Comparing modalities of opioid education in patients undergoing total knee arthroplasty: a randomized pilot trial.

BACKGROUND: Patients undergoing total knee arthroplasty (TKA) experience significant postoperative pain and routinely require opioids, yet they often lack knowledge regarding appropriate use and handling of these medications. Evidence suggests that educational interventions in various formats may help reinforce proper usage and improve postoperative pain control. The aim of this study is to compare the institution standard of care (webinar) with two novel educational interventions-one in-person and the other a video recording-that focus specifically on the use of opioids and pain control. METHODS: This prospective, randomized pilot study included 42 patients undergoing TKA. Patients were randomized into one of three groups: (1) webinar: 50 min virtual session standard of care at Hospital for Special Surgery (HSS), (2) in-person education, or (3) video education. The primary outcomes of this study were the number of opioid refill requests through postoperative day (POD) 30 and POD 60. The secondary outcomes evaluated Numerical Rating Scale (NRS) pain scores, opioid consumption in oral morphine equivalents (OME), surveys on medication usage and opioid knowledge, reported medication storage and disposal. We hypothesize that the novel educational interventions, presented either in-person or by video, will lead to a decrease in opioid refills within 60 days compared with current education delivered through virtual webinar. RESULTS: No significant differences were found among groups in the number of opioid refill requests, average NRS pain score, or OME consumption at any time point. Opioid refill requests ranged from 0% to 16.7% at POD 30 (Fisher's exact test, p=0.625) and from 0% to 8.3% at POD 60 (p=1.000). The median opioid refill request was zero requests per group from POD 21 to 60 (webinar 0 (0.0, 0.0), in-person 0 (0.0, 0.0), video 0 (0.0, 0.0), Kruskal-Wallis test, p=0.381). Average NRS pain scores were 5 or below for all groups on POD 1, 7 and 14. By POD 7, all groups had an average daily intake OME of 14 or below. CONCLUSIONS: Overall, patients in each group did well with postoperative pain management after TKA and had minimal opioid refill requests. There were no statistically significant differences in outcomes of NRS pain scores or opioid usage among groups suggesting that educational interventions were similarly effective. As a pilot trial, study demonstrated successful recruitment and retention of participants, and important feedback was elicited from patients regarding education, as well. Of note, this was a pilot study and was likely underpowered to detect a difference. TRIAL REGISTRATION NUMBER: NCT05593341.

Preoperative Cannabis Use Did Not Increase Opioid Utilization After Primary Total Knee Arthroplasty in a Propensity Score-Matched Model.

Background: Recreational and medicinal cannabis use is becoming increasingly popular, but there are little data on its effect on postoperative pain and opioid consumption after primary total knee arthroplasty (TKA). Purpose: We sought to evaluate the relationship between self-reported preoperative cannabis use and postoperative opioid consumption and post-discharge opioid prescriptions following elective primary TKA. Methods: We identified all patients who underwent unilateral, primary TKA for a diagnosis of osteoarthritis at a single institution between February 1, 2019, and April 30, 2021, and subdivided them into current cannabis users and non-users based on self-reported data. Regular users were propensity score-matched 1:6 with non-users using logistic regression on age, sex, body mass index (BMI), history of chronic pain, smoking status, history of anxiety/depression, American Society of Anesthesiology (ASA) classification, and type of anesthesia. Outcomes of interest included median inpatient (total, daily, and hourly) morphine milligram equivalents (MMEs), discharge MMEs, and outpatient MMEs within 90 days after surgery. Results: A cohort of 70 current cannabis users was matched with 420 non-users. There were no significant differences in opioid use in inpatient MMEs (hourly, daily, or total), discharge MMEs, or outpatient MMEs between cohorts. Also, there was no significant difference in hospital stay between cohorts. Conclusion: In this retrospective propensity score-matched model, preoperative cannabis use did not independently increase opioid use post-TKA in the inpatient or outpatient setting when compared with non-use. More rigorous, prospective study is warranted.

