HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in bunionectomy: phase III results from the randomized EPOCH 1 study.

BACKGROUND AND OBJECTIVES: There is a need for local anesthetics that provide consistent analgesia through 72 hours after surgery. This study evaluates the use of HTX-011 (bupivacaine and meloxicam in Biochronomerpolymer technology), an extended-release, dual-acting local anesthetic, in reducing both postoperative pain over 72 hours and postoperative opioid use when compared with bupivacaine hydrochloride (HCl) and saline placebo. Inclusion of low-dose meloxicam in HTX-011 is designed to reduce local inflammation caused by surgery, potentiating the analgesic effect of bupivacaine. Previously, significant synergy has been observed with bupivacaine and meloxicam with both given locally together. METHODS: EPOCH 1 was a randomized, double-blind, placebo-controlled and active-controlled phase III study in subjects undergoing a primary unilateral, distal, first metatarsal bunionectomy in which subjects received either a single intraoperative dose of HTX-011, immediate-release bupivacaine HCl or saline placebo. RESULTS: A total of 412 subjects were dosed. The results for the primary and all four key secondary endpoints were statistically significant in favor of HTX-011. HTX-011 demonstrated superior, sustained pain reduction through 72 hours, significantly reduced opioid consumption and resulted in significantly more opioid-free subjects compared with saline placebo and bupivacaine HCl. Safety was similar across groups with fewer opioid-related adverse events observed in the HTX-011 group. CONCLUSIONS: HTX-011 demonstrated significant reduction in postoperative pain through 72 hours with significant reduction in opioid consumption and a significant increase in the proportion of opioid-free subjects compared with saline placebo and the most widely used local anesthetic, bupivacaine HCl. TRIAL REGISTRATION NUMBER: NCT03295721

Efektivitas dan Efisiensi Pencatatan efek Opioid pada Pasien Pascaoperasi di RSUP Dr. Sardjito, Indonesia

Nyeri merupakan pengalaman sensoris dan emosional yang tidak menyenangkan terkait dengan kerusakan jaringan aktual atau potensial. Nyeri dapat terjadi saat preoperasi, durante, dan pascaoperasi. Pada umumnya, manajemen nyeri intra dan pascaoperasi menggunakan opioid. Penelitian ini bertujuan menilai efektivitas dan efisiensi pencatatan evaluasi penggunaan opioid intraoperatif dan pascaoperasi dan dilaksanakan pada Maret–Oktober 2019 di RSUP Dr. Sarjito Yogyakarta. Penelitian ini menggunakan desain kohort retrospektif untuk melihat efektivitas dan efisiensi pemberian opioid intraoperatif terhadap efek analgesia pascaoperasi dengan mengukur skala NRS, prevalensi kejadian efek samping opioid post-operative nausea and vomiting (PONV), recovery room length of stay (LOS), serta penggunaan obat analgetik pascaoperasi. Pencatatan rekam medis yang kurang lengkap sehingga tidak dapat menilai efektivitas penggunaan opioid intraoperative yang baik. Penggunaan opioid pascaoperasi memiliki hubungan yang bermakna dengan skor NRS 12 jam pascaoperasi dan kejadian komplikasi (p=0,025;p=0,028). Penggunaan opioid intraoperatif maupun pascaoperasi terhadap skor NRS, kejadian komplikasi, maupun lamanya waktu rawat di recovery room tidak terdapat hubungan yang bermakna. Simpulan, pencatatan evaluasi penggunaan opioid intraoperative dan pascaoperasi di rekam medis masih belum lengkap. Penggunaan opioid intraoperatif tidak bermakna dalam menurunkan skor NRS, menurunkan kejadian komplikasi pascaoperasi, memperpendek lama rawat di recovery room, namun apabila opioid dilanjutkan pemberian pascabedah menurunkan NRS, tetapi efek  samping opioid lebih tinggi. Effectiveness and Efficiency of Opioid Effects Recording in Postoperative Patients at Sardjito General Hospital, IndonesiaPain is “an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Postoperative pain is a pain felt by patients after a series of operations. In general, intraoperative and postoperative pains are treated with an opioid. This study aimed to determine the effectiveness and efficiency of recording evaluation of intraoperative and postoperative opioid use in patients. This study used a retrospective cohort design to identify the effectiveness and efficiency of intraoperative opioid administration on the postoperative analgesia effect by measuring the NRS scale, the prevalence of side effects of postoperative nausea and vomiting (PONV), Recovery Room length of stay (LOS), and the administration of postoperative analgesics. Due to incomplete medical records, it cannot assess the effectiveness of a good intraoperative opioid. Postoperative opioid use has a significant correlation with NRS score 12 hours postoperatively and the complication incidence (p=0.025, p=0.028). There was no significant relationship between either intraoperative or postoperative opioids to NRS score, adverse events, and length of stay in the Recovery Room. In conclusion, the recording of pain management in intraoperative and postoperative opioid use in the medical record is still incomplete. The intraoperative opioids use does not significantly reduce the NRS score, decrease the postoperative complications, and shorten the length of stay in the Recovery Room. If opioids are continued, postoperative administration significantly lower NRS; however, the side effects of opioids are higher

