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.

Association of circulating gene expression signatures with stiffness following total knee arthroplasty for osteoarthritis: a pilot study.

A subset of patients undergoing total knee arthroplasty (TKA) for knee osteoarthritis develop debilitating knee stiffness (reduced range of motion) for poorly understood reasons. Dysregulated inflammatory and immune responses to surgery correlate with reduced surgical outcomes, but the dysregulated gene signatures in patients with stiffness after TKA are poorly defined. As a consequence, we are limited in our ability to identify patients at risk of developing poor surgical outcomes and develop preventative approaches. In this pilot study we aimed to identify perioperative blood gene signatures in patients undergoing TKA for knee osteoarthritis and its association with early surgical outcomes, specifically knee range of motion. To do this, we integrated clinical outcomes collected at 6 weeks after surgery with transcriptomics analyses in blood samples collected immediately before surgery and at 24 h after surgery. We found that patients with stiffness at 6 weeks after surgery have a more variable and attenuated circulating gene expression response immediately after surgery. Our results suggest that patients with stiffness following TKA may have distinct gene expression signatures detectable in peripheral blood in the immediate postoperative period.

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.

Identification of biological risk factors for persistent postoperative pain after total knee arthroplasty.

BACKGROUND: There is growing evidence that cytokines and adipokines are associated with osteoarthritis (OA) severity, progression, and severity of associated pain. However, the cytokine response to total knee arthroplasty (TKA) and its association with persistent postoperative pain is not well understood. This study aims to describe the perioperative systemic (plasma) and local (synovial fluid) cytokine profiles of patients who do and do not develop persistent pain after TKA. METHODS: Patients undergoing primary unilateral TKA for end-stage OA were prospectively enrolled. Demographic and clinical data were gathered preoperatively and postoperatively. Synovial fluid was collected pre arthrotomy and plasma was collected at multiple time points before and after surgery. Persistent postoperative pain (PPP) was defined as Numerical Rating Score≥4 at 6 months. Cytokine levels were measured using the V-Plex Human Cytokine 30-Plex Panel (Mesoscale-Rockville, Maryland, USA). Cytokine levels were compared between PPP and minimal pain groups. Given that the study outcomes are exploratory, no adjustment was performed for multiple testing. RESULTS: Incidence of persistent pain at 6 months post TKA was 15/162 (9.3%). Postoperative plasma levels of four cytokines were significantly different in patients who developed persistent postoperative pain: interleukin (IL)-10, IL-1ß, vascular endothelial growth factor, and IL12/IL23p40. Significantly lower IL-10 levels in the prearthrotomy synovial fluid were associated with development of postoperative persistent pain. CONCLUSIONS: This prospective cohort study described a distinct acute perioperative inflammatory response profile in patients who developed persistent post-TKA pain, characterized by significant differences in four cytokines over the first 2 postoperative days. These results support the growing evidence that the patient-specific biologic response to surgery may influence longer-term clinical outcomes after TKA. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT02626533.

Controlled hypotension during neuraxial anesthesia is not associated with increased odds of in-hospital common severe medical complications in patients undergoing elective primary total hip arthroplasty - A retrospective case control study.

INTRODUCTION: The use of controlled hypotension during neuraxial anesthesia for joint arthroplasty is controversial. We conducted a large institutional database analysis to assess common in-hospital complications and mortality of patients undergoing primary total hip arthroplasty (THA) under controlled hypotension and neuraxial anesthesia. METHODS: We conducted a large retrospective case control study of 11,292 patients who underwent primary THA using neuraxial anesthesia between March 2016 and May 2019 in a single institution devoted to musculoskeletal care. The degree and duration of various mean arterial pressure (MAP) thresholds were analyzed for adjusted odds ratios with composite common severe complications (in-hospital myocardial infarction, stroke, and/or acute kidney injury) as the primary outcome. RESULTS: Sixty-eight patients developed common severe complications (0.60%). Patients with complications were older (median age 75.6 vs 64.0 years) and had a higher American Society of Anesthesiologists (ASA) classification (45.6% vs 17.6% ASA III). The duration of hypotension at various MAP thresholds (45 to 70 mm Hg) was not associated with increasing odds of common severe medical complications. CONCLUSIONS: Controlled hypotension (ranging from 45 to 70 mmHg) for a moderate duration during neuraxial anesthesia was not associated with increased odds of common severe complications (myocardial infarction, stroke, and/or acute kidney injury) among patients receiving neuraxial anesthesia for elective THA.

