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EQUINE VETERINARY EDUCATION / AE / MARCH 2015
Review Article
A review of the general pharmacology of ketamine and its clinical use for injectable anaesthesia in horses
H. C. Lin*, T. Passler, R. R. Wilborn, J. S. Taintor and F. J. Caldwell Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Alabama, USA. *Corresponding author email:
linhuic@auburn.edu
Keywords: horse; dissociative anaesthesia; ketamine; sedation; chemical restraint; anaesthesia; donkey; mules; draught horses
Summary Ketamine is the most commonly used injectable anaesthetic in horses. Combinations of ketamine have been used to produce short durations of anaesthesia or as total intravenous anaesthesia (TIVA) for longer diagnostic or surgical procedures. In recent years, ketamine has been used for pain management due to its effectiveness in producing analgesia at subanaesthetic doses. This paper provides a review of the pharmacological effects of ketamine in general and its clinical use for injectable anaesthesia and pain management in horses.
Introduction
Ketamine (Ketaset)1 is the most commonly used injectable anaesthetic in horses. The drug produces a rapid onset and short duration of dissociative anaesthesia. Dissociative anaesthesia is characterised by a cataleptoid state in which the eyes remain open with a slow nystagmic gaze. Varying degrees of hypertonus and purposeful or reflexive skeletal muscle movements often occur unrelated to surgical stimulation. Although analgesia is intense, it is of short duration after single bolus injection (Winters et al. 1972). Ketamine, when administered alone to horses, induces excitement during induction and emergence-hallucination during recovery from anaesthesia. Thus, the drug is usually used in combination with a tranquiliser or a sedative to ensure smooth induction and recovery. A wide variety of ketamine combinations have been used successfully to provide injectable anaesthesia. This paper reviews the pharmacological effects and clinical usefulness of ketamine in horses.
General pharmacology
The degree of unconsciousness and analgesia induced by ketamine are dose-related. The drug has a rapid onset of action, with the maximal effect occurring in approximately 1 min. In rats, termination of action after a single intravenous (i.v.) dose of ketamine is caused by rapid redistribution of the drug from the brain to other tissues (Cohen et al. 1973). Antagonism of ketamine on the N-methyl-D-aspartate (NMDA) receptors was demonstrated to be responsible for most of the anaesthetic, analgesic, psychotomimetic and neuroprotective effects of the drug (Kohrs and Durieux 1998). Intense analgesia produced by ketamine occurs at subanaesthetic doses and an elevated pain threshold occurs at plasma levels of 0.1 ng/ml or greater (Nimmo and Clements 1984). At anaesthetic doses, the degree of analgesia induced by ketamine appears to be greater for somatic pain than for visceral pain in cats (Haskins et al. 1975). In addition, the drug appears to be more effective for minor surgery and post
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operative analgesia involving skeletal/integumentary structures and extremities of the cat (Sawyer et al. 1990, 1993). However, when administered i.v. or intrathecally, ketamine significantly inhibited mean arterial pressure changes and abdominal electromyographic activity evoked by urinary bladder distension and inhibition of nociceptive responses indicating the presence of visceral analgesia as a result of its antagonism on NMDA receptors in the spinal cord of rats (Iwasaki et al. 1991; Alam et al. 1996; Olivar and Laird 1999; Castroman and Ness 2002). Furthermore, NMDA receptors appear to be more involved in hyperalgesic responses after peripheral tissue injury and inflammation rather than nonnoxious somatic inputs (Alam et al. 1996; Castroman and Ness 2002). Local infiltration of ketamine produces a brief period of
local anaesthetic effect in human models of inflammatory pain (Warncke et al. 1997; Pedersen et al. 1998). In horses, a brief period (10–15 min) of palmar digital nerve blockade was observed when ketamine (5 ml of 1, 2 or 3% solution) was administered at the base of the proximal sesamoid bone (abaxial sesamoid block) (Lopez-Sanroman et al. 2003). Caudal epidural injection of ketamine (0.5, 1 or 2 mg/kg bwt) produced perineal analgesia with dose-dependent intensity and duration (30 min for 0.5 and 1.0 mg/kg bwt, 75 min for 2.0 mg/kg bwt) in standing horses capable of preventing the nociceptive response initiated by incisional pain (deSegura et al. 1998; Redua et al. 2002). In halothane-anaesthetised ponies, epidural ketamine (0.8–1.2 mg/kg bwt) reduced the mean minimum alveolar concentration (MAC) of halothane by 12–14%, which is similar to the 14% reduction in MAC following epidural morphine (Morphine Sulfate)2 administration (Doherty et al. 1995). Similar studies investigating the reduction of isoflurane MAC as a result of the administration of epidural ketamine in horses have not been reported; however, we believe that a reduction in isoflurane MAC similar to that for halothane can be expected. Longer duration (>20 min) and wider distribution of perineal analgesia up to the thigh and flank regions was reported when xylazine (AnaSed3; 0.5 mg/kg bwt) was combined with ketamine (1 mg/kg bwt) and administered epidurally to horses (Kariman et al. 2000). In addition, subarachnoid injection of ketamine between T18 and L1 produced analgesia sufficient for abdominal surgery in the standing horse (Bolte and Igna 1994). In dogs, suppression of synaptic transmission in the spinal cord were demonstrated to be responsible for systemic analgesia following i.v. administration of ketamine, whereas suppression of axonal conduction in the spinal cord is the primary mechanism of intrathecal ketamine-induced analgesia (Iida et al. 1997). In human patients, surgery-induced tissue trauma produces continuous nociceptive stimulation of c-fibres that
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