Clinical trial NCT03969875: Comparison of Analgesic Efficacy Between of Interscalene Block With Liposomal Bupivacaine With Bupivacaine and Dexamethasone
Official title: Comparison of the Analgesic Efficacy of a Single Shot Interscalene Block With Liposomal Bupivacaine to Bupivacaine With Dexamethasone as an adjuvant-a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Conditions: Total Shoulder Arthroplasty
Shoulder Osteoarthritis
Keywords: Liposomal bupivacaine
Dexamethasone
Interscalene catheter
Interscalene single shot
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2019-05-31
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Pain management after shoulder surgeries poses a unique challenge to the surgeon as well as the anesthesiologist. Regional anesthesia in the form of interscalene approach to the brachial plexus as an adjunct to general anesthesia or as a sole primary technique comes to one's rescue. Interscalene block either as single shot or as a catheter is an established modality for effective analgesia which facilitates early mobilization helping in physical therapy and early discharge.

With the help of local anesthetic injected as a single shot, analgesia usually lasts less than 24 hours. Recent research in regional anesthesia is advancing towards adjuvants which will prolong the duration of local anesthesia. This has introduced the concept of "multimodal perineural analgesia (MMPNA)" whereby multiple agents with differing mechanisms of action are used with the goal of providing perineural analgesia while avoiding exposure to high and potentially toxic levels of individual agents. Some of the commonly used adjuvants in clinical studies are fentanyl, buprenorphine, morphine, tramadol, magnesium, epinephrine, ketamine, non-steroidal anti-inflammatory drug (NSAID), midazolam, parecoxib, ketorolac, clonidine, dexmedetomidine, dexamethasone, neostigmine and potassium. They find a distinct place in wide spread clinical practice as an off-label use.

Steroids have a long history of safe use in epidural space for treatment of radicular pain due to nerve irritation. Dexamethasone is used routinely as a part of anti- emetic prophylaxis and anti-inflammatory effect. Methyl prednisone was the first steroid to be used as an adjuvant. Dexamethasone was first used as an adjuvant in 2003.

It has been hypothesized that steroids induce a degree of vasoconstriction, thereby reducing local anesthetic absorption, tend to have an opioid sparing effect. Another theory suggests that it increases the activity of inhibitory potassium channels on nociceptive C-fibers (via glucocorticoid receptors), thus decreasing their activity.

Several studies have demonstrated promising results with the use of 8mg of perineural dexamethasone. No neuronal injury has been reported in in vivo studies. Though there are several studies which report usage of dexamethasone in varying doses of 2mg to 8mg, the optimal effective dose of dexamethasone as an adjuvant for nerve block remains unknown. Some studies have suggested perineural is more effective than IV as an adjuvant .

Liposomal bupivacaine, a formulation where bupivacaine is encapsulated into multivesicular liposomes, making it a slow and controlled release from the liposomes, was originally indicated for wound infiltration at the surgical site to provide post-surgical analgesia. Studies have demonstrated efficacy up to 24 hours in femoral nerve block in total knee arthroplasty. Recent approval of liposomal bupivacaine in interscalene block for shoulder surgeries by FDA opens an arena unexplored in the world of regional anesthesia.

Current opioid epidemic, a crisis in health care forces healthcare providers to consider alternate analgesic modalities without compromising patient comfort. Regional anesthesia has revolutionized peri-operative pain management by avoiding opioids and their side effects. Use of adjuvants to the current regional techniques holds promise in postsurgical analgesia.

The researchers propose to compare the analgesic efficacy of liposomal bupivacaine to bupivacaine with dexamethasone as an adjuvant in interscalene block with catheters for shoulder surgeries. Till date, there is not a single study comparing the three in current literature.

Detailed description: There have been several studies demonstrating efficacy of dexamethasone in prolonging the analgesic effect when administered both perineurally and intra-venously as an adjuvant to local anesthesia demonstrating a dose effect relationship. Liposomal bupivacaine has shown promising results in total knee arthroplasty and there are a limited number of studies demonstrating efficacy in total shoulder arthroplasty.

If by comparing dexamethasone as an adjuvant to bupivacaine and liposomal formulation is deciphered, it can help in avoiding costs associated with liposomal bupivacaine extending post-operative analgesia avoiding narcotics and reducing health care costs. And comparing the two to the standard catheters helps us understand if they have a role in pain management in the future.

Eligibility criteria: Inclusion Criteria:

* All patients between age 18-80 years undergoing elective primary total shoulder arthroplasty procedure.
* All patients who speak read and understand English will be included for follow up purposes.

Exclusion Criteria:

* Patient refusal
* ASA 5
* presence of coagulopathy
* severe lung disease
* contralateral diaphragmatic palsy
* insulin-dependent diabetes
* hepatic disease/failure
* kidney disease/failure
* pregnancy
* chronic opioid use (defined as opioid use for \>3 months), or allergy to any of the study medications.

Primary outcomes:
measure: Numerical Rating Score for Pain
timeFrame: at 6 hours, 12 hours, 18 hours, 24 hours, 36 hours, 48 hours
Secondary outcomes:
measure: Time to First Analgesic Request
timeFrame: Day 1
measure: Total Narcotic Consumption
timeFrame: hospital stay, up to 48 hours
measure: Arm Weakness
timeFrame: at 6 hours, 12 hours, 18 hours, 24 hours, 36 hours
measure: Arm Numbness
timeFrame: at 6 hours, 12 hours, 18 hours, 24 hours, 36 hours
measure: Time of Analgesia Duration
timeFrame: Day 1
measure: Time of Motor Recovery
timeFrame: Day 1
measure: Sensory Intact
timeFrame: at 6 hours, 12 hours, 18 hours, 24 hours, 36 hours
measure: Hand Strength
timeFrame: at 6 hours, 12 hours, 18 hours, 24 hours, 36 hours
measure: PACU Length of Stay
timeFrame: Day 1
measure: Hospital Length of Stay
timeFrame: up to 3 days
measure: Number of Complication Events
timeFrame: up to 3 days
measure: Number of Participants With Quality of Sleep Rating
timeFrame: average of 3 days
measure: Number of Participants With Patient's Satisfaction
timeFrame: during the hospital stay, up to 3 days
measure: Change in Patient Reported Outcomes Measurement Information System (PROMIS)
timeFrame: baseline and one week post-op
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
References:
citation: Vandepitte C, Kuroda M, Witvrouw R, Anne L, Bellemans J, Corten K, Vanelderen P, Mesotten D, Leunen I, Heylen M, Van Boxstael S, Golebiewski M, Van de Velde M, Knezevic NN, Hadzic A. Addition of Liposome Bupivacaine to Bupivacaine HCl Versus Bupivacaine HCl Alone for Interscalene Brachial Plexus Block in Patients Having Major Shoulder Surgery. Reg Anesth Pain Med. 2017 May/Jun;42(3):334-341. doi: 10.1097/AAP.0000000000000560.
citation: Abdallah FW, Brull R. Facilitatory effects of perineural dexmedetomidine on neuraxial and peripheral nerve block: a systematic review and meta-analysis. Br J Anaesth. 2013 Jun;110(6):915-25. doi: 10.1093/bja/aet066. Epub 2013 Apr 15.
citation: Bishop JY, Sprague M, Gelber J, Krol M, Rosenblatt MA, Gladstone J, Flatow EL. Interscalene regional anesthesia for shoulder surgery. J Bone Joint Surg Am. 2005 May;87(5):974-9. doi: 10.2106/JBJS.D.02003.