Fasting

Presurgical fasting time for pigs should be at least 12 h, though the stomach may still contain food due to the torus pyloricus, which is well developed in pigs. A full stomach may increase the risk of gastric dilation, nausea, vomiting, regurgitation, and aspiration. An overloaded stomach can produce significant pressure on the diaphragm, decreasing pulmonary functional residual capacity and alveolar ventilation [3]. When the surgical objective is to manipulate gastrointestinal or abdominal organs, the fasting time should be increased to 24–48 h to empty the large bowel. Neonates should be deprived of food for no more than 3 h in order to prevent hypoglycemia. All edible bedding must be removed from the cage in the fasting period, because pigs will readily consume it otherwise [4]. Water consumption is allowed until premedication is imminent although 4–6 h of complete nil per os may be warranted if the pig is going to undergo gastric or upper small bowel surgery [5].

Handling and restraint

Pigs can be difficult to restrain because of their body shape and lack of appendages that can be readily grasped by handlers [3]. Aggressive and/or fearful pigs pose several challenges from being difficult to fully evaluate to presenting a safety hazard to the staff and owners. Restraint can be facilitated by adapting the pig to the presence of humans and manipulation, resulting in a less stressful environment. In research environments, animals should be acclimatized at the institution for 2–3 weeks prior to experimental procedures [6]. During this time, the pigs should be spoken to and handled in a calm manner. However, in situations where time is limited and the animal is not trained, a partition known as a “crowd panel” or “hog board” can be used to isolate the pig in a corner or against a wall. This partition may be constructed of wood, plastic, or metal and should be the same height as the animal and two‐thirds to the full length of the pig. The hog board is used to protect the handler during examination or intramuscular (IM) injection.

Pigs can be restrained using other methods as well. For small pigs, the animal’s hind legs can be lifted by one hand, while the other is placed under the chest to provide support. However, pigs weighing more than 10 kg can be very strong and difficult to lift. These swine can be guided into a transport cart or coaxed out of the pen and into the cart with small amounts of food or treats. Another method of immobilization is the sling, where the pig is placed in a hammock with four holes for the limbs. This hammock is supported by a metal frame to which its limbs are loosely tied. One disadvantage is that the pig must be trained to use of the sling. A pig flipping technique has been described for either routine care in unsedated animals or to restrain sedated pigs for catheter placement or face‐mask induction [7,8]. Finally, the use of a back scratcher or “pig fork” has been promoted as a method of relaxation and distraction for pigs undergoing medical care.

For owned pigs, prehospital sedation can dramatically improve the response to handling and restraint in hospital. Oral (PO) trazodone (8–10 mg/kg PO) and gabapentin (20 mg/kg PO) may be helpful when administered together the night before and again 2 h prior to the veterinary visit [8].

Drug administration

Intranasal delivery can be used as a needleless route of drug administration in pigs. For example, Axiak et al. described intranasal administration of a mixture of ketamine 15 mg/kg, climazolam 1.5 mg/kg, and azaperone 1.0 mg/kg prior to castration. Drug administration is achieved using a catheter without the stylet and injected during inspiration in small volumes. Intranasal administration resulted in less effective anesthesia than IM injection, but with the advantages of minor temperature loss and shorter recovery time [9]. Lacoste et al. reported that the optimal intranasal midazolam dose in piglets was 0.2 mg/kg, producing rapid and reliable sedation [10].

Anesthetic induction of pigs can be complicated due to their behavior when physically restrained and the small number of vessels available for intravenous (IV) injections. Thus, IM administration of drugs is often preferred for initial immobilization and, in some situations, for induction of anesthesia in pigs. Intraperitoneal injection is described but requires specific training. Also, the consequences of improper administration can be severe if injection into the urinary bladder, intestines, or other organs occurs [11]. For IM injection in pigs, the muscles of the thigh are commonly used as the site of injection in piglets, but this is not recommended in growers/finishers because of the possibility of causing an abscess or needle breakage in edible tissue. Appropriate IM administration in adult pigs is behind the base of the ear where the layer of fat is thinner and the tissues have good perfusion [12]. Adequate needle size varies with the size of the animal, from a 20 gauge needle for a piglet up to a 14 gauge needle for a grower/finisher pig. Needles that are too short may result in injection of the drug into the fatty tissue, delaying the absorption, distribution, and ultimately the action of the anesthetic agent [3]. The use of a Luer‐lock needle and a low‐flow extension set connected to a syringe may reduce stress during the IM injection, allowing the administration of drugs from a relative distance from the animal. Alternately, a butterfly catheter can be used for IM injections in smaller animals [13]. Subcutaneous (SC) injection can be used in smaller or miniature pigs (e.g., Yorkshire and Yucatan). As pigs have very tight connective tissue, there are limited areas for SC injection such as the loose flap on the lateral cervical region [6,14], the axillary area caudal to the elbow, or in the inguinal region in the flank area [8].

