New Perspectives on the Drugs Used to Produce Sedation, Analgesia, and Anesthesia in Horses

Familiarity with select anesthetic drugs and anesthetic techniques reduces the risks involved in using anesthesia. Changing to new and unfamiliar anesthetic drugs and techniques must provide significant advantage over the familiar drugs and methods. Alpha-2 agonist (xylazine, detomidine, medetomidine, and romifidine), benzodiazepine (diazepam and midazolam) and dissociative (ketamine) drug combinations provide safe and effective anesthesia for short-term total IV anesthesia (TIVA). Additionally, they can be administered by infusion as an adjunct to inhalant anesthesia.

1. Introduction

The pharmacologic basis of practical equine anesthesia is based on the same tenants of all general anesthesia practice (i.e., hypnosis, analgesia, and muscle relaxation) [1]. The necessity to manage or reduce the stress associated with anesthesia and surgery that can have detrimental effects should also be added to this list [2]. Translation of these tenants to practical terms implies that drugs used to produce equine anesthesia should produce effects that render the horse oblivious to surgical stimulation (hypnosis), keep the horse free from pain (analgesia), and allow the horse to be easily positioned or manipulated (muscle relaxation) to facilitate the surgical procedure. All of these things need to be accomplished without fear of neurologic, cardiovascular, or respiratory consequences. The search for a single drug that produces all of these effects without producing significant side effects has been replaced by attempts to find the "ideal" anesthetic cocktail. Toward this goal, old and new drugs are being combined in an attempt to produce the "ideal" anesthetic state (Fig. 1).

Figure 1. Qualities of the "ideal" anesthetic.

With the exception of alpha-2 agonists, there are virtually no drugs being developed or available for use in horses that are not currently being used in humans. Trends in the pharmacologic practice of equine anesthesia have been and continue to be based on new developments in the practice of human anesthesia. Without exception, drugs that are currently used to produce hypnosis, analgesia, and muscle relaxation in humans have been investigated in horses with mixed results. The major factors contributing to the differences in response stem from the horses’ unique anatomical and physiological differences, behavioral considerations, and the routes, rates, and volumes of drug required to produce safe and effective anesthesia in horses compared with humans. Ideal anesthesia in the horse requires that every horse receive a complete physical examination and electrocardiogram. Additionally, horses should have blood drawn for a complete blood count (CBC), total protein, and packed cell volume. The horse should be placed in a quiet and distraction-free environment that is free of debris, equipment, and potentially hazardous objects. The horse’s temperament should be assessed, and consideration should be given to the estimated time of surgery and anesthetic-induced recumbency to determine the need for appropriate positioning and padding, particularly in field situations. The horse should be sedate, uninterested in its surroundings, reluctant to move, and relatively undisturbed or oblivious to the environment, people, and noises. There is little question that the single most effective family of drugs capable of producing the aforementioned effects in horses are the alpha-2 agonists (xylazine, detomidine, medetomidine, and romifidine) [3-6]. In addition to sedation, analgesia, and muscle relaxation, these drugs are noted for producing stupor and ataxia in many horses, necessitating care in the handling and movement of some horses to avoid a startle or violent response. The choice and dose of alpha-2 agonist should be tailored to the individual horse and the surgical procedure to be performed. Xylazine has a relatively rapid onset and time to peak effect when administered intravenously; however, it has a comparatively short duration of action that may not last long enough to influence the recovery period [4]. IV detomidine, by contrast, takes a longer time to produce peak effects, and it usually produces a greater degree of sedation that lasts longer than xylazine [5]. Medetomidine produces identical effects to detomidine, but it is effective for a shorter period of time. Romifidine produces effects more like those of xylazine, but it is effective for a longer period of time [4,7]. The equine surgeon’s knowledge and clinical experience should determine which alpha-2 agonists should be used and how it will be tailored to the individual horse and the procedure being performed. However, this is not the general practice. Most equine surgical facilities and equine surgeons get used to doing things one or two ways, and they anesthetize every horse in the same way. The advantage of this approach is that all surgical personnel become familiar with the anesthetic techniques being used, including what to expect from their administration and most importantly, what to do if something goes wrong. The disadvantage of this approach is that the anesthetic plan (drugs) is not tailored to the horses stature (weight versus size), condition (athletic versus sedentary), temperament (quiet versus anxious), or physical condition (healthy versus sick). Additionally, not all anesthetic plans are "ideal" for all equine surgical situations. What then are the best anesthetic drugs and anesthetic techniques that offer the safest and most effective anesthetic experience for horses?

