Opioid Analgesics Research Articles

Pain Control after Otologic Surgery: Do Nonopioid Analgesics Suffice?

Investigate whether nonopioid analgesics (NOA) provide adequate pain control after otologic surgery. Retrospective multicenter cohort. Two quaternary academic medical centers. Patients over 12 years old who underwent otologic surgery involving the middle ear and/or mastoid at two centers over a 5-month period. Patients were prescribed acetaminophen and ibuprofen postoperatively and instructed to contact the surgical team if pain control was inadequate, in which case an opioid medication was prescribed. Level of pain and medication use were assessed with a standardized questionnaire, 1 week after surgery. Postoperative pain levels during the first week after surgery (0-10); proportion of patients requiring opioid medication. Sixty-seven patients were included. Of these, 37% underwent tympanomastoidectomy, 27% cochlear implant, 19.5% postauricular tympanoplasty, 10.5% transcanal tympanoplasty, and 6% had a different surgery. The median of the average level of pain in the first 7 days was 5/10 (IQR 3-6). The median highest level of pain was 5 (IQR 4-8). The median current level of pain was 3 (IQR 1-5). Seven patients (10%) required breakthrough opioid pain medication. The remaining 90% utilized NOA only. One week after surgery, 60% were taking nonopioid analgesics only while the remaining 40% were not taking any pain medication at all. Although opioids were required infrequently, there were no significant differences in medication use between the two centers. NOA provide adequate pain control for most patients after middle ear and mastoid otologic surgery. Opioid analgesics do not routinely need to be prescribed.

Multicenter study of OPRM1 A118G and promoter-region DNA methylation associations with opioid outcomes and chronic postsurgical pain after pediatric musculoskeletal surgery

Abstract Introduction: Mu opioid receptor gene (OPRM1) variant rs1799971 introduces a CpG site, which may influence DNA methylation (DNAm) and opioid/pain outcomes. Objectives: In this nested analysis, we investigated both OPRM1 A118G genotype and promoter/immediate downstream blood DNAm sequencing data for associations with opioid effects and chronic postsurgical pain (CPSP) in a surgical cohort. Methods: Prospectively recruited opioid naïve patients undergoing Nuss procedure or spinal fusion with rs1799971 genotypes (Illumina arrays), DNAm (next generation enzymatic methylation sequencing at Chr6:154,039,209-154,039,803) and outcomes—opioid analgesia (integrated opioid use + pain over postoperative days 0 and 1 normalized to surgery type), safety—respiratory depression (RD) in high opioid use groups, and CPSP (Numerical Rating Scale >3/10 2-12 months postsurgery)—were included. Linear and logistic regression were performed to test genetic and epigenetic associations, adjusted for sociodemographics, cell types, and analgesics. Results: In this cohort (N = 112; 15.3 ± 2.0 years, 50% female, 83% White, 55% had CPSP, 13% had RD), DNAm at Chr6:154039216-154039217 was associated with CPSP (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.00-1.57; P = 0.03), Chr6:154039661-154039662 with acute integrated pain (β = −20.9, 95% CI, −40.70 to −1.10, P = 0.04), Chr6:154039520-154039521 (OR, 1.49; 95% CI, 1.09-2.03; P = 0.01), and Chr6:154039571-154039572 (OR, 1.47; 95% CI, 1.08-2.01; P = 0.02) with RD. Significant CpG sites were located in Repressed Polycomb chromatin states. Genotype was not associated with DNAm or outcomes. Conclusion: Our analyses support OPRM1 DNAm as predictors of acute and chronic pain/opioid outcomes in children after painful surgery. Study limitations included absent GG genotype, low sequencing coverage, and lack of correction for multiple testing.

