Pain After Unilateral Total Knee Arthroplasty: A Prospective Randomized Controlled Trial Examining the Analgesic Effectiveness of a Combined Adductor Canal Peripheral Nerve Block with Periarticular Infiltration Versus Adductor Canal Nerve Block Alone Versus Periarticular Infiltration Alone : Anesthesia & Analgesia

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Regional Anesthesia: Research Report

Pain After Unilateral Total Knee Arthroplasty: A Prospective Randomized Controlled Trial Examining the Analgesic Effectiveness of a Combined Adductor Canal Peripheral Nerve Block with Periarticular Infiltration Versus Adductor Canal Nerve Block Alone Versus Periarticular Infiltration Alone

Sawhney, Monakshi PhD, NP(Adult)*†; Mehdian, Hossein MD, FRCSC†‡; Kashin, Brian MD, FRCPC†§; Ip, Gregory MD, FRCPC†‡; Bent, Maurice MD, FRCSC†‡; Choy, Joyce RPh, BScPhm; McPherson, Mark MSc; Bowry, Richard MB, BS, FRAC, FRCPC†§

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Anesthesia & Analgesia 122(6):p 2040-2046, June 2016. | DOI: 10.1213/ANE.0000000000001210
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Effective pain management is essential for early mobilization and rehabilitation after total knee arthroplasty (TKA). Multimodal analgesia, including spinal analgesia, peripheral nerve blockade, periarticular infiltration (PI) of the knee joint intraoperatively, opioids, nonsteroidal antiinflammatory drugs (NSAIDs), acetaminophen, and gabapentinoids, has been shown to manage postoperative pain after arthroplasty effectively.1–3 However, the challenge of managing postoperative pain after TKA is to preserve motor function while providing adequate analgesia.1,2,4

The introduction of adductor canal (AC) peripheral nerve blocks to manage pain after TKA is relatively new. The AC is an aponeurotic space in the middle third of the thigh. It contains nerve branches that supply sensory innervation to the knee, including the posterior branch of the obturator nerve and the saphenous nerve. Blocking these nerves provides analgesia to the medial aspect but not to the lateral or posterior aspects, of the knee.5–7

Saranteas et al.5 examined the effectiveness of an ultrasound-guided saphenous nerve block in 23 healthy volunteers. They reported that 22 of 23 of the volunteers had a complete sensory block, and none of the volunteers had motor block of the hip flexor or knee extensor.5 Manickam et al.6 examined the feasibility and efficacy of ultrasound-guided block of the saphenous nerve in the AC in 20 patients undergoing lower limb surgery. They reported that all 20 patients developed complete sensory block and no motor block.6 AC block has also been compared with femoral nerve block and was found to have an early sparing of the quadriceps strength with no difference in pain intensity scores, analgesic use, or knee mobility.3,8,9

PI of the knee joint has been shown to improve pain management and to preserve motor function. With PI, the nerves, muscle, and tissue in the posterior, lateral, and medial aspects of the knee are infiltrated intraoperatively with local anesthetic, morphine, and ketorolac to provide analgesia.10 Randomized controlled trials have reported that patients undergoing TKA who received PI (with ropivacaine/ketorolac/epinephrine versus saline) used less morphine postoperatively, had less pain, and a shorter length of hospital stay.11–14

Randomized controlled trials also have examined the effectiveness of intermittent PI compared with continuous femoral nerve block for TKA. These trials have produced mixed results; therefore, it is unclear whether PI provides similar or better analgesia compared with femoral nerve block. Toftdahl et al.2 reported that patients who received intermittent PI (300 mg ropivacaine/30 mg ketorolac/0.5 mg epinephrine) reported lower pain intensity scores with physiotherapy, used less morphine, and were able to walk further on postoperative day (POD) 1 compared with those who received continuous femoral nerve block (10 mL/h ropivacaine 2 mg/mL). In contrast, Carli et al.1 reported that on PODs 1 and 2, pain scores (at rest) and morphine use were less in the patients who received continuous femoral nerve block (0.2% ropivacaine 8 mL/h) compared with those who received continuous PI (0.2% ropivacaine 100 mL/ketorolac 30 mg/epinephrine 0.5 mg). Affas et al.13 reported that the mean pain scores (at rest and movement) were similar for both patients who received either femoral nerve block with intermittent injection (ropivacaine 2 mg/mL) or intermittent intraarticular infiltration (150 mL ropivacaine 2 mg/mL/30 mg ketorolac/0.5 mg epinephrine).