2. Discussion

The safest anesthetic techniques for horses employ the use of potent sedative analgesics (xylazine and detomidine), muscle relaxants (guaifenesin and diazepam) [8-11], dissociative anesthetics (ketamine), and inhalant anesthesia (isoflurane, sevoflurane). Although thiobarbiturates (thiopental) have been traditionally used to induce and maintain anesthesia for short surgical procedures, their use can no longer be recommended for this purpose because of the high incidence for respiratory (hypoventilation and apnea), cardiovascular (tachycardia and hypotension), and other side effects (muscle weakness, delirium, and local inflammatory response) [12]. Similar comments can be made when considering the use of more recently developed hypnotics like etomidate and propofol. Only ketamine, and possibly tiletamine (tiletamine-zolazepam [a]), show a high degree of cardiorespiratory safety. When combined with adequate sedation and muscle relaxation (diazepam and midazolam), these new hypnotics produce excellent induction and recovery from anesthesia [13-16]. Indeed, the combination and administration of an alpha-2 agonist-dissociative anesthetic peripherally acting muscle relaxant (e.g., xylazine-diazepam-ketamine) to a properly sedated horse produces the most reproducible, predictable, and uneventful induction and maintenance of anesthesia in horses. Therefore, it is the standard to which all other anesthetics and anesthetic protocols should be compared (Table 1) [14]. Various analgesic drugs including butorphanol, buprenorphine, and morphine or analgesic techniques including preemptive administration of a non-steroidal anti-inflammatory drug (NSAID) like phenylbutazone and local infiltration with lidocaine or bupivacaine can be added to this protocol to enhance analgesia and limit stress [17-21]. However, a great deal of research and clinical experience has yet to be completed to identify the best drugs and procedures for pain control in horses [22,23]. Regardless, various anesthetic protocols have been used to produce anesthesia lasting from minutes (field anesthesia) to hours with minimal to no side effects [16]. However, there are concerns when administering injectable (IV) drugs to produce total IV anesthesia (TIVA) for longer anesthetic procedures, such as the total drug load administered and the potential for drug accumulation, a prolonged period for drug elimination, and the development of cumulative drug effects (prolonged weakness, ataxia, and/or prolonged recovery). This problem is not new, and it was a major catalyst for the transition from injectable to inhalant anesthetic techniques and the focus on the need to support arterial blood pressure with catecholamines (dobutamine; i.e., the ability to better control the depth, duration, and elimination of anesthesia at the expense of potentially producing hypotension) [24,25]. Today, the best of both worlds can be obtained by judiciously combining TIVA with inhalant anesthesia to limit the total injectable and inhalant anesthetic drug load. This will produce less cardiorespiratory depression, allow for greater control of anesthetic depth, and enable a more controlled and uneventful recovery from anesthesia [9]. This approach is facilitated by the intraoperative and post-operative administration of various analgesic drugs including a morphine-lidocaine-ketamine (MLK) drug combination with or without additional sedation (xylazine and/or detomidine). The near future will witness a refinement of these techniques, and hopefully, the development of newer injectable anesthetic drugs that possess good anesthetic qualities and minimize side effects.

Footnote

1. Tiletamine-zolazepam, Telazol, Fort Dodge Animal Health, Fort Dodge, IA 50501.