A Comprehensive Enhanced Recovery Pathway for Rotator Cuff Surgery Reduces Pain, Opioid Use, and Side Effects.

BACKGROUND: Patients often have moderate to severe pain after rotator cuff surgery, despite receiving analgesics and nerve blocks. There are many suggested ways to improve pain after rotator cuff surgery, but the effects of adopting a pathway that includes formal patient education, a long-acting nerve block, and extensive multimodal analgesia are unclear. QUESTIONS/PURPOSES: (1) Does adoption of a clinical pathway incorporating patient education, a long-acting nerve block, and preemptive multimodal analgesia reduce the worst pain during the first 48 hours after surgery compared with current standard institutional practices? (2) Does adoption of the pathway reduce opioid use? (3) Does adoption of the pathway reduce side effects and improve patient-oriented outcomes? METHODS: From September 2018 to January 2020, 281 patients scheduled for arthroscopic ambulatory rotator cuff surgery were identified for this paired sequential prospective cohort study. Among patients in the control group, 177 were identified, 33% (58) were not eligible, for 11% (20) staff was not available, 56% (99) were approached, 16% (29) declined, 40% (70) enrolled, and 40% (70) were analyzed (2% [4] lost to follow-up for secondary outcomes after postoperative day 2). For patients in the pathway cohort, 104 were identified, 17% (18) were not eligible, for 11% (11) staff was not available, 72% (75) were approached, 5% (5) declined, 67% (70) enrolled, and 67% (70) were analyzed (3% [3] lost to follow-up for secondary outcomes after postoperative day 2). No patients were lost to follow-up for primary outcome; for secondary outcomes, four were lost in the control group and three in the pathway group after postoperative day 2 (p = 0.70). The initial 70 patients enrolled received routine care (control group), and in a subsequent cohort, 70 patients received care guided by a pathway (pathway group). Of the 205 eligible patients, 68% (140) were included in the analysis. This was not a study comparing two tightly defined protocols but rather a study to determine whether adoption of a pathway would alter patient outcomes. For this reason, we used a pragmatic (real-world) study design that did not specify how control patients would be treated, and it did not require that all pathway patients receive all components of the pathway. We developed the pathway in coordination with a group of surgeons and anesthesiologists who agreed to apply the pathway as much as was viewed practical for each individual patient. Patients in both groups received a brachial plexus nerve block with sedation. Major differences between the pathway and control groups were: detailed patient education regarding reasonable pain expectations with a goal of reducing opioid use (no formal educational presentation was given to the control), a long-acting nerve block using bupivacaine with dexamethasone (control patients often received shorter-acting local anesthetic without perineural dexamethasone), and preemptive multimodal analgesia including intraoperative ketamine, postoperative acetaminophen, NSAIDs, and gabapentin at bedtime, with opioids as needed (control patients received postoperative opioids but most did not get postoperative NSAIDS and no controls received gabapentin or separate prescriptions for acetaminophen). The primary outcome was the numerical rating scale (NRS) worst pain with movement 0 to 48 hours after block placement. The NRS pain score ranges from 0 (no pain) to 10 (worst pain possible). The minimum clinically important difference (MCID) [12] for NRS that was used for calculation of the study sample size was 1.3 [18], although some authors suggest 1 [13] or 2 [5] are appropriate; if we had used an MCID of 2, the sample size would have been smaller. Secondary outcomes included NRS pain scores at rest, daily opioid use (postoperative day 1, 2, 7, 14), block duration, patient-oriented pain questions (postoperative day 1, 2, 7, 14), and patient and physician adherence to pathway. RESULTS: On postoperative day 1, pathway patients had lower worst pain with movement (3.3 ± 3.1) compared with control patients (5.6 ± 3.0, mean difference -2.7 [95% CI -3.7 to -1.7]; p < 0.001); lower scores were also seen for pain at rest (1.9 ± 2.3 versus 4.0 ± 2.9, mean difference -2.0 [95% CI -2.8 to -1.3]; p < 0.001). Cumulative postoperative opioid use (0-48 hours) was reduced (pathway oral morphine equivalent use was 23 ± 28 mg versus 44 ± 35 mg, mean difference 21 [95% CI 10 to 32]; p < 0.01). The greatest difference in opioid use was in the first 24 hours after surgery (pathway 7 ± 12 mg versus control 21 ± 21 mg, mean difference -14 [95% CI -19 to -10]; p < 0.01). On postoperative day 1, pathway patients had less interference with staying asleep compared with control patients (0.5 ± 1.6 versus 2.6 ± 3.3, mean difference -2.2 [95% CI -3.3 to -1.1]; p < 0.001); lower scores were also seen for interference with activities (0.9 ± 2.3 versus 1.9 ± 2.9, mean difference -1.1 [95% CI -2 to -0.1]; p = 0.03). Satisfaction with pain treatment on postoperative day 1 was higher among pathway patients compared with control patients (9.2 ± 1.7 versus 8.2 ± 2.5, mean difference 1.0 [95% CI 0.3 to 1.8]; p < 0.001). On postoperative day 2, pathway patients had lower nausea scores compared with control patients (0.3 ± 1.1 versus 1 ± 2.1, mean difference -0.7 [95% CI -1.2 to -0.1]; p = 0.02); lower scores were also seen for drowsiness on postoperative day 1 (1.7 ± 2.7 versus 2.6 ± 2.6, mean difference -0.9 [95% CI - 1.7 to -0.1]; p = 0.03). CONCLUSION: Adoption of the pathway was associated with improvement in the primary outcome (pain with movement) that exceeded the MCID. Patients in the pathway group had improved patient-oriented outcomes and fewer side effects. This pathway uses multiple analgesic drugs, which may pose risks to elderly patients, in particular. Therefore, in evaluating whether to use this pathway, clinicians should weigh the effect sizes against the potential risks that may emerge with large scale use, consider the difficulties involved in adapting a pathway to local practice so that pathway will persist, and recognize that this study only enrolled patients among surgeons and the anesthesiologists that advocated for the pathway; results may have been different with less enthusiastic clinicians. This pathway, based on a long-lasting nerve block, multimodal analgesia, and patient education can be considered for adoption. LEVEL OF EVIDENCE: Level II, therapeutic study.