NSW cannabis medicines advisory service retrospective enquiry analysis to inform clinical guidance resource development

AbstractBackgroundAn innovative New South Wales government funded statewide Cannabis Medicines Advisory Service (CMAS) operated between January 2018 and June 2022. The service provided comprehensive patient‐specific and evidence‐based information to support health professionals in prescribing and patient care decisions. This study aimed to describe real‐world data collected by CMAS.MethodsA sub‐set of de‐identified, patient‐specific enquiries collected between January 2021 and June 2022 (n = 123/567; 21.7%) were analyzed using R version 4.2.1. Diagnosis, indication, and comorbidities were coded using Medical Dictionary for Regulatory Activities (MedDRA) terminology.ResultsMost patient‐specific enquiries from medical practitioners were from general practitioners (n = 103/123; 83.7%). Female (n = 53/123; 43.1%) and male (n = 59/123; 48.0%) patients were similarly represented. Sex was not specified for 8.9% (n = 11/123) of patients. The mean age of patients was 52.1 years (range <10–90). The most common three diagnoses were osteoarthritis, anxiety, and chronic pain. Indications that were most frequently reported included chronic pain, anxiety, back pain, non‐neuropathic pain, and insomnia. Comedications were most commonly non‐opioid and opioid analgesics and antidepressants. Most practitioners were considering prescribing a cannabidiol (CBD) product for their patient. Cannabinoid composition selection guidance provided by CMAS was predominantly (delta‐9‐tetrahydrocannabinol) THC:CBD ~1:1, followed by CBD‐only products. CMAS was contacted by health professionals regarding the management of potential adverse events for five patients.ConclusionThe findings of this study shed light on the information medical practitioners were seeking to inform their clinical decision‐making about medical cannabis and can inform the development of clinical guidance resources.

Opioid analgesic and antidepressant use during pregnancy and the risk of spontaneous preterm birth: A nested case–control study

AbstractBackgroundGiven the high prevalence of both mental health and acute pain conditions during pregnancy, use of antidepressants and analgesic opioids in this period is widespread. Whether single and combined use of these medications is associated with spontaneous preterm birth (sPTB) remains unclear.ObjectivesTo investigate the association between maternal prescription opioid and antidepressant medication exposures for co‐occurring mental health and acute pain management, either alone or in combination, and sPTB.MethodsWe used Tennessee Medicaid data (2007–2019) linked to birth certificates to conduct a nested case–control study among 15‐ to 44‐year‐old pregnant patients with singleton live births. Cases were identified as spontaneous live births between 24 and <37 gestational weeks using a validated birth certificate‐based algorithm. We selected up to 10 controls per case, matched on estimated pregnancy start date and other factors. We identified analgesic opioid and antidepressant pharmacy fills to define medication exposures in the 60 days before index date (case delivery date) and categorised them as unexposed, opioid‐only, antidepressant‐only and combined exposure. We estimated odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression, adjusting for confounders. We assessed the additive interaction between opioids and antidepressants by estimating relative excess risk due to interaction.ResultsWe identified 25,406 eligible cases of sPTB and 225,771 matched controls. Opioid‐only and combined exposures were associated with higher odds of sPTB relative to unexposed (adjusted OR 1.29, 95% CI 1.23, 1.35 and 1.22, 95% CI 1.06, 1.40, respectively), while antidepressant‐only exposure was not (1.04, 95% CI 0.96, 1.12). No additive interaction was identified for combined exposure.ConclusionsExposure to prescription opioids during pregnancy, but not antidepressants, was associated with increased relative odds of sPTB. Co‐exposure to opioids and antidepressants did not elevate the odds of sPTB above what we observed for opioid‐only exposure.

HC-HA/PTX3 from Human Amniotic Membrane Induced Differential Gene Expressions in DRG Neurons: Insights into the Modulation of Pain

Background: The biologics derived from human amniotic membranes (AMs) demonstrate potential pain-inhibitory effects in clinical settings. However, the molecular basis underlying this therapeutic effect remains elusive. HC-HA/PTX3 is a unique water-soluble regenerative matrix that is purified from human AMs. We examined whether HC-HA/PTX3 can modulate the gene networks and transcriptional signatures in the dorsal root ganglia (DRG) neurons transmitting peripheral sensory inputs to the spinal cord. Methods: We conducted bulk RNA-sequencing (RNA-seq) of mouse DRG neurons after treating them with HC-HA/PTX3 (15 µg/mL) for 10 min and 24 h in culture. Differential gene expression analysis was performed using the limma package, and Gene Ontology (GO) and protein–protein interaction (PPI) analyses were conducted to identify the networks of pain-related genes. Western blotting and in vitro calcium imaging were used to examine the protein levels and signaling of pro-opiomelanocortin (POMC) in DRG neurons. Results: Compared to the vehicle-treated group, 24 h treatment with HC-HA/PTX3 induced 2047 differentially expressed genes (DEGs), which were centered on the ATPase activity, receptor–ligand activity, and extracellular matrix pathways. Importantly, PPI analysis revealed that over 50 of these DEGs are closely related to pain and analgesia. Notably, HC-HA/PTX3 increased the expression and signaling pathway of POMC, which may affect opioid analgesia. Conclusions: HC-HA/PTX3 induced profound changes in the gene expression in DRG neurons, centered around various neurochemical mechanisms associated with pain modulation. Our findings suggest that HC-HA/PTX3 may be an important biological active component in human AMs that partly underlies its pain inhibitory effect, presenting a new strategy for pain treatment.

