Effect of Preadministration of Nalmefene on Sufentanil-Induced Cough During Induction of General Anesthesia in Patients Undergoing Breast Surgery: A Double-Blind Randomized Controlled Trial.

Purpose: This study was designed to investigate the effects of preadministration of nalmefene before general anesthesia induction on sufentanil-induced cough (SIC) in patients undergoing breast surgery. Patients and Methods: A total of 105 patients scheduled for elective breast surgery under general anesthesia were selected and randomly assigned into three groups: normal saline (Group C), low-dose nalmefene 0.1 µg·kg-1 (Group LN), and high-dose nalmefene 0.25 µg·kg-1 (Group HN). Sufentanil 0.5 µg·kg-1 was injected intravenously within 2 s after 5 min of intervention. The count and severity of cough within 2 min after sufentanil injection, as well as the time to first cough, were recorded. In addition, we also collected intraoperative hemodynamic data, postoperative pain scores, the incidence of receiving rescue analgesics, and side effects up to 24 h after surgery. Results: Compared to Group C, the incidence of SIC was significantly lower in Group LN and HN (64.7% vs 30.3% and 14.7%, respectively; P < 0.001), but no significant difference was observed between the two groups (P=0.126). Compared to Group C, the risk factors decreased by 53.4% (95% confidence interval [CI] =0.181-0.735, P=0.008) in Group LN and by 75.9% (95% CI=0.432-0.898, P=0.001) in Group HN. Of the patients with SIC, less frequent SIC within 2 min after induction and a lower proportion of severe coughs were observed than Group C (P < 0.05), and no difference was detected between Group LN and HN. Additionally, the onset time to the first SIC did not differ significantly between the groups. Intraoperative hemodynamic data, postoperative pain scores, and side effects in the first 24 h did not differ among the groups. Conclusion: Preadministration of nalmefene prior to induction of general anesthesia effectively suppressed SIC in patients undergoing breast surgery, without affecting intraoperative hemodynamic fluctuation and postoperative pain intensity.

Assessing the Impact of Morphine on Adverse Outcomes in ACS Patients Treated with P2Y12 Inhibitors: Insights from Multiple Real-World Evidence.

Purpose: Mechanistic studies showed that morphine may impair the antiplatelet effect of P2Y12 inhibitors. However, Several clinical studies with cardiovascular events as an outcome are contradictory, and the broader impact of this drug interaction on additional organ systems remains uncertain. With multisource data, this study sought to determine the effects of morphine interaction with P2Y12 inhibitors on major adverse outcomes comprehensively, and identify the warning indicators. Patients and Methods: Interaction signals were sought in 187,919 safety reports from the FDA Adverse Event Reporting System (FAERS) database, utilizing reporting odds ratios (repOR). In a cohort of 5240 acute coronary syndrome patients, the analyses were validated, and the biological effects of warning indicators were further studied with Mendelian randomization and mediation analysis. Results: Potential risk of renal system adverse events in patients cotreated with morphine is significantly higher in FAERS (repOR 4.83, 95% CI 4.42-5.28, false discovery rate adjusted-P =3.55*10-209). The analysis of in-house patient cohorts validated these results with an increased risk of acute kidney injury (adjusted OR: 1.65; 95% CI: 1.20 to 2.26), and we also found a risk of myocardial infarction in patients treated with morphine (adjusted OR: 1.55; 95% CI: 1.14 to 2.11). The Morphine group exhibited diminished Plateletcrit (PCT) levels post-surgery and lower PCT levels were associated with an increased risk of AKI. Conclusion: The administration of morphine in patients treated with P2Y12 receptor inhibitors should be carefully evaluated. PCT may serve as a potential warning indicator for morphine-related renal injury.

Cannabis Co-Use Among Black Individuals with Chronic Pain Who Use Opioids: Associations with Other Substance Use and Pain Related Outcomes.

Background Black individuals with chronic musculoskeletal (MSK) pain tend to experience worse pain and opioid use-related outcomes, including other substance co-use, compared with non-Hispanic White individuals. Co-using cannabis with opioids could instigate a cascade of pain-related vulnerabilities and poor outcomes. Here, we test associations between cannabis/opioid co-use and pain-related outcomes among Black individuals with chronic MSK pain. Methods Black adults with chronic MSK pain who use opioids (N=401; 51.62% female, Mage=35.90, SD=11.03) completed online measures of pain intensity/interference, emotional distress, opioid dependence, and risky use of other substances. Results Compared with opioid use alone, opioid and cannabis co-use was associated with elevated anxiety and depression symptoms, opioid dependence, and risky substance use, but not pain. Conclusions Black individuals with chronic MSK pain who co-use opioids and cannabis warrant targeted interventions that address their needs. Tailored interventions could help address disparities in pain-related outcomes and opioid morbidity and mortality rates.