These studies demonstrate that AC block decreases pain after TKA without impact on quadriceps function and PI is effective in managing postoperative TKA pain without impairing motor function. Perlas et al.3 conducted a retrospective cohort study in which they examined the effect of analgesic modality after TKA. Patients who received femoral nerve block, PI, or PI + AC block charts were reviewed. Patients who received PI + AC block walked the longest distance on POD 1, and patients who received PI with or without AC block reported lower pain scores.3 Andersen et al.15 combined these analgesic techniques by comparing the effect of a continuous saphenous nerve block with ropivacaine versus saline, in addition to PI, on pain and ambulation. They reported that patients who received ropivacaine in their AC block reported lower pain scores on movement and rest and no difficulty with ambulation. No published prospective randomized trials, however, have compared single-injection AC block with PI to PI only to AC nerve block only.

The purpose of this trial is to examine the effectiveness of AC block with PI compared with PI only compared with AC nerve block only on pain after unilateral TKA. The primary outcome of this trial was pain on walking, using a 0 to 10 numeric rating scale (NRS) at POD 1. We hypothesized that there would be no difference between the 3 groups with regard to pain scores on walking, resting, or knee bending.

METHODS

This study design was a prospective, surgeon- and observer-blinded, randomized controlled trial. Research Ethics Board approval was obtained at North York General Hospital, Toronto, Ontario. The study was registered with ClinicalTrials.gov (NCT01797588). Between May 31, 2013, and February 28, 2014, all patients who were scheduled for primary TKA were identified in the preoperative assessment clinic and invited to meet with the research assistant in a private office, who would confirm eligibility, explain the study, and obtain informed written consent. The inclusion criteria were age 18 years or older, ASA physical status I to III, and able to speak, read, and understand English. The exclusion criteria were contraindication to neuraxial and/or regional anesthesia, allergy to local anesthetics, chronic pain unrelated to their knee joint, chronic (3 months or longer) opioid use, and preexisting neuropathy involving the operative site.

After consent was obtained, participants’ baseline demographic information was collected and randomly assigned to 1 of the 3 groups via a web-based computerized block randomization service (randomize.net). Group 1 received both an AC peripheral nerve block and intraoperative PI (AC + PI). Group 2 received an AC block and intraoperative saline infiltration (AC). Group 3 received 2 mL local anesthetic injected into the skin in the area of the AC and intraoperative PI. All participants, orthopedic surgeons, members of the acute pain service, and outcome assessors were blinded to the group allocation. Only the anesthesiologist responsible for intraoperative care and the anesthesia assistant performing the AC block/sham block were aware of the randomization. The pharmacy department prepared the blinded PI solution.

On the day of surgery, all participants received a premedication consisting of acetaminophen 1000 mg, celecoxib 200 mg, and gabapentin 300 mg on arrival at the day surgical unit. Participants were transferred to a designated block room to undergo peripheral nerve block and spinal anesthesia. AC block was performed under conscious sedation with fentanyl 50 μg and midazolam 1 mg. The medial aspect of the patient’s thigh was prepared for a block using 2% chlorhexidine. With both the hip and knee flexed at 45 degrees, the leg was externally rotated. The AC was identified using a Sonosite-Flex linear HFL38X-6MHz™, Bothell, WA, ultrasound probe. All patients then received a subcutaneous injection of 2 mL of 1% lidocaine to anesthetize the skin at the AC site. Patients assigned randomly to AC block had the block performed through the anesthetized skin using a 22G facet tip, 50-mm Pajunk SonoTAP™ needle (Pajunk, Germany). A total of 30 mL of 0.5% ropivacaine was injected into the canal. For participants randomly assigned to receive a sham block, the procedure stopped after they received 2 mL of 1% subcutaneous lidocaine to anesthetize the skin at the AC site. All participants received a standard spinal anesthetic using a 25G Pajunk Spinal needle and 2 mL of 0.5% bupivacaine with 0.1 mg preservative-free morphine.

