An Update on Multimodal Pain Management After Total Joint Arthroplasty.

➤: Multimodal analgesia has become the standard of care for total joint arthroplasty as it provides superior analgesia with fewer side effects than opioid-only protocols. ➤: Systemic medications, including nonsteroidal anti-inflammatory drugs, acetaminophen, corticosteroids, and gabapentinoids, and local anesthetics via local infiltration analgesia and peripheral nerve blocks, are the foundation of multimodal analgesia in total joint arthroplasty. ➤: Ideally, multimodal analgesia should begin preoperatively and continue throughout the perioperative period and beyond discharge. ➤: There is insufficient evidence to support the routine use of intravenous acetaminophen or liposomal bupivacaine as part of multimodal analgesia protocols.

Pharmacological evaluation of the gabapentin salicylaldehyde derivative, gabapentsal, against tonic and phasic pain models, inflammation, and pyrexia.

Gabapentinoids are effective drugs in most animal models of pain and inflammation with variable effects in humans. The current study evaluated the pharmacological activity of gabapentin (GBP) and its salicylaldehyde derivative (gabapentsal; [2-(1-(((2-hydroxybenzylidene) amino) methyl) cyclohexyl) acetic acid]; GPS) in well-established mouse models of nociceptive pain, inflammatory edema, and pyrexia at doses of 25-100 mg/kg. GPS allayed tonic visceral pain as reflected by acetic acid-induced nociception and it also diminished thermally induced nociception as a mimic of phasic thermal pain. Antagonism of GPS-induced antinociceptive activities by naloxone (NLX, 1.0 mg/kg, subcutaneously, s.c), beta-funaltrexamine (ß-FNT, 5.0 mg/kg, s.c), naltrindole (NT, 1.0 mg/kg, s.c), and nor-binaltorphimine (NOR-BNI, 5.0 mg/kg, s.c), and pentylenetetrazole (PTZ-15 mg/kg, intraperitoneally, i.p) implicated an involvement of both opioidergic and GABAergic mechanisms. Tail immersion test was conducted in order to delineate the mechanistic insights of antinociceptive response. Inflammatory edema induced by carrageenan, histamine, or serotonin was also effectively reversed by GPS in a fashion analogous to aspirin (150 mg/kg, i.p), chlorpheniramine (1.0 mg/kg, i.p), and mianserin (1.0 mg/kg, i.p), respectively. Additionally, yeast-induced pyrexia was decreased by GPS in a comparable manner to acetaminophen (50 mg/kg, i.p). These observations suggest that GPS possesses ameliorative properties in tonic, phasic, and tail immersion tests of nociception via opioidergic and GABAergic mechanisms, curbs inflammatory edema, and is antipyretic in nature.

Opioid, gabapentinoid, and nonsteroidal anti-inflammatory medication use and the risks of atrial fibrillation and supraventricular ectopy in the Multi-Ethnic Study of Atherosclerosis.

PURPOSE: Opioids, gabapentinoids, and nonsteroidal anti-inflammatory drugs (NSAIDs) may have adverse cardiovascular effects. We evaluated whether these medications were associated with incident clinically detected atrial fibrillation (AF) or monitor-detected supraventricular ectopy (SVE), including premature atrial contractions (PACs) and supraventricular tachycardia (SVT). METHODS: We used data from the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort study that enrolled 6814 Americans without clinically detected cardiovascular disease in 2000 to 2002. At the 2016 to 2018 examination, 1557 individuals received ambulatory electrocardiographic (ECG) monitoring. Longitudinal analyses investigated time-varying medication exposures at the first five exams (through 2011) in relation to incident clinically detected AF through 2015 using Cox proportional hazards regression models. Cross-sectional analyses investigated medication exposures at 2016 to 2018 examination and the risk of monitor-detected SVE using linear regression models. RESULTS: The longitudinal cohort included 6652 participants. During 12.4 years of mean follow-up, 982 participants (14.7%) experienced incident clinically detected AF. Use of opioids, gabapentinoids, and NSAIDs were not associated with incident AF. The cross-sectional analysis included 1435 participants with ECG monitoring. Gabapentinoid use was associated with an 84% greater average frequency of PACs/hour (95% CI, 25%-171%) and a 44% greater average number of runs of SVT/day (95% CI, 3%-100%). No associations were found with use of opioids or NSAIDs in cross-sectional analyses. CONCLUSIONS: In this study, gabapentinoid use was associated with SVE. Given the rapid increase in gabapentinoid use, additional studies are needed to clarify whether these medications cause cardiovascular complications.

