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Background: Cefazolin is the standard of care for perioperative antibiotic prophylaxis in total joint arthroplasty (TJA) in the United States. The potential allergic cross-reactivity between cefazolin and penicillin causes uncertainty regarding optimal antibiotic choice in patients who have a reported penicillin allergy (rPCNA). The purpose of this study was to determine the safety of perioperative cefazolin in PCNA patients undergoing primary TJA., Methods: We identified all patients (n = 49,842) undergoing primary total hip arthroplasty (n = 25,659) or total knee arthroplasty (n = 24,183) from 2016 to 2022 who received perioperative intravenous antibiotic prophylaxis. Patients who had an rPCNA (n = 5,508) who received cefazolin (n = 4,938, 89.7%) were compared to rPCNA patients who did not (n = 570, 10.3%), and to patients who did not have an rPCNA (n = 43,359). The primary outcome was the rate of allergic reactions within 72 hours postoperatively. Secondary outcomes included the rates of superficial infections, deep infections, and Clostridioides difficile infections within 90 days., Results: The rate of allergic reactions was 0.1% (n = 5) in rPCNA patients who received cefazolin, compared to 0.2% (n = 1) in rPCNA patients who did not (P = .48) and 0.02% (n = 11) in patients who have no rPCNA (P = .02). Allergic reactions were mild in all 5 rPCNA patients who received cefazolin and were characterized by cutaneous symptoms (n = 4) or dyspnea in the absence of respiratory distress (n = 1) that resolved promptly with antibiotic discontinuation and administration of antihistamines and/or corticosteroids. We observed no differences in the rates of superficial infections (0.1 versus 0.2%, P = .58), deep infections (0.3 versus 0.4%, P = .68), or C difficile infections (0.04% versus 0%, P = .99) within 90 days in rPCNA patients who received cefazolin versus alternative perioperative antibiotics., Conclusions: In this series of more than 5,500 patients who had an rPCNA undergoing primary TJA, perioperative prophylaxis with cefazolin resulted in a 0.1% incidence of allergic reactions that were clinically indolent. Cefazolin can be safely administered to most patients, independent of rPCNA severity., Level of Evidence: III., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Optimal analgesic protocols for total knee arthroplasty (TKA) patients remain controversial. Multimodal analgesia is advocated, often including peripheral nerve blocks and/or periarticular injections (PAIs). If 2 blocks (adductor canal block [ACB] plus infiltration between the popliteal artery and capsule of the knee [IPACK]) are used, also performing PAI may not be necessary. This noninferiority trial hypothesized that TKA patients with ACB + IPACK + saline PAI (sham infiltration) would have pain scores that were no worse than those of patients with ACB + IPACK + active PAI with local anesthetic., Methods: A multimodal analgesic protocol of spinal anesthesia, ACB and IPACK blocks, intraoperative ketamine and ketorolac, postoperative ketorolac followed by meloxicam, acetaminophen, duloxetine, and oral opioids was used. Patients undergoing primary unilateral TKA were randomized to receive either active PAI or control PAI. The active PAI included a deep injection, performed before cementation, of bupivacaine 0.25% with epinephrine, 30 mL; morphine; methylprednisolone; cefazolin; with normal saline to bring total volume to 64 mL. A superficial injection of 20 mL bupivacaine, 0.25%, was administered before closure. Control injections were normal saline injected with the same injection technique and volumes. The primary outcome was numeric rating scale pain with ambulation on postoperative day 1. A noninferiority margin of 1.0 was used., Results: Ninety-four patients were randomized. NRS pain with ambulation at POD1 in the ACB + IPACK + saline PAI group was not found to be noninferior to that of the ACB + IPACK + active PAI group (difference = 0.3, 95% confidence interval [CI], [-0.9 to 1.5], P = .120). Pain scores at rest did not differ significantly among groups. No significant difference was observed in opioid consumption between groups. Cumulative oral morphine equivalents through postoperative day 2 were 89 ± 40 mg (mean ± standard deviation), saline PAI, vs 73 ± 52, active PAI, P = .1. No significant differences were observed for worst pain, fraction of time in severe pain, pain interference, side-effects (nausea, drowsiness, itching, dizziness), quality of recovery, satisfaction, length of stay, chronic pain, and orthopedic outcomes., Conclusions: For TKA patients given a comprehensive analgesic protocol, use of saline PAI did not demonstrate noninferiority compared to active PAI. Neither the primary nor any secondary outcomes demonstrated superiority for active PAI, however. As we cannot claim either technique to be better or worse, there remains flexibility for use of either technique., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2024 International Anesthesia Research Society.)

