The goal of this clinical study is to improve upon the standard practice of utilizing nerve blocks to enhance the satisfaction of patients undergoing shoulder, or foot and ankle surgery regarding their quality of pain control, the duration of their nerve blocks, as well as the avoidance of opioid medications and subsequently their undesirable side effects. The researchers hypothesize that dexmedetomidine and dexamethasone (Dex-Dex) will work synergistically as adjuncts in a low, non-weight based formula. This would allow the investigators to improve patient satisfaction by providing them with a superior means of pain control that is longer in duration with a decreased probability of unwanted side effects.

The proposed clinical study will be a prospective, randomized control trial.

The standard practice for anesthesia in non-weight-bearing orthopedic foot and ankle surgery is to offer the patient popliteal (sciatic nerve) and saphenous (distal branch of femoral nerve) peripheral nerve blocks for postoperative pain control to minimize opioid requirements. Similarly, supraclavicular nerve blocks that decrease painful stimuli transmission through the brachial plexus are offered to patients undergoing shoulder joint procedures. For these peripheral nerve blocks, it is routine to use dexamethasone (glucocorticoid) as an additive in the local anesthetic injection which can prolong the local anesthetic effect of the blocks by 4-8 hours with minimal side effects observed and no dose-response relationship with perineural injection doses of 4, 8, 10, and 12mg. Though the precise mechanism of action has not been fully understood, it is largely believed that perineural injection of dexamethasone increases the effects of local anesthetics at least in part due to vasoconstriction.

Current literature suggests that 1-2 mcg/kg of dexmedetomidine will also prolong the peripheral nerve blocks but consistent utilization thus far has been limited by side-effects of higher, more efficacious doses. The potential dose-dependent side effects associated with the use of perineural dexmedetomidine include bradycardia, hypotension, and excessive sedation. There are minimal to no side-effects observed when perineural dexmedetomidine doses are kept below 1 mcg/kg. However, its effects on prolonging nerve blocks are not significant until the dose is increased to 1.5 mcg/kg where the nerve block is extended roughly 4-8 hours, similar to using dexamethasone as an adjunct. At doses greater than 2 mcg/kg, however, the nerve block can last up to 2-3 days but at the tradeoff of increased perioperative bradycardia and hypotension from presumed systemic absorption and dexmedetomidine's highly selective α2 agonist effects. Another study showed that when a low, non-weight-based dose of 50 mcg of dexmedetomidine was used in adults weighing over 50 kg, the duration of analgesia was improved, but its effects were less than 8 mg of dexamethasone as an adjunct, and the improvement of the duration of blockade at this low dose of dexmedetomidine was not significant. When both dexamethasone and dexmedetomidine were utilized as intravenous adjuncts administered at the time of performing the nerve blocks instead of in the perineural injection, Maagaard et al. discovered that dexamethasone improved the duration of analgesia of popliteal and saphenous nerve blocks in patients undergoing foot and ankle surgeries with or without dexmedetomidine. These findings support the theory that dexmedetomidine's local effects at the site of the injection, as opposed to its systemic analgesic effects on α2 receptors in the central nervous system, may be predominantly responsible for its role as an adjunct in prolonging the effects of local anesthetics in peripheral nerve blocks. The theory is also supported by Brummett et al and their findings that the analgesic effects of dexmedetomidine as an adjunct could not be reversed by an α2 receptor antagonist given systemically.

This study aims to determine a safe and effective approach for using dexamethasone and dexmedetomidine in combination using low, non-weight based (NWB) doses of both adjuncts. The researchers plan to track the duration of the blocks for 7 days postoperatively as well as any unwanted side effects in the post-anesthesia care unit including: hypotension, bradycardia, oversedation, and respiratory depression. The research team will contact subjects by email and rely on daily participant surveys (REDCap Survey POD #0) submitted electronically to provide subjective feedback on block duration and postoperative pain for 7 days using the PROMIS pain scale within the survey. Participants will also report pain medication usage for the same time frame including both opioid and non-opioid medications. Side effects in the post anesthesia care unit (PACU) will be documented by PACU nurses using the POSS sedation scale and comparing vital signs such as heart rate and blood pressure at 15- and 30-minute intervals to pre-operation recordings. Subjects might receive a phone call reminder to complete the daily surveys after their surgery, or if the research team notices that they have not completed the surveys on time.