BN SO45 - Reported criteria and safety for day case management of acute appendicitis

Abstract Background Acute appendicitis has an incidence of 7-8%. About 45,000 appendicectomies are performed in UK/year. Whilst day case surgery (DCS) is standard for cholecystectomies, hernia repair and even gastric bypass, reluctance exists in application of day care pathway for acute appendicitis. We aimed to review published literature on patient selection criteria, rates of day case discharge, readmission and re-intervention rates and patient satisfaction. Method A literature search was conducted in Embase, Pubmed and Medline for day case appendicectomy, Patient safety, selection criteria. A total of 116 papers were found. Once duplicates were removed, 75 studies underwent abstract screening from which 41 were full text screened. 29 publications were included in this review study. Data was collected on criteria for patient selection, length of stay, rate of DCS, rates of re-admission and re-intervention and patient/ relative satisfaction. Results Studies assessed DCS in children and/or adults. All authors included patients with uncomplicated appendicitis, well managed pain without opioid analgesia and adequate social support. Other authors additionally, only included patients under 65yrs old. The rates of DCS varied between 36.9% - 87%. Factors affecting DCS were time of admission and operation, female patients, symptom control and social factors. Rates of readmission ranged between 0-2.5% with no difference between DCS and admitted patients. Rates of re-intervention were low (0-2.5%) with a high patient satisfaction (87-91%). Late evening finishing of operation led to patient admission (77%) with no complications occurring within 48hrs. Conclusion Day case surgery for appendicectomy is reported to be safe provided adequate patient education and clear criteria for patient selection. No significant difference was found between the rates of re-intervention and re-admission between day case and admitted patients. We suggest standardising care pathways and provision of adequate education to both patients and staff as a method of safe day care discharge.

Safety and Effectiveness of Urologist-Directed Extracorporeal Shock Wave Lithotripsy for Pancreatolithiasis.

Introduction: Extracorporeal shock wave lithotripsy (SWL) can be used in conjunction with endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of large (≥5 mm) or impacted pancreatolithiasis. We report our experience demonstrating the safety and effectiveness of urologist-directed SWL for pancreatolithiasis. Methods: We performed a retrospective review of all patients undergoing SWL for pancreatolithiasis at our institution between 2016 and 2020. We defined a treatment cycle as one in which the patient underwent a predefined number of SWL procedures prior to performance of a post-SWL ERCP. Stone-free status was defined as the absence of stone fragments at post-SWL ERCP. Multivariable logistic regression was performed to determine characteristics associated with stone persistence after a treatment cycle. Results: There were 44 patients who underwent 59 treatment cycles consisting of 118 pancreatic SWL procedures. Forty-two cycles (71.2%) were staged, and 17 (28.8%) were not staged. The median size of the largest pancreatic stone was 9 mm [IQR 6-11] and was impacted in 38 cases (64.4%). Patients reported pain in 51 cases (86.4%), of which 28 required the use of opioid analgesics. Patients were rendered stone free in 38 cycles (64.4%). Pain improvement was noted in 39 cases (66.1%), and the reduction in opioid use was statistically significant (28 cases vs. 10 cases, P = 0.004). Impacted stones were associated with an increased odds of stone persistence (OR 7.04, 95% CI 1.14-43.43, P = 0.04). Conclusions: In this joint venture with gastroenterology, we demonstrate that urologist-directed SWL for pancreatolithiasis is safe, effective, and in line with published rates.

