1. Pigs have a marked variation in body size; however, most research animals are less than 50 kg. Therefore, most of the following guidelines apply to smaller (miniature or juvenile) pigs. Body conformation and anatomy make manual restraint difficult, necessitating use of mechanical restraint (e.g. slings, "pig board") and/or chemical agents.
   1. Vascular Access: Pigs have very few superficial veins making the intramuscular route (IM) the most common route of drug administration. When venous access is necessary, the auricular, lateral saphenous, or cephalic veins are the most common locations for catheterization or IV injections. The central ear vein is the most consistently used site. This vein can accept a 22 gauge or larger catheter depending on the size of the animal. If repeated vascular access is required, implantation of a vascular access port (VAP) is recommended. Swindle, et al. provides an excellent resource for VAP.
   2. Endotracheal Intubation: Swine are one of the more difficult species to intubate and improper technique can result in significant trauma. Trauma can result in laryngeal rupture or passage of the ET tube in the subcutaneous space. To facilitate proper intubation, the animal should be at a deeper anesthetic level and premedication/induction agent with sedatives, anxiolytics, dissociatives, or one of their combinations, is highly recommended. For a complete description of proper intubation technique, the reader is referred to the discussion by Swindle, 2015 (pg. 41-48).
   3. Cautions: Swine are also very susceptible to vasospasm and ventricular arrhythmias. They have very fragile pulmonary tissue, which is likely to be damaged by hyperinflation; maintain ventilator pressure between 18-22 cm H2O.
   4. Malignant Hyperthermia: Perhaps their most significant idiosyncrasy is the susceptibility of some breeds of swine to malignant hyperthermia with certain anesthetic protocols. Malignant hyperthermia (MH) affects mainly Landrace, Pietrain, and Poland China breeds and is described as a "fulminant and hypermetabolic state of skeletal muscle" induced by volatile inhalational anesthetics, succinylcholine, and stress and exercise (Kaplan, 1991). Early signs of MH include decreases in pH and pO2, and increases in lactate, PCO2, potassium, and temperature. The onset of MH is usually during induction.
      1. MH is best prevented by avoiding those breeds of pigs known to be susceptible. Perioperative stress and exercise should be avoided by use of appropriate preanesthetic regimes (ketamine, opioids, benzodiazepines have been used successfully). Agents that have been associated with MH include succinylcholine, halothane, isoflurane, enflurane, and desflurane (halothane seems to be most potent (Kaplan, 1991)). Dantrolene can be used both in the treatment and prevention of MH. A chart for managing MH is attached as an appendix.
      2. There is another postoperative condition in swine that resembles MH but is considered a distinct condition. It is characterized by critically-elevated body temperature and hyperlactatemia (>2.5 mmol/L) during the recovery period (Swindle, 2015). It can be treated with cooling interventions (ice, cold IV solution, fan).
   5. Pre-anesthetic Fasting:
      1. ​Withhold food for at least 8 hours but no longer than 24 hours prior to sedation or anesthesia in order to reduce the risk of regurgitation and aspiration.
         1. Fasting periods for greater than 24 hours related to specialized procedures (ie. gastrointestinal procedures) should be described in the protocol.
      2. Remove any bedding or enrichment items that may be ingested
      3. Do not withhold water prior to anesthesia or sedation.
      4. For neonatal or unhealthy animals, special care is required. Consult a ULAM faculty veterinarian prior to fasting these animals.
2. Apply sterile non-medicated ophthalmic ointment to the eyes to prevent corneal drying during anesthesia or sedation.

