Characterizing acute and postsurgical pain management in patients receiving buprenorphine or buprenorphine/naloxone.

BACKGROUND: There is currently a clinical dilemma in treating acute pain in patients receiving long-term buprenorphine products. METHODS: This is a retrospective cohort review involving patients receiving long-term buprenorphine therapy who either underwent a surgical procedure or presented to an emergency department (ED) for acute pain between January 1, 2012 and January 1, 2022. Patients were excluded if opioids were prescribed 30 days before the index date. Chart reviews were conducted to characterize buprenorphine treatment strategies and the addition of new pain medications. Chart review revealed (1) incidence of opioid use disorder (OUD) relapse, (2) hospital re-presentation for pain or OUD, (3) fatal and non-fatal overdose, and (4) all-cause mortality and suicidality. Descriptive statistics were used to analyze results. RESULTS: A total of 70 of 259 screened patients met inclusion criteria. The mean (±SD) age was 50.3 ± 13 years, 92.9% male, 64.3% White, and 78.6% had an OUD diagnosis. While 84.3% presented to the ED, 15.7% underwent surgical procedures. For the primary endpoint, the total daily dose of buprenorphine or buprenorphine/naloxone from index date to discharge was continued in 90.0%, increased in 2.9%, decreased in 1.4%, and discontinued in 5.7% of cases. At discharge, 46.2% were prescribed an additional pain medication. A total of 7.1% re-presented for pain or OUD relapse, 15.7% experienced an OUD relapse, 1.4% experienced new-onset suicidality, and 1.4% experience all-cause mortality within 90 days of the index date. No fatal or non-fatal opioid overdoses were observed. CONCLUSION: The most commonly observed practice was continuing buprenorphine doses in patients with acute or postsurgical pain, which was effective and safe. Although further data is necessary to fully elucidate these findings, the data herein may suggest that clinicians can safely continue buprenorphine doses in the acute pain setting in patients receiving these products chronically.

Role of memantine in the prophylactic treatment of episodic migraine: A systematic review.

OBJECTIVE: The purpose of this systematic review is to assess the efficacy and safety of memantine for the prophylactic treatment of episodic migraine. BACKGROUND: Migraine is a prevalent chronic disease with significant costs to the health care system. Although various prophylactic treatment options are available, these medications have limitations based on efficacy, potential side effects, and patient preference. Memantine is an N-methyl-d-aspartate receptor antagonist used in dementia treatment that may have potential benefit for migraine prophylaxis. METHODS: A systematic search of PubMed, Embase, and CENTRAL databases was conducted to identify relevant published studies through December 2020 using the search terms: migraine disorders, migraine, headache disorders, or headache and memantine. Studies selected for the systematic review included prospective, interventional designs and evaluated memantine for prophylaxis of migraine. Animal studies, case reports, abstracts, review articles, protocols without results, and studies not written in English were excluded. Data were extracted using a standardized systematic process and included author, publication date, study design, sample size, patient characteristics, treatment regimen, clinical efficacy outcomes, and adverse drug effects. RESULTS: Four articles were identified for inclusion representing two prospective open-label studies and two randomized, double-blind trials, evaluating 183 patients on memantine overall. A reduction in number of migraine days and headache severity were shown in all four studies in the participants treated with memantine. The most common adverse effects included somnolence, sedation, and nausea, none of which were severe. CONCLUSION: The studies in this review establish that memantine has the potential for use as a treatment option for episodic migraine. Additional long-term studies using an active comparator would be useful to further elucidate its role.

Quantifying cumulative anticholinergic and sedative drug load among US Medicare Beneficiaries.