An Overview of Cannabidiol.

Cannabidiol (CBD) is one of the most interesting constituents of cannabis, garnering significant attention in the medical community in recent years due to its proven benefit for reducing refractory seizures in pediatric patients. Recent legislative changes in the United States have made CBD readily available to the general public, with up to 14% of adults in the United States having tried it in 2019. CBD is used to manage a myriad of symptoms, including anxiety, pain, and sleep disturbances, although rigorous evidence for these indications is lacking. A significant advantage of CBD over the other more well-known cannabinoid delta-9-tetrahydroncannabinol (THC) is that CBD does not produce a "high." As patients increasingly self-report its use to manage their medical conditions, and as the opioid epidemic continues to drive the quest for alternative pain management approaches, the aims of this narrative review are to provide a broad overview of the discovery, pharmacology, and molecular targets of CBD, its purported and approved neurologic indications, evidence for its analgesic potential, regulatory implications for patients and providers, and future research needs.

Legal and Regulatory Aspects of Medical Cannabis in the United States.

Federal and state laws in the United States governing the use of cannabis are rapidly evolving. Under federal law, marijuana and its derivatives remain schedule I, defined as substances having no currently accepted medical use and a high potential for abuse. Hemp and its derivatives, in contrast, have been removed from schedule I. At the state level, a majority of states have passed laws legalizing cannabis in some form, although these laws vary from state to state in terms of the extent to which use is permitted, approved medical uses, and the types of regulation placed on commercial activity and quality control. This inconsistency has contributed to uncertainty among medical providers and their patients. In this review, we provide a brief account of the evolution and current state of federal and state laws and regulatory agencies involved in overseeing medical cannabis use in the United States.

The Basic Science of Cannabinoids.

The cannabis plant has been used for centuries to manage the symptoms of various ailments including pain. Hundreds of chemical compounds have been identified and isolated from the plant and elicit a variety of physiological responses by binding to specific receptors and interacting with numerous other proteins. In addition, the body makes its own cannabinoid-like compounds that are integrally involved in modulating normal and pathophysiological processes. As the legal cannabis landscape continues to evolve within the United States and throughout the world, it is important to understand the rich science behind the effects of the plant and the implications for providers and patients. This narrative review aims to provide an overview of the basic science of the cannabinoids by describing the discovery and function of the endocannabinoid system, pharmacology of cannabinoids, and areas for future research and therapeutic development as they relate to perioperative and chronic pain medicine.

Patients Undergoing Primary, Cementless TKA had Similar Pain, Opioid Utilization, and Functional Outcomes Compared to Matched Patients With Cemented Fixation.

BACKGROUND: Despite renewed interest in cementless fixation of total knee implants, many surgeons have anecdotal concerns about slower recovery and higher early pain scores. We sought to analyze 90-day opioid utilizations, inhospital pain scores, and patient-reported outcome measures (PROMs) in patients undergoing primary cemented versus cementless total knee arthroplasty (TKA). METHODS: We retrospectively identified a cohort of opioid naïve patients undergoing primary TKA for osteoarthritis. There were 186 patients who had cementless TKAs matched 1:6 with 1,116 who received a cemented TKAs based on age (±6 years), body mass index (BMI) (±5), and sex. We compared inhospital pain scores, 90-day opioid utilizations in morphine milligram equivalents (MMEs), and early postoperative PROMs. RESULTS: The cemented and cementless cohorts had similar lowest (0.09 versus 0.08), highest (7.36 versus 7.34), and average (3.26 versus 3.27) pain scores using numeric rating scale (P > .05). They received similar inhospital (90 versus 102, P = .176), discharge (315 versus 315, P = .483), and total (687 versus 720, P = .547) MMEs. They had similar average inpatient hourly opioid consumption (2.5 versus 2.5 MMEs/hour, P = .965). Average refills 90 days postoperatively were similar in both cohorts (1.5 versus 1.4 refills, P = .893). Also, preoperative, 6-week, 3-month, delta 6-week, and delta 3-month PROMs scores were similar between cemented and cementless cohorts (P > .05) CONCLUSION: This matched study demonstrated similar in-hospital pain scores and opioid utilization, total MMEs prescribed within 90 days, and PROMs at 6 weeks and 3 months postoperatively between cemented and cementless TKAs. LEVEL OF EVIDENCE: III, retrospective cohort study.

