Short-acting Opioids Research Articles

Perioperative anesthetic management of patients with hypoplastic left heart syndrome undergoing the comprehensive stage II surgery-A review of 148 cases.

Patients with hypoplastic left heart syndrome undergo the comprehensive stage 2 procedure as the second stage in the hybrid approach toward Fontan circulation. The complexity of comprehensive stage 2 procedure is considered a potential limitation, and limited information is available on its anesthetic management. This study aims to address this gap. A single-center retrospective cohort study analyzed 148 HLHS patients who underwent comprehensive stage 2 procedure, divided into Group A (stable condition, n = 116) and Group B (requiring preoperative intravenous inotropic therapy, n = 32). Demographic data, intraoperative hemodynamics, anesthetic management, and postoperative outcomes were collected. Etomidate (40%) was the most common induction agent, followed by esketamine (24%), midazolam (16%), and propofol (13%). Inhaled induction was rarely necessary (2%), occurring only in Group A patients. No statistical differences were found between groups for induction drug choice. Post-cardiopulmonary bypass management included moderate hypoventilation, inhaled nitric oxide (100%), and hemodynamic support with milrinone (97%) and norepinephrine (77%). Group B patients more frequently required additional levosimendan (20%) and epinephrine (18%). Extracorporeal membrane oxygenation was necessary in 8 patients (5%) with no between-group differences. Switching from fentanyl to remifentanil reduced postoperative ventilation time overall. However, Group B experienced significantly longer ventilation (6.3 vs. 3.5 h) and ICU stay (22 vs. 14 days). In-hospital mortality was 5% overall (Group A: 4%, Group B: 9%). Long-term survival analysis revealed a significant advantage for Group A. The use of short-acting opioids and adjusted ventilation modes enables optimal pulmonary blood flow and rapid transition to spontaneous breathing. Differentiated hemodynamic support with milrinone, norepinephrine, supplemented by levosimendan and epinephrine in high-risk patients, can mitigate the effects on the preoperatively volume-loaded right ventricle. However, differences in long-term survival probability were observed between groups. Local ethics committee, Medical Faculty, Justus-Liebig-University-Giessen (Trial Code Number: 216/14).

Enhanced Recovery After Surgery (ERAS) cardiac turnkey order set for perioperative pain management in cardiac surgery: Proceedings from the American Association for Thoracic Surgery (AATS) ERAS Conclave 2023

ObjectiveOptimal perioperative pain management is an essential component of perioperative care for the cardiac surgical patient. This turnkey order set is part of a series created by the Enhanced Recovery After Surgery Cardiac Society, first presented at the Annual Meeting of The American Association for Thoracic Surgery in 2023. Several guidelines and expert consensus documents have been published to provide guidance on pain management and opioid reduction in cardiac surgery. Our objective is to consolidate that guidance into an evidence-based order set that will assist in the implementation of a comprehensive multimodal approach to pain management. MethodsSubject matter experts were consulted to translate existing guidelines and peer-reviewed literature into a sample turnkey order set for pain management. Orders derived from consistent Class I, IIA, or equivalent recommendations across referenced guidelines and consensus manuscripts appear in the order set in bold type. Selected orders that were inconsistently Class I or IIA, Class IIB, or supported by published evidence, were also included in italicized type. ResultsOpioid-based analgesia is associated with delayed recovery and opioid-related adverse events. Several multimodal medications have been shown to reduce reliance upon opioids. These include the scheduled use of acetaminophen, gabapentinoids, and nonsteroidal anti-inflammatory drugs. In addition, intravenous analgesics such as dexmedetomidine, ketamine, magnesium, and lidocaine have been shown to both complement the maintenance of anesthesia as well as optimize pain control postoperatively. Long-acting opioids remain a key component of pain management when provided to reduce the overall use of short-acting synthetic opioids or in direct response to break though pain after exhausting other alternatives. When applied in a bundled fashion, several studies have demonstrated a reduction in overall opioid administration and improved rates of postoperative recovery. ConclusionsThere has been increased awareness regarding the potential short- and long-term adverse effects of both inadequate analgesia and excessive opioid administration after cardiac surgery. This turnkey order set aims to facilitate implementation of a comprehensive approach toward provision of multimodal, opioid-sparing medications to optimize pain management in cardiac surgery.