PURPOSE: Medications with anticholinergic and sedative properties are widely used among older adults despite strong evidence of harm. The drug burden index (DBI), a pharmacological screening tool, measures these properties across drug classes, and higher DBI drug exposure (DBI > 1) has been associated with certain physical function-related adverse events. Our aim was to quantify mean daily DBI drug exposure among older adults in the United States (US). METHODS: We screened medications for DBI properties and operationalized the DBI for US Medicare claims. We then conducted a retrospective cohort study of a 20% random, nationwide sample of 4 137 384 fee-for-service Medicare beneficiaries aged 66+ years (134 757 039 person-months) from January 2013 to December 2016. We measured the monthly distribution based on mean daily DBI, categorized as (a) >0 vs 0 (any use) and (b) 0, 0 < DBI ≤ 1, 1 < DBI ≤ 2, and DBI > 2, and examined temporal trends. We described patient-level factors (eg, demographics, healthcare use) associated with high (>2) vs low (0 < DBI≤1) DBI drug exposure. RESULTS: The distribution of the mean daily DBI, aggregated at the month-level, was: 58.1% DBI = 0, 29.0% 0 < DBI≤1, 9.3% 1 < DBI≤2, and 3.7% DBI > 2. Predictors of high monthly DBI drug exposure (DBI > 2) included certain indicators of increased healthcare use (eg, high number of drug claims), white race, younger age, frailty, and a psychosis diagnosis code. CONCLUSIONS: The predictors of high DBI drug exposure can inform discussions between patients and providers about medication appropriateness and potential de-prescribing. Future Medicare-based studies should assess the association between the DBI and adverse events.

Effects of Acetaminophen, NSAIDs, Gabapentinoids, and Their Combinations on Postoperative Pulmonary Complications After Total Hip or Knee Arthroplasty.

OBJECTIVE: Multimodal analgesia has gained popularity in total hip arthroplasty (THA) and total knee arthroplasty (TKA), but large multicenter studies evaluating specific analgesic combinations are lacking. DESIGN: A retrospective study using the Premier Healthcare Database (2009-2014). SUBJECTS: Adults who underwent elective primary THA or TKA. METHODS: We categorized day-of-surgery analgesic exposure using eight mutually exclusive categories: acetaminophen (Ac), nonsteroidal anti-inflammatory drugs (Ns), gabapentinoids (Ga; gabapentin or pregabalin), Ac+Ns, Ac+Ga, Ns+Ga, Ac+Ns+Ga, and none of the three drugs. Multilevel models measured associations of the analgesic categories with a composite of postoperative pulmonary complications (PPCs). RESULTS: Among 863,139 patients, 75.2% received at least one of the three drugs. In multilevel models, compared with none of the three drugs, Ga use was associated with increased odds of PPCs when used alone (adjusted odds ratio [aOR] = 1.35, 95% confidence interval [CI] = 1.27 to 1.44), combined with Ac (aOR = 1.16, 95% CI = 1.08 to 1.26), or combined with Ns (aOR = 1.28, 95% CI = 1.21 to 1.34). In contrast, the Ac+Ns pair was associated with decreased odds of PPCs (OR = 0.86, 95% CI = 0.83 to 0.90) and lower opioid consumption. Ac+Ns+Ga was not associated with PPCs, whereas it was associated with the lowest opioid consumption on the day of surgery. CONCLUSIONS: Gabapentinoids, alone and in single combination with either acetaminophen or nonsteroidal anti-inflammatory drugs, were associated with higher PPCs, whereas the Ac+Ns pair was associated with fewer PPCs and an opioid-sparing effect. Ac+Ns+Ga was not associated with PPCs, whereas it was associated with the lowest opioid consumption on the day of surgery.

Association 'Between Gabapentinoids on the Day of Colorectal Surgery and Adverse Postoperative Respiratory Outcomes.