1. Standard mammalian monitoring techniques are applicable to swine - the goal of monitoring should be to maintain cardiovascular homeostasis and core body temperature. Understanding the basic physiologic effects of the anesthetics used is paramount to correctly interpreting monitoring parameters. For uncomplicated, brief surgeries, monitoring vital signs (e.g. temperature, HR, RR), and pulse oximetry may be adequate. For more invasive procedures, blood pressure monitoring and blood gas analysis may be indicated. Monitoring body temperature is critical - especially in those breeds prone to MH.
2. Jaw tone most reliably reflects depth of anesthesia and should be assessed throughout the procedure. If the jaw is inaccessible, use ocular and other muscular reflexes.
3. Anesthetic Adjuncts:
   1. Premedication and induction with anesthetic adjuncts, such as the sedatives, helps facilitate animal handling for intubation and surgical preparation.
   2. Acepromazine (0.11 - 1.1 mg/kg IM, IV, SC) is commonly used alone for sedation or as an anesthetic premed. High doses can cause alpha- adrenergic blockade (resulting in low blood pressure, peripheral vasodilation, etc.), which may be a contraindication for their use in cardiovascular studies.
   3. Diazepam (0.5-10 mg/kg SQ; 0.44-2 mg/kg IV SLOWLY) or midazolam (0.1-0.5 mg/kg IM, SQ or IV) have successfully been used as pre-anesthetic tranquilizers. Diazepam infusion at 1 mg/kg/hr can cause profound hypothermia with prolonged use (>6 hr). Midazolam is preferred over diazepam for IM use because it has more consistent absorption from muscle.  Benzodiazepines can increase the recovery period, especially if used intraoperatively. Flumazenil (0.02 mg/kg IV), a selective benzodiazepine antagonist, can be used as a reversal agent for midazolam or diazepam.
   4. The anticholinergic glycopyrrolate (0.004-0.01 mg/kg IM) may be used to dry oral and respiratory secretions and for its vagolytic (ability to block vagal nerve stimulation and consequent bradycardia) effects during endotracheal intubation. This may be used intraoperatively if mean arterial pressure (MAP) decreases below 60 mmHg and fluid boluses are insufficient to correct hypotension. Sinus tachycardia can result from indiscriminate use of these agents.

1. Inhalant anesthetics are the preferred agents used in research settings. Anesthesia may be induced with many of the injectable anesthetic agents, after which the pigs are intubated endotracheally and maintained on gas anesthetics safely for prolonged periods. 
   1. Isoflurane has a low blood gas solubility resulting in more rapid anesthetic recoveries and the ability to rapidly alter depth of anesthesia. Although isoflurane also produces a dose-dependent depression of the cardiovascular system, it has the greatest margin of safety of all the inhalation anesthetics currently in use and is considered to be the inhalation agent of choice in swine. 
   2. Sevoflurane has similar physiologic effects and may be used instead of isoflurane.
2. Injectable anesthetic agents are encouraged as an adjunct to inhalant anesthetics for some experimental procedures. Dissociative anesthetic agents like ketamine are the most commonly used anesthetic agents in swine. Ketamine produces rapid and safe immobilization with minimal cardiovascular depression. Ketamine does not provide good visceral analgesia and provides very little muscle relaxation; therefore, it is usually used in combination with another agent like xylazine. Doses of ketamine alone and combined with other agents are listed in the table that follows.
   1. ULAM recommends the combination of Telazol® (tiletamine/zolazepam, 4.4 mg/kg) and xylazine (2.2 mg/kg). This is an excellent combination for induction IM, it provides rapid sedation for intubation and catheter placement.
      1. Large dose volumes may need to be split into multiple doses. See Guidelines on Administration of Substances to Laboratory Animals.
      2. Ketamine volume may be reduced by half using Zoopharm's 200 mg/mL formulation.
   2. Atipamezole is recommended as a reversal agent for xylazine. However, we do not recommend reversing this agent to facilitate recovery after painful procedures as it continues to provide some level of analgesia postoperatively.  Reversal should be reserved for emergencies or for nonsurgical procedures (e.g. chemical restraint for noninvasive procedures).