Intraoperative sedation was administered with a propofol infusion. Participants also received IV dexamethasone 8 mg and ondansetron 4 mg to reduce postoperative nausea and vomiting (PONV). The PI solution was administered by the surgeon during the TKA. A total of 6 different surgeons were involved in the administration of the infiltration solution for their respective patients. All surgeons were trained to perform the PI technique in a similar manner. A blinded 110-mL PI solution bag was prepared by the pharmacy and delivered to the operating room (OR). The PI solution bag contained either 110-mL normal saline solution containing 300 mg ropivacaine, 10 mg morphine, and 30 mg ketorolac or 110 mL saline 0.9%. The surgical team was blinded to the contents of the study bag. A 20-mL aliquot was injected into the posterior capsule and the medial and lateral ligaments just before implantation; after insertion of the implants, another 20 mL was infiltrated into the capsule and retinacular tissues. The remaining solution (approximately 60 mL) was used to infiltrate the muscle and subcutaneous tissues. Postoperative analgesia was standardized to hydromorphone patient-controlled analgesia (PCA; 0.2 mg bolus, 5-minute lockout, and a 4-hour maximum of 6 mg), celecoxib 200 mg every 12 hours, acetaminophen 1000 mg every 6 hours, hydromorphone control released 3 mg every 12 hours, and gabapentin 100 mg every 8 hours. Participants did not receive an NSAID if their creatinine was elevated. Creatinine was monitored daily, and the NSAID was discontinued if the creatinine was elevated during the participant’s hospital stay. This multimodal regimen was administered until discharge to home, with the exception of hydromorphone PCA that was discontinued on POD 2 or earlier. Once hydromorphone PCA was discontinued, oral hydromorphone immediate release 1 to 2 mg as needed was prescribed for breakthrough pain.

Outcomes were measured on PODs 1 and 2 by a research assistant or by the primary investigator. Outcomes examined included pain intensity, analgesic consumption, motor function, pain-related interference with activities, and length of stay. Baseline demographic information was collected at the time of consent to participate in the trial in the preadmission clinic. Surgical data including side of TKA and anesthetic administered were collected from the chart postoperatively. Pain intensity was measured using the 0 to 10 NRS and included in the Brief Pain Inventory-Short Form (BPI-SF). In addition to the primary outcome of pain intensity with walking, we measured pain intensity at rest and with knee bending on PODs 1 and 2. Pain-related interference with activities was measured with a modified version of the BPI-SF interference subscale. Analgesic consumption was collected from the participant’s electronic medication administration record and by recording the amount of breakthrough morphine or hydromorphone consumed via a PCA pump. All adjunct analgesics consumed, including acetaminophen, celecoxib, and gabapentin, were recorded per drug in milligram per day. Distance walked was measured in meters, as recorded by the physiotherapist or by the physiotherapy assistant on PODs 1 and 2. Length of stay in hospital was measured in hours from time of the surgery to time to discharge home.

Statistical Methodology

The primary outcome of this study was pain on walking on POD 1. With 3 equal groups, a pooled SD of 3 points on the 0 to 10 NRS, and a 2-tailed type I overall Bonferroni corrected error of 0.05, 48 individuals were required in the treatment arm. This would detect a difference of ≥2 points on the pain scale using the t test (independent samples) and a power of 80%. Accounting for a potential 15% attrition rate, a sample of 53 participants was required for each group. In total, 159 participants were recruited into this trial.

Data were analyzed using Statistical Analysis Software (SAS v.9.2; SAS Institute Inc., Cary, NC). The distribution of the data was analyzed for normality using histograms, quantile-quantile plots, and the Lilliefors test. Differences in mean scores between groups were assessed using 1-way analysis of variance (normally distributed data) and the χ2 test for independence (categorical data). In comparisons with a group that was determined to be statistically significant, a Bonferroni-adjusted significance level of 0.0167 was calculated to account for the increased possibility of type I error because of multiple testing.