Postoperative pain trajectory and opioid requirements after laparoscopic bariatric surgery: a single-centre historical cohort study.

Concerns around delayed emergence and opioid-induced ventilatory impairment in bariatric surgery can lead to intraoperative reliance on short-acting opioids and avoidance of long-acting analgesics with potential sedative effects. Nevertheless, an overly-conservative intraoperative analgesic strategy may result in significant pain at emergence and higher opioid requirements in later phases of care. We sought to establish the pattern of intraoperative analgesic use in bariatric surgical patients as well as their postoperative pain trajectory and opioid requirements. We undertook a single-centre historical cohort study. We explored associations between intraoperative analgesic interventions and pain scores and opioid requirements in postanesthesia care units (PACUs), and associations between the quality of analgesia at emergence and subsequent pain and patient-centred recovery outcomes. We extracted perioperative data for 939 patients who underwent bariatric metabolic surgery between January 2018 and October 2019. Only 39% of patients received long-acting opioids intraoperatively and there was minimal use of nonopioid analgesic adjuncts. Nearly 80% of patients reported moderate-to-severe pain on PACU arrival; 97% of patients received intravenous opioids for rescue analgesia (mean dose, 31mg oral morphine equivalents). Lower pain scores at PACU admission and discharge were associated with subsequent lower inpatient pain scores, lower opioid requirements, shorter time to ambulation, and shorter length of hospital stay. In bariatric surgical patients, effective intraoperative analgesic strategies that improve early pain control may have an impact on recovery and pain experience. Judicious use of intraoperative opioids coupled with opioid-sparing multimodal analgesic techniques should be considered and balanced against concerns regarding opioid-related adverse effects in this patient population.

How Should Risks and Benefits of Short-Acting Opioids Be Evaluated in the Care of Inpatients With OUD?

Severe opioid withdrawal, risk of patient-initiated discharge, and some inpatients' use of unregulated substances prompt clinical and ethical questions considered in this commentary on a case. Short-acting opioids can be used to manage inpatients' pain and opioid use disorder (OUD) withdrawal symptoms. Including evidence-based interventions-such as naloxone kits, substance use equipment, and supervised consumption-in some inpatients' care plans may make those patients safer and reduce their risk of death. These and other strategies align with clinicians' ethical duties to minimize harms and maximize benefits for inpatients with OUD.

Effectiveness of Short-Acting Opioid Escalation vs Initiation of a Long-Acting Opioid in Nursing Home Residents

ObjectivesModifications to opioid regimens for persistent pain are typically made after an initial period of short-acting opioid (SAO) use. Regimen changes may include an escalation of the SAO dosage or an initiation of a long-acting opioid (LAO) as a switch or add-on therapy. This study evaluates the comparative effectiveness between these alternative regimens in nursing home residents. DesignA retrospective observational cohort analysis of US long-stay nursing home residents. Setting and ParticipantsNursing home resident data were obtained from the national Minimum Dataset (MDS) version 3.0 and linked Medicare data, 2011–2016. MethodsOpioid regimen changes were identified using Part D dispensing claims to identify dosage escalation of SAOs, initiation of an LAO, or a switch to an LAO. Outcomes included indices of pain occurrence, frequency, and severity reported on the earliest MDS assessment within 3 months following the opioid regimen change. Resident attributes were described by opioid regimen cohort. Prevalence ratios of pain and depression indices were quantified using doubly robust inverse probability of treatment (IPT)-weighted log-binomial regression. ResultsThe study cohorts included 2072 SAO dose escalations, 575 LAO add-on initiations, and 247 LAO switch initiations. After IPT weighting, we observed comparable effects on pain and mood across the opioid regimen cohorts. A substantial number of residents continued to report frequent/constant pain (36% in SAO Escalation Cohort, 42% in LAO Add-on Cohort, 42% in the LAO Switch Cohort). The distribution of depressive symptoms was similar regardless of the opioid regimen change. Conclusions and ImplicationsInitiation of an LAO as an add-on to SAO or a switch from SAO had comparable effects on pain and mood to SAO dose escalation without initiation of an LAO. Although fewer residents reported any pain after the regimen change, persistent pain was reported by most residents.

Intraoperative methadone for day-case gynaecological laparoscopy: A double-blind, randomised controlled trial.