Background: Duloxetine, a serotonin-norepinephrine dual reuptake inhibitor, may improve analgesia after total knee arthroplasty (TKA). Previous studies had one primary outcome, did not consistently use multimodal analgesia, and used patient-controlled analgesia devices, potentially delaying discharge. We investigated whether duloxetine would reduce opioid consumption or pain with ambulation., Methods: A total of 160 patients received 60 mg duloxetine or placebo daily, starting from the day of surgery and continuing 14 days postoperatively. Patients received neuraxial anesthesia, peripheral nerve blocks, acetaminophen, nonsteroidal anti-inflammatory drugs, and oral opioids as needed. The dual primary outcomes were Numeric Rating Scale (NRS) scores with movement on postoperative days 1, 2, and 14, and cumulative opioid consumption surgery through postoperative day 14., Results: Duloxetine was noninferior to placebo for both primary outcomes and was superior to placebo for opioid consumption. Opioid consumption (mean ± SD) was 288 ± 226 mg OME [94, 385] vs 432 ± 374 [210, 540] (duloxetine vs placebo) P = .0039. Pain scores on POD14 were 4.2 ± 2.0 vs 4.8 ± 2.2 (duloxetine vs placebo) P = .018. Median satisfaction with pain management was 10 (8, 10) and 8 (7, 10) (duloxetine vs placebo) P = .046. Duloxetine reduced interference by pain with walking, normal work, and sleep., Conclusion: The 29% reduction in opioid use corresponds to 17 fewer pills of oxycodone, 5 mg, and was achieved without increasing pain scores. Considering the ongoing opioid epidemic, duloxetine can be used to reduce opioid usage after knee arthroplasty in selected patients that can be appropriately monitored for potential side effects of the medication., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Periarticular injection is a popular method to control postoperative pain after total knee replacement. An adductor canal block is a sensory block that can also help to alleviate pain after total knee replacement. We hypothesized that the combination of adductor canal block and periarticular injection would allow patients to reach discharge criteria 0.5 day faster than with periarticular injection alone., Methods: This prospective trial enrolled 56 patients to receive a periarticular injection and 55 patients to receive an adductor canal block and periarticular injection. Both groups received intraoperative neuraxial anesthesia and multiple different types of pharmaceutical analgesics. The primary outcome was time to reach discharge criteria. Secondary outcomes, collected on postoperative days 1 and 2, included numeric rating scale pain scores, the PAIN OUT questionnaire, opioid consumption, and opioid-related side effects., Results: There was no difference in time to reach discharge criteria between the groups with and without an adductor canal block. The Wilcoxon-Mann-Whitney odds ratio was 0.87 (95% confidence interval [CI], 0.55 to 1.33; p = 0.518). The median time to achieve discharge criteria (and interquartile range) was 25.8 hours (23.4 hours, 44.3 hours) in the adductor canal block and periarticular injection group compared with 26.4 hours (22.9 hours, 46.2 hours) in the periarticular injection group. Patients who received an adductor canal block and periarticular injection reported lower worst pain (difference in means, -1.4 [99% CI, -2.7 to 0]; adjusted p = 0.041) and more pain relief (difference in means, 12% [99% CI, 0% to 24%]; adjusted p = 0.048) at 24 hours after anesthesia. There was no difference in any other secondary outcome measure (e.g., opioid consumption, opioid-related side effects, numeric rating scale pain scores)., Conclusions: The time to meet the discharge criteria was not significantly different between the groups. In the adductor canal block and periarticular injection group, the patients had lower worst pain and greater pain relief at 24 hours after anesthesia. No difference was noted in any other secondary outcome measure (e.g., opioid consumption, opioid-related side effects, numeric rating scale pain scores)., Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Background: Duloxetine is effective for chronic musculoskeletal and neuropathic pain, but there are insufficient data to recommend the use of antidepressants for postoperative pain. The authors hypothesized that administration of duloxetine for 15 days would reduce pain with ambulation at 2 weeks after total knee arthroplasty., Methods: In this triple-blinded, randomized, placebo-controlled trial, patients received either duloxetine or placebo for 15 days, starting from the day of surgery. Patients also received a comprehensive multimodal analgesic regimen including neuraxial anesthesia, epidural analgesia, an adductor canal block, meloxicam, and oxycodone/acetaminophen as needed. The primary outcome was the pain score (0 to 10 numeric rating scale) with ambulation on postoperative day 14., Results: One hundred six patients were randomized and analyzed. On day 14, duloxetine had no effect on pain with ambulation; mean pain was 3.8 (SD, 2.3) for placebo versus 3.5 (SD, 2.1) for duloxetine (difference in means [95% CI], 0.4 [-0.5 to 1.2]; P = 0.386). Symptoms potentially attributable to duloxetine discontinuation at study drug completion (nausea, anxiety) occurred among nine patients (duloxetine) and five patients (placebo); this was not statistically significant (P = 0.247). Statistically significant secondary outcomes included opioid consumption (difference in mean milligram oral morphine equivalents [95% CI], 8.7 [3.3 to 14.1], P = 0.002 by generalized estimating equation) over the postoperative period and nausea on day 1 (P = 0.040). There was no difference in other side effects or in anxiety and depression scores., Conclusions: When included as a part of a multimodal analgesic regimen for knee arthroplasty, duloxetine does not reduce subacute pain with ambulation.