RESULTS

Two hundred sixty-five patients were screened for inclusion in this trial from June 2013 to March 2014. One hundred six patients did not meet the inclusion criteria or did not wish to participate. One hundred fifty-nine patients were included and randomly assigned to 1 of the 3 groups and 145 participants completed this trial (Fig. 1). Demographic information is presented in Table 1, and OR data are presented in Table 2. There were no significant differences between the groups in demographic information, including age, sex, and preoperative pain reported. There also were no significant differences between the groups in OR data.

T1
Table 1.:
Patient Demographics
T2
Table 2.:
OR Data
F1
Figure 1.:
Consolidated Standards of Reporting Trials Statement flow diagram. AC = adductor canal; NSAID = nonsteroidal antiinflammatory drug; PI = periarticular infiltration.

On PODs 1 and 2, pain intensity on walking was significantly lower for participants who received both AC block and PI compared with participants who received PI block only or AC block only (Fig. 2). Participants who received AC block only reported significantly greater pain intensity scores than participants who received AC block and PI, PI only for pain intensity on walking, at rest, and with knee bending. On POD 1, participants who received AC + PI reported significantly lower pain on walking (3.3) compared with those who received AC (6.2) or PI (4.9). Participants who received AC reported significantly greater pain scores at rest and knee bend compared with those who received AC + PI or PI. The difference in pain scores between participants who received AC + PI and those who received AC was 2.83 (95% confidence interval, 1.58–4.09) and the difference between those who received AC + PI and those who received PI was 1.61 (95% confidence interval, 0.37–2.86). Participants who received AC block only also reported significantly greater pain-related interference with activities, as measured using a modified version of the BPI-SF interference subscale on POD 1. There were no differences between the 3 groups for pain-related interference with activities on POD 2 (Tables 3 and 4). There was no difference between the groups for the distance walked, with the mean distance walked on POD 1 and POD 2 being 31 and 57 m, respectively. No participant reported quadriceps weakness.

T3
Table 3.:
Pain-Related Interference (Brief Pain Inventory, Interference Subscale)
T4
Table 4.:
Group Comparisons for Pain Scores and Pain-Related Interference with Activities on POD 1
F2
Figure 2.:
Pain scores (0–10 numeric rating scale: 0 = no pain, 10 = worst pain).
T5
Table 5.:
Standing Preoperative and Postoperative Analgesics Consumed
T6
Table 6.:
Postoperative Analgesics Consumed, as Needed

There were no differences between the 3 groups for the pre- and postoperative standing analgesics consumed on POD 0, POD 1, or POD 2 (Table 5). Participants who received AC only consumed more IV PCA hydromorphone on POD 0 and POD 1 (Tables 5 and 6). There were no documented cases of major or minor symptoms suggestive of local anesthetic systemic toxicity (LAST), and none of the participants reported symptoms of LAST when asked on POD 1. There were no differences between the groups in the rates of opioid-related adverse effects of nausea, vomiting, or pruritus.

DISCUSSION

An optimal analgesic regimen for patients undergoing TKA provides adequate pain management while not limiting the patients’ ability to ambulate. The AC block has gained increasing popularity because of its potential analgesic efficacy and its potentially limited impact on motor function.3,5,6,8,9 PI of local anesthetics is reported to be effective in reducing pain after TKA compared with placebo.2,10–14 In this trial, we compared 3 different methods of providing peripheral nerve block as part of an analgesic regimen that included a spinal anesthesia with intrathecal morphine and multimodal analgesics. Our results suggest that the combination of AC block and PI provides better pain relief and does not compromise ambulation compared with AC block only or PI block only. When the AC block is combined with PI, analgesia is improved because of the ability to provide local anesthetic to the anterior, medial, lateral, and posterior aspects of the knee, potentially providing more complete analgesia compared with using each technique individually. The results of this trial are similar to the results reported in other trials.3,16

As part of the multimodal analgesic regimen at our institution, patients receive an IV opioid via PCA postoperatively after TKA. All patients using IV PCA are closely monitored, as per our institutions policy, for pruritus, nausea, and vomiting. In this trial, the IV PCA use was greater in patients who received AC block only on PODs 0, 1, 2, and overall. Although opioid use was greater in this group, there was no difference in opioid-related adverse effects compared with the other groups including PONV. This finding could be related to the intraoperative administration of dexamethasone and ondansetron, which was included in our study protocol, to reduce PONV.

