Association of Patient Sex and Pregnancy Status With Naloxone Administration During Emergency Department Visits

OBJECTIVE: To evaluate the association of sex and pregnancy status with rates of naloxone administration during opioid overdose-related emergency department (ED) visits using the Nationwide Emergency Department Sample (NEDS). METHODS: A retrospective cohort study was conducted using NEDS 2016 and 2017 datasets. Eligible records included men and women, 15–49 years of age, with an opioid overdose-related ED visit; records for women were stratified by pregnancy status (ICD-10 O codes). A multivariable logistic regression model was used to assess the primary outcome of naloxone administration (CPT code: J2310). Secondary outcomes included subsequent admission and mortality. A subgroup analysis compared pregnant women who did versus did not receive naloxone. RESULTS: Records from 443,714 men, 304,364 non-pregnant women, and 25,056 pregnant women were included. Non-pregnant women had lower odds for naloxone administration (1.70% vs 2.10%; aOR: 0.86(0.83–0.89)) and mortality (2.21% vs 2.99%; aOR: 0.71(0.69–0.73)) but higher odds of subsequent admission (30.22% vs 27.18%; aOR: 1.04(1.03–1.06)) compared with men. Pregnant women had lower odds for naloxone administration (0..27% vs 1.70%; aOR: 0.16(0.13–0.21)) and mortality (0.41% vs 2.21%; aOR: 0.28(0.23–0.35)) but higher odds of subsequent admission (40.50% vs 30.22%; aOR: 2.04(2.00–2.10)) compared with non-pregnant women. Pregnant women who received naloxone had higher odds of mortality (14% vs 0.39%; aOR: 6.30(2.11–18.78)) compared with pregnant women who did not receive naloxone. Pregnant women who did not receive naloxone were more likely to have Medicaid as their expected insurance payer, be in the lowest quartile of median household income for residence ZIP code, and have a concurrent mental health diagnosis compared with pregnant women who did receive naloxone. CONCLUSION: Reproductive-aged non-pregnant and pregnant women were less likely to receive naloxone during opioid overdose-related ED visits compared to reproductive-aged men. Naloxone administration for reproductive-aged women should be prioritized in the efforts to reduce opioid- and pregnancy-related morbidity and mortality in the United States

Prenatal opioid exposure: The next neonatal neuroinflammatory disease.

The rates of opioid use disorder during pregnancy have more than quadrupled in the last decade, resulting in numerous infants suffering exposure to opioids during the perinatal period, a critical period of central nervous system (CNS) development. Despite increasing use, the characterization and definition of the molecular and cellular mechanisms of the long-term neurodevelopmental impacts of opioid exposure commencing in utero remains incomplete. Thus, in consideration of the looming public health crisis stemming from the multitude of infants with prenatal opioid exposure entering school age, we undertook an investigation of the effects of perinatal methadone exposure in a novel preclinical model. Specifically, we examined the effects of opioids on the developing brain to elucidate mechanisms of putative neural cell injury, to identify diagnostic biomarkers and to guide clinical studies of outcome and follow-up. We hypothesized that methadone would induce a pronounced inflammatory profile in both dams and their pups, and be associated with immune system dysfunction, sustained CNS injury, and altered cognition and executive function into adulthood. This investigation was conducted using a combination of cellular, molecular, biochemical, and clinically translatable biomarker, imaging and cognitive assessment platforms. Data reveal that perinatal methadone exposure increases inflammatory cytokines in the neonatal peripheral circulation, and reprograms and primes the immune system through sustained peripheral immune hyperreactivity. In the brain, perinatal methadone exposure not only increases chemokines and cytokines throughout a crucial developmental period, but also alters microglia morphology consistent with activation, and upregulates TLR4 and MyD88 mRNA. This increase in neuroinflammation coincides with reduced myelin basic protein and altered neurofilament expression, as well as reduced structural coherence and significantly decreased fractional anisotropy on diffusion tensor imaging. In addition to this microstructural brain injury, adult rats exposed to methadone in the perinatal period have significant impairment in associative learning and executive control as assessed using touchscreen technology. Collectively, these data reveal a distinct systemic and neuroinflammatory signature associated with prenatal methadone exposure, suggestive of an altered CNS microenvironment, dysregulated developmental homeostasis, complex concurrent neural injury, and imaging and cognitive findings consistent with clinical literature. Further investigation is required to define appropriate therapies targeted at the neural injury and improve the long-term outcomes for this exceedingly vulnerable patient population