L-NAC reverses of the adverse effects of fentanyl infusion on ventilation and blood-gas chemistry
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)...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222006667 |
| _version_ | 1811337890885533696 |
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| author | Paulina M. Getsy Santhosh M. Baby Walter J. May Tristan H.J. Lewis James N. Bates Yee-Hsee Hsieh Benjamin Gaston Stephen J. Lewis |
| author_facet | Paulina M. Getsy Santhosh M. Baby Walter J. May Tristan H.J. Lewis James N. Bates Yee-Hsee Hsieh Benjamin Gaston Stephen J. Lewis |
| author_sort | Paulina M. Getsy |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T18:02:34Z |
| format | Article |
| id | doaj.art-6ff878c2816540d6af32fc989e5eb70a |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-13T18:02:34Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-6ff878c2816540d6af32fc989e5eb70a2022-12-22T02:36:12ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-09-01153113277L-NAC reverses of the adverse effects of fentanyl infusion on ventilation and blood-gas chemistryPaulina M. Getsy0Santhosh M. Baby1Walter J. May2Tristan H.J. Lewis3James N. Bates4Yee-Hsee Hsieh5Benjamin Gaston6Stephen J. Lewis7Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USAGalleon Pharmaceuticals, Inc., 213 Witmer Road, Horsham, PA 19044, USAPediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USADepartment of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Anesthesiology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USADivision of Pulmonary, Critical Care and Sleep Medicine, Case Western Reserve University, Cleveland, OH 44106, USAHerman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA; Corresponding author at: Department of Pediatrics, Division of Pulmonology, Allergy and Immunology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4984, USA.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.http://www.sciencedirect.com/science/article/pii/S0753332222006667Fentanyl infusionOpioid-induced respiratory depressionN-acetyl-L-cysteineRats |
| spellingShingle | Paulina M. Getsy Santhosh M. Baby Walter J. May Tristan H.J. Lewis James N. Bates Yee-Hsee Hsieh Benjamin Gaston Stephen J. Lewis L-NAC reverses of the adverse effects of fentanyl infusion on ventilation and blood-gas chemistry Biomedicine & Pharmacotherapy Fentanyl infusion Opioid-induced respiratory depression N-acetyl-L-cysteine Rats |
| title | L-NAC reverses of the adverse effects of fentanyl infusion on ventilation and blood-gas chemistry |
| title_full | L-NAC reverses of the adverse effects of fentanyl infusion on ventilation and blood-gas chemistry |
| title_fullStr | L-NAC reverses of the adverse effects of fentanyl infusion on ventilation and blood-gas chemistry |
| title_full_unstemmed | L-NAC reverses of the adverse effects of fentanyl infusion on ventilation and blood-gas chemistry |
| title_short | L-NAC reverses of the adverse effects of fentanyl infusion on ventilation and blood-gas chemistry |
| title_sort | l nac reverses of the adverse effects of fentanyl infusion on ventilation and blood gas chemistry |
| topic | Fentanyl infusion Opioid-induced respiratory depression N-acetyl-L-cysteine Rats |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222006667 |
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