Lack of medication reviews in primary care contribute to patient deaths – thematic review of prevention of future deaths reports 2019-2023

Abstract Introduction With over 1 billion items dispensed in primary care each year, practices need robust systems to review repeat prescriptions and safeguard patients.1 The Care Quality Commission have reviewed areas of harm in relation to medicines.2 In general practice, errors in monitoring and review of repeat prescriptions create potential for harm and in some circumstances, death. When reviewing medicines-related patient deaths, coroners may write prevention of future deaths reports (PFDs) to highlight matters of concern to a person or organisation who may have power to act.3 Aim This retrospective case series aims to review coroners’ PFD reports over a 5-year period, with a focus on medicines-related deaths. The review will identify key themes, the most commonly prescribed medicines and any relevant patient demographics. Changes will be suggested to practice for any areas of concern or trends identified. Methods PFDs published on the judiciary website between 1st January 2019 and 31st December 2023 which reported on medication-related deaths were screened.3 Those relating to repeat prescribing were selected for analysis. Inductive thematic analysis was used to assess PFDs and identify where failures in repeat prescribing processes contributed to medication-related deaths. The “Matters for Concern” were reviewed by three research collaborators, who independently coded the data and identified the key themes. Following the initial screening process, demographic data (if known), relevant coroner notes, and available information on the drug(s) which contributed to patient deaths were extracted from the PFDs and recorded in a data table in Microsoft Excel. Ethical approval was not required as the research used publicly available information. Results 24 of 4781 PFDs related to repeat prescribing. The majority reported were female patients (67%, p<0.05) with average age of 48. Although the geographic distribution of PFDs was varied, a substantial proportion were published in Greater Manchester (9/24 38%). 76% of named medications were opioid analgesics, mentioned significantly more than any others (p<0.05). One third of the included PFDs described polypharmacy or repeat prescriptions taken alongside acute or over-the-counter medications. 57 matters of concern were raised by coroners, from which three key themes were identified: errors or discrepancies at the point of a transfer of care; the ability to obtain repeat prescriptions from multiple medication sources and a lack of robust medication review. Absence of medication review occurred most frequently (15/24 reports, 63%). Discussion This study identified where risks lie in repeat prescribing processes, with lack of robust medication reviews being most commonly linked to patient deaths. Inherently high-risk medicines, opioid analgesics, were most commonly described and should be prioritised for review. The average age was 48, suggesting older age may not be a risk factor in itself, but the contribution of polypharmacy was emphasised in the reports. The sample size was small and the time to extract the information from the reports impacted on the length of the study period chosen. However, pharmacy teams in general practice have an essential role to play in supporting medication reviews. Development of guidance to support repeat prescribing will also help to better safeguard patients receiving repeat medication.

A Comparative study of anterior cruciate ligament repair effectiveness in proximal ACL tears

Background. Anterior cruciate ligament (ACL) reconstruction is a gold standard surgical option for ACL tears. Another go-to method is primary ACL repair. The latter has its own limitations such as small range of indications – proximal tears only, which constitute a significant portion of ACL injuries. Although the primary repair has been known for a long time and is still developing, recent publications show conflicting outcomes. Aim of study was to compare functional outcomes of patients with ACL reconstruction and primary repair. Methods. During 2020-2023 we conducted randomized prospective multicenter control comparative study which included 170 patients with ACL tear types A, B, E according to Gächter classification, with injuries no older than 3 months. Patients were divided into two groups: 1st group – primary repair of ACL, 2nd group – ACL reconstruction. Knee function was assessed before surgery and 3, 6, 12, 24 months after the treatment using the IKDC 2000 and Lyshlom Knee Score. Results. Type E ACL injury prevailed in the sample. The most common associated injury in both cohorts was medial meniscus tear (39,3±0,05% and 45,3±0,05%). 15,5±0,04% patients with primary repair had chondrolabral defects, reconstruction group – 10,5±0,03%. 46,03±0,06% of 2nd and 25,35±0,05% of 1st group (p0,05) received pain relief therapy in the form of opioid analgesics. The proportion of patients requiring reoperation for ACL injury in 1st group was 3,5%, in 2nd group – 1,2%. Both groups had a statistically significant increase in functional outcomes at 3, 6, 12 months (p0,05). The difference of knee function between groups was not statistically significant (p0,05). Conclusion. Primary ACL repair still retains a large number of limitations: it cannot and should not replace ACL reconstruction, but should be used with strict adherence to the indications and surgical technique to show comparable functional outcomes.

