Intravenous Dexmedetomidine, Dexamethasone and Interscalene Block Duration After Arthroscopic Shoulder Surgery

Sponsor

University of Manitoba (Other)

Overall Status

Completed

CT.gov ID

NCT03270033

Collaborator

(none)

198

Enrollment

Location

Arms

12.8

Actual Duration (Months)

15.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In this single-centre, double-blinded, randomized controlled superiority trial, 189 participants having outpatient, arthroscopic shoulder surgery will be randomized into 3 equal sized groups. All participants will receive a standardized interscalene brachial plexus block and 4mg of dexamethasone or 50mcg of dexmedetomidine or both intravenously just prior to their surgery. The purpose of this study is to provide a head to head comparison of two types intravenous adjuncts to ISB, corticosteroids and alpha 2 agonists, and determine if their combination, or either one alone provides superior postoperative analgesia in arthroscopic shoulder surgery patients, as well as possibly show a synergistic relationship between the two adjuncts. The investigators hypothesize the combination of adjuncts will provide a longer duration of analgesia compared to either single agent.

Condition or Disease	Intervention/Treatment	Phase
Pain, Postoperative Shoulder Joint Disorder Ambulatory Surgical Procedures Brachial Plexus Block	Drug: Dexamethasone Drug: Dexmedetomidine	Phase 4

Detailed Description

BACKGROUND & RATIONALE Optimal postoperative analgesia is very important in the ambulatory arthroscopic shoulder surgery patient population; interscalene blocks are used for this surgery because they reduce acute pain and have opioid sparing effects postoperatively. While older patients, higher ASA grades and more complex arthroscopic procedures are risk factors for unplanned overnight admissions, in the ambulatory surgery setting, poor analgesia is one of the most common reasons a patient visits a health care provider after their surgery. Approximately 30 % of patients undergoing arthroscopic surgery globally experience significant postoperative pain within the first 24 hours post surgery. In light of this, interscalene brachial plexus blockade (ISB) has been found to be the most effective and preferred method of analgesia for arthroscopic shoulder surgeries when compared to subacromial/intra-articular injections, cryotherapy and oral pain medications. ISB usually consists of a single injection of local anesthetic, anywhere from 5 to 30 minutes prior to shoulder surgery. Although ISB reduces postoperative pain in arthroscopic shoulder surgeries, the length of analgesia from a single injection of local anesthetic is limited to 6 to 15 hours after surgery. Due to the limited duration of analgesia, interscalene catheters have been studied for prolongation of analgesia via continuous infusion of local anesthetics. Although continuous catheter infusions are effective and feasible, there exist several complications such as dyspnea, peripheral neuropathies, nausea, and practical challenges that limit their wider application in an ambulatory setting. Recently, different adjuncts given in combination with local anesthetics have been used to prolong the analgesic duration of a single injection ISB. These adjuncts have been given by both the intravenous and by the perineural routes, where perineural means the adjunct is injected with the local anesthetic around the brachial plexus.

Dexamethasone, a potent glucocorticoid, has been shown in multiple studies to prolong the duration of analgesia of the ISB compared to placebo when administered either perineurally or intravenously. A recently completed large trial (in press) at our centre showed that the duration of analgesia (mean (standard deviation), in hours (h)) with 4mg of intravenous dexamethasone (24.0 (4.6)h) is not significantly different from 8mg (24.8 (6.4)h) and only slightly shorter than perineural dexamethasone doses of 4mg (25.4 (6.6)h) or 8mg (27.2 (8.5)h). The 4mg intravenous dose was favored given the established safety of the intravenous route, its approximately equivalent effectiveness compared to the higher 8mg dose and the absence of differences in adverse effects between groups.

