What Is the Role of a Periarticular Injection for Knee Arthroplasty Patients Receiving a Multimodal Analgesia Regimen Incorporating Adductor Canal and Infiltration Between the Popliteal Artery and Capsule of the Knee Blocks? A Randomized Blinded Placebo-Controlled Noninferiority Trial.

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.

Effectiveness of oral versus intravenous tranexamic acid in primary total hip and knee arthroplasty: a randomised, non-inferiority trial.

BACKGROUND: Tranexamic acid (TXA) reduces rates of blood transfusion for total hip arthroplasty (THA) and total knee arthroplasty (TKA). Although the use of oral TXA rather than intravenous (i.v.) TXA might improve safety and reduce cost, it is not clear whether oral administration is as effective. METHODS: This noninferiority trial randomly assigned consecutive patients undergoing primary THA or TKA under neuraxial anaesthesia to either one preoperative dose of oral TXA or one preoperative dose of i.v. TXA. The primary outcome was calculated blood loss on postoperative day 1. Secondary outcomes were transfusions and complications within 30 days of surgery. RESULTS: Four hundred participants were randomised (200 THA and 200 TKA). The final analysis included 196 THA patients (98 oral, 98 i.v.) and 191 TKA patients (93 oral, 98 i.v.). Oral TXA was non-inferior to i.v. TXA in terms of calculated blood loss for both THA (effect size=-18.2 ml; 95% confidence interval [CI], -113 to 76.3; P<0.001) and TKA (effect size=-79.7 ml; 95% CI, -178.9 to 19.6; P<0.001). One patient in the i.v. TXA group received a postoperative transfusion. Complication rates were similar between the two groups (5/191 [2.6%] oral vs 5/196 [2.6%] i.v.; P=1.00). CONCLUSIONS: Oral TXA can be administered in the preoperative setting before THA or TKA and performs similarly to i.v. TXA with respect to blood loss and transfusion rates. Switching from i.v. to oral TXA in this setting has the potential to improve patient safety and decrease costs.

Effect of anterior approach compared to posterolateral approach on readiness for discharge and thrombogenic markers in patients undergoing unilateral total hip arthroplasty: a prospective cohort study.

INTRODUCTION: The direct anterior approach (DAA) for total hip arthroplasty (THA) is considered less invasive than the posterolateral approach (PLA), possibly leading to earlier mobilization, faster recovery, and lower levels of thrombogenic markers. The purpose of the current study was to prospectively compare readiness for discharge, rehabilitation milestones, markers of thrombosis and inflammation at 6 weeks postoperatively between DAA and PLA. METHODS: A total of 40 patients (20 anterior and 20 posterolateral) were prospectively enrolled. Readiness for discharge, length of stay (LOS), and related outcomes were additionally documented. Blood was drawn at baseline, wound closure, 5-h post-closure, and 24-h post-closure for assays of interleukin-6 (IL-6), PAP (plasmin anti-plasmin), a marker of fibrinolysis, and PF1.2 (Prothrombin fragment 1.2), a marker of thrombin generation. RESULTS: Compared to the PLA group, the DAA group was ready for discharge a mean 13 h earlier (p = 0.03), while rehabilitation milestones were met a mean 10 h earlier (p = 0.04), and LOS was 13 h shorter (p = 0.02) on average. Pain scores at all study timepoints and patient satisfaction at 6 weeks were similar (p > 0.05). At 24 h postoperatively, PAP levels were 537.53 ± 94.1 µg/L vs. 464.39 ± 114.6 µg/L (p = 0.05), and Il-6 levels were 40.94 ± 26.1 pg/mL vs. 60.51 ± 33.0 pg/mL (p = 0.03), in DAA vs. PLA, respectively. CONCLUSIONS: In the immediate postoperative period, DAA patients were ready for discharge before PLA patients. DAA patients had shorter LOS, a lower inflammatory response, and higher systemic markers of fibrinolysis. However, these differences may not be clinically significant. Future studies with larger study populations are warranted to confirm the validity and significance of these findings. LEVEL OF EVIDENCE: Level II, Therapeutic Study.

