Introduction

General anesthesia in horses is challenging. Nevertheless, a recent multicenter [1] and some single‐center surveys [2–4] indicate that general‐anesthesia‐related mortality has decreased compared to studies performed 20 years ago [5]. To avoid the risks of general anesthesia, there is a growing tendency to perform as many surgical interventions as possible in standing sedated horses [6]. Sedative techniques, along with better local anesthetic techniques, have been developed for this purpose. The risks of standing surgeries, however, remain to be determined and compared to those of general anesthesia [1,7]. There are still many unstudied and unanswered questions about how to best perform equine anesthesia for an optimal outcome. This chapter aims to provide an overview of peculiarities associated with horses and a focus on the management of anesthesia and solutions for common problems.

Preanesthetic considerations

Guidelines on how adult horses should be prepared prior to anesthesia, including transport, fasting, and behavioral considerations, have varied, and little evidence‐based guidance addressing these concerns is available. Horses that were transported the morning before surgery showed higher cortisol levels than horses that were kept in the clinic the night before [8], so stress might be reduced if preoperative transport of the animal is avoided.

In adult horses, the patient’s nutritional status before elective general anesthesia may influence intraoperative oxygenation and potentially impact the risk of postoperative colic. Postoperative colic is a significant problem [9,10], but the literature is mostly retrospective, and reported effects are confounded by the many factors involved. In horses where mainly dissociative‐based anesthesia induction protocols (e.g., ketamine) are used, unlike in other species, regurgitation and aspiration of gastric contents is uncommon as long as the horse is not suffering from colic. Since horses typically browse for their food, prolonged fasting can cause stress in individual horses, which will negatively influence motility of the gastrointestinal tract [11] or potentiate ulceration [12]. A negative energy balance might impair normal metabolism and derange oxygen–glucose physiology during the perioperative period, although that is usually not a concern for healthy adult horses. In foals up to about 4 weeks of age, however, fasting is best avoided.

Preanesthetic fasting also has potential benefits. Less material in the gastrointestinal (GI) tract places less pressure on the major abdominal vessels and causes less cranial displacement of the diaphragm. This may lessen impairment of venous return to the heart and improve ventilation via an increase in functional residual capacity, likely providing better oxygenation and oxygen delivery to the tissues. Further, ongoing microbial gas production within the GI tract is probably decreased in fasted horses. Since postoperative colic can be a major complication following anesthesia and surgery in horses, reduced gas production can limit ileus. This effect on colic rates has been shown in fasted in comparison with unfasted horses [10]. However, the use of a muzzle to limit oral intake of solid feed has been associated with more postoperative colic than the simple avoidance of preoperative feeding while allowing the horse to consume some of its bedding [13]. Many anesthesiologists are convinced that preoperative overnight fasting for 8–12 h is beneficial for most horses. Easy access to water is important and may be impaired by a muzzle; however, for certain horses, this will necessitate limiting the amount of edible bedding available.

Horses instinctively tend to flee when they are threatened or frightened. Therefore, the periods immediately before losing and after regaining consciousness can be difficult to manage in horses unaccustomed to close human contact, those experiencing injuries, or simply due to the unusual environment. Once a horse is excited or frightened, it can be very difficult to calm it down again. Often, higher sedative doses (with potentially more untoward side effects) will be needed. Therefore, it is important to avoid excitement and reduce pain and stress through proper use of sedative and analgesic drugs before anesthesia induction and during the recovery period.

In addition to the judicious use of sedatives, common principles of physical restraint should be applied to the handling of horses. Some degree of physical restraint is combined with appropriate sedatives to yield a tractable horse. The method of physical restraint will be based on a number of factors, including the size and temperament of the horse, the availability of personnel, and the duration or type of procedure.

