TIVA and TCI in non-human animals

 Derek Flaherty BVMS, DVA, DipECVAA, MRCA, MRCVS, FHEA, RCVS and European Specialist in Veterinary Anaesthesia

Head of Veterinary Anaesthesia, University of Glasgow

TIVA is much less commonly performed in veterinary species than in humans. This probably arises for a couple of reasons:

1. veterinary surgeons in general practice have limited training in anaesthesia, and are more familiar with inhalational anaesthetic maintenance, and

2. the only licensed full opioid agonist in animals is pethidine, so access to drugs such as alfentanil and remifentanil is more limited in the general practice setting.

TIVA in cats and dogs

Cats are comparatively poor at glucuronide conjugation, so they metabolise propofol at a significantly slower rate than most other species. As a result, recovery is usually relatively protracted when propofol is administered by infusion for prolonged periods of time. In addition, phenolic compounds are relatively toxic in cats, and studies have shown than oxidative-induced Heinz body haemolytic anaemia can develop in cats subjected to consecutive daily propofol anaesthesia after periods as short as 3 days. For these reasons, although propofol is widely used as an induction agent in cats, it is seldom used for TIVA.

In dogs, on the other hand, propofol is commonly used for both induction and maintenance of anaesthesia. In general practice, when propofol is used for canine TIVA, it is usually administered by intermittent bolus injection for short procedures (e.g. wound suturing). In the larger referral practices and academic institutions, where there are specialist anaesthetists, propofol based TIVA is used in similar situations to those in human anaesthesia (e.g. cardiac, neurosurgical etc.). In these cases, it is most commonly administered in combination with remifentanil, alfentanil or fentanyl. Most TIVA techniques in the dog rely on propofol administration by variable-rate infusion, although a TCI system has been developed and validated at the University of Glasgow Veterinary School, in conjunction with Dr. Iain Glen. This is not currently commercially available. TCI systems have not, to date, been developed for any other veterinary species.

Saffan^®, a combination of alphadalone and alfaxalone solubilised in Cremophor EL (similar to the human product, Althesin^®) has been licensed for use in cats for many years, and has had some (limited) use for TIVA in this species. Cremophor can cause histamine release in cats, and it was common to observe swelling of paws and pinnae when this product was used. In dogs, Cremophor causes massive histamine release, so Saffan^® was not used in this species. Recently, Alfaxan^® has gained a licence for dogs and cats. This comprises alfaxalone in a cyclodextrin vehicle, so the problems of Cremophor-induced histamine release have been removed. The pharmacokinetics suggest this product will be useful for TIVA in both dogs and cats, but, to date, there have only been limited experimental and clinical studies performed on this. 

Equine TIVA

Although propofol has been used experimentally for TIVA in equidae, several problems preclude its widespread use in equine practice:

1. propofol is not licensed in horses, and the cost is relatively prohibitive in the volumes required.

2. propofol often produces poor induction quality in horses, with limb paddling for several minutes after recumbency, before the animal relaxes.

3. as in all species, propofol is a poor reflex suppressant, and additional analgesic agents have to be administered to horses to facilitate acceptable anaesthesia when propofol is used as the hypnotic. Unfortunately, the situation is more complex than that in humans and small animals: controversy exists in equine anaesthesia regarding the routine use of opioids, since the majority of MAC studies in this species have demonstrated either minimal effects or an increase in MAC when opioids (particularly full agonists) are administered. This may be due to the fact that horses are one of the species who tend to respond to opioid analgesics by demonstrating excitatory, rather than sedative, effects. Consequently, TIVA with propofol and short-acting opioids is not an option in equidae. Although studies have also assessed the use of propofol with ketamine as the analgesic component, and demonstrated improved anaesthetic quality over propofol alone, the authors suggested that use of this combination long-term would lead to poor quality recovery due to cumulation of norketamine.

Most commonly, TIVA in horses is achieved with a combination of an alpha-2 adrenoceptor agonist (xylazine, detomidine or romifidine), guaiphenesin and ketamine. This so-called ‘triple drip’ admixture is widely used for field procedures, such as castration, but its use is generally limited to 60 min to avoid cumulation of the drugs producing poor recovery.

Consequently, at the moment, there is no TIVA technique or drug combination suitable for long-term administration in horses.

Food animal TIVA

Due to a relatively high incidence of complications (and also their poor monetary value), general anaesthesia is less commonly performed in the food animal species when compared to dogs, cats and horses, with the majority of surgical procedures being carried out in the standing animal under regional analgesia and sedation. Where general anaesthesia is used, it is most usually performed under inhalational anaesthesia. In the few situations where TIVA is utilised, ‘triple drip’ combinations, similar to those in horses, tend to be used.

References

Nolan A, Reid J, Welsh E, Flaherty D, McCormack R, Monteiro AM. (1996) Simultaneous infusions of propofol and ketamine in ponies premedicated with detomidine: a pharmacokinetic study. Res Vet Sci 60:262–6

Flaherty D, Reid J, Welsh E, Monteiro A, Lerche P, Nolan A. (1997)

A pharmacodynamic study of propofol or propofol and ketamine infusions in ponies undergoing surgery. Res Vet Sci 62: 179-184

Musk G, Pang D, Beths T, Flaherty D. (2005)

Target-controlled infusion of propofol in dogs – evaluation of four targets for induction of anaesthesia. Vet Rec 157: 766-770