Guidelines on Anesthesia and Analgesia in Swine

Principal Investigator: Responsible to ensure appropriate anesthesia and/or analgesia is provided for all swines undergoing potentially painful procedures including survival surgery unless otherwise indicated in the relevant approved protocol.

1. Pigs vary markedly in body size – these guidelines apply to otherwise healthy miniature swine or juvenile farm breeds weighing < 50 kg. A ULAM veterinarian can provide advice for larger animals, neonates, and other special cases.
   1. Manual restraint is difficult in pigs due to their strength and conformation.
      1. Acclimate to handling or gentle restraint via sling where possible using positive reinforcement training.
      2. Consider using specialized equipment such as “pig boards” to briefly limit movement (e.g. when giving injections) or to guide animals when moving within or outside of the primary enclosure.
   2. Piglets may be briefly manually restrained by hand.
   3. Hearing protection is recommended during restraint or aversive procedures in swine as this species produces loud vocalizations.
2. Vascular Access: The auricular (ear), lateral saphenous, or cephalic veins are common locations for catheterization or IV injections.
   1. The central ear vein is easy to access and can accept a 22 gauge or larger catheter, depending on the size of the animal.
   2. If repeated vascular access is required, implantation of a vascular access port (VAP) is recommended.
3. Endotracheal Intubation: Intubation in swine is challenging. Improper technique can result in swelling, bleeding, laryngeal rupture or passage of the ET tube into the subcutaneous space.
   1. Pre-oxygenation via mask whenever possible to avoid oxygen desaturation during and following the intubation process.
   2. Premedication with anxiolytic or sedative agents is highly recommended.
   3. Ensure the animal is at a deep enough plane prior to attempting intubation
   4. Intubation can be performed in dorsal or ventral recumbency. Descriptions are available in Swindle, 2015 (p. 41 – 48), Costea et al 2023, and Renberg et al 2024.
   5. Devices that facilitate intubation include laryngoscopes with long blades, flexible fiberoptic endoscopes (Ruemmler et al 2020), and plastic guides (Janiszewski et al 2014) are described.
      1. Your ULAM faculty veterinarian can assist you with training and equipment recommendations.
4. Ventilator Use: Swine are susceptible to vasospasm and ventricular arrhythmias and have very fragile pulmonary tissue, which is easily damaged by hyperinflation.
   1. Maintain ventilator pressure between 18-22 cm H2O.
5. Malignant Hyperthermia (MH): Multiple breeds of swine are prone to malignant hyperthermia when anesthetized using certain protocols. These include Landrace, Pietrain, and Poland China as well as crosses of these breeds.
   1. Malignant hyperthermia is induced by volatile inhalational anesthetics, succinylcholine, stress and exercise (Kaplan, 1991).
   2. 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.
   3. To prevent MH:
      1. Avoid breeds of pigs known to be susceptible.
      2. Avoid agents associated with MH in susceptible animals, such as succinylcholine, halothane, isoflurane, enflurane, and desflurane.
      3. Avoid perioperative stress or high activity.
      4. Reduce anxiety using appropriate preanesthetic agents (such as ketamine, opioids, and/or benzodiazepines.
      5. Dantrolene can be used to treat and prevent MH (see chart in Appendix A).
6. Other causes of hyperthermia: other conditions resembling but distinct from MH have been reported in the postoperative period in multiple breeds of swine.
   1. Mutations in the dystrophin gene are associated with signs similar to MH in male and female pigs (Corrigan et al. 2025).
      1. Animals develop temperature increases, loss of mobility, and death when exposed to stress (e.g. handling, transport) or while anesthetized with volatile anesthetics.
      2. Avoid this condition by reducing stress when handling and by reducing or eliminating volatile anesthetics.
   2. Hyperthermia and hyperlactatemia (>2.5 mmol/L) can be seen sporadically in pigs during the recovery period (Swindle, 2015).
      1. Treat with cooling interventions (ice, cold IV solution, fans, acetaminophen suppository, etc.).
      2. Assess and treat any sources of pain experienced by the animal.
      3. Minimize direct handling, noise, or other sources of stress.
7. Pre-anesthetic Fasting: pigs can vomit or regurgitate and aspirate food material while anesthetized.
   1. ​Withhold food for at least 8 hours but no longer than 24 hours prior to sedation or anesthesia.
      1. Describe and justify fasting periods greater than 24 hours in your protocol.
   2. Remove bedding or enrichment items that may be ingested at initiation of the fasting period.
   3. Do not withhold water prior to anesthesia or sedation.
   4. For neonatal or unhealthy animals, consult a ULAM Faculty Veterinarian prior to fasting.
   5. Anti-nausea and/or anti-emetic medications can be administered prior to an anesthetic event to reduce post-operative nausea and vomiting.
   6. Table 1: Anti-nausea and anti-emetic medications