Standing sedation

Sedation of horses for physical examination or standing procedures is commonly performed using readily available sedatives and analgesics (Table 61.1). Intravenous (IV) administration of α₂‐adrenergic receptor agonists (e.g., xylazine, detomidine, romifidine, medetomidine, or dexmedetomidine) forms the basis of most drug combinations used to achieve moderate or heavy sedation in horses. Their combination with opioid analgesic drugs will lead to more reliable sedation and, therefore, is strongly recommended. Sublingual administration of detomidine (Dormosedan Gel^®, Zoetis) may be useful for horses that cannot be given injections. For standing surgeries, use of sedation is combined with administration of both systemic and local analgesics. Epidural injection of local anesthetics in combination with xylazine or detomidine at the first intercoccygeal space is recommended for perineal surgeries. Various combinations of epidural α₂‐adrenergic receptor agonists, local anesthetics, and opioids have been proposed for perioperative pain control for surgeries distal to the thoracic region [14].

Preanesthetic sedation

For most cases, it is possible to catheterize a jugular vein using local anesthetic infiltration with or without prior administration of a sedative. Intramuscular (IM) acepromazine (e.g., 0.03–0.05 mg/kg) at least 30 min before placement of an IV catheter may help calm some horses [17]. In uncooperative animals where catheter placement is difficult, acepromazine alone at the above‐mentioned dose rates does not usually result in adequate sedation. In those horses, it can be beneficial to sedate them with IM injection of a longer acting α₂‐adrenergic receptor agonist (e.g., 0.04 mg/kg romifidine, or 0.01 mg/kg detomidine) and subsequently add an opioid such as butorphanol (0.02 mg/kg). Yearlings, thoroughbreds, and Arabians tend to need higher dosages and, in very difficult horses, doubling the initial dose of the sedative will avoid the repetitive stress of injection and resulting stimulation. Most important is to leave horses given IM sedation (detomidine at least 20 min, and romifidine 30 min) in an undisturbed environment to allow peak effects to develop before handling. If further doses of sedatives are needed to achieve satisfactory calming effects, long‐lasting cardiopulmonary effects dominated by reduced cardiac output, peripheral vasoconstriction and reduced tissue perfusion may result [18,19]. This might be detrimental in the case of general anesthesia. Myopathies and neuropathies are a consequence of inadequate tissue blood flow and contribute to the incidence of equine perioperative fatalities [20]. As acepromazine is relatively long acting, cannot be antagonized, and has numerous potential adverse effects, the anesthetist should avoid its use in cases involving pre‐existing hypotension, anemia, hypothermia, or moderate to severe liver impairment.

Following catheter placement, unsedated horses are ideally left undisturbed for at least 5–10 min. Stress‐free transfer of the horse to the surgical area is facilitated by administering approximately one‐third of the total intended IV dose of chosen α₂‐adrenergic receptor agonist. (Table 61.1). As soon as some sedation becomes apparent, horses can usually be walked into the anesthesia induction area with minimal resistance.

Once in the induction area, the remainder of the sedative is administered slowly to reach the desired depth of sedation (i.e., the horse becomes unresponsive to surrounding stimuli). In horses that do not become heavily sedated within 5–10 min, depending on the choice of α₂‐adrenergic receptor agonist, an additional injection of approximately 25% of the initial dose may be administered, or an opioid may be added, to enhance sedation and analgesia. Generally, reduction of the dose of α₂‐adrenergic receptor agonists is reserved only for severely compromised horses that cannot be stabilized before anesthesia induction. In such patients, a higher dose of benzodiazepine during anesthesia induction (up to 0.1 mg/kg instead of 0.02 mg/kg) or the use of guaifenesin may improve muscle relaxation.

Some veterinarians consider sedation before general anesthesia with shorter acting α₂‐adrenergic receptor agonists such as xylazine (0.5–1.0 mg/kg), medetomidine (7 μg/kg), or dexmedetomidine (3–5 μg/kg) safer. Their untoward cardiopulmonary effects are shorter lasting than those associated with detomidine or romifidine, and peak intensity of adverse effects is less pronounced [21,22].