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.

Clinical Experience with COVID-19 at a Specialty Orthopedic Hospital Converted to a Pandemic Overflow Field Hospital.

BACKGROUND: COVID-19, the illness caused by the novel coronavirus, SARS-CoV-2, has sickened millions and killed hundreds of thousands as of June 2020. New York City was affected gravely. Our hospital, a specialty orthopedic hospital unaccustomed to large volumes of patients with life-threatening respiratory infections, underwent rapid adaptation to care for COVID-19 patients in response to emergency surge conditions at neighboring hospitals. PURPOSES: We sought to determine the attributes, pharmacologic and other treatments, and clinical course in the cohort of patients with COVID-19 who were admitted to our hospital at the height of the pandemic in April 2020 in New York City. METHODS: We conducted a retrospective observational cohort study of all patients admitted between April 1 and April 21, 2020, who had a diagnosis of COVID-19. Data were gathered from the electronic health record and by manual chart abstraction. RESULTS: Of the 148 patients admitted with COVID-19 (mean age, 62 years), ten patients died. There were no deaths among non-critically ill patients transferred from other hospitals, while 26% of those with critical illness died. A subset of COVID-19 patients was admitted for orthopedic and medical conditions other than COVID-19, and some of these patients required intensive care and ventilatory support. CONCLUSION: Professional and organizational flexibility during pandemic conditions allowed a specialty orthopedic hospital to provide excellent care in a global public health emergency.