Optimal pain relief in day-case surgery is imperative to patient comfort and timely discharge from hospital. Short-acting opioids are commonly used for analgesia in modern anaesthesia, allowing rapid recovery after surgery. Plasma concentration fluctuations from repeated dosing of short-acting opioids can cause patients to oscillate between analgesia with potential adverse effects, and inadequate analgesia requiring rescue dosing. Methadone's unique pharmacology may offer effective and sustained analgesia with less opioid consumption, potentially reducing adverse effects. Using a double-blind, randomised controlled trial, we compared post-anaesthesia care unit opioid consumption between day-case gynaecological laparoscopy patients who received either intravenous methadone (10 mg), or short-acting opioids intraoperatively. The primary outcome was post-anaesthesia care unit opioid consumption in oral morphine equivalents. Secondary outcomes included total opioid consumption, discharge opioid consumption, pain scores (0-10) until discharge, adverse effects (respiratory depression, postoperative nausea and vomiting, excess sedation), and rate of admission. Seventy patients were randomly assigned. Patients who received methadone consumed on average 9.44 mg fewer oral morphine equivalents in the post-anaesthesia care unit than the short-acting group (18.02 mg vs 27.46 mg, respectively, 95% confidence interval 0.003 to 18.88, P = 0.050) and experienced lower postoperative pain scores at every time point, although absolute differences were small. There was no evidence of lower hospital or discharge opioid consumption. No significant differences between the methadone and short-acting groups in other outcomes were identified: respiratory depression 41.2% versus 31.4%, Padjusted >0.99; postoperative nausea and vomiting 29.4% versus 42.9%, Padjusted >0.99; overnight admission 17.7% versus 11.4%, Padjusted >0.99; excess sedation 8.82% versus 8.57%, Padjusted >0.99. This study provides evidence that, although modestly, methadone can reduce post-anaesthesia care unit opioid consumption and postoperative pain scores after day-case gynaecological laparoscopy. There were no significant differences in any secondary outcomes.

Non-scheduled short-acting opioid to taper off opioids?

This commentary discusses the issues related to the current pharmacotherapy using super long-acting opioids (for the potential convenience for both patients and medical providers) for opioid addiction and argues for the potential to use a non-scheduled short-acting opioid to taper off opioids to reduce total number of patients on opioids and ultimately reduce opioid-related death. This article also proposes to develop short-acting opioids for addiction management instead of the current long-acting regimen. The authors further suggest that dezocine, a previously FDA approved medication for perioperative pain management and a non-scheduled opioid, be brought back to clinical practice in the US as a potential alternative addiction management medication, especially for those who are highly motivated to quit opioids completely using a taper off strategy.

The role of methadone in cardiac surgery for management of postoperative pain

BackgroundThis retrospective study evaluated the efficacy and safety of intraoperative methadone compared with short-acting opioids. MethodsPatients undergoing cardiac surgery with cardiopulmonary bypass (n=11 967) from 2018 to 2023 from a single health system were categorised into groups based on intraoperative opioid administration: no methadone (Group O), methadone plus other opioids (Group M+O), and methadone only (Group M). ResultsPatients in Groups M and M+O had lower mean pain scores until postoperative day (POD) 7 compared with Group O after adjusting for covariates (P<0.01). Both Groups M and M+O had lower total opioid administered compared with Group O for all days POD0–POD6 (all P<0.001). The median number of hours until initial postoperative opioid after surgery was 2.55 (inter-quartile range [IQR]=1.07–5.12), 6.82 (IQR=3.52–12.98), and 7.0 (IQR=3.82–12.95) for Group O, Group M+O, and Group M, respectively. The incidence of postoperative complications did not differ between groups. ConclusionsIntraoperative administration of methadone was associated with better pain control without significant side-effects after cardiac surgery.

Short-acting opioid prescriptions and Workers' Compensation using theNational Ambulatory Medical Care Survey.