   7. Drug	Route	Dosage	Notes
      Ondansetron	PO, IM, IV	0.1-0.5 mg/kg q 24 hrs	Selective 5-HT3 receptor antagonist
      Maropitant (Cerenia®) Recommended	SC	1 mg/kg q 24 hrs for up to 5 days	Counteracts appetite suppression from buprenorphine SR. Evidence for visceral analgesia.

8. Apply sterile non-medicated ophthalmic ointment to the eyes throughout the anesthesia/sedation period as needed to prevent corneal drying.

1. Standard mammalian monitoring techniques are applicable to swine. Refer to Anesthesia and Sedation Monitoring Guidelines for more information.
   1. Jaw tone is a reliable method to assess depth of anesthesia and should be checked throughout the procedure.
   2. Ocular or muscular reflexes are other options to assess depth if jaw is inaccessible.

Anesthetic adjuncts facilitate animal handling for intubation and surgical preparation by reducing stress and/or providing sedation.

Table 2: Anesthetic Adjuncts

1. Inhalant anesthetics are preferred for longer procedures because depth is easily titrated and recovery from inhalant agents is rapid.
   1. Anesthesia may be induced with injectable anesthetic agent(s), after which the pigs are intubated endotracheally and maintained on inhalant anesthetics safely for prolonged periods.
   2. Isoflurane has a high margin of safety, but produces dose-dependent depression of the cardiovascular system.
   3. Sevoflurane has similar physiologic effects and may be used instead of isoflurane.
2. Injectable anesthetic agents are encouraged as adjuncts to inhalant anesthetics. See section 6 below for examples of agents and combinations for use in swine.
   1. Oxygen supplementation is highly recommended, even when using injectable agents only.
   2. Ketamine does not provide good visceral analgesia or muscle relaxation; therefore, it is usually used in combination with another agent like xylazine. See Table in Section 6 for dose information.
   3. 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.
   4. Atipamezole is recommended as a reversal agent for xylazine. Reversing xylazine will also reverse any analgesia provided by this agent postoperatively. Prepare a plan for rescue analgesic use if needed.

1. Inhalant
   1. Nitrous Oxide may reduce the concentration of isoflurane required by 50% and may be useful for some cardiovascular studies.
      1. Cannot be used as a sole anesthetic agent
      2. Must be delivered in a 1:1 or 2:1 mixture of nitrous oxide to oxygen combined with other inhalant anesthetics.
      3. Not absorbed by charcoal canisters – 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.
      1. 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 TX.
      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 zolazepam), and 50 mg/mL each of xylazine and ketamine. 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.

Table 3: Anesthetics Medications

1. Signs of Pain: Signs of pain in swine 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. Grimacing (i.e. orbital tightening/”squinting”, tight appearing cheek/bulging nose muscles, ears pinned back)
   11. A ULAM veterinarian can help develop pain scoring methods for your study.
2. Prevention and Management of Pain: Most analgesics used in swine have a relatively short half-life.
   1. Administer analgesics prior to surgery (pre-emptive analgesia) to diminish the afferent nerve impulses involved in the nociceptive process.
   2. Consider intravenous infusion (Continuous Rate Infusion or CRI) or alternative delivery systems for procedures likely to cause significant post-operative pain.
   3. Preemptive analgesia, particularly opioids like buprenorphine, can reduce the dose of anesthetics required for surgical anesthesia and increase the respiratory depression associated with anesthetics.
      1. Consider reducing the dose of anesthetic (whether inhalant or injectable) to the low end of the recommended range when using.