Pharmacokinetic and neuroimmune pharmacogenetic impacts on slow-release morphine cancer pain control and adverse effects.

The aim was to determine if opioid neuroimmunopharmacology pathway gene polymorphisms alter serum morphine, morphine-3-glucuronide and morphine-6-glucuronide concentration-response relationships in 506 cancer patients receiving controlled-release oral morphine. Morphine-3-glucuronide concentrations (standardised to 11 h post-dose) were higher in patients without pain control (median (interquartile range) 1.2 (0.7-2.3) versus 1.0 (0.5-1.9) µM, P = 0.006), whereas morphine concentrations were higher in patients with cognitive dysfunction (40 (20-81) versus 29 (14-60) nM, P = 0.02). TLR2 rs3804100 variant carriers had reduced odds (adjusted odds ratio (95% confidence interval) 0.42 (0.22-0.82), P = 0.01) of opioid adverse events. IL2 rs2069762 G/G (0.20 (0.06-0.52)), BDNF rs6265 A/A (0.15 (0.02-0.63)) and IL6R rs8192284 carrier (0.55 (0.34-0.90)) genotypes had decreased, and IL6 rs10499563 C/C increased (3.3 (1.2-9.3)), odds of sickness response (P ≤ 0.02). The study has limitations in heterogeneity in doses, sampling times and diagnoses but still suggests that pharmacokinetics and immune genetics co-contribute to morphine pain control and adverse effects in cancer patients.

United States marijuana legalization and opioid mortality trends before and during the first year of the COVID-19 pandemic.

BACKGROUND: To determine if marijuana legalization was associated with reduced opioid mortality. STUDY DESIGN: The United States (US) opioid mortality trend during the 2010-2019 decade was compared in states and District of Columbia (jurisdictions) that had implemented marijuana legalization with states that had not. Acceleration of opioid mortality during 2020, the first year of the coronavirus disease 2019 (COVID-19) pandemic, was also compared in recreational and medicinal-only legalizing jurisdictions. METHODS: Joinpoint methodology was applied to the Centers for Disease Control and Prevention WONDER data. Trends in legalizing jurisdictions were cumulative aggregates. RESULTS: The overall opioid and fentanyl death rates and the percentage of opioid deaths due to fentanyl increased more during 2010-2019 in jurisdictions that legalized marijuana than in those that did not (pairwise comparison p = 0.007, 0.05, and 0.006, respectively). By 2019, the all-opioid and fentanyl death rates were 44 and 50 percent greater in the legalizing than in the nonlegalizing jurisdictions, respectively. When the COVID-19 pandemic hit in 2020, jurisdictions that implemented recreational marijuana legalization before 2019 had significantly greater increases in both overall opioid and fentanyl death rates than jurisdictions with medicinal-only legalization. For all-opioids, the mean (95 percent confidence interval) 2019-to-2020 increases were 46.5 percent (36.6, 56.3 percent) and 29.1 percent (20.2, 37.9 percent), respectively (p = 0.02). For fentanyl, they were 115.6 percent (80.2, 151.6 percent) and 55.4 percent (31.6, 79.2 percent), respectively (p = 0.01). CONCLUSIONS: During the past decade, marijuana legalization in the US was associated at the jurisdiction level with a greater acceleration in opioid death rate. An even greater increase in opioid mortality occurred in recreational-legalizing jurisdictions with the onset of the COVID-19 pandemic. Marijuana legalization is correlated with worsening of the US opioid epidemic.

Prenatal opioid exposure by likelihood of exposure and risk to prenatal development: Medicaid-covered births in Wisconsin, 2010-2019.

Prenatal opioid exposure is an established public health problem, in particular among Medicaid-covered births. Yet, existing prevalence rates are plausibly underestimated. We leverage extensive linked longitudinal administrative data for all Medicaid-covered live births in Wisconsin from 2010 to 2019 to estimate a range of prevalence rates using an innovative strategy that jointly accounts for both likelihood of exposure and potential risk to prenatal development. We find that 20.8% of infants may have been prenatally exposed to opioids, with 1.7% diagnosed with neonatal abstinence syndrome and an additional 1.2% having a high combined likelihood of exposure and potential risk to prenatal development, 2.6% a moderate combined likelihood and risk, and 15.3% a low or uncertain combined likelihood and risk. We assess improvements in prevalence estimates based on our nuanced classification relative to those of prior studies. Our strategy could be broadly used to quantify the scope of the opioid crisis for pregnant populations, target interventions, and promote child health and development.