Short-acting opioids have been utilized for pain management with little known about their use in patients on Workers' Compensation (WC) insurance. Our goal was to investigate this association in the ambulatory care setting. Using the National Ambulatory Medical Care Survey, visits from patients aged 18-64 during the years 2010 until 2018 were evaluated (excluding 2017 due to data availability). Demographic and co-morbidity data from each visit was obtained along with the visit year. The first short-acting opioid medication prescribed in the database was considered. Survey-weighted frequencies were evaluated. Logistic regression estimated the crude and adjusted odds ratios (OR) with 95% confidence intervals for the use of short-acting opioid prescription. There were 155,947 included visits with 62.5% for female patients. Most patients were White with 11.7% identifying as Black, and 6% identifying as another race. Over 13% of the sample was of Hispanic descent. WC was the identified insurance type in 1.6% of the sample population. Of these patients, 25.6% were prescribed a short-acting opioid, compared with 10.1% of those with another identified insurance. On multivariable regression, Black patients had increased odds of being prescribed a short-acting opioid compared to white patients (OR: 1.22, 95%CI: 1.11-1.34). Those on WC had 1.7-fold higher odds of being prescribed short-acting opioids (95%CI: 1.46-2.06). Certain patient characteristics, including having WC insurance, increased the odds of a short-acting opioid prescription. Further work is needed to identify prescribing patterns in specific high-risk occupational groups, as well as to elicit potential associated health outcomes.

Caesarean Delivery: A Narrative Review on the Choice of Neuraxially Administered Opioid and Its Implications for the Multimodal Peripartum Pain Concept.

Nowadays, obstetrical anesthesia-related mortality is a very rare complication in industrialized countries. The recommended choice of intrathecal opioid for spinal anesthesia in the context of a multimodal peripartum pain management concept is discussed in this narrative review. Nowadays, there is a consensus that a perioperative multimodal pain concept should be used for caesarean delivery. This pain concept should include neuraxial opioids for spinal anesthesia, acetaminophen, NSAIDs, intravenous dexamethasone, and postoperative local or regional anesthetic procedures. Long-acting lipophobic opioids (diamorphine and morphine) have a significant analgesic advantage over short-acting lipophilic opioids (sufentanil and fentanyl). The risk of clinically relevant respiratory depression after neuraxial long-acting opioids is nowadays considered negligible, even if the data situation is weak in this regard. The question remains as to whether a pain concept that is ideally adapted to a neuraxial short-acting opioid shows benefit to a pain concept that is optimally adapted to neuraxial morphine. If long-acting opioids are used, the timing of each additional component of the multimodal analgesia strategy could ideally be adjusted to this longer duration of action.

Inpatient Growth in Infants Requiring Pharmacologic Treatment for Neonatal Opioid Withdrawal Syndrome.

Aim: To assess inpatient growth parameter trajectories and to identify the type of opioid exposure and treatment characteristics influencing growth parameters of infants admitted to the newborn intensive care unit (NICU) for pharmacological treatment of neonatal opioid withdrawal syndrome (NOWS). Methods: Charts of term infants with NOWS admitted to NICU from 2012 to 2019, who received pharmacologic treatment, were reviewed. Intake (volume: mL/kg/day; calorie: kcal/kg/day) and growth parameter trajectories (weight, head circumference, and length) were analyzed based on the type of prenatal opioid exposure (short-acting opioids (SAOs), long-acting opioids (LAOs), and polysubstance), pharmacologic treatment, and sex. Growth measurement patterns over time were compared between groups using longitudinal mixed-effects models. Results: One hundred nineteen infants were included in the study with median birth weight Z-score of -0.19 at birth and decreased to a median of -0.72 at discharge. Exposure to SAO was associated with an increase in Z-scores nearing discharge across all growth parameters (Z-score for weight p = 0.03). Polysubstance exposure was associated with a decrease in Z-scores for length and head circumference throughout hospitalization. Infants with adjunct clonidine treatment had an increase in Z-score for weight trends. Male infants had a decrease in Z-scores for weight (male -0.96, female -0.59, interaction p = 0.06) and length (male -1.17, female -0.57, interaction p = 0.003) at Day 28. Despite the difference in growth trajectories, intake in terms of amount (mL/kg/day) and calorie intake (kcal/kg/day) was similar based on prenatal exposure, treatment, and sex. Conclusion: Infants with NOWS requiring pharmacologic treatment have a decrease in Z-scores for weight, length, and head circumference at birth and at hospital discharge. Infants with prenatal polysubstance exposure were at particular risk for poorer inpatient growth relative to infants exposed to SAO and LAO, indicated by lower Z-scores for length and occipital frontal circumference (OFC).

Exploring Factors Associated with Prescribers' Comfort Levels in Analgesic Prescribing in Quebec.