Concomitant Use of Gabapentinoids with Opioids Is Associated with Increased Mortality and Morbidity among Dialysis Patients.

BACKGROUND: The opioid epidemic is a public health emergency and appropriate medication prescription for pain remains challenging. Physicians have increasingly prescribed gabapentinoids for pain despite limited evidence supporting their use. We determined the prevalence of concomitant gabapentinoid and opioid prescriptions and evaluated their associations with outcomes among dialysis patients. METHODS: We used the United States Renal Data System to identify patients treated with dialysis with Part A, B, and D coverage for all of 2010. Patients were grouped into 4 categories of drugs exposure status in 2010: (1) no prescriptions of either an opioid or gabapentinoid, (2) ≥1 prescription of an opioid and no prescriptions of gabapentinoids, (3) no prescriptions of an opioid and ≥1 prescription of gabapenbtinoids, (4) ≥1 prescription of both an opioid and gabapentinoid. Outcomes included 2-year all-cause death, dialysis discontinuation, and hospitalizations assessed in 2011 and 2012. RESULTS: The study population included 153,758 dialysis patients. Concomitant prescription of an opioid and gabapentin (15%) was more common than concomitant prescription of an opioid and pregabalin (4%). In adjusted analyses, concomitant prescription of an opioid and gabapentin compared to no prescription of either was associated with increased risk of death (hazard ratio [HR] 1.16, 95% CI 1.12-1.19), dialysis discontinuation (HR 1.14, 95% CI 1.03-1.27), and hospitalization (HR 1.33, 95% CI 1.31-1.36). Concomitant prescription of an opioid and pregabalin compared to no prescription of either was associated with increased mortality (HR 1.22, 95% CI 1.16-1.28) and hospitalization (HR 1.37, 95% CI 1.33-1.41), but not dialysis discontinuation (HR 1.13, 95% CI 0.95-1.35). Prescription of opioids and gabepentinoids compared to only being prescribed opioids was associated with higher risk of hospitalizations, but not mortality, or dialysis discontinuation. CONCLUSIONS: Concomitant prescription of opioids and gabapentinoids among US dialysis patients is common, and both drugs have independent effects on outcomes. Future research should prospectively investigate the potential harms of such drugs and identify safer alternatives for treatment of pain in end-stage renal disease patients.

Use of gabapentinoid medications among US adults with cancer, 2005-2015.

BACKGROUND: Gabapentinoid use for long-term cancer pain control may be problematic, given unclear mechanisms of action and increased concerns for physical dependence. The purpose of this report is to examine trends of gabapentinoid use among US adults with cancer from 2005 to 2015. METHODS: We conducted a serial, cross-sectional study using data from the Medical Expenditure Panel Survey (MEPS). We performed multiple logistic regression to examine the annual percentages of gabapentinoid users, which were adjusted for age, sex, and US region of residence. The amount of gabapentinoid prescriptions filled in 2015 was also estimated. RESULTS: The adjusted percentage of gabapentinoid users in 2015 was 5.60% (3.79%, 7.41%), 2.39 times greater than the percentage in 2005 (p < .001). By 2015, the number of gabapentinoid prescriptions had grown to approximately 3.52 million (2.40 million, 4.65 million). CONCLUSION: We observed greater than a twofold increase in the trend of gabapentinoid medication use among US adults with cancer. Investigations on the long-term efficacy of gabapentinoids for complex pain syndromes, and mitigation of risks, is essential to guide informed clinical management and keep patients safe.