Pigs have limited superficial veins that can be accessed easily to inject drugs. The marginal ear veins (i.e., auricular veins) are the only veins that are easily visible on pigs of any size (Fig. 65.1). In larger animals, the lateral and medial veins on the outer surface of the ears are preferable because of their increased size. A rubber band can be placed around the base of the ear to facilitate distention of the auricular veins [15]. The central auricular vessels are usually arteries (as in the rabbit) and should not be used for drug administration. Note that ear notching to identify pigs can damage some of these vessels.

Another option for venous access is the cephalic vein located along the craniomedial surface of the leg. This vein usually cannot be visualized but may be entered using blind venipuncture after applying a tourniquet [16]. In small pigs, it may be visualized continuing across the ventral surface of the neck after applying digital pressure at the thoracic inlet. The saphenous vein, on the lateral surface of the rear leg, is usually not a reliable injection site. Larger vessels such as the external or internal jugular vein or anterior vena cava can be catheterized but are usually reserved for blood sample collection or in research settings [5]. The subcutaneous abdominal vein (cranial superficial epigastric vein) is an alternative to the auricular vein for blood collection and IV administration of fluids and medication. This vein courses along the ventral portion of the abdomen and lies dorsolateral to the mammary chain. Firm digital pressure applied directly behind the elbow joint, along the thorax, will assist in visualization and/or palpation of this vein [17]. The subcutaneous abdominal vein can be useful for administration of large volumes of fluids, whereas auricular vessels are fragile and catheters may fail.

Parasympatholytic drugs

Atropine and glycopyrrolate are the two principal parasympatholytic drugs used in pigs. The use of these anticholinergic agents together with sedative/analgesic premedications may decrease the possibility of bradycardia caused by such agents as morphine, thiopental, and xylazine [20–23]. Anticholinergic agents also reduce bronchoconstriction, diminish airway secretion volume, and inhibit salivation, possibly improving conditions for orotracheal intubation. However, neither anticholinergic agent is routinely required, and it should be noted that an increased heart rate results in increased myocardial work and oxygen consumption.

In emergent situations in pigs without an IV catheter, atropine (and other resuscitation drugs, including epinephrine) can be administered via the endotracheal tube. Hörnchen et al. [24] concluded that 2 mg of atropine diluted in 5–10 mL of saline and instilled in the endotracheal tube was rapidly absorbed by the pulmonary circulation and increased heart rate within 1 min after administration. Compared to baseline, significant increases in heart rate were documented between 9 and 30 min after endotracheal instillation and between 12 and 15 min after IV injection.

Sedation and chemical restraint

The major sedatives that are commonly used in pigs are butyrophenones, phenothiazines, benzodiazepines, and α₂‐adrenergic receptor agonists [25]. As azaperone, acepromazine, and the benzodiazepines offer minimal analgesia, these drugs should be given in combination with other agents for invasive surgical procedures. Any full μ‐opioid receptor agonist can be administered to pigs, typically at doses similar to those used in dogs. In many situations, a lack of cooperativity on the part of the pig may make chemical restraint or IM induction of anesthesia an attractive approach.