Minimizing Opioid Use After Total Hip Arthroplasty: Comparing Periarticular Injection Versus Patient-Controlled Epidural Analgesia Versus a Combination Protocol.

BACKGROUND: Effective management of postoperative pain after total hip arthroplasty (THA) may be challenging. We sought to develop an opioid-sparing pain management pathway by comparing the relative effectiveness of 3 different protocols: (1) Local anesthetic administered patient-controlled epidural analgesia (PCEA) without intrathecal opioids; (2) Periarticular injection (PAI); and (3) PCEA + PAI. METHODS: In this double-blinded randomized controlled trial, 180 patients undergoing THA were randomized to receive either (1) PCEA with 0.06% bupivacaine, (2) PAI, or (3) a PAI + PCEA with 0.06% bupivacaine. All patients received the same postoperative multimodal analgesic regimen. The primary outcome was opioid consumption, measured in oral morphine equivalents, at 24, 48, and 72 hours after anesthesia stop time. Secondary measures included pain at rest and with movement, opioid side effects, patient satisfaction, and quality of recovery, as assessed via standardized self-reporting scales and surveys. RESULTS: Opioid consumption was significantly higher in the PAI group in the first 24 hours postoperatively compared to the PAI + PCEA group (30 versus 15, P = .012). No differences were detected among groups for length of stay, pain scores, patient satisfaction, or duration of surgery. More patients in the PAI + PCEA group were opiate-free in the first 24 hours compared to PAI (23.7 versus 8.5%, P = .043). CONCLUSION: Use of PAI + PCEA regimen was opioid-sparing in the first 24 hours after surgery, favoring this group when opioid reduction is desired. Increased drowsiness was noted in the subsequent 24 to 48 hours once the epidural catheter was removed and opioid consumption also increased.

The Use of Critical Care Services After Orthopedic Surgery at a High-Volume Orthopedic Medical Center: A Retrospective Study.

Background: With an aging population, orthopedics has become one of the largest and fastest growing surgical fields. However, data on the use of critical care services (CCS) in patients undergoing orthopedic procedures remain sparse. Purpose: We sought to elucidate the prevalence and characteristics of patients requiring CCS and intermediate levels of care after orthopedic surgeries at a high-volume orthopedic medical center. Methods: We retrospectively reviewed inpatient electronic medical record data (2016-2020) at a high-volume orthopedic hospital. Patients who required CCS and intermediate levels of care, including step-down unit (SDU) and telemetry services, were identified. We described characteristics related to patients, procedures, and outcomes, including type of advanced services required and surgery type. Results: Of the 50,387 patients who underwent orthopedic inpatient surgery, 1.6% required CCS and 21.6% were admitted to an SDU. Additionally, 482 (1.0%) patients required postoperative mechanical ventilation and 3602 (7.1%) patients required continuous positive airway pressure therapy. Spine surgery patients were the most likely to require any form of advanced care (45.7%). Conclusions: This retrospective review found that approximately one-fourth of orthopedic surgery patients were admitted to units that provided critical and intermediate levels of care. These results may prove useful to hospitals in estimating needs and allocating resources for advanced and critical care services after orthopedic surgery.

Effect of Duloxetine on Opioid Use and Pain After Total Knee Arthroplasty: A Triple-Blinded Randomized Controlled Trial.

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.

Low-Dose Perioperative Corticosteroids Can Be Administered Without Additional Morbidity in Patients Undergoing Bilateral Total Knee Replacement: A Retrospective Follow-up Study of a Randomized Controlled Trial.

