Liposomal Bupivacaine After Arthroscopic Rotator Cuff Repair

Arthroscopic rotator cuff repair is among the most painful of orthopedic surgeries (1-3). Hundreds of thousands of these procedures are carried out in the U.S. each year. Many involve the use of a brachial plexus nerve block, which serves to control pain for 12 to 14 hours. However, when the block wears off, many patients are left with severe pain. (4-5) This severe pain must then be managed at home with oral opioids, which have numerous undesirable side effects, and may lead to chronic opioid dependence. Thus, any therapy which might reduce the pain burden on these patients and therefore reduce opioid use and side effects, would be advantageous.

Recently, a long-acting form of bupivacaine, prepared in liposomes, has been approved for use by injection in the surgical field, though not for peripheral nerve blockade (6). The drug has been used to improve postoperative pain after total knee arthroplasty and total hip arthroplasty when injected in the peri-articular tissues by the orthopedist (7-12), as well as in other surgeries, both orthopedic and non-orthopedic.(13-16) Unfortunately, preliminary studies utilizing liposomal bupivacaine as the injectate in peripheral nerve blocks have been disappointing, largely because the gradual release of the drug did not permit establishment of effective nerve blockade; it appears to be more effective in the role of analgesic as opposed to anesthetic (17).

In addition to lower extremity orthopedic procedures, liposomal bupivacaine has also been demonstrated to reduce pain after shoulder arthroplasty (joint replacement), a similarly painful shoulder procedure. Liposomal bupivacaine is FDA approved for administration into surgical sites to produce postsurgical analgesia and mitigate pain, but it hasn't been evaluated yet as an intervention to provide analgesia for rotator cuff surgery, though the pain mechanisms for these two procedures, including joint capsule violation and boney intervention are likely similar.

In this prospective, comparative, randomized, double blinded, placebo controlled trial, we propose to provide standard therapy for both groups of patients, consisting of interscalene block with 16 ml of standard 0.5% bupivacaine, as well as propofol infusion to provide general anesthesia in the operating room and low doses of ketamine for analgesia. In addition, half of the patients will receive an injection of 266 mg liposomal bupivacaine (FDA approved dosage) into the subacromial space and peri-articular tissues at the end of surgery. The other half of the patients will receive an injection of an inert solution of comparable volume into the peri-articular tissues at the conclusion of surgery (control group).

The primary outcome measure is pain score at the time of block resolution, as noted by patients when called at 24 hours after surgery. Secondary outcomes include maximal pain score on postoperative day 1, 2 and 3, total oral opioid morphine equivalent after 3 days, and occurrence of typical opioid side effects (nausea, vomiting, drowsiness). In addition to follow up phone call on postoperative day 1, patients will keep a pain diary, documenting pain scores and opioid use for the first 72 hours, which will be collected by the surgeon in his office at the first postoperative visit. Any adverse occurrences related to nerve blockade or prolonged bupivacaine effect will also be recorded.

We expect to enroll 25 patients in each group (total of 50). Sample size is based upon the a priori assumption that liposomal bupivacaine will result in reduced pain scores by at least 2 units on the NRS scale at the time of nerve block resolution. Inclusion criteria include adult patients, undergoing rotator cuff repair as outpatients at our facility, ASA physical status category 1 through 3. Exclusion criteria include inability to receive local anesthetic medications for any reason, contraindications to peripheral nerve block (coagulopathy, patient refusal, local infection and pre-existing nerve injury or dysfunction in the operative arm), chronic opioid dependence, pregnancy and pediatric age group. This study will involve anesthesiology, orthopedics, physical therapy, pain management and the center for translational science institute at the University of Pittsburgh.

References:

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17. Ilfeld BM, Malhotra N