OBJECTIVE: The aim of this study was to determine the association between gabapentinoids on the day of surgery and adverse postoperative outcomes in patients undergoing colorectal surgery in the United States. BACKGROUND: Gabapentinoids, gabapentin and pregabalin, are recommended in multimodal analgesia protocols for acute postoperative pain management after colorectal surgery. However, current literature focuses on the efficacy in reducing opioid consumption, but provides limited information about adverse risks. METHODS: This was a retrospective study including 175,787 patients undergoing elective colorectal surgery using the Premier database between 2009 and 2014. Multilevel regression models measured associations of receipt of gabapentinoids with naloxone use after surgery, non-invasive ventilation (NIV), invasive ventilation (IMV), hospital length of stay (LOS), and parental morphine equivalents (PMEs) on the day of surgery and on the day before discharge. RESULTS: Overall, 4677 (2.7%) patients received gabapentinoids on the day of surgery, with use doubling (1.7% in 2009 to 4.3% in 2014). Compared with patients who were unexposed to ganapentinoids, gabapentinoid exposure was associated with lower PMEs on the day of surgery [-2.7 mg; 95% confidence interval (CI), -5.2 to -0.0 mg], and with higher odds of NIV [odds ratio (OR) 1.22, 95% CI, 1.00-1.49] and receipt of naloxone (OR 1.58, 95% CI, 1.11-2.26). There was no difference between the groups with respect to IMV or PMEs on the day before discharge. CONCLUSIONS: Although use of gabapentinoids on the day of surgery was associated with slightly lower PMEs on the day of surgery, it was associated with higher odds of NIV and naloxone use after surgery.

Impact of an Opioid Safety Initiative on Patients Undergoing Total Knee Arthroplasty: A Time Series Analysis.

BACKGROUND: The Opioid Safety Initiative decreased high-dose prescriptions across the Veterans Health Administration. This study sought to examine the impact of this intervention (i.e., the Opioid Safety Initiative) on pain scores and opioid prescriptions in patients undergoing total knee arthroplasty. METHODS: This was an ecological study of group-level data among 700 to 850 patients per month over 72 consecutive months (January 2010 to December 2015). The authors examined characteristics of cohorts treated before versus after rollout of the Opioid Safety Initiative (October 2013). Each month, the authors aggregated at the group-level the differences between mean postoperative and preoperative pain scores for each patient (averaged over 6-month periods), and measured proportions of patients (per 1,000) with opioid (and nonopioid) prescriptions for more than 3 months in 6-month periods, preoperatively and postoperatively. The authors compared postintervention trends versus trends forecasted based on preintervention measures. RESULTS: After the Opioid Safety Initiative, patients were slightly older and sicker, but had lower mortality rates (postintervention n = 28,509 vs. preintervention n = 31,547). Postoperative pain scores were slightly higher and the decrease in opioid use was statistically significant, i.e., 871 (95% CI, 474 to 1,268) fewer patients with chronic postoperative prescriptions. In time series analyses, mean postoperative minus preoperative pain scores had increased from 0.65 to 0.81, by 0.16 points (95% CI, 0.05 to 0.27). Proportions of patients with chronic postoperative and chronic preoperative opioid prescriptions had declined by 20% (n = 3,355 vs. expected n = 4,226) and by 13% (n = 5,861 vs. expected n = 6,724), respectively. Nonopioid analgesia had increased. Sensitivity analyses confirmed all findings. CONCLUSIONS: A system-wide initiative combining guideline dissemination with audit and feedback was effective in significantly decreasing opioid prescriptions in populations undergoing total knee arthroplasty, while minimally impacting pain scores.

Freedom From Opioids After Total Knee Arthroplasty.

BACKGROUND: In the United States, opioids are commonly prescribed to treat knee pain after total knee arthroplasty (TKA). While surgery leads to decreased pain in most patients, a sizable minority continue to experience severe pain and consume opioids chronically after TKA. We sought to determine the population-level effect of TKA on opioid consumption by detailing the pattern of opioid prescriptions before and after surgery. METHODS: We retrospectively identified US Veterans Health Administration TKA patients from 2010 to 2015. Outpatient opioid prescriptions were identified from 18 months before to 18 months after surgery, and mean daily opioid doses were calculated. Our primary end point was the achievement of opioid-freedom, defined as a period of at least 6 months without opioids. We compared the percentage of patients who were opioid-free preoperatively to the percentage who were opioid-free 18 months after surgery (no prescriptions after postoperative month 12). We identified factors associated with opioid-freedom. RESULTS: In a cohort of 33,927 patients, 41% were opioid-free in the month before surgery compared to 54% 18 months after surgery (P < .001). Preoperative freedom from opioids (odds ratio, 4.59; 95% confidence interval, 4.34 to 4.85; P < .001) was more strongly associated with postoperative freedom from opioids than patient medical and social factors. CONCLUSION: TKA was associated with an increase in postoperative freedom from opioids. Low preoperative dose of opioids was more strongly associated with postoperative opioid-freedom than patient characteristics, suggesting that opioid prescription patterns are a chief driver of opioid use after surgery. LEVEL OF EVIDENCE III: Retrospective cohort study.