Background: Short-term benefits of perioperative corticosteroid injections (CSIs) for bilateral total knee replacement (BTKR) include suppressed inflammation, improved knee motion, and reduced pain. Very little is known about the long-term benefits, complications, and safety of corticosteroids administered in the perioperative period. Purpose: We sought to compare 3-year follow-up outcomes of BTKR patients who received perioperative CSI with those who received placebo. We hypothesized that there would be no statistically significant differences in functional outcomes or adverse events based on whether or not CSIs were administered in the perioperative period. Methods: We conducted a retrospective review of chart and registry data of BTKR patients from a prior randomized controlled trial to compare outcomes in patients who received hydrocortisone vs placebo injections after BTKR (ClinicalTrials.gov: NCT01399268 and NCT01815918). Outcomes were compared at 6 and 12 weeks and at 1, 2, and 3 years. The Knee Injury and Osteoarthritis Outcome Scores (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used to evaluate clinical outcomes. Cochran-Mantel-Haenszel tests were used to compare the risk of complications between treatments after adjustment for trial. When possible, summary relative risk estimates were calculated using the Mantel-Haenszel method. Results: No BTKR patients in the treatment group developed an infection. The risk of complications did not increase in patients who received CSI compared with those who received placebo. Patients in the CSI group experienced greater reductions in pain and stiffness, though these results were not statistically significant. There were no statistically significant differences in the KOOS-Symptoms, KOOS-Activities of Daily Living, KOOS-Sports, KOOS-Quality of Life, or WOMAC Function scores. Conclusions: Low-dose corticosteroids can be administered in selected patients who undergo BTKR without increasing the risk of adverse events. At 3-year follow-up, administration of low-dose corticosteroids did not result in superior clinical outcomes scores when compared with placebo.

Development and Internal Validation of Machine Learning Algorithms for Predicting Hyponatremia After TJA.

BACKGROUND: The development of hyponatremia after total joint arthroplasty (TJA) may lead to several adverse events and is associated with prolonged inpatient length of stay as well as increased hospital costs. The purpose of this study was to develop and internally validate machine learning algorithms for predicting hyponatremia after TJA. METHODS: A consecutive cohort of 30,703 TJA patients from an institutional registry at a large, tertiary academic hospital were included. A total of 19 potential predictor variables were collected. Hyponatremia was defined as a serum sodium concentration of <135 mEq/L. Five machine learning algorithms were developed using a training set and internally validated using an independent testing set. Algorithm performance was evaluated through discrimination, calibration, decision-curve analysis, and Brier score. RESULTS: The charts of 30,703 patients undergoing TJA were reviewed. Of those patients, 5,480 (17.8%) developed hyponatremia postoperatively. A combination of 6 variables were demonstrated to optimize algorithm prediction: preoperative serum sodium concentration, age, intraoperative blood loss, procedure time, body mass index (BMI), and American Society of Anesthesiologists (ASA) score. Threshold values that were associated with greater hyponatremia risk were a preoperative serum sodium concentration of ≤138 mEq/L, an age of ≥73 years, an ASA score of >2, intraoperative blood loss of >407 mL, a BMI of ≤26 kg/m2, and a procedure time of >111 minutes. The stochastic gradient boosting (SGB) algorithm demonstrated the best performance (c-statistic: 0.75, calibration intercept: -0.02, calibration slope: 1.02, and Brier score: 0.12). This algorithm was turned into a tool that can provide real-time predictions (https://orthoapps.shinyapps.io/Hyponatremia_TJA/). CONCLUSIONS: The SGB algorithm demonstrated the best performance for predicting hyponatremia after TJA. The most important factors for predicting hyponatremia were preoperative serum sodium concentration, age, intraoperative blood loss, procedure time, BMI, and ASA score. A real-time hyponatremia risk calculator was developed, but it is imperative to perform external validation of this model prior to using this calculator in clinical practice. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Perioperative Nonsteroidal Anti-Inflammatory Agents in the COVID-19 Orthopedic Patient.

