Clinical trial NCT02798835
Conditions: Total Knee Arthroplasty
Sponsor: University of British Columbia
Start date: 2016-07-01; Completion date: 2016-12-01
Enrollment: 180 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study investigates single injection adductor canal block (ACB) with or without intravenous dexamethasone and adductor canal catheter for pain management of total knee arthroplasty. This is a non-inferiority trial seeking to determine whether single injection ACB with dexamethasone is "no worse" than a continuous catheter.

Detailed description:
1. Purpose

   To determine whether single shot adductor canal nerve blocks with intravenous dexamethasone are non-inferior to continuous adductor canal blockade.
2. Hypotheses

   The use of adductor canal nerve block with intravenous dexamethasone will not be inferior to continuous adductor canal blockade for opioid requirements 24h post operatively.

   The single injection adductor canal block without dexamethasone will have the most opioid consumption. The dexamethasone and catheter groups will be superior to single injection alone in terms of 12 and 48h opioid consumption, length of stay, anti-emetic usage, pain score and quality of recovery score.
3. Justification

   Total knee arthroplasty is a very commonly performed operation in North America, with a high propensity for postoperative pain. Inadequate analgesia limits functional recovery and leads to delays in hospital discharge, as a result of poor mobility. Effective analgesia allows for earlier mobilization and improved postoperative recovery, with a multi-modal regime being the ideal method to achieve this.

   Currently a multi-modal regime is provided to patients: intraoperatively with a neuraxial technique (spinal anesthesia), along with surgeon infiltrated local anesthetic at the end of the operation, and then postoperatively using systemic opioids via patient controlled analgesia (PCA). Opioids have many side effects, including nausea and vomiting, sedation, respiratory depression and urinary retention. These all lead to delay in ambulation and recovery.

   Many centers now incorporate peripheral nerve blocks as part of the multi-modal analgesic regime, with continuous femoral nerve blockade being commonly used for analgesia. This does decrease the amount of postoperative opioid used, but has the downside of causing quadriceps muscle weakness leading to an increased risk of falls and delayed ambulation. For this reason, there has been an increase in the use of the adductor canal block, a nerve block of the distal femoral nerve at the mid-thigh level, that has been shown to preserve quadriceps function better than a femoral nerve block, whilst still ensuring decreased opioid use. To date, no studies have compared single shot adductor canal block with continuous adductor canal blockade, but both have been shown to be comparable to femoral nerve blockade, whilst decreasing the likelihood of quadriceps muscle weakness.

   Further to this, it has been shown that the addition of dexamethasone, administered via the intravenous or perineural route to peripheral nerve blockade, prolongs the duration of analgesia. Perineural administration of dexamethasone is an off label use and there is also a theoretical risk of neurotoxicity from dexamethasone itself. Findings to date indicate that the efficacy of dexamethasone administered intravenously is non-inferior to perineural injection. Both routes prolong the analgesic benefit of peripheral nerve blocks with similar reductions in opioid requirements.

   Opioid PCA is the most commonly used modality for postoperative analgesia following total knee arthroplasty. The information from this study will enable ascertainment of the best method for allowing patients good functional recovery, whilst minimizing opioid side effects.
4. Objectives

   The primary aim of this study is to compare the efficacy of adductor canal nerve block, with and without intravenous dexamethasone, and continuous adductor canal blockade with a catheter to ascertain cumulative opioid consumption post-operatively. Specifically, the trial seeks to answer whether the adductor canal block with dexamethasone fares no worse (non-inferior) than a continuous catheter.

   The secondary aims are to compare the quality of anesthesia recovery using the QoR-40 questionnaire administered at 48 hours postoperatively, pain score, length of hospital stay, complications of nerve blockade, incidence of catheter dislodgement and opioid side effects (nausea/vomiting) with the different techniques.
5. Research Methods

   Trial Design

   This will be a randomize controlled, non-blinded, non-inferiority trial, involving patients having primary unilateral total knee arthroplasty. There are three arms: adductor canal single injection (baseline control), adductor canal single injection plus dexamethasone (test intervention) and adductor canal catheter (active control).

   Setting

   This will be a single-centre trial at UBC Hospital (UBCH).

