Principal Investigator: Stephanie Hon

DESCRIPTION (provided by applicant): 

Pigs undergoing major survival surgeries should receive full mu agonist analgesia for acute pain control, but opioid pharmacokinetics/pharmacodynamics (PK/PD) in this species has not been investigated. Intravenous (IV) catheters for opioid administration are difficult to insert and maintain in pigs, and this route requires repeated, frequent administration. Subcutaneous (SC) catheters are used in human hospice care for opioid administration as constant rate infusions (CRI) and could provide superior analgesia to the pig while conserving technical ease of administration similar to sustained-release partial mu agonists. A complete PK/PD profile for morphine, the prototypical full mu opioid agonist, is not available for pigs, and yet they form the basis for determining analgesic dosing and evaluation. 

Goals:
Goal 1. To develop a complete pharmacokinetic (PK) profile for a single 0.5 mg/kg bolus of morphine administered IV and SC.
Goal 2. To use the PK profile of SC morphine to calculate a dose for a SC CRI of morphine.
Goal 3. To confirm antinociceptive effects of a SC CRI of morphine by demonstrating that TNT is greater after a SC loading dose followed by a CRI of morphine vs. saline and increases from baseline during the morphine phase.
Goal 4. To determine the presence and severity of sedation and nausea induced by morphine.
Goal 5. To demonstrate that SC catheters are well-tolerated by pigs.
Goal 6. To demonstrate that SC catheters do not cause infection when aseptically placed and maintained in vivo over 7 days.