BACKGROUND: SARS-CoV-2 infection can cause serious complications beyond lung injury and respiratory failure, including sepsis, cardiovascular injury, renal failure, coagulation abnormalities, and neurologic injury. Widely used medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) have been flagged as having the potential to cause harm in the context of COVID-19. It is unknown if the benefits of NSAID use in the orthopedic population will outweigh the potential risks of increased morbidity in COVID-19 orthopedic patients. METHODS: We conducted a narrative review of the use of NSAIDs in the orthopedic patient with COVID-19, focusing on the effects of NSAIDs on the inflammatory process, the role of NSAIDs in orthopedics, and the associations between NSAID use and complications of pneumonia. RESULTS: We found that it may be appropriate to consider NSAID use in otherwise healthy orthopedic patients with COVID-19 and significant pain. CONCLUSIONS: In this context, we recommend that NSAIDs be used at the lowest effective dose for the shortest duration possible in orthopedic patients with COVID-19. However, pending further data and based on the concerns outlined in this review, we recommend avoiding NSAIDs in orthopedic patients with significant comorbidities and those who are undergoing major orthopedic surgery.

Comparison of Topical and Intravenous Tranexamic Acid for Total Knee Replacement: A Randomized Double-Blinded Controlled Study of Effects on Tranexamic Acid Levels and Thrombogenic and Inflammatory Marker Levels.

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic drug. Topical administration of TXA during total knee arthroplasty (TKA) is favored for certain patients because of concerns about thrombotic complications, despite a lack of supporting literature. We compared local and systemic levels of thrombogenic markers, interleukin (IL)-6, and TXA between patients who received intravenous (IV) TXA and those who received topical TXA. METHODS: Seventy-six patients scheduled for TKA were enrolled in this randomized double-blinded study. The IV group received 1.0 g of IV TXA before tourniquet inflation and again 3 hours later; a topical placebo was administered 5 minutes before final tourniquet release. The topical group received an IV placebo before tourniquet inflation and again 3 hours later; 3.0 g of TXA was administered topically 5 minutes before final tourniquet release. Peripheral and wound blood samples were collected to measure levels of plasmin-anti-plasmin (PAP, a measure of fibrinolysis), prothrombin fragment 1.2 (PF1.2, a marker of thrombin generation), IL-6, and TXA. RESULTS: At 1 hour after tourniquet release, systemic PAP levels were comparable between the IV group (after a single dose of IV TXA) and the topical group. At 4 hours after tourniquet release, the IV group had lower systemic PAP levels than the topical group (mean and standard deviation, 1,117.8 ± 478.9 µg/L versus 1,280.7 ± 646.5 µg/L; p = 0.049), indicative of higher antifibrinolytic activity after the second dose. There was no difference in PF1.2 levels between groups, indicating that there was no increase in thrombin generation. The IV group had higher TXA levels at all time points (p < 0.001). Four hours after tourniquet release, wound blood IL-6 and TXA levels were higher than systemic levels in both groups (p < 0.001). Therapeutic systemic TXA levels (mean, 7.2 ± 7.4 mg/L) were noted in the topical group. Calculated blood loss and the length of the hospital stay were lower in the IV group (p = 0.026 and p = 0.025). CONCLUSIONS: Given that therapeutic levels were reached with topical TXA and the lack of a major difference in the mechanism of action, coagulation, and fibrinolytic profile between topical TXA and a single dose of IV TXA, it may be a simpler protocol for institutions to adopt the use of a single dose of IV TXA when safety is a concern. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

A comparison of two different concentrations and infusion rates of ropivacaine in perineural infusion administered at the same total dose for analgesia after foot and ankle surgery: a randomized, double blinded, controlled study.