Identifying the factors associated with comfort level when prescribing medications is important for tailoring education and training. This study aimed to explore factors associated with the comfort level of healthcare professionals regarding dispensing and adjusting prescriptions for the treatment of chronic pain (CP). A cross-sectional survey was conducted among licensed physicians, pharmacists, and nurse practitioners across the province of Quebec, Canada. Comfort level regarding dispensing and/or adjusting prescriptions for CP treatment was measured on a 0-10 rating scale (0 = very uncomfortable, 10 = very comfortable). In total, 207 prescribers participated in this study (83 physicians, 58 pharmacists, and 66 nurse practitioners). 56.5% reported a comfort level in dispensing and/or adjusting prescriptions for the treatment of CP <6/10. The median comfort level score was 6 (interquartile range - IQR: 2). Differences in median scores were found between physicians (6), pharmacists (7) and nurses (5; p < 0.001). Multivariable logistic regression revealed that the factors associated with an increased likelihood of reporting a high comfort level (≥6/10) were: being a pharmacist, having a relative living with CP, a greater percentage of past year continuing educational activities about CP management, and higher perception of short-acting opioids risks. Factors associated with lower comfort levels were as follows: being a nurse practitioner, having fewer years of experience, living in a remote region, living with CP, and a higher perception of long-acting opioids risks. The practice setting and sex at birth were also associated with comfort level. The comfort level regarding prescribing for CP varies according to socioeconomic/professional factors, which can lead to disparities in the quality of care and outcomes for patients. Our results reinforce the importance of investing in initial training and continuing education of prescribers.

Opioid, methamphetamine, and polysubstance use: perinatal outcomes for the mother and infant.

The escalation in opioid pain relief (OPR) medications, heroin and fentanyl, has led to an increased use during pregnancy and a public health crisis. Methamphetamine use in women of childbearing age has now eclipsed the use of cocaine and other stimulants globally. Recent reports have shown increases in methamphetamine are selective to opioid use, particularly in rural regions in the US. This report compares the extent of our knowledge of the perinatal outcomes of OPRs, heroin, fentanyl, two long-acting substances used in the treatment of opioid use disorders (buprenorphine and methadone), and methamphetamine. The methodological limitations of the current research are examined, and two important initiatives that will address these limitations are reviewed. Current knowledge of the perinatal effects of short-acting opioids, OPRs, heroin, and fentanyl, is scarce. Most of what we know about the perinatal effects of opioids comes from research on the long-acting opioid agonist drugs used in the treatment of OUDs, methadone and buprenorphine. Both have better perinatal outcomes for the mother and newborn than heroin, but the uptake of these opioid substitution programs is poor (<50%). Current research on perinatal outcomes of methamphetamine is limited to retrospective epidemiological studies, chart reviews, one study from a treatment center in Hawaii, and the US and NZ cross-cultural infant Development, Environment And Lifestyle IDEAL studies. Characteristics of pregnant individuals in both opioid and MA studies were associated with poor maternal health, higher rates of mental illness, trauma, and poverty. Infant outcomes that differed between opioid and MA exposure included variations in neurobehavior at birth which could complicate the diagnosis and treatment of neonatal opioid withdrawal (NOWs). Given the complexity of OUDs in pregnant individuals and the increasing co-use of these opioids with MA, large studies are needed. These studies need to address the many confounders to perinatal outcomes and employ neurodevelopmental markers at birth that can help predict long-term neurodevelopmental outcomes. Two US initiatives that can provide critical research and treatment answers to this public health crisis are the US Environmental influences on Child Health Outcomes (ECHO) program and the Medication for Opioid Use Disorder During Pregnancy Network (MAT-LINK).

Using short-acting opioids to relieve opioid withdrawal in hospital.

Using short-acting opioids to relieve opioid withdrawal in hospital.

Effectiveness and safety of opioids on breathlessness and exercise endurance in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis of randomised controlled trials.