Some anesthetists prefer to combine sedatives with opioids. The combination of α₂‐adrenergic receptor agonists with an opioid receptor agonist improves quality of sedation [23–25], and better analgesia is provided. In horses, the minimum alveolar concentration (MAC) of inhaled anesthetics is not consistently decreased following opioids [26], but if α₂‐adrenergic receptor agonists are used together with opioids, the effect of the α₂‐adrenergic receptor agonist on MAC is consistent and more pronounced [27]. Opioids might contribute to respiratory depression caused by general anesthetics [28] and also carry the potential to reduce fecal output and predispose to colic after anesthesia [29]. However, evidence supporting this contention is poor [30], and a more recent study showed that hydromorphone did not increase incidence of postoperative colic [31]. Still, some anesthetists do not routinely administer opioids before anesthesia induction, and intraoperative analgesia is provided by other means.

Induction of anesthesia

For most veterinarians, the preferred anesthetic induction agent in horses is ketamine. Other induction drugs are available and may be used in horses (Table 61.2). When used appropriately, the horse will slowly assume sternal and then lateral recumbency. A significant disadvantage of ketamine in comparison with other alternatives (propofol, alfaxalone, and barbiturates) is poor muscle relaxation and hypnosis when used alone. To minimize these undesirable effects, horses should be deeply sedated before anesthetic induction with ketamine. Additionally, the use of centrally acting muscle relaxants significantly enhances the quality of equine anesthesia induction. Guaifenesin (35–50 mg/kg) can be given intravenously to effect (until the horse becomes ataxic and buckles its knees) just prior to the bolus of ketamine (with or without additional muscle relaxants such as the benzodiazepines, diazepam or midazolam). These drugs reduce muscle hypertonus and reflex activity, which facilitates endotracheal intubation. Guaifenesin administration can be cumbersome in adult horses as effective dosages result in the need for relatively large volumes to be administered. Furthermore, it can cause phlebitis even if used at a relatively low concentration of 5% [32]. For this reason, many prefer to use a benzodiazepine for muscle relaxation. An additional advantage of benzodiazepine use is the availability of an antagonist, flumazenil. It has not been extensively studied or routinely used in equine anesthesia because of expense, but in cases of emergency a dose of 0.02 mg/kg IV can reverse the respiratory side effects of benzodiazepines and eventually shorten recovery [33]. A more recent study compared the use of ketamine in combination with propofol (0.5 mg/kg) or midazolam (0.1 mg/kg) for anesthesia induction [34] and found slightly better recoveries with propofol following 1 h of isoflurane anesthesia.

Some anesthetists prefer to keep the dose of the benzodiazepines for co‐induction low (0.02 mg/kg), which minimizes the impact on respiration and reduces ataxia during recovery. An IV bolus of ketamine of 2–3 mg/kg in combination with diazepam or midazolam results in recumbency within 1.5–2 min and is associated with relatively deep anesthesia for about 8–15 min. Nevertheless, for surgical manipulations, the use of additional local or systemic analgesia is advised. If the surgical procedure is not successfully performed within this time frame, or if the trachea is intubated and maintenance of anesthesia with an inhalation agent is begun, additional ketamine (1–1.5 mg/kg IV) may be administered. If a short‐acting α₂‐adrenergic receptor agonist was used for sedation (xylazine, medetomidine, or dexmedetomidine), it should also be readministered at 50% of the initial dose.

Following anesthesia induction with ketamine, some animals will have rapid nystagmus, limb movements, or muscle tremors. Under such circumstances, additional anesthetic drug(s) should be given without delay to prevent emergence from anesthesia during critical periods such as hoisting onto the surgical table. As short‐acting barbiturates have the fastest onset of action, many anesthetists prefer thiopental for this purpose when it is available. A dose of 0.5 mg/kg in most horses will relax muscles without causing apnea, and intubation can be easily performed. Other alternatives to barbiturates with good hypnotic properties that have been described for anesthesia in horses are alfaxalone and propofol. Propofol induction of an adult horse requires a large volume of drug that may prove cost prohibitive [35]. Alfaxalone (1 mg/kg IV) has been compared with ketamine or thiopental for induction of anesthesia [36] and showed similar induction and recovery qualities; however, in another study, horses receiving alfaxalone had a higher incidence (5/6 horses) of muscle tremors during induction [37]. Similar to the use of propofol, alfaxalone induction requires administration of a large volume, and, to date, this remains expensive.