Evaluating the impact of gabapentinoids on sleep health in patients with chronic neuropathic pain: a systematic review and meta-analysis.

Chronic neuropathic pain (NP) is debilitating and impacts sleep health and quality of life. Treatment with gabapentinoids (GBs) has been shown to reduce pain, but its effects on sleep health have not been systematically evaluated. The objective of this systematic review and meta-analysis was to assess the relationship between GB therapy dose and duration on sleep quality, daytime somnolence, and intensity of pain in patients with NP. Subgroup comparisons were planned for high- vs low-dose GBs, where 300 mg per day or more of pregabalin was used to classify high-dose therapy. Trial data were segregated by duration less than 6 weeks and 6 weeks or greater. Twenty randomized controlled trials were included. Primary outcome measures included pain-related sleep interference and incidence of daytime somnolence. Secondary outcomes included daily pain scores (numerical rating scale 0-10) and patient global impression of change. Significant improvement in sleep quality was observed after 6 weeks of GB treatment when compared with placebo (standardized mean difference 0.39, 95% confidence interval 0.32-0.46 P < 0.001). Increased daytime somnolence was observed among all GB-treated groups when compared with placebo. Treated patients were also more likely to report improvement of patient global impression of change scores. Pain scores decreased significantly in patients both after 6 weeks of treatment (P < 0.001) and in trials less than 6 weeks (P = 0.017) when compared with placebo. Our data demonstrate that GBs have a positive impact on sleep health, quality of life, and pain in patients with NP syndromes. However, these benefits come at the expense of daytime somnolence.

The role of gabapentinoids in acute and chronic pain after surgery.

PURPOSE OF REVIEW: Gabapentinoid use has increased substantially in the past several years after initial promising data with regard to acute perioperative pain control. The purpose of this review is to critically appraise the evidence for the use of gabapentinoids for acute pain management and its impact on the development of chronic pain after surgery. RECENT FINDINGS: Recent meta-analyses have revealed that prior data likely have overestimated the beneficial effects of gabapentinoids in acute perioperative pain while underestimating the associated adverse effects. The utility of gabapentinoids in the setting of enhanced recovery pathways and for the prevention of chronic postsurgical pain is still unclear. Moreover, there has been increasing concern regarding the potential for misuse and abuse of gabapentinoids. SUMMARY: Current evidence does not support the routine use of gabapentinoids as part of a multimodal analgesic regimen in enhanced recovery pathways. We recommend being selective with regard to using gabapentinoids for acute postoperative pain management after careful consideration of the potential side effect profile based on patient comorbidities as well as the expected severity of postoperative pain. Large, high-quality trials are needed to identify the impact of gabapentinoids in the context of multimodal anagelsia.

Use of Systemic Treatment in Patients with Chronic Pruritus: A Survey of Dermatologists in the Netherlands.

Treatment of chronic pruritus can be a challenge for clinicians. Several systemic treatments have been suggested to reduce itch, such as gabapentinoids and antidepressants. The aim of this study was to assess the current practice of dermatologists regarding systemic treatment in patients with chronic pruritus, and to identify possible barriers in the prescription of these treatments. An online survey was sent to all dermatologists and dermatology residents in the Netherlands between July 2017 and April 2018. A total of 193 physicians completed the questionnaire (response rate 27.0%). Overall, 61.7% prescribed gabapentinoids or antidepressants in patients with chronic pruritus. Amitriptyline was prescribed most frequently, followed by gabapentin, doxepin and mirtazapine. Reasons not to prescribe systemic treatment included lack of knowledge or experience, risk of side-effects, and lack of available evidence. As only a minority of respondents felt comfortable prescribing these drugs, more education on effective and safe dosing is needed.