Opioids are recommended to treat advanced refractory dyspnoea despite optimal therapy by the American Thoracic Society clinical practice guidelines, while newly published randomised controlled trials of opioids in chronic obstructive pulmonary disease yield conflicting results. This study aimed to evaluate the effectiveness and safety of opioids for patients with chronic obstructive pulmonary disease. Systematic review and meta-analysis (PROSPERO CRD42021272556). Databases of PubMed, EMBASE and CENTRAL were searched from inception to 2022 for eligible randomised controlled trials. Twenty-four studies including 975 patients, were included. In cross-over studies, opioids improved breathlessness (standardised mean difference, -0.43; 95% CI, -0.55 to -0.30; I2 = 18%) and exercise endurance (standardised mean difference, 0.22; 95% CI, 0.02-0.41; I2 = 70%). However, opioids failed to improve dyspnoea (standardised mean difference, -0.02; 95% CI, -0.22 to 0.19; I2 = 39%) and exercise endurance (standardised mean difference, 0.00; 95% CI, -0.27 to 0.27; I2 = 0%) in parallel control studies that administered sustained-release opioids for more than 1 week. The opioids used in most crossover studies were short-acting and rarely associated with serious adverse effects. Only minor side effects such as dizziness, nausea, constipation and vomiting were identified for short-acting opioids. Sustained-release opioids did not improve dyspnoea and exercise endurance. Short-acting opioids appeared to be safe, have potential to lessen dyspnoea and improve exercise endurance, supporting benefit in managing episodes of breathlessness and providing prophylactic treatment for exertional dyspnoea.

Evaluating the Effect of COVID-19 on Outpatient Opioid Utilization Among Health First Colorado Members and a National Non-Medicaid Cohort: An Interrupted Time Series Analysis.

COVID-19, coinciding with the opioid epidemic in the United States, has had significant impacts on health-care utilization. While mixed, early analyses signaled a potential resurgence in opioid use following the pandemic. The primary study objective was to assess the association of the COVID-19 pandemic with opioid utilization among Health First Colorado (Colorado's Medicaid Program) members and a non-Medicaid managed care cohort who did not have a diagnosis of cancer or sickle cell disease. Using an interrupted time series and segmented regression analysis, this population-level study assessed the association of the COVID-19 pandemic on prescribed utilization of long- and short-acting opioid analgesics among Health First Colorado members and a random sample of non-Medicaid managed care members. Pharmacy claims data for both cohorts were assessed between October 1, 2018, and September 30, 2021, with April 2020 identified as the interruption of interest. We evaluated the following monthly opioid use measures separately for short-acting and long-acting opioids: number of members filling an opioid, total fills, and total days supplied. Short- and long-acting opioid utilization was significantly decreasing among Health First Colorado members in the 18 months prior to the start of COVID-19. After the onset of the pandemic, utilization stabilized and slopes were not significantly different from zero. Among the non-Medicaid managed care cohort, short- and long-acting opioid utilization significantly decreased in the 18 months leading up to the onset of the pandemic. After the onset of the pandemic, utilization of long-acting opioids stabilized, while utilization of short-acting opioids significantly increased. While we observed an increase in opioid utilization measures post-pandemic in the non-Medicaid managed care cohort, a similar increase was not observed in Health First Colorado members suggesting that thoughtful opioid policies put in place pre-pandemic may have been effective at controlling potential inappropriate opioid utilization.

Neuroimmune Mechanisms of Opioid Use Disorder and Recovery: Translatability to Human Studies, and Future Research Directions.

Opioid use disorder (OUD) is a major current cause of morbidity and mortality. Long-term exposure to short-acting opioids (MOP-r agonists such as heroin or fentanyl) results in complex pathophysiological changes to neuroimmune and neuroinflammatory functions, affected in part by peripheral mechanisms (e.g., cytokines in blood), and by neuroendocrine systems such as the hypothalamic-pituitary-adrenal (HPA) stress axis. There are important findings from preclinical models, but their role in the trajectory and outcomes of OUD in humans is not well understood. The goal of this narrative review is to examine available data on immune and inflammatory functions in persons with OUD, and to identify major areas for future research. Peripheral blood biomarker studies revealed a pro-inflammatory state in persons with OUD in withdrawal or early abstinence, consistent with available postmortem brain studies (which show glial activation) and diffusion tensor imaging studies (indicating white matter disruptions), with gradual abstinence-associated recovery. The mechanistic roles of these neuroimmune and neuroinflammatory changes in the trajectory of OUD (including recovery and medication management) cannot be examined practically with postmortem data. Collection of longitudinal data in larger-scale human cohorts would allow examination of these mechanisms associated with OUD stage and progression. Given the heterogeneity in presentation of OUD, a precision medicine approach integrating multi-omic peripheral biomarkers and comprehensive phenotyping, including neuroimaging, can be beneficial in risk stratification, and individually optimized selection of interventions for individuals who will benefit, and assessments under refractory therapy.