1. Local anesthetics have many benefits:
   1. Highly effective
   2. May be given as local or regional blocks and as epidurals.
      1. Soaker catheters and Beir blocks may be especially helpful in large animals.
      2. Application at the incision site decreases post-operative pain an can be used as part of a multimodal analgesic plan.
   3. Prevention of wind-up pain
   4. Non-controlled
   5. High degree of safety
      1. Cardiotoxic effects if inadvertently given IV
2. Available local anesthetics range in duration of onset and duration of action. Factors such as dose, temperature, and lipid solubility affect absorption. Consult your ULAM veterinarian to assist you in selecting the best dose and formulation for your study. General information is as follows:
   1. Lidocaine: 2-5 minute onset of action; duration 90 – 180 minutes
      1. Total dosage should not exceed 8 mg/kg.
   2. Bupivacaine: 10-15 minute onset of action; duration 180 – 300 minutes
      1. Total dosage should not exceed 2 mg/kg
      2. Liposomal formulations (Exparel, Nocita) extend duration up to 72 hours. (Recommended)
      3. May be mixed 1:1 with bupivacaine to maximize kinetics.
   3. Ropivacaine: similar onset, duration to bupivacaine, but with less motor blockade and less potential for cardiotoxicity.
      1. Total dosage should not exceed 2 mg/kg.
3. Extending duration of local anesthetics can be accomplished via:
   1. Use of liposomal preparations (see bupivacaine above)
   2. Combination with adjunctive drugs: extend duration to 12+ hours.
      1. Buprenorphine (0.004 mg/kg)
      2. Dexmedetomidine (1 mcg/kg)

1. Opioid analgesics
   1. Table 4: Analgesics Use in Swine

1. Non-steroidal anti-inflammatory drugs (NSAIDs)
   1. Preferable for musculoskeletal pain.
   2. Swine are prone to gastric ulcers precipitated by stress and NSAID use. To reduce incidence, consider:
      1. Use of COX-2 selective drugs (e.g. carprofen, meloxicam) (Recommended)
      2. Short courses and/or minimum dose possible of COX-1 selective drugs when they must be used (e.g. flunixin, aspirin)
      3. Enteric-coated products if using COX-1 selective drugs when they must be used.
      4. Use of gastroprotective agents. (Where recommended)
   3. Oral medications are readily accepted if placed in enrichment (e.g. peanut butter, canned dog food, marshmallow fluff, yogurt etc.)
   4. Table 5: NSAID Routes and Doses

1. In the event of an anesthetic crisis, turn anesthetic gases off and contact a ULAM veterinarian at (734) 936-1037 or (734) 763-1131 immediately. Use the following guidelines to support the animal until the veterinarian arrives:
   1. Ensure a patent Airway: Place an endotracheal tube or confirm patency of tube already in place.
   2. Assist in Breathing if necessary: Turn anesthetic gases off and ventilate with 100% oxygen. A rapid ventilatory rate (30 per min) is recommended to remove carbon dioxide, prevent acidosis, and decrease cerebral pressure.
   3. Provide Cardiovascular Support as indicated: Chest compressions in ruminant species are often futile due to animal size. Administer the following agents as indicated by the situation:
   4. Table 6: Emergency Drugs

Please contact the ULAM Training Core at [email protected] or 734-763-8039 if further instruction on emergency resuscitation is desired

1. Sinclair Research (external link)
2. Wedgewood: Compounds drug formulations for special circumstances (external link)

1. Step by Step Procedures
   1. Stop use of all triggering agents – continue with “safe agents” if surgery cannot be stopped.
   2. Hyperventilate with 100% oxygen. Use new anesthetic circuit and soda lime.
   3. If available, administer 2.5 mg/kg dantrolene IV immediately. Continue dosing up to 10-20 mg/kg until all signs normalize. Maintain IV dantrolene at 1 mg/kg/hr.
      1. If dantrolene is unavailable, acepromazine can be administered. Refer to the table in section 3 of Anesthetic Adjuncts dosing and route of administration.
   4. Once the animal is stabilized, call a veterinarian for further direction or assistance:
      1. Normal business hours (M-F, 08:00-17:00): 734-936-1037
      2. After hours and holidays: 734-763-1131
2. Request unrelated swine from the same or different breeder to prevent this from recurring.