1. Inhalant
   1. Nitrous Oxide may reduce the concentration of isoflurane required by 50% and may be useful for some cardiovascular studies. It cannot be used as a sole anesthetic agent and must be delivered in a 1:1 or 2:1 mixture of nitrous oxide to oxygen combined with other inhalant anesthetics. Additionally, nitrous oxide is not absorbed by charcoal canisters and can only be used with vacuum scavenging anesthetic systems.
2. Injectable
   1. Opioids may be used as continuous IV infusions with other anesthetics because they enhance analgesia, produce minimal cardiovascular depression, and protect against cardiac arrhythmias. Fentanyl, sufentanil, and combinations of fentanyl are the most common opioids used with pigs. Fentanyl causes dose-dependent NMDA-receptor activation, so combination with ketamine or dextromethorphan is recommended.
   2. A variation of the telazol/xylazine combination is TKX: telazol, ketamine, and xylazine. The advantage to this preparation is that it increases the dissociative component of anesthesia, which reduces posterior weakness that may be seen with TK.
      1. Preparation: reconstitute an unused vial of Telazol with 2.5 mL ketamine (100 mg/mL) and 2.5 mL xylazine (100 mg/mL). This results in 100 mg/mL dissociative (tiletamine and ketamine), and 50 mg/mL each of xylazine and zolazepam. The benzodiazepine component is reduced to 25% of the total drug dose compared to the TX mixture.
   3. GKX (Guaifenesin-Ketamine-Xylazine; "Triple Drip"): the major advantage to this drug combination is that recovery is very rapid (30 to 45 min). The disadvantage is that, as an induction agent, it must be given I.V. It is prepared by adding 2 mg ketamine and 1 mg xylazine to each milliliter of 5% guaifenesin prepared in 5% dextrose in water.

1. If used as the only form of anesthesia, regional anesthetics should be combined with sedatives and manual restraint in a sling. The most commonly used regional anesthetic is lidocaine. The onset of action is rapid and duration of action of lidocaine is 90-180 minutes. Longer acting local anesthetics, like bupivacaine, can provide 180-300 minutes of analgesia, but onset is slow. Local anesthetics are only appropriate for minimally invasive procedures with the exception of epidural analgesia. Epidural anesthesia can be helpful for abdominal surgeries - for a more complete description, the reader is referred to the discussion by R.T. Skarda, 1987 and Swindle, 2015.
2. Wound infusion catheters, aka "soaker catheters," can be used to deliver continuous infusions of local anesthetics to the surgical site. Contact your ULAM veterinarian for more information.
3. Lidocaine and bupivacaine can be mixed 1:1 prior to administration to maximize their kinetics. Total dosages should not exceed 8 mg/kg for lidocaine and 2 mg/kg for bupivacaine.

1. Signs of Pain: Signs of pain in swine may include, but are not limited to, the following:
   1. Abnormal gait
   2. Abnormal posture
   3. Reluctance to move
   4. Social isolation
   5. Abnormal vocalizations
   6. Abnormal aggression
   7. Decreased appetite
   8. "Tucked up" abdomen
   9. Elevated respiratory rate
   10. *Contact a ULAM veterinarian to develop a pain scale for your specific studies.
2. Prevention and Management of Pain: Most analgesics used in swine have a relatively short half-life. Buprenorphine is considered the analgesic of choice because it is effective for 8-12 hours at higher dosages.
   1. It is good practice to administer analgesics prior to surgery (preemptive analgesia) to diminish the afferent nerve impulses involved in the nociceptive process. For procedures and surgeries that are likely to cause only minor pain and discomfort, this may be the only analgesic dose necessary.
   2. Consideration of continuous intravenous infusion (Continuous Rate Infusion or CRI) or alternative delivery systems is appropriate for procedures likely to cause significant post-operative pain.
   3. Lidocaine and bupivacaine are encouraged because they provide local anesthesia and analgesia that decrease post-operative pain association with incision sites.
   4. Preemptive analgesia, particularly opioids like buprenorphine, can reduce the dose of anesthetics required for surgical anesthesia and increase the respiratory depression associated with anesthetics. When preemptive analgesia is used, consider reducing the dose of anesthetic (whether inhalant or injectable) to the low end of the recommended range. Anesthetic depth must be carefully monitored and drug doses may need to be titrated to maintain appropriate levels. With new projects, sexes, strains or anesthetic and analgesic combinations, assess a subset of animals before expanding to use in a larger cohort.

For musculoskeletal pain, non-steroidal anti-inflammatory drugs (NSAIDs) like phenylbutazone, aspirin, ketoralac, and ketoprophen have all been used in swine. Enteric-coated products are recommended because of this species' susceptibility to gastric ulcers. Oral medications are readily accepted if placed in canned dog food or chocolate syrup. Carprofen (Rimadyl®) comes in a convenient chewable tablet form.