Deprescribing electronic case reviews for older veterans at risk for falls: Effects on drug burden and falls.

BACKGROUND: Falls are the most common medication-related safety event in older adults. Deprescribing fall risk-increasing drugs (FRIDs) may mitigate fall risk. This study assesses the effects of an innovative deprescribing program in reducing FRID burden and falls-related acute visits over 1 year. METHODS: The Falls Assessment of Medications in the Elderly (FAME) Program is a pilot deprescribing program designed to improve medication safety in Veterans aged ≥65, screening positive for high fall risk at the Durham Veterans Affairs Health Care System. Central case finding and electronic case reviews with deprescribing recommendations were completed by an interdisciplinary team, forwarded to prescribers for approval, then implemented during follow-up telephone visits by FAME team. Primary outcome was change in FRID burden calculated by modified Drug Burden Index (DBI) at 1 year and an exploratory outcome was 1-year fall-related acute visits. RESULTS: Overall, 472 patients (236 intervention cases, 236 matched controls) were included in the study. Of the 236 patients receiving a FAME deprescribing plan, 147 had recommendations approved by prescriber and patient. In the intention-to-treat analysis, the 1-year change in modified DBI was -0.15 (95% CI -0.23, -0.08) in the intervention cohort and -0.11 (-0.21, -0.00) in the matched control cohort (p = 0.47). The odds of increasing DBI by a clinically important threshold of 0.5 was significantly lower in the FAME cohort (OR 0.37, 0.21, 0.66). Fall-related acute events occurred in 6.3% of patients in the intervention group versus 11.0% in control patients over a one-year period (p = 0.10). CONCLUSIONS: The program was associated with a significantly lower odds of further increasing FRID burden at 1 year compared to matched controls. An electronic case review and telephone counseling program has the potential to reduce drug-related falls in high-risk older adults.

Resident involvement in cataract surgery at the Veterans Health Administration: complications, case complexity, and the role of experience.

PURPOSE: To characterize intraoperative complications, case complexity, and changes in complication rates with surgical experience for cataract surgeries involving residents at the Veterans Health Administration (VHA). SETTING: All VHA facilities where cataract surgery was performed. DESIGN: Multicenter, retrospective cohort study. METHODS: A retrospective review of all cataract surgeries within the VHA between July 2010 and June 2021 was conducted. Several parameters, including resident involvement, intraoperative complications, and case complexity as determined by Current Procedural Terminology codes, and use of pupil expansion or capsular support devices, were collected. Complication rates were compared between residents and attendings. RESULTS: Of 392 428 cataract surgeries completed across 108 VHA facilities, 90 504 were performed by attendings alone, while 301 924 involved a resident. Of these, 10 244 (11.3%) of attending cases were complex compared with 32 446 (10.7%) of resident cases. Pupil expansion devices were required in 8191 of attending cases (9.05%) and 31 659 (10.5%) of cases involving residents ( P < .001). Similarly, cases involving residents were more likely than attending-only cases to require a capsular support device (0.835% vs 0.586%, P < .001). Cases involving residents were more likely to have posterior capsular rupture (4.75% vs 2.58%, P < .001) and dropped nucleus (0.338% vs 0.198%, P < .001). Higher resident case volumes were associated with significantly lower complication rates for posterior capsular rupture, dropped nucleus, zonular loss, and suprachoroidal hemorrhage. CONCLUSIONS: Although residents had higher intraoperative complication rates than attendings, these rates were reduced with surgical experience. Residents were involved in a similar number of complex surgical cases as attendings.