Comparative safety of adding serotonin and norepinephrine reuptake inhibitors (SNRIs) versus nonsteroidal anti-inflammatory drugs (NSAIDs) to short-acting opioids for non-malignant pain in nursing homes.

The comparative safety of serotonin and norepinephrine reuptake inhibitors (SNRIs) as adjuvants to short-acting opioids in older adults is unknown even though SNRIs are commonly used. We compared the effects of SNRIs versus nonsteroidal anti-Inflammatory drugs (NSAIDs) on delirium among nursing home residents when SNRIs or NSAIDs were added to stable regimens of short-acting opioids. Using 2011-2016 national Minimum Data Set (MDS) 3.0 and Medicare claims data to implement a new-user design, we identified a cohort of nursing home residents receiving short-acting opioids who initiated either an SNRI or an NSAID. Delirium was defined from the Confusion Assessment Method in MDS 3.0 assessments and ICD9/10 codes using Medicare hospitalization claims. Propensity score matching balanced underlying differences for initiating treatments on 39 demographic and clinical characteristics (nSNRIs = 5350; nNSAIDs = 5350). Fine and Gray models provided hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for the competing risk of death. Hydrocodone was the most commonly used short-acting opioid (48%). Residents received ~23 mg daily oral morphine equivalent at the time of SNRIs/NSAIDs initiation. The majority were women, non-Hispanic White, and aged ≥75 years. There were no differences in any of the confounders after propensity matching. Over 1 year, 10.8% of SNRIs initiators and 8.9% of NSAIDs initiators developed delirium. The rate of delirium onset was similar in SNRIs and NSAID initiators (HR(delirium in nursing home or hospitalization for delirium):1.10; 95% CI: 0.97-1.24; HR(hospitalization for delirium): 1.06; 95% CI: 0.89-1.25), and were similar regardless of baseline opioid daily dosage. Among nursing home residents, adding SNRIs to short-acting opioids does not appear to increase risk of delirium relative to initiating NSAIDs. Understanding the comparative safety of pain regimens is needed to inform clinical decisions in a medically complex population often excluded from clinical research.

General pharmacology of long-acting, extended-release, and sustained-release opioids for the treatment of chronic nonmalignant pain.

Both short-acting (SA) opioids and long-acting (LA) opioids have been used for chronic pain (defined as pain lasting &gt;3 months). SA opioids have a duration of action ranging between 2 and 4 hours, result in rapidly fluctuating drug levels and are suitable for acute, unstable, intermittent, breakthrough, and procedure-related pain.

Retrospective Study of the Safety and Efficacy of Intraoperative Methadone for Pain Management in Patients Undergoing Elective Intracranial Surgery

Patients undergoing intracranial surgery experience significant perioperative pain and are typically treated with short-acting opioids. Methadone, with its prolonged half-life and multimodal central nervous system effects, presents a promising option for managing postcraniotomy pain. Despite its proven efficacy in other types of surgeries, the use of methadone in patients undergoing craniotomy has not yet been explored. A retrospective chart review was conducted for 60 adult patients ranging in age from 18 to 81 years who received methadone during intracranial surgeries. The primary outcome of interest was the total opioid consumption in oral morphine milligram equivalents (MMEs) and patient-reported pain scores within 24 hours and up to 72 hours postoperatively. The methadone dosage varied from 5 to 20 mg. In the infratentorial group, the median total MME on postoperative day 1, 2, and 3 was 30.5, 17, and 0.8, respectively, with mean pain scores of 3.56, 3.91, and 2.71. In the supratentorial group, the median total MME on postoperative day 1, 2, and 3 was 17.85, 15.4, and 1.2, with mean pain scores of 2.31, 1.68, and 2.21, respectively. Patients who were chronic opioid users had significantly higher pain scores and average opioid use (P < 0.05). None of the patients required administration of naloxone or airway interventions. Comparison with the historical control showed that our study patients had lower pain scores and MME. The single intraoperative dose of methadone is well tolerated by adult patients undergoing various types of intracranial surgeries, with minimal side effects, including elderly patients aged 65 years or older.