation, either by passing an endotracheal tube blindly down the lumen of a correctly positioned layrngeal mask airway or by first using it as a guide for the passage of a fibreoptic laryngoscope.[37] Such techniques are invaluable in the management of patients who are difficult to intubate using direct laryngoscopy (an important cause of morbidity and mortality in anaesthesia), as studies have shown that the success rate for placement of the laryngeal mask airway in the abnormal airway is at least 97%. [38] These methods are, however, cumbersome, and only narrow endotracheal tubes can be inserted in this way. Recently a purpose designed intubating laryngeal mask airway has been described, which allows blind successful placement of endotracheal tubes up to 8.0 mm in diameter, a normal sized tube for use in adults. [39] This device should prevent many cases of failed intubation and, in any case, creates a safety margin by allowing oxygenation to continue while intubation is attempted.

McCoy laryngoscope

The McCoy laryngoscope is a recent aid for difficult intubations.[40] It is shaped like a standard Macintosh laryngoscope but has a hinged tip to its blade, which can be activated by a lever on the handle. Use of this hinged tip has been shown to improve the view of the larynx in a substantial proportion of difficult laryngoscopies,[41] and as a result the McCoy laryngoscope has become popular.

Competing interests: DJR has been reimbursed for attending several conferences and has received lecture fees from GlaxoWellcome (manufacturer of remifentanil).

Recent advances

New inhalational anaesthetics allow rapid, pleasant gaseous induction of anaesthesia and rapid recovery with a minimal "hangover" effect

Target controlled infusion techniques have improved the accuracy of total intravenous anaesthesia and pave the way for "dosed loop" automatic anaesthesia

A unique opioid, remifentanil, allows fine control of intraoperative analgesia but its effects wear off within minutes of stopping infusion

Separation of stereoisomers has allowed the development of improved safer local anaesthetics

Mobile epidurals are rapidly gaining popularity in labour wards because they allow normal mobility with high quality pain relief

Neurokinin type I receptor antagonists promise to further improve management of postoperative nausea and vomiting

Recent developments in equipment have helped to minimise the problems of anaesthetising patients with "difficult" airways

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[40] McCoy EP, Mirakhur RK. The levering laryngoscope. Anaesthesia 1993;48:516-9.

[41] Tuckey JP, Cook TM, Render CA. An evaluation of the levering laryngoscope. Anaesthesia 1996;51:71-3.

University Department of Anaesthesia, University of Leicester, Leicester Royal Infirmary, Leicester LEI 5WW Andrew J Fox lecturer David J Rowbotham professor

Correspondence to: DJ Rowbotham David. Rowbotham@leicester.ac.uk

BMJ 1999;319:557-60

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