Browsing by Subject "Opioid-induced respiratory depression"

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    L-NAC reverses of the adverse effects of fentanyl infusion on ventilation and blood-gas chemistry
    (Elsevier, 2022) Getsy, Paulina M.; Baby, Santhosh M.; May, Walter J.; Lewis, Tristan H.J.; Bates, James N.; Hsieh, Yee-Hsee; Gaston, Benjamin; Lewis, Stephen J.; Pediatrics, School of Medicine
    There is an urgent need for development of drugs that are able to reverse the adverse effects of opioids on breathing and arterial blood-gas (ABG) chemistry while preserving opioid analgesia. The present study describes the effects of bolus injections of N-acetyl-L-cysteine (L-NAC, 500 μmol/kg, IV) on ventilatory parameters, ABG chemistry, Alveolar-arterial (A-a) gradient, sedation (righting reflex) and analgesia status (tail-flick latency assay) in unanesthetized adult male Sprague Dawley rats receiving a continuous infusion of fentanyl (1 μg/kg/min, IV). Fentanyl infusion elicited pronounced disturbances in (1) ventilatory parameters (e.g., decreases in frequency of breathing, tidal volume and minute ventilation), (2) ABG chemistry (decreases in pH, pO2, sO2 with increases in pCO2), (3) A-a gradient (increases that were consistent with reduced alveolar gas exchange), and (4) sedation and analgesia. Bolus injections of L-NAC given 60 and 90 min after start of fentanyl infusion elicited rapid and sustained reversal of the deleterious effects of fentanyl infusion on ventilatory parameters and ABG chemistry, whereas they did not affect the sedative or analgesic effects of fentanyl. Systemic L-NAC is approved for human use, and thus our findings raise the possibility that this biologically active thiol may be an effective compound to combat opioid-induced respiratory depression in human subjects.
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    Naloxone Prescribing Among Long-Term Opioid-Prescribed Patients: Disparities and Opportunities
    (Springer Nature, 2025-04-13) Yorkgitis, Brian; Harmon, Ira; Khan, Azad; Webb, Fern; Brat, Gabriel; Surgery, School of Medicine
    Introduction: Opioids have a risk for opioid-induced respiratory depression (OIRD) that can be fatal. Naloxone has been proven to reverse opioid effects. However, co-prescribing of naloxone with opioids is underutilized. Through the query of a national outpatient healthcare dataset, the study aims to discern differences in co-prescribing naloxone to provide a framework of education to formulate recommendations on naloxone prescribing. Methods: A retrospective review of a de-identified, national outpatient healthcare dataset was analyzed for patients with a pain-provoking condition and receipt of ≥3 opioid prescriptions. Demographics, medical history, and prescribing data were used to identify high-risk patients for OIRD along with co-prescribing of naloxone between 2015 and 2021 and analysis between 2022 and 2024. Results: Among 181,964 patients, 1807 (1%) received a naloxone prescription of the total cohort. Examining co-prescribing for high-risk patients only, 107 (3.3%) were receiving >50 MME/day opioids, 468 (2.6%) were concomitantly prescribed benzodiazepines, and 273 (7.8%) who had opioid use disorder (OUD) history received naloxone prescriptions. Upon logistic regression, the likelihood of naloxone co-prescribing among patients with a history of OUD showed an odds ratio (OR) of 6.63 (95% CI 5.76-7.63; p>0.001), and that among patients concomitantly prescribed benzodiazepines showed an OR of 2.76 (95% CI 2.47-3.09; p>0.001). Hispanic patients (OR 0.87; 95% CI 0.76-0.98; p=0.27) and those uninsured or with unknown insurance (OR 0.65; 95% CI 0.51-0.81; p<0.001) were less likely to receive a naloxone prescription. Black (OR 1.30; 95% CI 1.15-1.47; p>0.001) and unknown race (OR 1.38; 95% CI 1.15-1.66; p=0.001) patients were more likely to receive naloxone prescriptions. Conclusion: Despite recommendations that high-risk opioid-prescribed patients receive naloxone prescriptions, only a fraction are in receipt. There is variation among patient populations in co-prescribing, leaving opportunities to improve universal precautions that include naloxone co-prescribing to all high-risk patients for OIRD.