Development of a specialty medication clinical dashboard to improve tumor necrosis factor-α inhibitor safety and adherence monitoring.

PURPOSE: To describe the development of a pilot specialty medication clinical dashboard targeting tumor necrosis factor (TNF)-α inhibitor therapy. SUMMARY: This was a quality improvement project conducted between August 2019 and April 2020. The dashboard was designed with collaboration between clinical pharmacists and specialty providers in rheumatology, gastroenterology, and dermatology. Data was queried from the Veterans Affairs Corporate Data Warehouse. Patients with an active prescription or intravenous order for a TNF-α inhibitor were included. Dashboard flag criteria focused on TNF-α inhibitor safety and adherence monitoring. Flag results from the dashboard were characterized from data captured at a single time point. For 431 patients on TNF-α inhibitor treatment at the institution, 304 flags corresponding to 223 unique patients (51.7%) were identified on the dashboard: 3% of patients had a new infection, 9% had overdue monitoring laboratory tests, 5% had a critical laboratory result, 2% were on 2 biologic agents, 27% were overdue for a refill, 6% had an emergency department visit, and 2% had an inpatient admission. No patients were flagged for heart failure exacerbation or new malignancy. Seventeen percent of patients were prescribed high-dose etanercept or adalimumab, representing a potential annual cost savings of $302,497 if 50% of these patients had their dose successfully reduced to labeled dosing. Opportunities for pharmacist intervention utilizing the dashboard were identified and characterized through chart review of flagged patients. CONCLUSION: Pharmacists have the opportunity to improve safety and adherence for TNF-α inhibitor therapy through use of a specialty medication clinical dashboard. The dashboard should be used in conjunction with collaborative practice protocols.

Effects of anticholinergic and sedative medication use on fractures: A self-controlled design study.

BACKGROUND/OBJECTIVES: Unintentional falls are a leading cause of injury for older adults, and evidence is needed to understand modifiable risk factors. We evaluated 1-year fall-related fracture risk and whether dispensing of medications with anticholinergic/sedating properties is temporally associated with an increased odds of these fractures. DESIGN: A retrospective cohort study with nested self-controlled analyses conducted between January 1, 2014, and December 31, 2016. SETTING: Twenty percent nationwide, random sample of US Medicare beneficiaries. PARTICIPANTS: New users of medications with anticholinergic/sedating properties who were 66+ years old and had Medicare Parts A, B, and D coverage but no claims for medications with anticholinergic/sedating properties in the year before initiation were eligible. MEASUREMENTS: We followed new users of medications with anticholinergic/sedating properties until first non-vertebral, fall-related fracture (primary outcome), Medicare disenrollment, death, or end of study data. We estimated the 1-year risk with corresponding 95% confidence intervals (CIs) of first fracture after new use. We applied the self-controlled case-crossover and case-time-control designs to estimate odds ratios (ORs) and 95% CIs by comparing anticholinergic and/or sedating medication exposure (any vs. none) during a 14-day hazard period preceding the fracture to exposure to these medications during an earlier 14-day control period. RESULTS: A total of 1,097,989 Medicare beneficiaries initiated medications with anticholinergic/sedating properties in the study period. The 1-year cumulative incidence of fall-related fracture, accounting for death as a competing risk, was 5.0% (95% CI: 5.0%-5.0%). Using the case-crossover design (n = 41,889), the adjusted OR for the association between anticholinergic/sedating medications and fractures was 1.03 (95% CI: 0.99, 1.08). Accounting for the noted temporal trend using the case-time-control design (n = 209,395), the adjusted OR was 1.60 (95% CI: 1.52, 1.69). CONCLUSION: Use of anticholinergic/sedating medication was temporally associated with an increased odds of fall-related fractures. Patients and their healthcare providers should consider pharmacologic and non-pharmacologic treatments for the target condition that are safer.