Azaperone (Stresnil^®) is one of the most widely used sedatives in pigs where it is available [16]. This drug is classified as a short‐acting butyrophenone neuroleptic agent and is relatively safe compared to other drugs in this same category, such as haloperidol, when given intramuscularly [21]. IV injection of azaperone is contraindicated because it may cause excitation [20]. Azaperone may be used as a sedative in combination with local anesthetics for minor surgical procedures, as a premedicant with anxiolytic properties, as an anxiolytic in weanlings when they are mixed for the first time, and in maiden sows after their first litter to reduce the rejection of piglets [16]. The effects of azaperone are dose‐dependent wherein doses of 0.25 mg/kg produce mild sedation without ataxia in domestic pigs, 0.5–2 mg/kg will produce greater sedation but with mild ataxia, and doses of 2–4 mg/kg produce significant sedation and possible recumbency in adult pigs [21,26]. In younger pigs, it may be necessary to use a much higher dose of azaperone, such as 8 mg/kg, for appropriate sedation [3]. Vietnamese Pot‐bellied pigs require a dose of 0.25–2 mg/kg for sedation and a higher dose of 2–8 mg/kg for induction of anesthesia. However, doses exceeding 2 mg/kg are also more likely to cause adverse effects such as hypotension, bradycardia, and decreased cardiac output and contractility [21]. Note that in large boars, it has been suggested that azaperone doses should not exceed 1 mg/kg in order to reduce the risk of priapism [20].

Azaperone can be combined with other drugs to improve sedation and reduce its dosage, decreasing negative effects. Flores et al. suggested that azaperone (2 mg/kg) and xylazine (2 mg/kg) given intramuscularly produced good sedation and muscular relaxation [27]. Others have reported that animals pretreated with azaperone (2 mg/kg) and anesthetized with ketamine (15 mg/kg IM) and midazolam (0.3 mg/kg IM) demonstrated a good anesthetic induction and analgesia [28]. A combination of azaperone (4 mg/kg) and midazolam (1 mg/kg) provides sedation in Göttingen minipigs [4].

Acepromazine is a phenothiazine that can be used as part of a sedative combination in pigs, although by itself its sedative effects are often considered inadequate. Acepromazine is contraindicated in debilitated animals due to its potential adverse effects such as hypotension, bradycardia, hypothermia, and decreased respiratory rate [20,21]. The recommended IM dose of acepromazine is 0.03–0.1 mg/kg; however, in Göttingen minipigs, higher doses of 0.1–0.45 mg/kg have been suggested [4].

α₂‐Adrenergic receptor agonists, such as xylazine, romifidine, medetomidine, and dexmedetomidine, are widely used in pigs, usually in combination with a dissociative agent. Note that pigs require higher doses of α₂‐adrenergic receptor agonists than ruminants. Ketamine at a dose of 10–12 mg/kg IM with a dose of 1–2 mg/kg of xylazine will immobilize a pig in approximately 5 min [29]. However, this combination decreases cardiac output significantly for 30 min after administration and the arterial partial pressure of oxygen (PaO₂) may decrease, whereas total vascular resistance increases [30]. Sakaguchi et al. demonstrated that ketamine (10 mg/kg) and medetomidine (80 μg/kg) IM induced chemical restraint for 49.4 min on average, which was 14.8 min longer than a xylazine (2 mg/kg) and ketamine (10 mg/kg) combination [31]. In addition, the duration of muscle relaxation in pigs is twice as long with dexmedetomidine–ketamine as with the xylazine–ketamine mixture. In another study, Sakaguchi et al. studied ketamine and medetomidine combined with 25 μg/kg of atropine and concluded that the cardiovascular effects were limited in healthy pigs [32]. A combination of ketamine (8 mg/kg), romifidine (0.12 mg/kg), and butorphanol (0.1 mg/kg) given IM provides reliable anesthesia for 20–30 min after a single injection [33].

All of the combinations containing α₂‐adrenergic receptor agonists offer the advantage of being reversible by yohimbine (0.1–0.2 mg/kg IM, IV), atipamezole (0.12–1 mg/kg IM, IV, SC), or tolazoline (1–2 mg/kg IV, IM) [34–36]. The reversal of the α₂‐adrenergic receptor agonist is independent of the metabolism and clearance of ketamine. Therefore, when the α₂‐adrenergic receptor agonist is reversed before the effect of the ketamine has waned, an undesirable recovery may result (e.g., hyperkinesia of limbs, severe and prolonged ataxia, and vocalization) [21].