Preliminary data has been very promising. The investigator's facility has thus far declined the use of liposomal bupivacaine, which has limited the ability to offer the patients peripheral nerve blocks lasting greater than 24 hours. Therefore, to extend the length of our peripheral nerve blocks the research team added both 4 mg dexamethasone and 50 mcg dexmedetomidine to 30 ml of 0.5% ropivacaine for lower extremity blocks for patients that would benefit from a prolonged nerve block for postoperative pain. The roughly 31.5 ml solution is then split evenly between the popliteal and saphenous nerve blocks. The investigators observed that these blocks frequently extended the duration of the block to 2-5 days compared to the standard 20-24 hours normally observed with dexamethasone adjunct alone. Similarly, the exact same additives (4 mg dexamethasone and 50 mcg dexmedetomidine) have been added to 15 ml of 0.5% Ropivacaine for shoulder procedures with similar observations noted of increased duration. This posed a research question that the investigators wishe to investigate further that compares their usual practice of blocks with ropivacaine and dexamethasone alone to blocks utilizing both dexamethasone and dexmedetomidine as adjuncts. The investigators chose the dexmedetomidine dose in combination with their inclusion criteria of adults weighing more than 50 kg so that the patients in this study will not receive a dexmedetomidine adjunct dose that is greater than 1 mcg/kg.

For the initial research the investigators plan on recruiting patients who are undergoing foot and ankle surgery who are not expected to participate in weight-bearing physical rehabilitation immediately after surgery and that would benefit from a potential multi-day nerve block for primary pain management. The investigators also plan on recruiting patients undergoing extensive shoulder surgery such as total shoulder arthroplasty and rotator cuff repairs because these procedures tend to have higher observed post-operative pain associated and the patients are not expected to participate in active rehabilitation immediately after surgery.

Inclusion Criteria:

• Healthy adults (18 years and older but less than 75)
• Speaks and understands English.
• Capable of performing all activities of daily living independently
• Normal development for age and without cognitive impairment
• Weight over 50 kg
• Undergoing scheduled, elective foot, ankle, and shoulder surgery
• Patient is not expected to perform weight-bearing rehabilitation post-op for 1 week.
• Regular access to the internet

Exclusion Criteria:

• Under 18 or older than 75 years of age
• Pregnancy
• Known allergy to local anesthetics including lidocaine and ropivacaine.
• Known allergy to glucocorticoid steroids or necessary abstinence for medical reasons.
• Known allergy to dexmedetomidine or other α2 agonist derivatives.
• Severe organ dysfunction: end-stage renal disease, liver failure
• Severe psychiatric disease that alters sense of reality and interferes with pain perception.
• Severe cognitive impairment that interferes with pain perception
• Chronic opioid use, alcohol abuse, or any other substance abuse
• Urgent/emergent procedure
• Emergency return to OR after initial surgery
• Infection at block or surgical site
• Hemodynamic instability preoperatively
• Hemodynamic instability during surgery affects timely extubating at the end of surgery.
• Failed nerve blocks that did not end up blocking the nerves as intended, or inadequate nerve blocks requiring repeat rescue blocks in PACU.

Clinical researchers may contact the principal investigator (Ronald Tang, MD) to request the raw data for the study. All shared data will be void of personal identifiers. Sharing of data will be granted on a case by case basis determined by the credentials of the requesting researcher and necessity for requesting the data.

Beginning 3 months and ending 3 years after the publication of results.

Researchers studying the effects of Dexmedetomidine and Dexamethasone may request access to the IPD and supporting information. The principal investigator will ultimately decide if criteria is met for data to be shared. In addition, a data sharing agreement may need to be signed on accordance with the University of Arizona and Banner University Medical Center policies.