Efficacy of an mHealth intervention to support pain self-management and improve analgesia in patients with rib fractures: protocol for a randomised controlled trial

IntroductionIn light of the risks of over-reliance on opioid analgesia during recovery from rib fractures, there is increased interest in the efficacy of non-pharmacological approaches to pain management. This paper...

Clinical Decision Support to Increase Emergency Department Naloxone Coprescribing: Implementation Report.

Coprescribing naloxone with opioid analgesics is a Centers for Disease Control and Prevention (CDC) best practice to mitigate the risk of fatal opioid overdose, yet coprescription by emergency medicine clinicians is rare, occurring less than 5% of the time it is indicated. Clinical decision support (CDS) has been associated with increased naloxone prescribing; however, key CDS design characteristics and pragmatic outcome measures necessary to understand replicability and effectiveness have not been reported. This study aimed to rigorously evaluate and quantify the impact of CDS designed to improve emergency department (ED) naloxone coprescribing. We hypothesized CDS would increase naloxone coprescribing and the number of naloxone prescriptions filled by patients discharged from EDs in a large health care system. Following user-centered design principles, we designed and implemented a fully automated, interruptive, electronic health record-based CDS to nudge clinicians to coprescribe naloxone with high-risk opioid prescriptions. "High-risk" opioid prescriptions were defined as any opioid analgesic prescription ≥90 total morphine milligram equivalents per day or for patients with a prior diagnosis of opioid use disorder or opioid overdose. The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework was used to evaluate pragmatic CDS outcomes of reach, effectiveness, adoption, implementation, and maintenance. Effectiveness was the primary outcome of interest and was assessed by (1) constructing a Bayesian structural time-series model of the number of ED visits with naloxone coprescriptions before and after CDS implementation and (2) calculating the percentage of naloxone prescriptions associated with CDS that were filled at an outpatient pharmacy. Mann-Kendall tests were used to evaluate longitudinal trends in CDS adoption. All outcomes were analyzed in R (version 4.2.2; R Core Team). Between November 2019 and July 2023, there were 1,994,994 ED visits. CDS reached clinicians in 0.83% (16,566/1,994,994) of all visits and 15.99% (16,566/103,606) of ED visits where an opioid was prescribed at discharge. Clinicians adopted CDS, coprescribing naloxone in 34.36% (6613/19,246) of alerts. CDS was effective, increasing naloxone coprescribing from baseline by 18.1 (95% CI 17.9-18.3) coprescriptions per week or 2,327% (95% CI 3390-3490). Patients filled 43.80% (1989/4541) of naloxone coprescriptions. The CDS was implemented simultaneously at every ED and no adaptations were made to CDS postimplementation. CDS was maintained beyond the study period and maintained its effect, with adoption increasing over time (τ=0.454; P<.001). Our findings advance the evidence that electronic health record-based CDS increases the number of naloxone coprescriptions and improves the distribution of naloxone. Our time series analysis controls for secular trends and strongly suggests that minimally interruptive CDS significantly improves process outcomes.

Chronic pain among primary fentanyl users: The concept of self-medication.

