Liposomal Bupivacaine After Arthroscopic Rotator Cuff Repair
Condition: Rotator Cuff Tear
MeSH terms: Rotator Cuff Injuries
Study type: Interventional
Phase: Phase 4

Summary: 
      Liposomal bupivacaine, a long-acting form of bupivacaine, has been found to be effective for
      postoperative pain control after total knee, total hip and total shoulder arthroplasty. We
      are conducting a randomized, controlled trial to evaluate pain control after arthroscopic
      rotator cuff repair in ambulatory patients, comparing standard care in the control group,
      with standard care plus the addition of injection of liposomal bupivacaine in the
      experimental group.
    

Detailed description: 
      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:

        1. Kim CW, Kim JH, Kim DG. The factors affecting pain pattern after arthroscopic rotator
           cuff repair. Clin Orthop Surg. 2014;6:392-400.

        2. Uquillas CA, Capogna BM, Rossy WH, Mahure SA, Rokito AS. Post operative pain control
           after arthrosopic rotator cuff repair. Review JSES 2016.25(7): 1204-13.

        3. Shin SJ, Do NH, Lee J, Ko YW. Efficacy of a subacromial corticosteroid injection for
           persistent pain after arthroscopic rotator cuff repair. Am J Sports Med 2016.
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        4. Abdallah FW, Halpern SH, Aoyama K, Brull R. Will the real benefits of single-shot
           interscalene block please stand up? A systematic review and meta-analysis. Anesth Analg.
           2015. 120(5):1114-29.

        5. Mifune Y, Inui A, Nagura I, Sakata R, Muto T, Harada Y, TAkase F, Kurosaka M, Kokubu T.
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        6. Ilfeld BM. Liposome bupivacaine in peripheral nerve blocks and epidural injections to
           manage postoperative pain. Exp Opin Pharm. 2013. 14(17):2421-31.

        7. Iorio R. The role of liposomal bupivacaine in vale-based care. Am J Ortho. 2016.
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        8. Sporer SM, Rogers T. Postoperative pain management after primary total knee
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        9. Chugtai M, Cherian JJ, Mistry JB, Elmallah RD, Bennett A, Mont MA. Liposomal bpuivicaine
           suspension can reduce lengths of stay and improve discharge status of patients
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       10. Yu SW, Szulc AL, Walton SL, Davidovitch RI, Bosco JA, Iorio R. Liposomal bupivacaine as
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       11. Cien AJ, Penny PC, Horn BJ, Popovich JM, Taunt CJ. Comparison between liposomal
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       12. Barrington JW, Olugbode O, Lovald S, Ong K, Watson H, Emerson RJ. Liposomal bupivacaine:
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       14. Huh J, Parekh SG. Liposomal bupivacaine in hallux valgus surgery: a multimodal pain
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       15. Hutchins JL, Kesha R, Blanco F, Dunn T, Hochhalter R. Ultrasound-guided subcostal
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Intervention name(s): Liposomal bupivacaine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Liposomal bupivacaine solution (Exparel) for injection; Inert solution created to appear as liposomal bupivacaine (Exparel) for injection
Other intervention name(s): Exparel; Placebo solution for liposomal bupivacaine (Exparel)
Intervention MeSH terms: Bupivacaine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, controlled, parallel
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care