Adding another muscle relaxant drug to anesthetic combinations should provide a better recovery following reversal of α₂‐adrenergic receptor agonists. Ajadi et al. reported using ketamine at 20 mg/kg IM with xylazine (2 mg/kg IM) and midazolam (0.25 mg/kg IM). This combination appeared to almost double the duration of anesthesia with adequate analgesia for at least 30 min, compared to a lower dose of ketamine (10 mg/kg IM) added to this same combination of drugs [23]. However, recoveries after benzodiazepine–ketamine combinations are longer than xylazine–ketamine sedation. The administration of one part flumazenil (benzodiazepine antagonist) to 13 parts of a benzodiazepine agonist should reduce the recovery time in pigs. However, if flumazenil is given before ketamine effects are diminishing, the recovery will be similar to that with ketamine alone [3,21].

Opioids can be used in anesthetic combinations in swine. Ketamine (10 mg/kg), medetomidine (80 μg/kg), and butorphanol (0.2 mg/kg) given intramuscularly prolonged the duration of the loss of protective reflexes in pigs and permitted surgical procedures to be performed for at least 30 min [32]. Another option is to use tramadol, where available, instead of butorphanol. Tramadol appears to cause less respiratory depression compared with morphine or other μ‐opioid receptor agonists [37]. Pigs that received tramadol (5 mg/kg IM) prior to sedation with ketamine (25 mg/kg), xylazine (2.5 mg/kg), and atropine (0.04 mg/kg) intramuscularly had better quality of sedation that facilitated endotracheal intubation compared to the saline, ketamine, and xylazine treated animals. Also, this combination increased the duration of analgesia compared to ketamine–xylazine sedation [38]. At present, tramadol is not available in an injectable form in a number of countries including the United States. Morphine and fentanyl are widely used as analgesics for pet and research pigs, though this species may be relatively resistant to the minimum alveolar concentration (MAC)‐reducing effects [39–41]. Pigs appear to require higher doses of buprenorphine than dogs [42].

If chemical restraint or IM induction to anesthesia is desired, an actual anesthetic agent must be included in the drug protocol. Ketamine is the most commonly used dissociative anesthetic in humans, non‐human primates, cats, laboratory animals, and pigs. Ketamine has a wide safety margin as it generally stimulates cardiovascular function via its sympathomimetic effect [23,43]. Another advantage is that it can be given intramuscularly as well as intravenously. However, dissociative agents given alone can cause analgesia with no muscle relaxation, referred to as a “cataleptoid state,” as well as excessive salivation and hyperresponsiveness during recovery [3,16]. To minimize these negative effects, ketamine is combined with adjunctive agents to improve muscle relaxation, decreasing the ketamine dose required to achieve effective immobilization (Table 65.1). Yucatan and Yorkshire pigs may require a higher dose of ketamine and midazolam to be fully sedated compared to other breeds. For 5–10 min of sedation in Yucatan pigs, a combination of ketamine (25 mg/kg) and midazolam (0.6 mg/kg) can be used. For Yorkshire pigs, ketamine (5 mg/kg) combined with midazolam (0.5 mg/kg) is usually sufficient [14]. It should be noted that in this study, the combination of drugs was given subcutaneously in the lateral cervical region, which may have contributed to the relatively greater dosages needed.

Recently, several reports involving alfaxalone as part of sedation/anesthesia protocols have been published. Alfaxalone is a synthetic neuroactive steroid, which activates the GABA_A receptor [44], producing anesthesia and some muscular relaxation but no analgesia. The new formulation of alfaxalone‐2‐hydroxypropyl‐β‐cyclodextrin, (Alfaxan^®) has been used IV at a dose of 0.7–0.9 mg/kg in pigs premedicated with azaperone [45]. This formulation of alfaxalone has been administered successfully IM in pigs alone or in combination with other agents. IM injection of 5 mg/kg of alfaxalone with 0.5 mg/kg of diazepam produced a rapid onset of recumbency and deep sedation with minimal side effects in pigs [46]. Alfaxalone (5 mg/kg) and dexmedetomidine (10 μg/kg) IM also induced moderate to deep sedation with fair to smooth quality in pigs [47]. The main limitation for using alfaxalone in pigs is the large volume of injection required with the currently available 10 mg/mL alfaxalone solution, easily 10–20 mL depending on the size of the pig [45].