Tranexamic acid administration during total joint arthroplasty surgery is not associated with an increased risk of perioperative seizures: a national database analysis.

BACKGROUND: Tranexamic acid (TXA) has been used extensively to minimize blood loss in cardiac surgery and more recently in orthopedic surgery. Despite a generally good safety profile, an increased risk of seizures has been observed in patients with cardiac disease. However, this issue has not been adequately addressed in the orthopedic literature. METHODS: After institutional review board approval, we queried a large national database to identify patients who had undergone total hip and total knee arthroplasties (2012-2016). Patients were divided based on their exposure to TXA and history of seizures. The main outcome of interest was a perioperative seizure. We conducted univariable comparisons and a multivariable regression analysis to elucidate a potential independent association between TXA administration and seizures in the perioperative period (with or without a history of seizures). RESULTS: TXA was used overall in 45.9% (n=4 21 890) of joint arthroplasty recipients (n=9 18 918), with more frequent use over time. Utilization rates did not differ between those with and without a history of seizures; 42.2% (3487/8252) of patients with a seizure history received TXA. Rates of perioperative seizure were low and did not differ between those who did and did not receive TXA (0.01% vs 0.02%, p=0.11); when subgrouping patients by history of seizures, we found no difference in incidence of perioperative seizures between groups (0.06% vs 0.02%, p=0.39). Our adjusted analysis further confirmed these results. CONCLUSION: Despite increasing TXA utilization in total joint arthroplasty, we found an overall low seizure incidence. TXA use was not associated with elevated odds of perioperative seizure, even in patients with history of seizure.

Postoperative Serum Cytokine Levels Are Associated With Early Stiffness After Total Knee Arthroplasty: A Prospective Cohort Study.

BACKGROUND: Inflammatory cytokines have been implicated in organ fibrosis; however, their role in the development of arthrofibrosis after total knee arthroplasty (TKA) has not been well explored. The purpose of this study is to assess whether perioperative synovial fluid or blood plasma cytokine levels are associated with reduced early post-TKA range of motion. METHODS: A total of 179 patients with end-stage idiopathic osteoarthritis undergoing TKA were enrolled in this prospective cohort study. Synovial fluid and blood plasma were collected prearthrotomy and plasma was collected longitudinally in the postacute care unit and on postoperative days (PODs) 1 and 2. Stiffness was defined as ≤95° range of motion measured with a goniometer at 6 weeks (±2 weeks). RESULTS: Thirty-two of 162 (19.8%) patients analyzed were stiff at 6 weeks postoperatively. Postoperative plasma levels of 9 cytokines (Eotaxin3, IL-5, IL12_23p40, IP10, VEGF, IL-7, IL-12p70, IL-16, IL-17a) were significantly different between stiff and nonstiff patients on POD1 and/or POD2. An association between preoperative plasma and synovial fluid cytokine levels and the development of postoperative stiffness was not detected. CONCLUSION: The results of this study suggest that there is a distinct acute postoperative cytokine response profile in patients who develop stiffness 6 weeks after TKA. This profile was characterized by significant differences in levels of 9 cytokines over the first 2 postoperative days. These results identify cytokines that are potential biomarkers for risk of early stiffness after TKA and may play a role in the pathophysiology of this outcome.

Integrating complementary medicine in the perioperative period: a simple, opioid-sparing addition to your multimodal analgesia strategy?