The role of suvorexant in the prevention of delirium during acute hospitalization: A systematic review.

PURPOSE: To assess the efficacy and safety of suvorexant for the prevention of delirium during acute hospitalization. MATERIALS AND METHODS: Pubmed (1946 to December 2019) and Embase (1947 to December 2019) were queried using the search term combination: delirium, confusion, cognitive defect, encephalopathy, critically ill patient, critical illness, or hospitalization and suvorexant or orexin receptor antagonist. Studies analyzed for relevance evaluated clinical outcomes of patients treated with suvorexant for prevention of delirium. Studies appropriate to the objective were evaluated, including two randomized controlled trials and four retrospective studies. RESULTS: In acutely hospitalized patients, treatment with suvorexant 15 to 20 mg alone or in combination with ramelteon resulted in a reduction in development of delirium, time until delirium onset, and length of hospital stay. When assessed, suvorexant was well tolerated and adverse effects were no worse than placebo. CONCLUSION: Based on the reviewed literature, suvorexant has shown positive outcomes in the prevention of delirium during an acute hospitalization. Larger trials comparing the efficacy of suvorexant to other sleep modulating options are necessary to further delineate its role for the prevention of delirium.

Description of Pharmacist Recommendations in the Caring for Older Adults and Caregivers at Home (COACH) Program.

OBJECTIVE: To describe recommendations made by geriatric clinical pharmacists within an innovative care model focusing on patients with dementia living at home. DESIGN: Retrospective chart review. SETTING: Outpatients in a tertiary care Veterans Affairs health care system. PARTICIPANTS: Veterans who underwent a Caring for Older Adults and Caregivers at Home (COACH) Program assessment and had at least one medicationrelated recommendation made by a geriatric clinical pharmacist. MAIN OUTCOME MEASURES: The primary endpoint was the number and category of medication-related recommendations made by a geriatric clinical pharmacist at the initial COACH program assessment. Secondary endpoints were recommendation acceptance rates and change in potentially inappropriate medications (PIMs) at six months. RESULTS: There were 104 patients included. The mean age was 81 years and the majority of patients were male and Caucasian. At baseline, patients were receiving a mean of 12 medications/person, and 59% of patients were receiving at least one PIM. There were 248 total medication recommendations made, with a mean of 2.4 recommendations/person (range 1-5). The three most common recommendation categories were to discontinue a drug, decrease the dose, and switch to a potentially safer alternative. Providers accepted 110 (44%) recommendations within six months. Patients were receiving a mean of one PIM/person at baseline, and no change was observed at six months.CONCLUSION: This study describes recommendations made through medication reviews by geriatric clinical pharmacists within an innovative care model for patients with dementia living at home. These data may provide information to other clinical pharmacists implementing consult services in similar settings.

Impact of Supervised Exercise on One-Year Medication Use in Older Veterans with Multiple Morbidities.

Exercise is touted as the ideal prescription to treat and prevent many chronic diseases. We examined changes in utilization and cost of medication classes commonly prescribed in the management of chronic conditions following participation in 12-months of supervised exercise within the Veterans Affairs Gerofit program. Gerofit enrolled 480 veterans between 1999 and 2017 with 12-months participation, with 453 having one or more active prescriptions on enrollment. Active prescriptions overall and for five classes of medications were examined. Changes from enrollment to 12 months were calculated, and cost associated with prescriptions filled were used to estimate net cost changes. Active prescriptions were reduced for opioids (77 of 164, 47%), mental health (93 of 221, 42%), cardiac (175 of 391, 45%), diabetes (41 of 166, 25%), and lipid lowering (56 of 253, 22%) agents. Cost estimates resulted in a net savings of $38,400. These findings support the role of supervised exercise as a favorable therapeutic intervention that has impact across chronic conditions.