Dexmedetomidine, a highly selective α2 adrenergic agonist with sedative and analgesic properties, has also been shown to potentiate peripheral nerve blockade and prolong the duration of analgesia versus placebo when used as an adjunct to local anesthetic for regional anesthesia, including interscalene block. Most studies have compared perineural dexmedetomidine to placebo, as is the case for other adjuncts such as dexamethasone, even though there is less experience with the perineural route for dexmedetomidine compared to dexamethasone. Interestingly, a recent study found both intravenous and perineural dexmedetomidine reduced the 24 hour opioid consumption and comparably prolonged the duration of ISB analgesia compared to placebo. In a recent meta-analysis, a 50-60ug Dexmedetomidine perineural or intravenous dose maximized sensory block duration while minimizing hemodynamic side effects.

To our knowledge, there are no published studies comparing the analgesic duration of ISB between dexamethasone and dexmedetomidine, and no studies have evaluated whether there is additional benefit to administering these widely available medications in combination. Three ongoing studies are comparing dexamethasone and dexmedetomidine as single adjuncts, without a combination. All three of these studies are using the perineural route, despite the established safety and effectiveness of the intravenous route for both drugs. With this study we are seeking to improve our patients' postoperative experience with superior analgesia by better defining the relative analgesic effectiveness of dexamethasone and dexmedetomidine when given alone or in combination as intravenous adjuncts to ISB.

OBJECTIVES AND HYPOTHESES

In outpatients undergoing arthroscopic shoulder surgery with Interscalene Block:

To determine if there is a significant increase in duration of analgesia when combining intravenous dexamethasone and dexmedetomidine compared to administering each adjunct individually. We hypothesize the combination of adjuncts will provide a longer duration of analgesia compared to either single agent.
To compare the effect of Dexamethasone to Dexmedetomidine on duration of analgesia when given individually. We hypothesize that there will be no significant difference between the two adjuncts.

METHODS This single-centre, double-blinded, randomized controlled superiority trial has three parallel groups and 1:1:1 randomization. Consenting and eligible adult ambulatory patients undergoing arthroscopic shoulder surgery will receive preoperative, ultrasound guided ISB with 30 millilitres (mL) of 0.5% bupivacaine and 4mg of preservative free dexamethasone or 50mcg of dexmedetomidine or both intravenously. The remainder of the intraoperative and postoperative care is at the discretion of the attending anesthesiologist and surgeon. The primary outcome is analgesic block duration. The power analysis for this study was based on published results from previous studies, as well as our recent work. With a two-tailed alpha error of 0.05, and a standard deviation of 5.0 hours in each group, 180 total patients would provide greater than 90% power to detect a difference of 3.0 hours in block duration. To account for a 5% attrition rate we propose recruiting 63 patients per group (189 patient's total). Outcomes will be assessed by chart review and telephone follow up on postoperative day one, postoperative day 2 (if necessary), and postoperative day 14.

After collecting 102 primary outcomes, we will compare the primary outcome between the combination and each of the single adjuncts. At this point the study will be 90% powered to detect a difference of 6.0h in block duration, even if the standard deviations are higher than expected, at 7.5 hours. If the combination is superior to both of the single agents, the study will be terminated. The principle investigator cancelled this interim analysis on 18 December 2017 after consultation with the study statistician and research team. After reconsidering the original power calculations, the clinically plausible differences between groups, and the high level of statistical significance recommended for interim analyses, it was determined that this interim analysis would be very unlikely to convincingly demonstrate the superiority of the combination over the single agents. As of 18 December 2017 90 patients have participated in the study and recruitment is on schedule. The entire research team has been and will continue to be blinded to outcome data by group assignment until all 189 patients have participated, which is expected to occur in the second quarter of 2018.

The primary outcome analysis will analyze by intention to treat only those patients who were randomized and did receive an attempt at an interscalene block. A secondary analysis will exclude patients who had a "failed" interscalene block in the post anesthesia care unit. A tertiary analysis will be a multivariable analysis adjusted for demographics, preoperative naproxen use, use of general anesthesia, cumulative analgesic use and failed interscalene block.