What's New on the Street?: An Update on New Opioids, Psychoactive Drugs, and Synthetic Marijuana.

Substance abuse is a widespread problem in the United States and worldwide. This use within the pregnant population is thought to reflect a pattern similar to the general population, with estimates of 10% to 15% of pregnant women experiencing substance abuse. Illicit substance use during pregnancy has increased substantially during the past decade in the United States. During the past decade, novel or atypical substances have emerged and become increasingly popular. Occurrences of toxicity and untoward fetal effects from designer drug use must be kept high on the watch list for all who practice in maternal-fetal, newborn, and emergency departments.

Transitioning Care Approach for Neonatal Opioid Withdrawal Syndrome and Neonatal Abstinence Syndrome.

The increase in substance use during pregnancy results in a higher incidence of neonatal abstinence syndrome/neonatal opioid withdrawal syndrome (NAS/NOWS), straining health care and social systems and creating an economic burden. There is a paradigm shift in transitioning the care approach for NAS/NOWS from a medical model of care to a family-centered individualized non-pharmacological care approach with non-pharmacological interventions as the first line of treatment. Supporting families after birth with a nurturing environment and providing them with a toolbox of non-pharmacological interventions prepares them for the transition from hospital to home.

Prescription Opioids and Brain Structure in Community-Dwelling Older Adults.

OBJECTIVE: To evaluate the associations between prescription opioid exposures in community-dwelling older adults and gray and white matter structure by magnetic resonance imaging. METHODS: Secondary analysis was conducted of a prospective, longitudinal population-based cohort study employing cross-sectional imaging of older adult (≥65 years) enrollees between November 1, 2004, and December 31, 2017. Gray matter outcomes included cortical thickness in 41 structures and subcortical volumes in 6 structures. White matter outcomes included fractional anisotropy in 40 tracts and global white matter hyperintensity volumes. The primary exposure was prescription opioid availability expressed as the per-year rate of opioid days preceding magnetic resonance imaging, with a secondary exposure of per-year total morphine milligram equivalents (MME). Multivariable models assessed associations between opioid exposures and brain structures. RESULTS: The study included 2185 participants; median (interquartile range) age was 80 (75 to 85) years, 47% were women, and 1246 (57%) received opioids. No significant associations were found between opioids and gray matter. Increased opioid days and MME were associated with decreased white matter fractional anisotropy in 15 (38%) and 16 (40%) regions, respectively, including the corpus callosum, posterior thalamic radiation, and anterior limb of the internal capsule, among others. Opioid days and MME were also associated with greater white matter hyperintensity volume (1.02 [95% CI, 1.002 to 1.036; P=.029] and 1.01 [1.001 to 1.024; P=.032] increase in the geometric mean, respectively). CONCLUSION: The duration and dose of prescription opioids were associated with decreased white matter integrity but not with gray matter structure. Future studies with longitudinal imaging and clinical correlation are warranted to further evaluate these relationships.

Neonatal Abstinence Syndrome/Neonatal Opioid Withdrawal Syndrome: An Ecological View of Non-Pharmacologic Interventions for Feeding Success.

The number of infants diagnosed with neonatal abstinence syndrome (NAS) or neonatal opioid withdrawal syndrome (NOWS) has increased. The expression of NAS/NOWS symptoms differs and typically begins within the first few days of life, considered a critical period for feeding skill establishment, nourishment, and attachment. Non-pharmacologic interventions may be deployed to reduce or eliminate the need for replacement opioids while targeting outcomes like feeding dysfunction. Critical care providers can benefit from a structured examination of disordered feeding experiences to inform their selection of non-pharmacologic interventions. This structure can be provided using the Ecology of Human Performance model.

Low-Dose Alfentanil Inhibits Sufentanil-Induced Cough During Anesthesia Induction: A Prospective, Randomized, Double-Blind Study.

