Optimising anaesthesia and analgesia of brachial plexus blocks: dose-volume relationship for interscalene catheters and efficacy of a new local anaesthetic formulation, bupivacaine liposome injectable suspension (EXPAREL®).

INTRODUCTION
The control of postoperative pain is challenging. Although opioids are commonly used to treat postoperative pain, their use is associated with nausea, vomiting, bowel dysfunction, respiratory depression and opioid addiction. Efforts have been made to reduce or eliminate the use of opioids for postoperative analgesia by introducing optimized regional anesthesia techniques, multimodal analgesia and novel, long-acting local anesthetic formulations.
Upper extremity nerve blocks are commonly used modalities for anesthesia and/or analgesia for a wide variety of shoulder and hand surgeries. Particularly with the recent introduction of ultrasound guidance, they can improve recovery profiles after upper extremity surgery.
Before the advent of ultrasound guidance in the practice of nerve blocks,  large volumes/doses of local anesthetic (LA) were necessary for efficacy.  LA disposition using ultrasound guidance now requires new studies to determine minimum dose and/or volume requirements to accomplish effective peripheral nerve block anesthesia/analgesia. For example, the minimum volume for effective interscalene brachial plexus block (ISBPB) through an indwelling catheter has not been determined, while this is a common peripheral nerve block with a moderate risk of side effects.
The analgesic benefits of brachial plexus blocks, such as ISBPB and forearm blocks (median + ulnar nerve blocks) are typically limited to <24 hours using currently available local anesthetics. To prolong analgesia postoperatively, several adjuvants to local anesthetics have been studied, albeit with inconsistent or clinically insignificant prolongation of analgesia.
Bupivacaine liposome injectable suspension (EXPAREL®; Pacira Pharmaceuticals Inc, Parsippany, NJ, USA) is the first new formulation of local anesthetic in the last 20 years. This multivesicular formulation of bupivacaine is FDA approved for soft tissue infiltration into the surgical site to produce postsurgical analgesia. EXPAREL® has not yet been approved by the FDA for nerve block infiltration. Prolonged release of the LA bupivacaine from the formulation could provide sustained sensory nerve blockade and analgesia. However, EXPAREL® in brachial plexus and upper extremity nerve blocks has not been previously studied. Clinical trials on both efficacy and safety are required before the use of EXPAREL® for application in nerve blocks can be recommended.

The AIMS of this PhD project are to:
(1) Determine the minimum volume of local anesthetic (ropivacaine) to accomplish anesthesia and prolonged analgesia with ISBPB through an indwelling catheter.
(2) Determine the ability of the novel formulation of bupivacaine (bupivacaine liposome injectable suspension (EXPAREL®) when added to bupivacaine HCl to prolong the duration of ISBPB for postoperative analgesia after major shoulder surgery.
(3) Determine the ability of EXPAREL® to prolong the duration of median and ulnar nerve blocks in patients undergoing Dupuytren’s contracture release procedure.
(4) Determine the safety of administration of EXPAREL® with respect to phrenic nerve blockade and its respiratory effects, if any, in patients receiving Exparel® in ISBPB.