The current US opioid health-related crisis underscores the importance for perioperative physicians to optimize various approaches to pain management. Multimodal techniques and enhanced recovery after surgery (ERAS) protocols are frequently cited as the most effective strategies for improving the experience of pain and reducing opioid exposure. Complementary medicine (CM) techniques, while frequently shown to be effective at reducing opioid and other pharmacologic agent use, are rarely discussed as part of these multimodal strategies. In general, CM therapies are low-cost with minimal associated risk, making them an ideal choice for incorporation into ERAS and other opioid-sparing protocols. In this Daring Discourse, we discuss the benefits and challenges of incorporating CM therapy into anesthetic practice. We hope that anesthesiologists can become more familiar with the current evidence regarding perioperative CM therapy, and begin incorporating these therapies as part of their comprehensive multimodal approach to perioperative pain management.

Focused assessment with sonography in trauma (FAST) for the regional anesthesiologist and pain specialist.

This article in our point-of-care ultrasound (PoCUS) series is dedicated to the role the focused assessment with sonography in trauma (FAST) exam plays for the regional anesthesiologist and pain specialists in the perioperative setting. The FAST exam is a well-established and extensively studied PoCUS exam in both surgical and emergency medicine literature with over 20 years demonstrating its benefit in identifying the presence of free fluid in the abdomen following trauma. However, only recently has the FAST exam been shown to be beneficial to the anesthesiologist in the perioperative setting as a means to identify the extravasation of free fluid into the abdomen from the hip joint following hip arthroscopy. In this article, we will describe how to obtain the basic FAST views (subcostal four-chamber view, perihepatic right upper quadrant view, perisplenic left upper quadrant view, and pelvic view in the longitudinal and short axis) as well as cover the relevant sonoanatomy. We will describe pathological findings seen with the FAST exam, primarily free fluid in the peritoneal space as well as in the pericardial sac. As is the case with any PoCUS skill, the application evolves with understanding and utilization by new clinical specialties. Although this article will provide clinical examples of where the FAST exam is beneficial to the regional anesthesiologist and pain specialist, it also serves as an introduction to this powerful PoCUS skill in order to encourage clinical practitioners to expand the application of the FAST exam within the scope of regional anesthesia and pain management practice.

Teaching a Point-of-Care Ultrasound Curriculum to Anesthesiology Trainees With Traditional Didactic Lectures or an Online E-Learning Platform: A Pilot Study.

BACKGROUND: Point-of-care ultrasonography (PoCUS) provides real-time, dynamic clinical evidence for providers to make potentially lifesaving medical decisions; however, these tools cannot be used effectively without appropriate training. Although there is always the option of traditional didactic methods, there has been a recent trend toward a "reverse classroom" web-based model using online e-learning modules. Our objective was to collect pilot data that would justify a future randomized controlled trial, comparing traditional didactics to an e-learning PoCUS curriculum for lung ultrasonography (LUS) and the focused assessment with sonography in trauma (FAST) exam. METHODS: Anesthesiology interns, residents (CA 1-3), and fellow trainees enrolled in a LUS and FAST exam course and were randomized to receive didactic lectures or e-learning. Trainees completed knowledge pre- and posttests. Surveys were administered to gauge learning satisfaction. All trainees completed a hands-on-training (HOT) workshop. Image acquisition was assessed through practical tests before HOT, immediately after HOT, and 5 months later. RESULTS: Eighteen trainees completed the study. There was no evidence of a difference in change in LUS knowledge test score from baseline to posttest between the e-learning and didactic groups (difference in median percentage point change [95 % CI]: 6.6 [-10.0, 23.2]; P = .411). There was no evidence of a difference in LUS knowledge posttest scores (difference in median percentage points [95% CI]: -0.9 [-4.8, 3.0]; P = .629), FAST knowledge posttest score (0 [incalculable]; P = .999), or post-HOT practical test score (-4.2 [-24.6, 16.3]; P = .672) between groups. There was no evidence of a difference in degree of satisfaction with learning experience between groups (odds ratios [95% CI]: 1.75 [0.31, 9.94]; P = .528). CONCLUSIONS: There was no evidence of a difference between the e-learning and traditional didactic groups in learning or satisfaction outcomes. These results justify establishing an adequately powered, randomized controlled trial assessing the noninferiority of e-learning to traditional didactics for teaching LUS and FAST.