Patient perceptions of pain management and opioid use prior to hip arthroplasty.

OBJECTIVE: Qualitative assessment investigating patients' perceptions related to opioids including their role in pain control, risks, and handling and disposal prior to undergoing hip replacement. DESIGN: A prospective, cross-sectional survey study. SETTING: Large urban teaching hospital specializing in orthopedic surgery affiliated with Weill Cornell Medical College. PARTICIPANTS: Patients aged 18-80, English-speaking, without recent or chronic opioid use, and planning to undergo primary total hip replacement. A total of 128 patients were enrolled and completed the study. INTERVENTION: A 27-item interview evaluating perceptions on opioid-related -topics. MAIN OUTCOME MEASURES: Responses to interview questions were documented by research assistant. RESULTS: Most patients believe that there should be minimal or no pain with the use of opioids, though they also agree that opioids should be limited to pain that interferes with function or activity. Patients generally appreciate risks of addiction with opioids but are less familiar with risks associated with sleep apnea and sedatives. Minority of patients understand that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in combination with opioids would effectively reduce pain. Majority of patients were unsure of how to properly store and dispose of opioids. CONCLUSIONS: Qualitative assessment demonstrates that patients may benefit from education and discussion specifically about pain expectations, the role of opioids in treating pain, multimodal analgesia, and proper storage and disposal.

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.

Preoperative cannabis use does not increase opioid utilization following primary total hip arthroplasty in a propensity matched analysis.

PURPOSE: The recreational and medical use of cannabis is being legalized worldwide. Its use has been linked to an increased risk of developing opioid use disorders. As opioids continue to be prescribed after total hip arthroplasty (THA), the influence that preoperative cannabis use may have on postoperative opioid consumption remains unknown. The purpose of this study was to assess the relationship between preoperative cannabis use and opioid utilization following primary THA. METHODS: We identified all patients over the age of 18 who underwent unilateral, primary THA for a diagnosis of osteoarthritis at a single institution from February 2019 to April 2021. Our cohort was grouped into current cannabis users (within 6 months of surgery) and those who reported never using cannabis. One hundred and fifty-six current users were propensity score matched 1:6 with 936 never users based on age, sex, BMI, history of chronic pain, smoking status, history of anxiety/depression, ASA classification and type of anesthesia. Outcomes included inpatient and postdischarge opioid use in morphine milligram equivalents. RESULTS: Total inpatient opioid utilization, opioids refilled, and total opioids used within 90 postoperative days were similar between the groups. CONCLUSION: In propensity score matched analyses, preoperative cannabis use was not independently associated with an increase in inpatient or outpatient, 90-days opioid consumption following elective THA.

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.

Cannabis and Cannabinoids in the Perioperative Period.

Cannabis use is increasingly common, and with a growing number of jurisdictions implementing legalization frameworks, it is likely that providers will encounter more patients who use cannabis. Therefore, it is important for providers to understand the implications of cannabis use and practical considerations for the perioperative period. Cannabis affects multiple organ systems and may influence intraoperative anesthesia, as well as postoperative pain management. The effects of cannabis and key anesthetic considerations are reviewed here.

Effectiveness of Perioperative Opioid Educational Initiatives: A Systematic Review and Meta-Analysis.