   B. Randomization

   Prior to surgery, for each consented patient, a sealed unmarked opaque envelope will be opened to determine the modality of analgesia that the patient will receive. The patients will either receive an adductor canal block postoperatively, an adductor canal block postoperatively along with intravenous dexamethasone, or have an adductor canal catheter placed postoperatively for continuous adductor canal blockade.

   D. Data Collection

   Demographic data including patient age, sex, height, weight, BMI, and medications including analgesics, comorbidities and American Society of Anesthesia (ASA) classification will be determined from the anesthetic record.

   Numerical Rating Scale (NRS) pain scores from 0-10 as well as cumulative opioid consumption in oral morphine equivalents will be determined at set time points of 12, 24, 48 hours. The data will be determined from the patient's pain flow sheet and medication administration record (MAR), which are part of the standard charting found on the hospital ward. Opioid data from PCA will be obtained from the hospital database which electronically logs usage. The patient's chart will also be used to note anti-emetic medication usage. At 48 hours, all participants will be provided with a QoR-40 questionnaire, a validated 40 item questionnaire on the quality of recovery from anesthesia. The time of discharge will be recorded from the hospital data base.

   Complications from adductor canal catheters will be recorded, such as catheter dislodgement and site infection. For patients unable to complete the study, the reason will be noted and data will be included in an intention to treat analysis.

   E. Statistical Analysis

   Sample Size:

   The investigators do not have institutional data of standard deviation (SD) of morphine equivalent consumption for primary total knee arthroplasty. Based on previous studies, the standard deviation of morphine equivalent consumption at 24h is estimated to be 20 mg IV. We consider a reduction of 10 mg to be clinically relevant at this time point and therefore set it as the non-inferiority margin. Using the following online calculator: https://www.sealedenvelope.com/power/continuous-noninferior/ based on a power of 80% and significance level of 5%, the number of patients required per group is 50. The aim is to recruit 60 patients per group to account for potential drop outs.
6. Data Analysis: Categorical data will be analysed with chi-squared tests. Numeric variables will be compared with independent T-tests if distributions were normal. If Kolmogorov-Smirnoff test for normality of distribution was significant non-parametric Mann Whitney U tests will be utilized. Statistical significance will be assumed if P \<0.05.

Arms: arm 1: Postoperatively in the PACU, this group will receive 20ml 0.5% ropivacaine for their ACB. arm 2: Postoperatively in the PACU, this group will receive 20ml 0.5% ropivacaine for their ACB along with 8mg IV dexamethasone. arm 3: Postoperatively in the PACU, this group will receive 20ml 0.5% ropivacaine for their adductor canal block and have a catheter placed in the adductor canal at the mid-thigh. 0.2% ropivacaine at 5ml/hr will be run for 48 hours.
Interventions: intervention 1: Adductor canal block intervention 2: Adductor canal block with dexamethasone intervention 3: Adductor canal catheter intervention 4: Bupivacaine intervention 5: Fentanyl intervention 6: Ropivacaine 0.5% Injectable Solution intervention 7: Dexamethasone
Intervention descriptions: intervention 1: Spinal anesthesia with 2-3 ml 0.5% bupivacaine and 0-20mcg of fentanyl. At the end of the case, the surgeon will infiltrate 30ml 0.5% ropivacaine peri-articularly. 20ml 0.5% ropivacaine in the adductor canal in PACU. intervention 2: Spinal anesthesia with 2-3 ml 0.5% bupivacaine and 0-20mcg of fentanyl. At the end of the case, the surgeon will infiltrate 30ml 0.5% ropivacaine peri-articularly. 20ml 0.5% ropivacaine in the adductor canal along with 8mg dexamethasone IV in PACU. intervention 3: Spinal anesthesia with 2-3 ml 0.5% bupivacaine and 0-20mcg of fentanyl. At the end of the case, the surgeon will infiltrate 30ml 0.5% ropivacaine peri-articularly. 20ml 0.5% ropivacaine and a catheter placed in PACU, with a continuous infusion of 0.2% ropivacaine started. intervention 4: Used in spinal anesthetic intervention 5: May or may not be used in spinal anesthetic intervention 6: Local anesthetic to be used by surgeon as local infiltration and by anesthesiologist in adductor canal block. intervention 7: To be given intravenously at time of nerve block to one of the study arms.

Protocol documents: