24 Feb 2025
Ronald Jones OBE, DVSc, FRCA, FRCVS discusses the differences over the past 60 years with this medical treatment in animals
Image: Laura Battiato / Adobe Stock
In January 1964, a small group met at the University of Bristol and agreed to proceed with the formation of the Association of Veterinary Anaesthetists of Great Britain and Ireland. In April that year, the inaugural meeting was held in London with 20 members present1.
Coincidentally, in the same year, the Protection of Animals (Anaesthetics) Act 1964 was published. A special edition of the Veterinary Record was published to mark the event and included a paper: a review of anaesthesia in domestic animals.
At that time, the standard methods for anaesthetising horses were either intravenous chloral hydrate or chloroform administered by Cox’s mask. Most surgery on ruminants was performed under local or regional anaesthesia; dog and cat anaesthesia was with intravenous agents, pentobarbital or thiopental.
Cats were also anaesthetised with “open” ether. Halothane had just been marketed for humans and a few individuals began to use it in horses and small animals; specialist equipment for its administration to large animals was being developed.
One of the simplest and effective introductions to veterinary anaesthesia was that of intravenous catheters.
A number of different types were available, including the commonly used “over the needle” type and the “butterfly” variety. A less common one is the “Seldinger” technique, which involves the insertion of a wire into a blood vessel, the catheter threaded over the wire and the wire then removed.
The use of catheters ensures venous access and is particularly effective in preventing extravascular injection of potentially irritant drugs, and for the longer-term administration of fluids. They were also later used for insertion into arteries to facilitate the taking of arterial blood samples for acid base measurement and for direct arterial blood pressure measurement.
In 1971, a new steroid agent was developed for intravenous administration to a number of species of animals and humans. It was mixture of alfaxalone and alfadolone dissolved in polyethoxylated castor oil, and was used mainly in cats, but also in other species. It was not suitable for use in dogs. It did produce histamine release in a relatively small number of cats where it could be administered by intravenous or intramuscular injection.
However, after a number of adverse reactions in humans, it was withdrawn from use. More recently, alfaxalone, solubilised in cyclodextrin, has been developed for use mainly in animals, although its use has been reported in other species.
Propofol, which is 2,6-di-isopropolphenol, is an emulsion in a formulation of soya bean oil, purified egg phosphatide and glycerol. Its clinical use is in dogs and cats. Metomidate, an imidazole derivate, was developed for intravenous use in combination with azaperone in pigs.
Dissociative anaesthetic agents are cyclohexylamine derivates that have been used in a number of species of animals and humans. The state produced by these agents is clinically different to that produced by conventional anaesthetic agents.
Phencyclidine was used extensively in pigs, but has since been withdrawn from use. Tiletamine is a similar drug to phencyclidine and is normally used in combination with a benzodiazepine compound, zolazepam. The combination has been used in a number of species including cats and wildlife species; however, its use appears to have been superseded to a greater degree by ketamine.
Ketamine had a relatively slow introduction to veterinary anaesthesia and was used initially in cats, and usually in combination with xylazine. It is now used extensively in a wide variety of species, including humans. Ketamine can be administered by a variety of routes to provide perioperative analgesia with inhalational anaesthesia. In horses, ketamine is administered in combination with guaifenesin and an alpha-2 agonist, such as xylazine or romifidine.
It is unfortunate that ketamine is used extensively in humans as a drug of addiction, leading to a number of problems affecting the kidneys and bladder.
The first alpha-2 agonist to be introduced into veterinary anaesthesia was xylazine, and initially it was used for sedation in cattle. Its use soon spread to other species including cats and horses, and it can be administered by a variety of routes. Its potency seems to vary between species, leading to wide variety of doses depending on species.
Detomidine was developed mainly for use in horses, where it is a very effective sedative and analgesic. It is used for premedication before induction of anaesthesia with ketamine or as a component of the triple drip technique. Detomidine has been used in cattle in a number of countries.
Medetomidine was developed mainly for use in cats and dogs, although it has been used in a variety of species including horses. Atipamezole was developed specifically to antagonise the actions medetomidine in cats and dogs, but is also effective against other alpha-2 agonists. Dexmedetomidine is more potent than medetomidine, but appears to have similar actions.
In the early 1960s, halothane was being used in a number of domestic species, and specialised equipment for its use in large animals was being developed.
Methoxyflurane is a potent analgesic with a slow uptake and elimination. Due to its physical properties, it was very difficult to overdose with the drug. Enflurane is a non-flammable fluorinated ether with a higher solubility than halothane and, therefore, produced a more rapid onset and elimination.