Background: Pregabalin may reduce postoperative pain and opioid use. Higher doses may be more effective, but may cause sedation and confusion. This prospective, randomized, blinded, placebo-controlled study tested the hypothesis that pregabalin reduces pain at 2 weeks after total knee arthroplasty, but increases drowsiness and confusion., Methods: Patients (30 per group) received capsules containing pregabalin (0, 50, 100, or 150 mg); two capsules before surgery, one capsule twice a day until postoperative day (POD) 14, one on POD15, and one on POD16. Multimodal analgesia included femoral nerve block, epidural analgesia, oxycodone-paracetamol, and meloxicam. The primary outcome was pain with flexion (POD14)., Results: Pregabalin did not reduce pain at rest, with ambulation, or with flexion at 2 weeks (P=0.69, 0.23, and 0.90, respectively). Pregabalin increased POD1 drowsiness (34.5, 37.9, 55.2, and 58.6% in the 0, 50, 100, and 150 mg arms, respectively; P=0.030), but did not increase confusion (0, 3.5, 0, and 3.5%, respectively; P=0.75). Pregabalin had no effect on acute or chronic pain, opioid consumption, or analgesic side-effects. Pregabalin reduced POD14 patient satisfaction [1-10 scale, median (first quartile, third quartile): 9 (8, 10), 8 (7, 10), 8 (5, 9), and 8 (6, 9.3), respectively; P=0.023). Protocol compliance was 63% by POD14 (50.0, 70.0, 76.7, and 56.7% compliance, respectively), with no effect of dose on compliance. Per-protocol analysis of compliant patients showed no effect of pregabalin on pain scores., Conclusions: Pregabalin had no beneficial effects, but increased sedation and decreased patient satisfaction. This study does not support routine perioperative pregabalin for total knee arthroplasty patients., Clinical Trial Registration: ClinicalTrials.gov: http://www.clinicaltrials.gov/ct2/show/study/NCT01333956., (© The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: This prospective double-blinded, randomized controlled trial compared adductor canal block (ACB) with femoral nerve block (FNB) in patients undergoing total knee arthroplasty. The authors hypothesized that ACB, compared with FNB, would exhibit less quadriceps weakness and demonstrate noninferior pain score and opioid consumption at 6 to 8 h postanesthesia., Methods: Patients received an ACB or FNB as a component of a multimodal analgesic. Quadriceps strength, pain score, and opioid consumption were assessed on both legs preoperatively and at 6 to 8, 24, and 48 h postanesthesia administration. In a joint hypothesis test, noninferiority was first evaluated on the primary outcomes of strength, pain score, and opioid consumption at 6 to 8 h; superiority on each outcome at 6 to 8 h was then assessed only if noninferiority was established., Results: Forty-six patients received ACB; 47 patients received FNB. At 6 to 8 h postanesthesia, ACB patients had significantly higher median dynamometer readings versus FNB patients (median [interquartile range], 6.1 kgf [3.5, 10.9] (ACB) vs. 0 kgf [0.0, 3.9] (FNB); P < 0.0001), but was not inferior to FNB with regard to Numeric Rating Scale pain scores (1.0 [0.0, 3.5] ACB vs. 0.0 [0.0, 1.0] FNB; P = 0.019), or to opioid consumption (32.2 [22.4, 47.5] ACB vs. 26.6 [19.6, 49.0]; P = 0.0115). At 24 and 48 h postanesthesia, there was no significant statistical difference in dynamometer results, pain scores, or opioid use between the two groups., Conclusion: At 6 to 8 h postanesthesia, the ACB, compared with the FNB, exhibited early relative sparing of quadriceps strength and was not inferior in both providing analgesia or opioid intake.

In a randomised controlled pragmatic trial we investigated whether local infiltration analgesia would result in earlier readiness for discharge from hospital after total knee replacement (TKR) than patient-controlled epidural analgesia (PCEA) plus femoral nerve block. A total of 45 patients with a mean age of 65 years (49 to 81) received a local infiltration with a peri-articular injection of bupivacaine, morphine and methylprednisolone, as well as adjuvant analgesics. In 45 PCEA+femoral nerve blockade patients with a mean age of 67 years (50 to 84), analgesia included a bupivacaine nerve block, bupivacaine/hydromorphone PCEA, and adjuvant analgesics. The mean time until ready for discharge was 3.2 days (1 to 14) in the local infiltration group and 3.2 days (1.8 to 7.0) in the PCEA+femoral nerve blockade group. The mean pain scores for patients receiving local infiltration were higher when walking (p = 0.0084), but there were no statistically significant differences at rest. The mean opioid consumption was higher in those receiving local infiltration. The choice between these two analgesic pathways should not be made on the basis of time to discharge after surgery. Most secondary outcomes were similar, but PCEA+femoral nerve blockade patients had lower pain scores when walking and during continuous passive movement. If PCEA+femoral nerve blockade is not readily available, local infiltration provides similar length of stay and similar pain scores at rest following TKR.