Chronic pain is among the leading causes of disability worldwide, of which only a small percentage of patients receive adequate treatment for. Non-prescribed opioid analgesics are commonly sought out in effort to alleviate unrelieved pain. This study assesses the prevalence and correlates of chronic pain among primary fentanyl users. A cross-sectional and structured survey was conducted with 200 adults who reported fentanyl as their drug of choice from a Vancouver acute care hospital. Presence and levels of chronic pain were determined through self-report. The majority of participants (n = 130, 72.6%) reported having chronic pain in the past 6 months, with the mean level of pain on a typical day to be 7.6 out of a scale of 10 (SD = 1.9). Majority (n = 85, 65.4%) reported using street opioids to self-medicate, while only 9 (6.9%) reported that their chronic pain was unrelated. Regression analysis indicated that increasing age and co-use of cannabis and opioids were independent associated factors of chronic pain. Higher levels of reported pain on a typical day were further associated with age and self-medication. The findings of this study demonstrate a significant association between self-medication and chronic pain among primary fentanyl users in British Columbia. For these individuals, inadequate pain relief may drive continued opioid use, which in turn may increase risks of treatment discontinuation and overdose. Appropriate pain management strategies are crucial to avoid opioid misuse and decrease the large societal burden caused by chronic pain. Our work points to the high prevalence of self-reported chronic pain among individuals who primarily use fentanyl. Among those with self-reported fentanyl use and chronic pain, self-medication with street opioids was found to be common and associated with higher reported pain levels on a typical day. This highlights the need for pain management strategies to be integrated into opioid dependence treatment and more research in the overlap of pain and fentanyl use.

Comparative study between effect of preoperative multimodal analgesia and pregabalin as unimodal analgesia in reduction of postoperative opioids consumption and postoperative pain in laparoscopic cholecystectomy

BackgroundLaparoscopic cholecystectomy is a popular abdominal surgery and the most common problem for patients undergoing laparoscopic cholecystectomy is the postoperative pain, and associated side effects due to opioids use for pain management and multimodal analgesia is suggested to reduce postoperative pain and need for postoperative opioids. This controlled clinical trial compares the effects of multimodal analgesia and pregabalin as unimodal analgesia on postoperative pain management, postoperative opioids consumption, and reduction of opioids accompanied adverse effects in patients undergoing laparoscopic cholecystectomy where large multicenter studies evaluating specific analgesic combinations are lacking.MethodThis comparison randomized controlled trial between multimodal analgesia approach and pregabalin as unimodal analgesia included 95 laparoscopic cholecystectomy patients that were randomly allocated to three groups using a simple randomization method where multimodal and pregabalin groups included 30 patients in each and the drugs was administered orally one hour before the incision and control group included 35 patients that did not receive any preoperative analgesia. Multimodal analgesic therapy included acetaminophen 1 g, pregabalin 150 mg and celecoxib 400 mg while pregabalin group received pregabalin 150 mg only.ResultsMultimodal group showed a significantly lower need for total opioid analgesics mean ± SD (1.33 ± 1.918) as compared to the control group mean ± SD (3.31 ± 2.784) with p-value 0.014. Pregabalin and multimodal groups showed significantly lower postoperative visual analogue scale used for pain assessment mean ± SD (3.50 ± 2.543) and mean ± SD (3.70 ± 2.231), respectively, compared to the control group mean ± SD (5.89 ± 2.857) with p-value 0.001.ConclusionMultimodal analgesia reduced postoperative opioids consumption more than pregabalin alone when used preoperatively in laparoscopic cholecystectomy and consequently reduced opioids associated adverse effects, but they have the same efficacy in reducing postoperative pain, so pregabalin can be used alone preoperatively in patients with contraindications for using some analgesics included in multimodal analgesia protocol. The study was registered retrospectively in clinical trials; Trial registration ID: NCT05547659.

Effects of a Revision to the Standard Admission Order Set on Laxative Prescribing for Opioid-Induced Constipation

Purpose: Opioid-induced constipation (OIC) is highly prevalent in patients with cancer-related pain on opioid analgesics and has negative consequences on physical and psychological well-being and quality of life. Oncology clinical practice guidelines recommend the use of osmotic and stimulant laxatives for the prevention and management of opioid-induced constipation, not stool softeners such as docusate sodium. Prescribing practices continue to fall behind these recommendations. Methods: This quality improvement project revised the laxative options available in the standard admission order set in the electronic medical record. Specifically, docusate sodium was removed and replaced with senna and polyethylene glycol 3350. Results: A total of 2,742 patient admissions preintervention were compared to 2,752 admissions postintervention. The number of orders for docusate (p &lt; .001) and docusate-senna (p = .002) orders decreased significantly after the intervention, in addition to the number of OIC diagnoses (p &lt; .001). However, the number of orders for polyethylene glycol (p = .559), senna (p = .582), other laxatives (p = .245), or functional bowel disorder medications (p = .533) did not change significantly. No significant differences were observed in the frequency of laxative orders placed within 24 hours of an opioid order, number of laxatives prescribed at discharge, admissions related to bowel-related complications, or length of stay. Conclusions: Interventions utilizing the electronic medical record can facilitate evidence-based management of OIC. Development of clinical practice guidelines and tailoring these interventions further is needed to adapt this approach at other institutions and sustain practice change.