Background: Cough is one of the most common complications following intravenous administration of sufentanil during anesthesia induction. The study aimed to investigate the protective effect of alfentanil, afentanyl derivative with short onset time and short duration, in reducing sufentanil-induced cough. Patients and methods: Eighty patients that scheduled for thyroid surgery under general anesthesia were randomly divided into the alfentanil group and normal saline group, with 40 cases per group. Patients in the alfentanil group received intravenous administration of 2 µg/kg alfentanil prior to sufentanil injection during general anesthesia induction, while the same dose of normal saline was administered in the normal saline group. The outcomes measures included the incidence and severity of cough and common side effects of opioids following the administration of sufentanil during the induction of general anesthesia, intraoperative hemodynamics parameters and major adverse events during anesthesia recovery period. Results: The incidence of cough within one minute after the injection of sufentanil during anesthesia induction was 40% in the normal saline group, and the pretreatment of alfentanil significantly reduced the incidence of sufentanil-induced cough to 5% (p < 0.05). Correspondingly, the patients in the alfentanil group had decreased severity of sufentanil-induced cough compared with the normal saline group (p < 0.05). No significant differences in the incidences of common side effects of opioids (dizziness, nausea and vomiting, chest tightness and respiratory depression) within one minute after sufentanil injection were found (p > 0.05). Furthermore, there were no significant differences between the two groups in intraoperative hemodynamic parameters, extubation time, or the incidences of emergence agitation, respiratory depression, delayed recovery from anesthesia and postoperative nausea and vomiting during Postanesthesia Care Unit stay (p > 0.05). Conclusion: Pretreatment with low-dose alfentanil (2 µg/kg) effectively and safely reduced both the incidence and severity of sufentanil-induced cough during anesthesia induction. Clinical Trial Registration Number: Chinese Clinical Trial Registry (identifier: ChiCTR2300069286).

Machine learning identifies risk factors associated with long-term opioid use in fibromyalgia patients newly initiated on an opioid.

OBJECTIVES: Fibromyalgia is frequently treated with opioids due to limited therapeutic options. Long-term opioid use is associated with several adverse outcomes. Identifying factors associated with long-term opioid use is the first step in developing targeted interventions. The aim of this study was to evaluate risk factors in fibromyalgia patients newly initiated on opioids using machine learning. METHODS: A retrospective cohort study was conducted using a nationally representative primary care dataset from the UK, from the Clinical Research Practice Datalink. Fibromyalgia patients without prior cancer who were new opioid users were included. Logistic regression, a random forest model and Boruta feature selection were used to identify risk factors related to long-term opioid use. Adjusted ORs (aORs) and feature importance scores were calculated to gauge the strength of these associations. RESULTS: In this study, 28 552 fibromyalgia patients initiating opioids were identified of which 7369 patients (26%) had long-term opioid use. High initial opioid dose (aOR: 31.96, mean decrease accuracy (MDA) 135), history of self-harm (aOR: 2.01, MDA 44), obesity (aOR: 2.43, MDA 36), high deprivation (aOR: 2.00, MDA 31) and substance use disorder (aOR: 2.08, MDA 25) were the factors most strongly associated with long-term use. CONCLUSIONS: High dose of initial opioid prescription, a history of self-harm, obesity, high deprivation, substance use disorder and age were associated with long-term opioid use. This study underscores the importance of recognising these individual risk factors in fibromyalgia patients to better navigate the complexities of opioid use and facilitate patient-centred care.

The impact of more restrictive hydrocodone rescheduling on unintentional pediatric opioid exposures.

PURPOSE: To evaluate the impact of rescheduling hydrocodone combination products (HCPs) from schedule III of the Controlled Substances Act to the more restrictive schedule II on unintentional pediatric exposures (≤5 years old). METHODS: Using U.S. data on outpatient retail pharmacy dispensing, emergency department (ED) visits, and poison center (PC) exposure cases, we assessed trends in prescriptions dispensed and unintentional pediatric exposure cases involving hydrocodone (rescheduled from III to II) compared to oxycodone (schedule II) and codeine (schedule III for combination products) using descriptive and interrupted time-series (ITS) analyses during the 16 quarters before and after the October 2014 rescheduling of HCPs. RESULTS: Dispensing of hydrocodone products was declining before rescheduling but declined more steeply post-rescheduling. In ITS analyses, both hydrocodone and oxycodone had significant slope decreases in PC case rates in the post versus pre-period that was larger for hydrocodone, while codeine had a small but significant slope increase in PC case rates. An estimated 4202 ED visits for pediatric hydrocodone exposures occurred in the pre-period and 2090 visits occurred in the post-period, a significant decrease of 50.3%. Oxycodone exposures showed no significant decrease. CONCLUSIONS: Pediatric hydrocodone unintentional exposure ED visits and PC cases decreased after HCP rescheduling more than would be expected had the pre-rescheduling trend continued; the acceleration in the decrease in hydrocodone PC cases was partially offset by a slowing in the decrease in codeine-involved cases. The trend changes were likely due to multiple factors, including changes in dispensing that followed the rescheduling. Unintentional pediatric medication exposures and poisonings remain a public health concern requiring ongoing, multifaceted mitigation efforts.