1. Step by Step Procedures
   1. Discontinue gas anesthetic and provide the animal with 100% oxygen.
   2. Cool the animal by administering cold I.V. fluids and/or submerging the animal in an ice bath.
   3. If available, acetaminophen suppositories may be used.
   4. Administer methylprednisolone 1-5 mg/kg I.V. for shock.
   5. Administer diazepam 0.5-1 mg/kg I.V. for muscular tremors.
   6. Once the animal is stabilized, call a veterinarian for further direction or assistance:
      1. Normal business hours (M-F, 08:00-17:00): 734-936-1037
      2. After hours and holidays: 734-763-1131
2. Request unrelated swine from the same or different breeder to prevent this from recurring

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8. Kaplan, R.F. (1991). Malignant Hyperthermia. Am. Soc. Anesthesiol., 1991 Annu. Refresher Course Lec., San Francisco, No. 231, pp. 1-7.
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11. Plumb, D.C. (2011). “Plumb’s Veterinary Drug Handbook“. 8th Edition. Wiley-Blackwell.
12. Renberg M, Karlsson T, Dahlquist A, et al. The anesthesiologist’s guide to swine trauma physiology research: a report of two decades of experience from the experimental traumatology laboratory. Eur J Trauma Emerg Surg. 2024;50(4):1879-1889. doi:10.1007/s00068-024-02542-7
13. Ruemmler R, Ziebart A, Ott T, Dirvonskis D, Hartmann EK. Flexible fibreoptic intubation in swine – improvement for resident training and animal safety alike. BMC Anesthesiol. 2020;20(1):206. Published 2020 Aug 17. doi:10.1186/s12871-020-01127-2
14. Sinclair Bio-Resources Technical Bulletins (http://sinclairresearch.com/). Here you will find several practical technical documents written by Swindle.
15. Skarda, R.T. (1987). Local and Regional Anesthesia. In “Principles and Practice of Veterinary Anesthesia” (C.E. Short, ed.) pp. 101-106. Williams and Wilkins, Baltimore, Maryland.
16. Smith, A.C., Ehler, W.J., & Swindle, M.M. (1997). Anesthesia and Analgesia In Swine. In “Anesthesia and Analgesia in Laboratory Animals” (D.F. Kohn, S.K. Wixson, W.J. White, and G.J. Benson, eds.), pp. 313-336. Academic Press, San Diego, California.
17. Smith AC, Swindle M. Chapter 15 – Anesthesia and Analgesia in Swine. In “Anesthesia and Analgesia in Laboratory Animals (Second Edition)“. San Diego: Academic Press; 2008. pp. 413–440. Available from: http://www.sciencedirect.com/science/article/pii/B978012373898150019X
18. Swindle, M.M. (1991). “Anesthetic and Perioperative Techniques in Swine,” Charles River Technical Bulletin, Winter, 1991. Charles River Laboratories, Wilmington, Massachusetts.
19. Swindle, M.M. and Smith, A.C. (1994). Swine: Anesthesia and Analgesia. In “Research Animal Anesthesia, Analgesia and Surgery” (A.C. Smith and M.M. Swindle, eds.) pp. 107-111. Scientists Center for Animal Welfare, Greenbelt, Maryland.
20. Swindle MM, Nolan T, Jacobson A, Wolf P, Dalton MJ, Smith AC. Vascular access port (VAP) usage in large animal species. Contemporary topics in laboratory animal science / American Association for Laboratory Animal Science. 2005 May (44) 7–17.
21. Swindle, M.M. (2015). “Swine in the Laboratory: Surgery, Anesthesia, Imaging, and Experimental Techniques” Second Edition. CRC Press. (HIGHLY RECOMMENDED READING)
22. Thiede, A.J. (2014). Pharmacokinetics of Sustained Release and Transdermal Buprenorphine in Göttingen Minipigs (Sus scrofa domestica). American Association for Laboratory Animal Science. (53) 6: 692-699.
23. Tranquilli, W.J., Thurmon, J.C., and Grimm, K.A. (2007). Lumb & Jones’ Veterinary Anesthesia and Analgesia. Wiley-Blackwell.