Can Second Step Opioid Analgesics Reduce MMEs While Preserving Adequate Pain Management Following Rotator Cuff Repair?

Can Second Step Opioid Analgesics Reduce MMEs While Preserving Adequate Pain Management Following Rotator Cuff Repair?

Impact of Interventions by Certified Pharmacists for Outpatients with Cancer Pain on Hospital Admission after the Introduction of Opioid Analgesics.

The treatment of patients with cancer in an outpatient setting is important for maintaining patients' QOL and reducing the social burden of therapy, thus requiring extensive intervention by pharmacists in the outpatient setting. Japan has a system to certify pharmacists with specialized knowledge and skills in palliative care. However, few studies have investigated the impact of certified pharmacists' activities and of pharmacists' interventions on hospitalization and outpatient visits. Therefore, in this study, we retrospectively investigated the effects of interventions by certified pharmacists during the period from the introduction of opioid analgesics to hospitalization for pain management and the duration of outpatient visits at a single acute care hospital. Analysis using the Cox proportional hazards model showed that interventions by certified pharmacists significantly reduced hospitalizations for pain management (p = 0.014). Further, the results of the log-rank test showed that interventions by certified pharmacists significantly prolonged the period from the introduction of opioid analgesics to hospitalization compared with the absence of such interventions (p = 0.013). Additionally, interventions by certified pharmacists significantly increased the duration of outpatient visits compared with the absence of such interventions (p < 0.001). These results suggest that active and careful interventions by pharmacists, including certified pharmacists, contribute to the maintenance of the patients' QOL and healthcare economics by extending the period from the introduction of opioid analgesics to hospitalization for pain management and the duration of outpatient visits.

Minimising Harm and Managing Pain: Deprescribing Opioids in Older Adults.

Approximately one in three older adults (aged 65 years and over) experience pain, negatively impacting their quality of life. Opioid analgesics are commonly prescribed to manage pain; however, balancing the benefits and harms of these high-risk analgesics can be challenging for both healthcare professionals and patients. This is particularly true for older adults, as factors such as polypharmacy, age-related physiological changes and cognitive decline may impact upon opioid safety and efficacy. Deprescribing is the patient-centred process of reducing or discontinuing a medication that is no longer appropriate, or where the risks of continuation are deemed to outweigh the anticipated benefits. Opioid deprescribing has been proposed as a mechanism to reduce individual and societal opioid-related harm; however, to date, research has predominantly focused on the general adult population, rather than older adults. This current opinion aims to summarise the existing opioid deprescribing literature, discussing its applicability for older adults. Drawing on a non-systematic review of the literature, it identifies unique challenges and considerations for this population, highlights international initiatives to enhance opioid deprescribing in clinical practice and proposes future directions to advance the field.

DBPR116, a Prodrug of BPRMU191, in Combination with Naltrexone as a Safer Opioid Analgesic Than Morphine via Peripheral Administration.

The development of opioid analgesics with reduced adverse effects is an unmet need. In a previous study, we discovered a unique combination of BPRMU191 and morphinan antagonists that produced potent antinociception with reduced adverse effects after central administration (intrathecal or intracerebroventricular). BPRMU191/naltrexone exhibits notable in vitro and in vivo pharmacological properties. However, the poor blood-brain barrier penetrative ability of BPRMU191 restricts its clinical application. In this study, we utilized a prodrug strategy to deliver sufficient brain concentrations of BPRMU191 and selected compound 2 (DBPR116) with the best physicochemical and pharmacological properties among other in vivo active prodrugs. The in vivo pharmacological studies of compound 2/naltrexone, including thermally stimulated pain, cancer pain, constipation, sedation, psychological dependence, heart rate, and respiratory frequency measurements, demonstrated that it was a safer opioid analgesic than morphine in pain control.

The Effect of Obesity on Postoperative Analgesia Practices and Complications Following Endoscopic Sinus Surgery: A Propensity Score-Matched Cohort Study.