BACKGROUND: Continuous popliteal nerve block is utilized for postoperative analgesia after foot and ankle surgery. Whether only the total dose of local anesthetic or the combination of concentration and volume determine the characteristics of a continuous popliteal nerve infusion remains currently unknown. We hypothesized a reduction of the incidence of insensate extremity in patients given ropivacaine 0.4% at 4 mL/h compared to patients given ropivacaine 0.2% at 8 mL/h. METHODS: Sixty-four patients scheduled for major foot and ankle surgery requiring a continuous popliteal catheter infusion for postoperative analgesia were studied. Thirty-three patients were randomized to receive a continuous popliteal nerve block with 0.2% (basal 8 mL/h) and thirty-one with 0.4% (basal 4 mL/h) ropivacaine, reaching the same total dose (16 mg/h). The primary outcome was the incidence of persistent sensory block in the distal sciatic nerve distributions in the postoperative period. Secondary outcomes were the incidence of motor block, NRS pain scores at rest in the postoperative period up to 48 hours after surgery, opioid use and related side effects, patients' satisfaction. RESULTS: The incidence of persistent sensory block was similar in patients given 0.2% and in patients receiving 0.4% ropivacaine. The incidence of motor block, postoperative pain scores at rest, use of oral opioids, side effects and patients' satisfaction with the quality of recovery were also similar in both groups. CONCLUSIONS: Our results suggest that local anesthetic total dose is the primary determinant of continuous popliteal perineural infusion effects.

Clinical Indicators of the Need for Telemetry Postoperative Monitoring in Patients With Suspected Obstructive Sleep Apnea Undergoing Total Knee Arthroplasty.

BACKGROUND AND OBJECTIVES: Obstructive sleep apnea is associated with increased complication rates postoperatively. Current literature does not provide adequate guidance on management of these patients. This study used the STOP-Bang questionnaire to diagnose patients with possible obstructive sleep apnea (score ≥3). We hypothesized that a STOP-Bang score of 3 or greater would significantly correlate with the number of oxygen desaturation episodes during the first 48 hours after total knee arthroscopy. METHODS: The STOP-Bang questionnaire was administered to 110 patients preoperatively. All patients underwent spinal-epidural anesthesia with a saphenous nerve block and sedation and were connected to the Nellcor OxiMax N-600x pulse oximeter for 48 hours postoperatively. RESULTS: Final analysis included 98 patients. There was no significant difference in the total number of desaturation events between STOP-Bang groups (score <3 vs ≥3 and score <5 vs ≥5). The total number of desaturation events on postoperative day 1 was greater than that on day 0 (32.8 ± 42.7 vs 4.1 ± 10.0, P < 0.0001). The total number of desaturation events correlated with length of hospital stay (r = 0.329, P = 0.0001). Patients with a preoperative serum CO2 of 30 mmol/L or greater had significantly longer episodes of desaturation on postoperative day 0 compared with CO2 of less than 30 mmol/L (233.7 ± 410.1 vs 82.0 ± 126.2 seconds, P = 0.044). CONCLUSIONS: A high preoperative value of CO2 should be a warning for possible prolonged episodes of desaturation postoperatively. An attempt to limit postoperative desaturation events should be made to minimize length of stay.

Mycobacterium avium Complex Septic Arthritis Presenting as Osteonecrosis of the Femoral Head in a Patient With Systemic Lupus Erythematosus.

Mycobacterium avium complex is a rare cause of musculoskeletal infection, usually occurring in patients with compromised immune systems. Obtaining the diagnosis requires a high index of suspicion, and treatment can be delayed because of difficulty with isolating the organism. Treatment involves prolonged, targeted combination antibiotic therapy, and it is unclear whether eradication of the infection can occur in the presence of a foreign body, such as antibiotic spacers. The authors report a case of M avium infection presenting as presumed osteonecrosis of the femoral head in a young woman with systemic lupus erythematosus. She presented with collapse of her femoral head coinciding with several months of progressive, debilitating hip pain. She had mild fevers during that time, but results from multiple infectious workups, including hip aspiration, were negative. Purulent fluid was found in the operating room, but diagnosis was delayed for 5 weeks while waiting for cultures. The patient required 3 subsequent operations, eventually being left with a resection arthroplasty. Pertinent issues concerning diagnosis, therapy, and treatment challenges in M avium infections of the musculoskeletal system are discussed in this case report. [Orthopedics. 2017; 40(3):e549-e552.].