The Association of Prescription Opioid Exposure and Patient Factors with Prolonged Postoperative Opioid Use in Opioid Naive Patients

Background Research suggests prolonged postoperative opioid use occurs in 4-13% of opioid naïve patients and is related to factors other than surgical pain. However, it is unclear which patient factors and prescribing practices are associated with prolonged use after surgery among opioid naïve patients. Objectives To identify factors associated with prolonged postoperative opioid use (refills 90-180 days after surgery) in opioid naïve patients in two domains: specific patient characteristics (demographics, smoking status, comorbidities, etc.) and exposure through postoperative opioid prescriptions (in oral morphine milligram equivalents [OME]). Methods An electronic medical record dataset analysis of inpatient and outpatient opioid naïve adult orthopedic surgery patients at the University of Cincinnati Medical Center from January 1, 2012 through December 31, 2017 was conducted. Opioid naïve was defined as no opioid prescription filled in the past twelve months or only a perioperative prescription filled 30 days or less prior to surgery. Patients were excluded if they had a diagnosis of cancer or if they underwent a second surgery within 180 days of the first. A multivariate logistic regression model was used to evaluate the relationship of each domain to opioid refills 90-180 days after surgery. Results Of the 7,323 patients met inclusion criteria, 4% continued to refill opioid prescriptions more than 90 days after their surgical procedure. Independent predictors of prolonged postoperative opioid use were alcoholism (O.R. 2.0, C.I. 1.5-2.6), OME \u3e 675 (O.R. 2.3, C.I. 1.5-3.4), female gender (O.R. 1.7, C.I. 1.3-2.1), black race (O.R. 1.6, C.I. 1.2-2.2), Medicaid insurance (O.R. 1.8, C.I. 1.3-2.5), and the following co-morbidities: diabetes (O.R.1.5, C.I. 1.1-2.0), mood disorders (O.R. 1.4, C.I. 1.1-1.9), hypertension (O.R. 1.4, C.I. 1.1-1.9), and chronic kidney disease (O.R. 1.6, C.I. 1.1-2.4). Conclusions Both opioid exposure and patient characteristics increase risk for prolonged opioid use following orthopedic surgery. Since the risk of overdose increases with increased OME, patients with high OME prescriptions should also receive a prescription for naloxone. This study sheds light on the need for postoperative prescribing guidelines for clinicians. To decrease the rate of prolonged postoperative opioid use, clinical changes can be investigated and implemented including collaborative perioperative pain management strategies utilizing non-opioid pain control methods; perioperative patient screening; education of patients and clinicians; and close postoperative follow-up, especially for the most vulnerable populations

Functional Outcomes after Lumbar Fusion in Opioid-Tolerant Patients

Introduction: Prolonged opioid use after lumbar fusion surgery is implicated with increased hospital readmissions, higher postoperative pain scores, and longer return to work time. There are several non-modifiable risk factors for postoperative opioid use including socioeconomic status and gender. The purpose of this study was to determine the effects of opioid-tolerance on PROMs and to determine risk factors for prolonged opioid use after lumbar spine surgery. Method: Using retrospective cohort analysis, patients who underwent lumbar spinal fusion at TJUH were identified and determined to be either opioid-naïve or opioid-tolerant using the Pennsylvania PDMP. Outcomes included number of opioid tablets consumed, duration of time using opioids, and patient-reported outcome measures (ODI, PCS-12, MCS-12, VAS Back, VAS Leg). Univariate and multivariate analysis were used to compare outcomes between the two groups. Logistic regression was used to determine independent predictors for prolonged opioid use which was defined as greater than one postoperative opioid prescription script filled. Results: A total of 260 patients were included in the final cohort, of which, 138 were opioid-tolerant and 122 were opioid naïve. Opioid-tolerant patients showed decreased improvement in PROMs compared to the opioid-naïve patients (p=0.043). The number of preoperative pills prescribed was a significant predictor for prolonged opioid use after lumbar fusion. Conclusion: The number of pills prescribed preoperatively was found to be a predictor for prolonged opioid use after lumbar fusion surgery. Overall, our results demonstrated that naïve patients have improved health-related quality of life outcome scores compared to opioid-tolerant patients after lumbar fusion

In-hospital postoperative opioid use and its trends in neurosurgery between 2007 and 2018

