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activates the NMDA receptors in the CNS. Activation of NMDA receptors thus increases the sensitivity of the receptors to glutamate (central sensitisation), making them more responsive to subthreshold stimuli. As a result, a ‘wind-up’ phenomenon develops which is clinically manifested as an exaggerated painful response to subthreshold stimuli following a primary injury and thus results in amplification of the post operative pain (Woolfe and Thompson 1991; Stubhaug et al. 1997). Therefore, effective pre-emptive treatment of surgery- induced central sensitisation and ‘wind-up’ phenomenon has become an important part of anaesthetic management. Administration of subanaesthetic doses of ketamine intermittently (Fu et al. 1997; Kee et al. 1997; Lucas et al. 2001; Guillou et al. 2003; Kwok et al. 2004) or as constant rate infusion (CRI) (Lucas et al. 2001; Wagner et al. 2002) pre- and post operatively has gained popularity to minimise pain subsequent to surgery in both people and animals. The cardiovascular action of ketamine is characterised by
indirect cardiovascular stimulation as a result of the combined actions of sympathomimetic effects mediated within the CNS (Ivankovitch et al. 1974), inhibition of neuronal uptake of catecholamines by sympathetic nerve endings (Salt et al. 1979), direct vasodilation of vascular smooth muscle (Altura et al. 1980) and an inotropic effect on the myocardium (Tweed et al. 1972). The heart rate and arterial blood pressure increase due to direct stimulation of the CNS, leading to increased sympathetic outflow (Wong and Jenkins 1974). However, the cardiovascular stimulating effects induced by ketamine are blunted or prevented by prior administration of a tranquiliser, sedative or the concomitant administration of inhalation anaesthetics, including N2O (Bidwai et al. 1975; Jackson et al. 1978; Bålfors et al. 1983; Reich and Silvay 1989). The survival rate of rats in haemorrhagic shock is reportedly
greater when they are anaesthetised with ketamine vs. halothane (Longnecker and Sturgill 1976). Ketamine was demonstrated to suppress the activation of endotoxin- induced neuronal nuclear factor-κB, which regulates the production of proinflammatory cytokines, including tumour necrosis factor-α in human glioma cells in vitro and intact mouse brain cells in vivo (Sakai et al. 2000). Therefore, ketamine may offer some neuroprotective effects during endotoxaemia. Furthermore, i.v. administration of ketamine (10 mg/kg bwt/h) prior to injection of endotoxin to rats completely inhibited the haemodynamic effects (profound hypotension), metabolic acidosis and the release of cytokine associated with endotoxin shock. While blood pressure may be better maintained with ketamine during hypovolaemia, greater increases in arterial lactate concentration and base deficit were observed in dogs under ketamine anaesthesia, as compared to dogs anaesthetised with a volatile anaesthetic, suggesting that the O2 demand was not met during ketamine anaesthesia (Weiskopf et al. 1981). Critically ill human patients occasionally respond to ketamine with an unexpected decrease in blood pressure and cardiac output (Waxman et al. 1980). This likely results from depletion of catecholamine stores and an uncovering of ketamine’s direct myocardial depressant effects (Stoelting and Hillier 2006). Ketamine differs from most other anaesthetics in that it
does not depress the ventilatory response to hypoxia (Booth 1988). In man, the skeletal muscle tone is maintained or even increased; thus, arterial oxygenation and functional residual capacity are usually well maintained during ketamine anaesthesia (Domino et al. 1965; Gooding et al. 1977; Shulman
et al. 1985; Mankikian et al. 1986). A consistently lower shunt fraction and higher PaO2 values were observed during continuous infusion of ketamine as compared to halothane during one lung anaesthesia in dogs (Lumb et al. 1979). Laryngeal and pharyngeal reflexes are usually well maintained during ketamine anaesthesia. Nevertheless, swallowing reflexes may be somewhat obtunded because most species can be intubated when anaesthetised with ketamine (Wright 1982).
Ketamine undergoes extensive hepatic metabolism in the
horse (Heath et al. 1982). Rapid recovery following ketamine administration is caused by rapid redistribution of ketamine from the CNS to all body tissues, primarily body fat, lung, liver and kidney (Lanning and Harmel 1975). Animals with hepatic dysfunction do not metabolise ketamine as rapidly as normal animals. Animals with renal dysfunction or obstruction to urine flow also have prolonged recovery times (Short 1987). Thus, ketamine should be given cautiously to horses with hepatic or renal dysfunction. In people, a slight but statistically significant increase in
intraocular pressure (IOP), independent of changes in blood pressure during ketamine anaesthesia, was reported (Falls et al. 1966; Yoshikawa and Murai 1971). However, IOP tended to decrease in horses anaesthetised with xylazine and ketamine (Trim et al. 1985). Although there are no reports of corneal rupture in horses associated with this drug, ketamine should be used with caution in horses with corneal injuries where increased IOP may result in expulsion of intraocular contents.
Clinical uses
Horses Ketamine should not be used as a monoanaesthetic in horses. Preanaesthetic sedation and tranquilisation must be present before ketamine is administered. Xylazine is most commonly used for this purpose. Xylazine, followed by ketamine after 5–10 min, induces a short period of safe and effective anaesthesia in all breeds of horses (Table 1). Higher doses of ketamine (2.75–3.0 mg/kg bwt i.v.) are required for ponies, young fractious Arabians, Hackneys and Thoroughbreds (Benson and Thurmon 1990). Ketamine should not be administered if xylazine fails to produce adequate sedation and an alternative anaesthetic technique (e.g. guaifenesin [Glyceryl Guaiacolate]4 and propofol [PropoFlo]5 or guaifenesin, ketamine and xylazine mixtures) should be considered. A decrease of the heart and respiratory rates by one third after xylazine administration is not uncommon. After ketamine injection, the heart rate may remain decreased while the respiratory rate returns to prexylazine values. The duration of anaesthesia (15–20 min) is related to redistribution of ketamine to other body tissues and hepatic metabolism. Anaesthesia can be extended by redosing with one-third to one-half of the original dose of each drug for an additional 5–10 min of anaesthesia. Continuous infusion of xylazine (2–4 mg/kg bwt/h) and ketamine (5–7 mg/kg bwt/h) were used to maintain satisfactory anaesthesia for 60–70 min following induction with i.v. xylazine (0.75 mg/kg bwt), guaifenesin (75 mg/kg bwt) and ketamine (2 mg/kg bwt). Although cardiovascular function was minimally affected by the anaesthetic infusion, O2 supplementation was considered to be beneficial for maintaining adequate tissue oxygenation during longer duration of anaesthesia. Nevertheless, all horses
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