A Review of Opioid-Sparing Modalities in Perioperative Pain Management: Methods to Decrease Opioid Use Postoperatively.

There is an epidemic of opioid use, abuse, and misuse in the United States, which results in significant morbidity and mortality. It may be difficult to reduce perioperative opioid use given known acute surgical trauma and resultant pain; however, the discrete and often limited nature of postoperative pain also may make management easier in part by utilizing nonopioid modalities, such as regional anesthesia/analgesia, and multimodal analgesia, which may decrease the need for powerful opioids. This article reviews the relevant literature describing the use of adjunct medications, regional anesthesia and analgesic techniques, and regional block additives in the context of providing adequate pain control while lessening opioid use.

Local Anesthetic Peripheral Nerve Block Adjuvants for Prolongation of Analgesia: A Systematic Qualitative Review.

BACKGROUND: The use of peripheral nerve blocks for anesthesia and postoperative analgesia has increased significantly in recent years. Adjuvants are frequently added to local anesthetics to prolong analgesia following peripheral nerve blockade. Numerous randomized controlled trials and meta-analyses have examined the pros and cons of the use of various individual adjuvants. OBJECTIVES: To systematically review adjuvant-related randomized controlled trials and meta-analyses and provide clinical recommendations for the use of adjuvants in peripheral nerve blocks. METHODS: Randomized controlled trials and meta-analyses that were published between 1990 and 2014 were included in the initial bibliographic search, which was conducted using Medline/PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Only studies that were published in English and listed block analgesic duration as an outcome were included. Trials that had already been published in the identified meta-analyses and included adjuvants not in widespread use and published without an Investigational New Drug application or equivalent status were excluded. RESULTS: Sixty one novel clinical trials and meta-analyses were identified and included in this review. The clinical trials reported analgesic duration data for the following adjuvants: buprenorphine (6), morphine (6), fentanyl (10), epinephrine (3), clonidine (7), dexmedetomidine (7), dexamethasone (7), tramadol (8), and magnesium (4). Studies of perineural buprenorphine, clonidine, dexamethasone, dexmedetomidine, and magnesium most consistently demonstrated prolongation of peripheral nerve blocks. CONCLUSIONS: Buprenorphine, clonidine, dexamethasone, magnesium, and dexmedetomidine are promising agents for use in prolongation of local anesthetic peripheral nerve blocks, and further studies of safety and efficacy are merited. However, caution is recommended with use of any perineural adjuvant, as none have Food and Drug Administration approval, and concerns for side effects and potential toxicity persist.

Impact of Melatonin on Sleep and Pain After Total Knee Arthroplasty Under Regional Anesthesia With Sedation: A Double-Blind, Randomized, Placebo-Controlled Pilot Study.

This pilot study explores sleep disruption after total knee arthroplasty and the impact of melatonin on sleep and postoperative pain. Sleep time was decreased on the last preoperative night and first two postoperative nights. Sleep efficiency was decreased on all three postoperative nights. Compared to placebo, melatonin increased sleep efficiency by 4.4% (mean; 95% CI -1.6, 10.4; P=0.150) and sleep time by 29 min (mean; 95% CI -2.0, 60.4; P=0.067). Melatonin appeared to have no effect on subjective sleep quality or daytime sleepiness, pain at rest or pain with standardized activity. In conclusion, sleep quality is impaired after total knee arthroplasty and exogenous melatonin does not appear to improve postoperative sleep or pain to a significant degree.