Duloxetine and Subacute Pain after Knee Arthroplasty when Added to a Multimodal Analgesic Regimen: A Randomized, Placebo-controlled, Triple-blinded Trial.

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.

The Effect of Perioperative Corticosteroids in Total Hip Arthroplasty: A Prospective Double-Blind Placebo Controlled Pilot Study.

BACKGROUND: Surgery produces a rapid rise in interleukin 6 (IL-6) which may increase the risk of deep vein thrombosis and medical complications. Perioperative corticosteroids suppress IL-6 release in patients undergoing total knee arthroplasty. This study evaluates the effects of a perioperative corticosteroid regimen on IL-6 formation, thrombogenesis, fibrinolysis, and clinical outcomes in patients undergoing unilateral, uncemented, total hip arthroplasty. METHODS: Twenty-seven patients (14 placebo and 13 study) were enrolled in this randomized, double-blind, placebo-controlled trial. The study group received 20 mg of prednisone orally followed by 2 doses of intravenous hydrocortisone, each 8 hours apart. Blood was drawn at several time points for IL-6, prothrombin fragment 1.2, and plasmin-alpha-2-antiplasmin complex, a marker of fibrinolysis. In-hospital visual analog pain (visual analog scale) scores, patient-controlled analgesia use, and ability to climb stairs were recorded. RESULTS: Mean serum IL-6 levels at 6 and 24 hours postoperatively were significantly lower for the study group, whereas serum prothrombin fragment 1.2 and plasmin-alpha-2-antiplasmin were not statistically different at any study time point. Average pain scores were similar (P > .05), but study group experience less severe pain (P < .01) and less patient-controlled analgesia (P = .02). At 3 months, 4 patients in the placebo and 1 patient in the study group had difficulty going up and down staircases (P = .08). CONCLUSION: The use of corticosteroids was associated with a statistically significant decrease in IL-6 at 6 and 24 hours postoperatively but did not affect thrombogenic markers. The study group had improved postoperative analgesia and a trend toward improved functional outcome at 3 months postoperatively.

Patient-controlled epidural analgesia or multimodal pain regimen with periarticular injection after total hip arthroplasty: a randomized, double-blind, placebo-controlled study.

BACKGROUND: The optimal postoperative analgesia after primary total hip arthroplasty remains in question. This randomized, double-blind, placebo-controlled study compared the use of patient-controlled epidural analgesia (PCEA) with use of a multimodal pain regimen including periarticular injection (PAI). We hypothesized that PAI would lead to earlier readiness for discharge, decreased opioid consumption, and lower pain scores. METHODS: Forty-one patients received PAI, and forty-three patients received PCEA. Preoperatively, both groups were administered dexamethasone (6 mg, orally). The PAI group received a clonidine patch and sustained-release oxycodone (10 mg), while the PCEA group had placebo. Both groups received combined spinal-epidural anesthesia and used an epidural pain pump postoperatively; the PAI group had normal saline solution, while the PCEA group had bupivacaine and hydromorphone. The primary outcome, readiness for discharge, required the discontinuation of the epidural, a pain score of <4 (numeric rating scale) without parenteral narcotics, normal eating, minimal nausea, urination without a catheter, a dry surgical wound, no acute medical problems, and the ability to independently transfer and walk 12.2 m (40 ft). RESULTS: The mean time to readiness for discharge (and standard deviation) was 2.4 ± 0.7 days (PAI) compared with 2.3 ± 0.8 days (PCEA) (p = 0.86). The mean length of stay was 3.0 ± 0.8 days (PAI) compared with 3.1 ± 0.7 days (PCEA) (p = 0.46). A significant mean difference in pain score of 0.74 with ambulation (p = 0.01; 95% confidence interval [CI], 0.18 to 1.31) and 0.80 during physical therapy (p = 0.03; 95% CI, 0.09 to 1.51) favored the PCEA group. The mean opioid consumption (oral morphine equivalents in milligrams) was significantly higher in the PAI group on postoperative day 0 (43 ± 21 compared with 28 ± 23; p = 0.002) and postoperative days 0 through 2 (136 ± 59 compared with 90 ± 79; p = 0.004). Opioid-Related Symptom Distress Scale (ORSDS) composite scores for severity and bothersomeness as well as scores for nausea, vomiting, and itchiness were significantly higher in the PCEA group (p < 0.05). Quality of Recovery-40 scores and patient satisfaction were similar. CONCLUSIONS: PAI did not decrease the time to discharge and was associated with higher pain scores and greater opioid consumption but lower ORSDS scores compared with PCEA. The choice for analgesic regimen may depend on a particular patient's threshold for pain and the potential side effects.