Despite growing concern regarding over-prescription of narcotic pain medication following ambulatory surgery, little is known about the analgesic prescribing practices following endoscopic sinus surgery (ESS) in obese patients in comparison to non-obese patients. To compare the rates of opioid versus non-opioid prescriptions, the need for steroids, and post-operative adverse events between obese and non-obese adult patients undergoing ESS. Using TriNetX Live database, we identified all patients aged ≥18 years who underwent ESS (n = 1303) between 2014 and 2022 across several healthcare institutions across the state of Tennessee. We 1:1 propensity score-matched obese (BMI ≥ 30 kg/m2) and non-obese (18.5 kg/m2 ≤ BMI < 30 kg/m2) cohorts for age, gender, race, and comorbidities including asthma, nicotine dependence, and sleep apnea. Rates of prescriptions and post-operative adverse events between cohorts were analyzed using risk ratios (RR) and confidence intervals (CI). A toal of 532 obese patients were compared to 532 propensity score-matched non-obese patients in the first 14 post-operative days following ESS. The obese cohort was significantly more likely to be prescribed analgesics generally (RR = 1.72; 95% CI = 1.20-2.47), non-opioid analgesics (RR = 1.73; 95% CI = 1.19-2.50), and opioid analgesics (RR = 1.64; 95% CI = 1.14-2.36) than non-obese patients. There was no difference in rates of antibiotic or antiemetic prescription, prednisone/methylprednisolone, dexamethasone, ED visits, critical care service, epistaxis, transfusion, anemia, revision sinus surgery, mechanical ventilation, CPAP, or inhalation airway treatments. Obese patients undergoing ESS were significantly more likely to be prescribed non-opioid and opioid analgesia in the first 14 days post-operatively compared to non-obese patients. There were no differences in post-operative adverse events or other prescriptions. Otolaryngologists should be aware that obese patients are at increased risk of opioid induced airway obstruction and steroid induced hyperglycemia, especially in patients with comorbid sleep apnea or diabetes. Emphasis on non-opioid analgesics and multimodal pain management should be advocated for this population.

The preventive efficacy of lipid emulsion on the occurrence of local anesthetic systemic toxicity in patients receiving local infiltration analgesia for total joint arthroplasty

BackgroundMotor-sparing local infiltration analgesia (LIA) enhances recovery after total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, LIA can induce local anesthetic systemic toxicity (LAST), sometimes necessitating rescue lipid emulsion therapy. Our institute initiated a pilot study to pretreat patients with lipid emulsion (SMOFlipid®) to test its efficacy in mitigating LIA-induced LAST events.MethodsThis retrospective study enrolled 1,621 adult patients who received LIA with bupivacaine (2–3 mg/kg, maximum 300 mg) for unilateral primary THA or TKA under general anesthesia between January 2020 and April 2022. A total of 439 patients received lipid pretreatment, while 1,182 did not. Demographics, surgical and anesthesia profiles, along with LAST events affecting the neurological, cardiovascular, and respiratory systems, were compared after propensity score matching for age, sex, body mass index (BMI), and surgery type.ResultsThe incidence of severe LAST events requiring rescue lipid emulsion slightly decreased after lipid pretreatment (from 2.54 to 2.28 per 1000). Lipid pretreatment significantly reduced the incidence of bradycardia and new-onset arrhythmia (odds ratio: 0.13, adjusted p-value: 0.024) but increased postoperative opioid requirement (odds ratio: 1.71, adjusted p-value: 0.032) after Benjamini-Hochberg correction for multiplicity.ConclusionsThe efficacy of lipid pretreatment (SMOFlipid® 1.5 ml/kg, maximum 100 ml) in mitigating LIA-induced LAST remains controversial. While lipid pretreatment reduced the incidence of new-onset arrhythmia, it showed no clear benefits for neurologic and respiratory outcomes. Additionally, lipid pretreatment might hinder postoperative recovery by increasing the need for rescue opioid analgesia. Further prospective pharmacokinetic studies are required to assess plasma bupivacaine concentrations following LIA and lipid pretreatment, examine their relationship to LAST events, and establish the efficacy and safety of lipid pretreatment.