Background Postoperative opioid use plays an important role in the global opioid crisis, but little is known about in-hospital opioid use trends of large surgical units. We investigated whether postoperative in-hospital opioid consumption changed in a large academic neurosurgical unit between 2007 and 2018. Methods We extracted the data of consumed opioids in the neurosurgical intensive care unit and two bed wards between 2007 and 2018. Besides overall consumption, we analyzed the trends for weak (tramadol and codeine), strong, and the most commonly used opioids. The use of various opioids was standardized using the defined daily doses (DDDs) of each opioid agent. A linear regression analysis was performed to estimate annual treatment day-adjusted changes with 95% confidence intervals. Results Overall, 121 361 opioid DDDs were consumed during the 196 199 treatment days. Oxycodone was the most commonly used postoperative opioid (49% of all used opioids) in neurosurgery. In the bed wards, the use of oral oxycodone increased 375% (on average 13% (9-17%) per year), and the use of transdermal buprenorphine 930% (on average 26% (9-45%) per year) over the 12-year period. Despite the increased use of strong opioids in the bed wards (on average 3% (1-4%) per year), overall opioid use decreased 39% (on average 6% (4-7%) per year) between 2007 and 2018. Conclusions Due to the increase of strong opioid use in the surgical bed wards, we encourage other large teaching hospitals and surgical units to investigate whether their opioid use trends are similarly worrisome and whether the opioid consumption changes in the hospital setting are transferred to opioid use patterns or opioid-related harms after discharge.Peer reviewe

Perioperative Methadone Use And Postoperative Pain Control In Adult Patients Undergoing Elective Spinal Fusion Surgery

Patients undergoing elective spinal fusion surgeries often experience moderate to severe postoperative pain (Murphy et al., 2017). The use of perioperative methadone has been suggested as an effective adjunct for patients to reduce postoperative pain, decrease opioid use, and improve patient satisfaction (Murphy et al., 2017). Traditional opioid management of orthopedic spine surgeries include intermittent injections or patient-controlled analgesia devices. These approaches may cause fluctuating levels of opioids or require patient education and cooperation to be effective (Murphy & Szokol, 2019). Methadone has a much longer elimination half-life when compared to other opioids, and therefore may provide patients with a stable blood concentration of opioid to improve postoperative pain control (Murphy & Szokol, 2019). In adult patients undergoing elective spine surgery, how effective is perioperative methadone use compared to traditional opioid management in controlling postoperative pain in the first 24 hours

Managing Opioid-Tolerant Patients in the Perioperative Surgical Home.

Management of acute postoperative pain is important to decrease perioperative morbidity and improve patient satisfaction. Opioids are associated with potential adverse events that may lead to significant risk. Uncontrolled pain is a risk factor in the transformation of acute pain to chronic pain. Balancing these issues can be especially challenging in opioid-tolerant patients undergoing surgery, for whom rapidly escalating opioid doses in an effort to control pain can be associated with increased complications. In the perioperative surgical home model, anesthesiologists are positioned to coordinate a comprehensive perioperative analgesic plan that begins with the preoperative assessment and continues through discharge

The Efficacy of Peripheral Opioid Antagonists in Opioid-Induced Constipation and Postoperative Ileus: A Systematic Review of the Literature.

Opioid-induced constipation has a negative impact on quality of life for patients with chronic pain and can affect more than a third of patients. A related but separate entity is postoperative ileus, which is an abnormal pattern of gastrointestinal motility after surgery. Nonselective μ-opioid receptor antagonists reverse constipation and opioid-induced ileus but cross the blood-brain barrier and may reverse analgesia. Peripherally acting μ-opioid receptor antagonists target the μ-opioid receptor without reversing analgesia. Three such agents are US Food and Drug Administration approved. We reviewed the literature for randomized controlled trials that studied the efficacy of alvimopan, methylnaltrexone, and naloxegol in treating either opioid-induced constipation or postoperative ileus. Peripherally acting μ-opioid receptor antagonists may be effective in treating both opioid-induced bowel dysfunction and postoperative ileus, but definitive conclusions are not possible because of study inconsistency and the relatively low quality of evidence. Comparisons of agents are difficult because of heterogeneous end points and no head-to-head studies

Managing Prolonged Pain After Surgery: Examining the Role of Opioids.

A notable minority of patients experience persistent postsurgical pain and some of these patients consequently have prolonged exposure to opioids. Risk factors for prolonged opioid use after surgery include preoperative opioid use, anxiety, substance abuse, and alcohol abuse. The window to intervene and potentially prevent persistent opioid use after surgery is short and may best be accomplished by both surgeon and anesthesiologist working together. Anesthesiologists in particular are well positioned in the perioperative surgical home model to affect multiple aspects of the perioperative experience, including tailoring intraoperative medications and providing consultation for possible discharge analgesic regimens that can help minimize opioid use. Multimodal analgesia protocols reduce opioid consumption and thereby reduce exposure to opioids and theoretically the risk of persistent use. Regional anesthesia and analgesia techniques also reduce opioid consumption. Although many patients will recover without difficulty, the small minority who do not should receive customized care which may involve multiple office visits or consultation of a pain specialist. Enhanced recovery pathways are useful in optimizing outcomes after surgery