Dose-Dependent Association of Gabapentinoids with Pulmonary Complications After Total Hip and Knee Arthroplasties.

BACKGROUND: Gabapentinoids are commonly prescribed in perioperative multimodal analgesia protocols. Despite widespread use, the optimal dose to reduce opioid consumption while minimizing risks is unknown. We assessed dose-dependent effects of gabapentinoids on opioid consumption and postoperative pulmonary complications following total hip or knee arthroplasty (THA or TKA). We hypothesized that use of a gabapentinoid on the day of THA or TKA is associated with an increased risk of postoperative pulmonary complications in a dose-response fashion compared with the risk for patients who did not receive the drug. METHODS: Using the Premier Database, we identified adults who underwent elective primary THA or TKA from 2009 to 2014. The exposure was receipt of a gabapentinoid (gabapentin or pregabalin) on the day of surgery. Gabapentin dose was categorized into 5 groups: none, 1 to 350, 351 to 700, 701 to 1,050, and >1,050 mg per day. Pregabalin dose was categorized into 4 groups: none, 1 to 110, 111 to 250, and >250 mg per day. The primary outcome was a composite of postoperative pulmonary complications, defined as respiratory failure, pneumonia, reintubation, pulmonary edema, noninvasive ventilation, or invasive mechanical ventilation. RESULTS: Of 858,306 patients who underwent THA or TKA, 11.0% received gabapentin and 10.2% received pregabalin. The mean age (and standard deviation) of the patients was 65.6 ± 10.7 years, 39.6% were male, 78.2% were Caucasian, and 55.2% were covered by Medicare. In multilevel regression analysis, receipt of gabapentinoid at any dose on the day of surgery was associated with increased odds of postoperative pulmonary complications. Compared with no exposure to the drug being used by the particular group, all dose ranges of gabapentin and pregabalin were associated with greater odds of postoperative pulmonary complications (odds ratio, 95% confidence interval = 1.51, 1.40 to 1.63, for >1,050 mg of gabapentin and 1.81, 1.57 to 2.09, for >250 mg of pregabalin). We found no clinically meaningful associations between exposure to either gabapentin or pregabalin and perioperative opioid consumption or the length of the hospital stay. CONCLUSIONS: Exposure to gabapentinoids at any dose on the day of THA or TKA was associated with increased odds of postoperative pulmonary complications in a dose-response fashion, with minimal effects on perioperative opioid consumption. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Adjunctive memantine for opioid use disorder treatment: A systematic review.

Memantine is commonly used for the treatment of moderate-to-severe Alzheimer's disease. Due to its antagonism of the N-methyl-d-aspartate (NMDA) receptor, which has been shown to block rewarding and reinforcing effects of morphine, memantine has been investigated for potential utilization in opioid use disorder (OUD). The objective of this systematic review is to assess the evidence available to determine the safety and efficacy of memantine as treatment for OUD. Pubmed (1946-August 2019) and Embase (1947-August 2019) were queried using the following search terms: opioid-related disorders, opioids, substance withdrawal syndrome, withdrawal syndrome, opiate addiction, opiate, opiate dependence, opiate substitution treatment, managed opioid withdrawal, or drug withdrawal and memantine. After assessing studies appropriate for the objective, one single-blind and five double-blind, placebo-controlled trials were included. Of the included studies, four demonstrated beneficial effects of memantine either as monotherapy or adjunct to methadone or buprenorphine on reducing opioid cravings and methadone dose, increasing retention rates, and improving cognitive performance in patients with OUD. Two studies did not show benefit on patient retention rates with memantine adjunct to naltrexone. Study durations ranged from 3 to 13 weeks, and memantine dosing ranged from 5 to 60 mg/day. Memantine was well tolerated with similar rates of adverse effects between treatment groups. Based on the reviewed literature, memantine appears most beneficial as an adjunctive treatment for OUD when combined with methadone or buprenorphine, but not naltrexone. Larger studies with longer periods of treatment and follow-up are needed to support the use of memantine in the management of OUD.