Isoflurane is an isomer of enflurane with low blood solubility that produces a rapid induction and recovery from anaesthesia. As it has similar physical properties to halothane, vaporisers can be used for its administration. It is widely used in a variety of species and is the inhalational agent of choice. Desflurane has a similar structure to isoflurane, but has a low boiling point and requires a special vaporiser, and its low potency requires the use of large quantities. In addition, it has a high greenhouse gas potential and its use is being discontinued.
Sevoflurane is another fluorinated ether and has a reaction with metals, so is marketed in glass bottles and reacts with soda lime. It is used widely in a variety of species, probably due to its ease of use in maintain anaesthesia and smooth recoveries.
In the early 1980s, two non-depolarising neuromuscular blocking agents were developed. Atracurium is a bisquaternary isoquinoline compound with a novel metabolism: the Hofmann degradation, which is pH and temperature dependent. Therefore it does not depend on the liver or kidneys for its metabolism. Cis-atracurium, which is one of its more potent isomers, also became available. Vecuronium, which is a steroid agent, with minimal cardiovascular effects also became available.
Later, another more rapidly acting steroid was developed. These drugs can be used as an adjunct to anaesthesia in domestic a species. Reversal of the neuromuscular block was by the use of neostigmine preceded by an anticholinergic agent. However, recently, sugammadex, an agent with a novel action, has become available in that it encapsulates the steroid molecules of both vecuronium and rocuronium. Its use has been recorded in both dogs and horses.
Monitoring in anaesthesia was limited to the measurement of pulse and respiratory rates. The use of oesophageal stethoscopes meant that direct communication with the anaesthetised animal was achieved.
Following on developments in human anaesthesia, a number of monitoring devices have become available. Blood gas measurements, usually from arterial samples, recorded blood pH, oxygen and carbon dioxide tensions plus base deficit. The cardiovascular system can be monitored by continuous display of the ECG and direct or indirect measurement of arterial blood pressure; central venous pressure can also be monitored.
Capnography can be used to measure end-tidal carbon dioxide; the apparatus can also be modified to incorporate the measurement of end-tidal inhalational agents and oxygen concentrations in the anaesthetic circuit.
Neuromuscular block can be monitored by stimulation of a peripheral nerve using techniques such as train of four method. More recently, the acceleromyograph machine has been used.
Considerable advances were made in the recognition, treatment and prevention of pain. A number of pain assessment scales have been devised and published mainly in relation to small animals and horses.
Potent analgesic drugs including etorphine and fentanyl were discovered. Etorphine was originally developed due to its high potency for use in wild animals and usually administered by darting. It was then combined with acepromazine for large animals and with alimemazine for small animals.
In view of the potency and possible dangers to humans, these drugs must be handled with extreme care. Fentanyl has been developed for use in horses and dogs, and can be administered by injection or as patches, which have a long duration of action due to slow release. Fentanyl has been combined with droperidol to form a neuroleptanalgesia mixture.
A number of other agents, such as butorphanol, buprenorphine and methadone, have also become available. Emphasis should be on the prevention rather than the treatment of pain, and multimodal analgesia is often used to this end.
In addition to the use of drugs to produce analgesia, further developments have been made in the use of local and regional anaesthesia. The publication of the seminal text on epidural anaesthesia laid the groundwork for further developments2.
In addition to local anaesthetics, morphine and alpha-2 agonists have also been injected in to the spinal canal to produce analgesia. A wide variety of techniques of local anaesthesia techniques of the head and limbs have been described, and their accuracy has been improved by the use of a nerve stimulator.
During the past 60 years, a number of physiological and pathological changes associated with anaesthesia have been described. Following the seminal paper by Hall et al3 on arterial-alveolar oxygen gradients in the anaesthetised horse, a number of techniques have been described to elicit and prevent the problem ischaemic myopathy and neuropathy has been described in horses, and methods to prevent the conditions have been described.
A relatively rare condition of spinal malacia has also been described. The stress responses to anaesthesia in pigs and horses has been studied, as has techniques to reduce its effects.
Ronald Jones is the emeritus professor of veterinary anaesthesia at the University of Liverpool. He is a past-president of RCVS and the Association of Veterinary Anaesthetists. He is a medallist and honorary fellow of the Royal College of Anaesthetists.
Clarke KW et al (2014). Veterinary Anaesthesia (11th edn), Saunders Elsevier, St Louis.
Grimm KA et al (2015). Veterinary Anesthesia and Analgesia (5th edn), Wiley-Blackwell, Hoboken.