Addition of Dexamethasone and Buprenorphine to Bupivacaine Sciatic Nerve Block: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Sciatic nerve block provides analgesia after foot and ankle surgery, but block duration may be insufficient. We hypothesized that perineural dexamethasone and buprenorphine would reduce pain scores at 24 hours. METHODS: Ninety patients received ultrasound-guided sciatic (25 mL 0.25% bupivacaine) and adductor canal (10 mL 0.25% bupivacaine) blockade, with random assignment into 3 groups (30 patients per group): control blocks + intravenous (IV) dexamethasone (4 mg) (control); control blocks + IV buprenorphine (150 µg) + IV dexamethasone (IV buprenorphine); and nerve blocks containing buprenorphine + dexamethasone (perineural). Patients received mepivacaine neuraxial anesthesia and postoperative oxycodone/acetaminophen, meloxicam, pregabalin, and ondansetron. Patients and assessors were blinded to group assignment. The primary outcome was pain with movement at 24 hours. RESULTS: There was no difference in pain with movement at 24 hours (median score, 0). However, the perineural group had longer block duration versus control (45.6 vs 30.0 hours). Perineural patients had lower scores for "worst pain" versus control (median, 0 vs 2). Both IV buprenorphine and perineural groups were less likely to use opioids on the day after surgery versus control (28.6%, 28.6%, and 60.7%, respectively). Nausea after IV buprenorphine (but not perineural buprenorphine) was severe, frequent, and bothersome. CONCLUSIONS: Pain scores were very low at 24 hours after surgery in the context of multimodal analgesia and were not improved by additives. However, perineural buprenorphine and dexamethasone prolonged block duration, reduced the worst pain experienced, and reduced opioid use. Intravenous buprenorphine caused troubling nausea and vomiting. Future research is needed to confirm and extend these observations.

Effects of steroids on thrombogenic markers in patients undergoing unilateral total knee arthroplasty: a prospective, double-blind, randomized controlled trial.

Venous thromboembolism (VTE) remains an important complication after total knee arthroplasty (TKA). Systemic thrombin generation starts perioperatively. Inflammation, characterized by a rise in interleukin-6 (IL6), initiates the coagulation cascade, but low-dose steroids can reduce post-TKA IL6 levels. This double-blinded, randomized, placebo-controlled study enrolled 30 patients undergoing unilateral TKA to assess the effect of perioperative steroids on serum prothrombin fragment (PF1.2), a marker of thrombin generation, and plasmin-alpha-2-antiplasmin complex (PAP), a marker of fibrinolysis. Study patients received 100 mg of intravenous hydrocortisone 2 h prior to surgery, and controls received normal saline. Blood samples, drawn pre-incision and at 4 h post tourniquet release, were assayed for PF1.2 and PAP. The study group had significantly lower mean PF1.2 at 4 h compared to controls (616 ± 358 pMol/L vs. 936 ± 332 pMol/L, p = 0.037). The mean rise in PF1.2 in the control group was significantly greater compared to the study group (672 ± 173 pMol/L vs. 350 ± 211 pMol/L, p < 0.001). Mean PAP was higher in the study group at 4 h (1639 ± 823 µg/L vs. 1087 ± 536 µg/L), but did not reach statistical significance (p = 0.07). These results may have clinical implications in terms of postoperative VTE risk and management.