BACKGROUND: Opioids are the most commonly prescribed analgesics in the United States. Current guidelines have proposed education initiatives to reduce the risk of chronic opioid consumption, yet there is lack of efficacy data on such interventions. Our study evaluates the impact of perioperative opioid education on postoperative opioid consumption patterns including opioid cessation, number of pills consumed, and opioid prescription refills. METHODS: The MEDLINE/PubMed, Embase, Cochrane Library, Scopus, and Google Scholar databases were systematically searched for randomized controlled trials (RCTs) assessing the impact of perioperative educational interventions (using either paper- or video-based instruments regarding pain management and drug-induced side effects) on postoperative opioid patterns compared to standard preoperative care among patients undergoing elective surgery. Our end points were opioid consumption (number of pills used), appropriate disposal of unused opioids, opioid cessation (defined as no use of opioids), and opioid refills within 15 days, 6 weeks, and 3 months. RESULTS: In total, 11 RCTs fulfilled the inclusion criteria, totaling 1604 patients (804 received opioid education, while 800 received standard care). Six trials followed patients for 15 days after surgery, and 5 trials followed patients up to 3 months. After 15 days, the opioid education group consumed a lower number of opioid pills than those in the control group (weighted mean difference [WMD], -3.39 pills; 95% confidence interval [CI], -6.40 to -0.37; P =.03; I2 = 69%) with no significant difference in overall opioid cessation (odds ratio [OR], 0.25; 95% CI, 0.04-1.56; P = .14; I2 = 83%). Likewise, perioperative opioid education did not have significant effects on opioid cessation at 6 weeks (OR, 0.69; 95% CI, 0.45-1.05; P = .10; I2 = 0%) and 3 months (OR, 0.59; 95% CI,0.17-2.01; P = .10; I2 = 0%) after surgery, neither reduced the need for opioid refills at 15 days (OR, 0.57; 95% CI, 0.28-1.15; P = .12; I2 = 20%) and 6 weeks (OR, 1.08; 95% CI, 0.59-1.98; P = .80; I2 = 37%). There was no statistically significant difference in the rate of appropriate disposal of unused opioids between both groups (OR, 1.99; 95% CI, 0.66-6.00; P = .22; I2 = 71%). Subgroup analysis by type of educational intervention showed a statistical reduction of opioid consumption at 15 days when implementing multimedia/audiovisual strategies (4 trials: WMD, -4.05 pills; 95% CI, -6.59 to -1.50; P = .002; I2 = 45%), but there was no apparent decrease when using only paper-based strategies (2 trials: WMD, -2.31 pills; 95% CI, -12.21 to 7.59; P = .65; I2 = 80%). CONCLUSIONS: Perioperative educational interventions reduced the number of opioid pills consumed at 15 days but did not demonstrate a significant effect on opioid cessation or opioid refills at 15 days, 6 weeks, and 3 months. Further randomized trials should focus on evidence-based educational interventions with strict homogeneity of material to draw a more definitive recommendation.

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.

BDNF produced by cerebral microglia promotes cortical plasticity and pain hypersensitivity after peripheral nerve injury.

Peripheral nerve injury-induced mechanical allodynia is often accompanied by abnormalities in the higher cortical regions, yet the mechanisms underlying such maladaptive cortical plasticity remain unclear. Here, we show that in male mice, structural and functional changes in the primary somatosensory cortex (S1) caused by peripheral nerve injury require neuron-microglial signaling within the local circuit. Following peripheral nerve injury, microglia in the S1 maintain ramified morphology and normal density but up-regulate the mRNA expression of brain-derived neurotrophic factor (BDNF). Using in vivo two-photon imaging and Cx3cr1CreER;Bdnfflox mice, we show that conditional knockout of BDNF from microglia prevents nerve injury-induced synaptic remodeling and pyramidal neuron hyperactivity in the S1, as well as pain hypersensitivity in mice. Importantly, S1-targeted removal of microglial BDNF largely recapitulates the beneficial effects of systemic BDNF depletion on cortical plasticity and allodynia. Together, these findings reveal a pivotal role of cerebral microglial BDNF in somatosensory cortical plasticity and pain hypersensitivity.