Maintenance of general anesthesia

The use of several drugs in combination is called “balanced anesthesia” if their net effects produce unconsciousness, muscle relaxation, amnesia, and antinociception. In modern equine practice, there are multiple combinations that can achieve this balance. The use of inhalant‐only anesthesia for maintenance has largely been replaced by the use of inhalation anesthesia in combination with sedatives, analgesics, and muscle relaxants, given either by infusion or by repetitive bolus administration. This type of anesthesia is called “partial intravenous anesthesia” (PIVA). If no inhalation agent is used and only IV drugs are administered, it is called “total intravenous anesthesia” (TIVA).

The aim of PIVA is to provide analgesia and reduce inhalation anesthetic requirements. By modulating antinociception intraoperatively, a balanced anesthesia protocol is expected to reduce postoperative pain while better maintaining cardiopulmonary function compared to inhalation anesthesia alone. While PIVA with lidocaine [38] compared to pure inhalant anesthesia did not result in improved cardiopulmonary function, there is general agreement among practitioners that PIVA is, under most circumstances, superior to the use of inhalation anesthesia alone. Preliminary results of a large multicenter study (CEPEF 4) reported that the use of PIVA has increased from 38% to 62% over the last two decades [1]. For surgeries where the surgical field can be locally or regionally anesthetized, the use of PIVA is not mandatory. However, the use of such techniques is limited in horses compared to other species because regional desensitization of extremities persisting into the recovery phase can result in injuries during the horse’s attempts to stand.

For PIVA, lidocaine, ketamine, different α₂‐adrenergic receptor agonists, and various opioids (alone or in combination with each other) have been used as adjuncts to inhalation anesthesia [39,40]. Some anesthetists have also advocated additional midazolam or guaifenesin to enhance muscle relaxation, although the impact of muscle relaxants on recovery needs to be considered carefully. The problem with all these polypharmacy combinations is that the pharmacokinetic and pharmacodynamic interactions can be difficult to predict in individual animals [41]. During clinical anesthesia, plasma levels cannot be rapidly measured, so some drugs with a narrow therapeutic window (e.g., lidocaine) might result in toxic levels when standard dose rates are used under certain circumstances [41,42], for example in colics with compromised hepatic blood flow.

The half‐life of most drugs will be prolonged with increased infusion time (so‐called “context‐sensitive half‐life”). Also, the pathophysiologic status of the individual horse can influence half‐lives of drugs, in particular differences in cardiac output and hepatic blood flow. Metabolites with pharmacological activity, such as norketamine, that are metabolized more slowly than the parent drug [43], can potentially accumulate and influence recovery after longer infusions. If PIVA is used, the anesthetist has to be aware of the pharmacokinetic and pharmacodynamics effects of all the drugs used.

A discussion of some of the drugs that are used for PIVA and important aspects of their use follows. Additional reviews, including dose rates for common drugs, are available [39,40,44].

α₂‐Adrenergic receptor agonists

All available α₂‐adrenergic receptor agonists have been used successfully for PIVA in horses and cause reliable sedation, good analgesia, and inhalant anesthetic dose reduction. Accumulation will not lead to excitement in recovery but to prolonged sedation, eventually leading to a longer but smoother recovery phase. α₂‐Adrenergic receptor agonists are used for sedation prior to induction of anesthesia in almost all horses, and this acts as an effective loading dose, thereby reducing the time required to achieve a target plasma concentration without the need to administer an intraoperative loading dose.

Dexmedetomidine, medetomidine, and xylazine [45,46] are shorter acting than detomidine or romifidine [47], making them better suited for titration of effect during PIVA. Numerous PIVA studies involving α₂‐adrenergic receptor agonists have been published. Because dose and study designs varied widely, with only two different protocols compared or only successful use of a single protocol reported [48,49

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