Limitations of this trial included only measuring distance walked once a day by the physiotherapist. If either the investigator or the research assistant walked with the physiotherapist and measured the distance walked, it would have provided more consistency, and possibly accuracy, in this measurement. Also, in our study, patients stated that they ambulated more than once a day; however, no attempt was made to assess distance walked for the entire 48-hour period, because these data were not extractable from the patient record. Providing each participant with a pedometer or other recording device would have assisted in collecting this information.

Using a combination of an AC and PI requires the use of a high total dose of local anesthetic with the potential for LAST. During this trial, participants were monitored closely and asked about signs and symptoms of LAST. No participants reported symptoms of LAST. This includes no reported changes in neurological status or evidence of cardiac toxicity. However, this trial was not powered to assess the safety of the combined AC + PI technique. We did not retrieve plasma levels of local anesthetic to assess for concentration of local anesthetic in the blood stream and thus cannot conclude there is no risk of LAST. The AC blocks also were not tested for sensory blockade because of the blinded nature of the study. Therefore, it is not known whether any of the AC blocks had failed. In addition, the AC blocks were performed by multiple anesthesiologists, and the PI infiltrations were performed by multiple orthopedic surgeons. Despite these limitations, the addition of both AC block and PI has patient advantages when used in combination of with an already established multimodal regimen that includes opioids, gabapentinoids, and antiinflammatory drugs. The preservation of knee strength without the risk of perioperative leg weakness has the potential to reduce the risk of patient falls. Additional research on the safety of these analgesic techniques, including the risk of falls and the incidence of LAST, needs to be conducted. Future research and outcomes could focus on determining whether this analgesic regimen can result in early discharge from hospital and its impact on patient satisfaction. In this trial, we were specifically interested in examining pain in the acute postoperative period. Therefore, future trials could also assess patient outcomes at regular intervals for a longer period (i.e., 6 months or a year) to provide information on the long-term impact of these analgesic techniques.

DISCLOSURES

Name: Monakshi Sawhney, PhD, NP(Adult).

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Monakshi Sawhney has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.

Name: Hossein Mehdian, MD, FRCSC.

Contribution: This author helped design the study, conduct the study, and write the manuscript.

Attestation: Hossein Mehdian has seen the original study data and approved the final manuscript.

Name: Brian Kashin, MD, FRCPC.

Contribution: This author helped design the study, conduct the study, and write the manuscript.

Attestation: Brian Kashin has seen the original study data and approved the final manuscript.

Name: Gregory Ip, MD, FRCPC.

Contribution: This author helped design the study, conduct the study, and write the manuscript.

Attestation: Gregory Ip has seen the original study data and approved the final manuscript.

Name: Maurice Bent, MD, FRCSC.

Contribution: This author helped design the study, conduct the study, and write the manuscript.

Attestation: Maurice Bent has seen the original study data and approved the final manuscript.

Name: Joyce Choy, RPh, BScPhm.

Contribution: This author helped conduct the study and write the manuscript.

Attestation: Joyce Choy has seen the original study data and approved the final manuscript.

Name: Mark McPherson, MSc.

Contribution: This author helped analyze the data and write the manuscript.

Attestation: Mark McPherson has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Richard Bowry, MB, BS, FRAC FRCPC.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Richard Bowry has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

This manuscript was handled by: Terese T. Horlocker, MD.

ACKNOWLEDGMENTS

The authors acknowledge Kristin Clarke, Dr. Daisy Therese Joo, Jason Proudman, Marty McKinlay, and Linda Jussaume for their advice during the trial study design. They also acknowledge the Department of Pharmacy, the operating room nurses, the preadmission department staff, the orthopaedic surgeons and the staff on the orthopaedic inpatient unit, and the Department of Anesthesia at North York General Hospital for their support in running this trial.

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