Study Design

Study Type:

Interventional

Actual Enrollment :

198 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Analgesic Duration of Interscalene Block After Outpatient Arthroscopic Shoulder Surgery With Intravenous Dexamethasone, Dexmedetomidine or Their Combination: A Randomized Controlled Trial

Actual Study Start Date :

Sep 18, 2017

Actual Primary Completion Date :

Apr 14, 2018

Actual Study Completion Date :

Oct 13, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Dexamethasone 4 milligrams dexamethasone administered once intravenously with a 30 millilitres 0.5% bupivacaine interscalene brachial plexus block	Drug: Dexamethasone 0.4 millilitres (mL) of 10 milligram per mL sterile, preservative free solution diluted in 50 or 100mL of normal saline and administered once, over approximately 15 minutes, in the immediate preoperative period. Other Names: Dexamethasone Omega Unidose (Omega Laboratories Limited) Dexamethasone Sodium Phosphate USP (1 millilitre vial)
Active Comparator: Dexmedetomidine 50 micrograms dexmedetomidine administered once intravenously with a 30 millilitres 0.5% bupivacaine interscalene brachial plexus block	Drug: Dexmedetomidine 0.5 millilitres (mL) of 100 microgram per mL sterile, preservative free solution diluted in 50 or 100mL of normal saline and administered once, over approximately 15 minutes, in the immediate preoperative period. Other Names: Precedex (Hospira Healthcare Corporation) Dexmedetomidine Hydrochloride for Injection
Active Comparator: Dexamethasone and Dexmedetomidine 4 milligrams dexamethasone and 50 micrograms dexmedetomidine administered once intravenously with a 30 millilitres 0.5% bupivacaine interscalene brachial plexus block	Drug: Dexamethasone 0.4 millilitres (mL) of 10 milligram per mL sterile, preservative free solution diluted in 50 or 100mL of normal saline and administered once, over approximately 15 minutes, in the immediate preoperative period. Other Names: Dexamethasone Omega Unidose (Omega Laboratories Limited) Dexamethasone Sodium Phosphate USP (1 millilitre vial) Drug: Dexmedetomidine 0.5 millilitres (mL) of 100 microgram per mL sterile, preservative free solution diluted in 50 or 100mL of normal saline and administered once, over approximately 15 minutes, in the immediate preoperative period. Other Names: Precedex (Hospira Healthcare Corporation) Dexmedetomidine Hydrochloride for Injection

Arm

Intervention/Treatment

Active Comparator: Dexamethasone

4 milligrams dexamethasone administered once intravenously with a 30 millilitres 0.5% bupivacaine interscalene brachial plexus block

Drug: Dexamethasone

0.4 millilitres (mL) of 10 milligram per mL sterile, preservative free solution diluted in 50 or 100mL of normal saline and administered once, over approximately 15 minutes, in the immediate preoperative period.

Other Names:

Dexamethasone Omega Unidose (Omega Laboratories Limited)

Dexamethasone Sodium Phosphate USP (1 millilitre vial)

Active Comparator: Dexmedetomidine

50 micrograms dexmedetomidine administered once intravenously with a 30 millilitres 0.5% bupivacaine interscalene brachial plexus block

Drug: Dexmedetomidine

0.5 millilitres (mL) of 100 microgram per mL sterile, preservative free solution diluted in 50 or 100mL of normal saline and administered once, over approximately 15 minutes, in the immediate preoperative period.

Other Names:

Precedex (Hospira Healthcare Corporation)

Dexmedetomidine Hydrochloride for Injection

Active Comparator: Dexamethasone and Dexmedetomidine

4 milligrams dexamethasone and 50 micrograms dexmedetomidine administered once intravenously with a 30 millilitres 0.5% bupivacaine interscalene brachial plexus block

Drug: Dexamethasone

Other Names:

Dexamethasone Omega Unidose (Omega Laboratories Limited)

Dexamethasone Sodium Phosphate USP (1 millilitre vial)

Drug: Dexmedetomidine

Other Names:

Precedex (Hospira Healthcare Corporation)

Dexmedetomidine Hydrochloride for Injection

Outcome Measures

Primary Outcome Measures

Duration of analgesia after ISB [Time-to-event outcome measure, assessed up to the end of postoperative day 3 (approximately 84 hours from performance of the block]
Time from block performance to the first time shoulder pain was experienced after the surgery, rounded to the nearest 0.1 hours, as reported by the participant at telephone follow-up on postoperative day one, or if necessary, postoperative day 2.

Secondary Outcome Measures

Block Success or Failure [Assessed at discharge from the post anesthesia care unit, an expected average of 5 hours after the performance of the block.]
The block will be considered "failed" if the patient required opioid analgesia for surgical site pain during their stay in the post anesthesia care unit, as determined by the patient's nurse. At our facility, patients are discharged home directly from the post anesthesia care unit.
Cumulative Analgesic Consumption in the post anesthesia care unit ["Change" outcome measure: From admission to the post anesthesia care unit (an expected average of 2.5 hours after performance of the block), to discharge from the post anesthesia care unit (an expected average of 4 hours after performance of the block)]
Measured as equivalent milligrams of morphine
Cumulative Analgesic Consumption from post anesthesia care unit discharge until the time the primary outcome occurred ["Change" outcome measure: From discharge from the post anesthesia care unit (an expected average of 5 hours after performance of the block), to the occurrence of the primary outcome (an expected average of 28 hours after performance of the block)]
Measured as equivalent milligrams of morphine
Unplanned Postoperative Hospital Admission, as reported at telephone follow up or chart review [Assessed at telephone follow up on postoperative day one and chart review]
Transfer or admission to hospital during the postoperative period between admission to the post anesthesia care unit and telephone follow up on postoperative day one
New Persistent Neurologic Symptoms [Assessed at postoperative day 14]
Patient will be asked whether they are experiencing any tingling, numbness or weakness in the surgical limb, or hoarseness or dyspnea. Patients answering yes to any of the above will have a detailed telephone assessment and be reassessed by telephone at 6 months postoperatively
Post anesthesia care unit length of stay in minutes [Assessed at discharge from the post anesthesia care unit, an expected average of 4 hours after performance of the block.]
Amount of time between admission and discharge from the post anesthesia care unit.
The QoR-15 questionnaire [Assessed at postoperative day one.]
A standardized and validated 15 item questionnaire consisting exclusively of 11 point integer scale questions (10 = all the time, 0 = none of the time) designed to assess quality of recovery, physical and mental wellbeing in patients recovering from surgery. A total composite score is measured as the total of all 15 individual scores.

Other Outcome Measures

Intraoperative and post anesthesia care unit use of cardiovascular medications, as recorded in the patient's chart [Assessed at discharge from the post anesthesia care unit, an expected average of 4 hours after the performance of the block]
The use of Intraoperative vasopressors, inotropes, antimuscarinics or antihypertensives at any time between the performance of the block and discharge from the post anesthesia care unit
Adverse events previously related to the inter scalene block and unlikely related to dexamethasone or dexmedetomidine, as recorded in the patient's chart. [Assessed at discharge from the post anesthesia care unit, an expected average of 4 hours after the performance of the block]
The occurrence of seizure, systemic local anesthetic toxicity, pneumothorax, hemothorax, epidural spread of local anesthetic, or hoarse voice at any time between the performance of the block and discharge from the post anesthesia care unit.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Elective ambulatory surgery patients undergoing arthroscopic shoulder surgery
Including rotator cuff repair
Stabilization procedures
Acromioplasty
Debridement and distal clavicle excision

Exclusion Criteria:

Patient refusal
Diabetes
Pregnancy
Coagulopathy significant enough to be a contraindication to regional anesthesia as determined by the attending anesthesiologist
Sensitivity to local anesthetics, dexamethasone or dexmedetomidine
Severe chronic obstructive pulmonary disease
Contralateral vocal cord paralysis
Contralateral diaphragmatic paralysis
Surgical limb brachial plexus neuropathy
Interscalene block site infection
Systemic glucocorticoids in the last 2 weeks
Epidural or intraarticular steroid injection in the past 3 months
Chronic opioid use defined as daily use for the last two weeks
Active peptic ulcer disease
End-stage renal disease
Cirrhotic liver disease
Ventricular dysfunction
Advanced heart block
Previous participation in the study.