دورية أكاديمية
أعرض في EDS

A comparative examination of morphine and fentanyl: unravelling the differential impacts on breathing and airway stability.

التفاصيل البيبلوغرافية
العنوان: A comparative examination of morphine and fentanyl: unravelling the differential impacts on breathing and airway stability.
المؤلفون: Burgraff NJ; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA., Baertsch NA; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.; Department of Pediatrics, University of Washington, Seattle, WA, USA., Ramirez JM; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.; Department of Pediatrics, University of Washington, Seattle, WA, USA.; Department of Neurological Surgery, University of Washington, Seattle, WA, USA.
المصدر: The Journal of physiology [J Physiol] 2023 Oct; Vol. 601 (20), pp. 4625-4642. Date of Electronic Publication: 2023 Oct 01.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Cambridge Univ. Press Country of Publication: England NLM ID: 0266262 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-7793 (Electronic) Linking ISSN: 00223751 NLM ISO Abbreviation: J Physiol Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford : Blackwell : Cambridge Univ. Press
Original Publication: London, Cambridge Univ. Press.
مواضيع طبية MeSH: Morphine*/pharmacology , Respiratory Insufficiency*/chemically induced, Mice ; Animals ; Fentanyl/pharmacology ; Analgesics, Opioid ; Bronchodilator Agents/adverse effects ; Respiration ; Hypoxia ; Albuterol ; Epinephrine
مستخلص: This study provides an in-depth analysis of the distinct consequences of the opioid drugs morphine and fentanyl during opioid-induced respiratory depression (OIRD). We explored the physiological implications of both drugs on ventilation and airway patency in anaesthetized mice. Our results revealed a similar reduction in respiratory frequency with equivalent scaled dosages of fentanyl and morphine, though the onset of suppression was more rapid with fentanyl. Additionally, fentanyl resulted in transient airflow obstructions during the inspiratory cycle, which were absent following morphine administration. Notably, these fentanyl-specific obstructions were eliminated with tracheostomy, implicating the upper airways as a major factor contributing to fentanyl-induced respiratory depression. We further demonstrate that bronchodilators salbutamol and adrenaline effectively reversed these obstructions, highlighting the bronchi's contribution to fentanyl-induced airflow obstruction. Our study also uncovered a significant reduction in sighs during OIRD, which were eliminated by fentanyl and markedly reduced by morphine. Finally, we found that fentanyl-exposed mice had reduced survival under hypoxic conditions compared to mice given morphine, demonstrating that fentanyl becomes more lethal in the context of hypoxaemia. Our findings shed light on the distinct and profound impacts of these opioids on respiration and airway stability and lay the foundation for improved opioid use guidelines and more effective OIRD prevention strategies. KEY POINTS: Both morphine and fentanyl significantly suppressed respiratory frequency, but the onset of suppression was faster with fentanyl. Also, while both drugs increased tidal volume, this effect was more pronounced with fentanyl. Fentanyl administration resulted in transient obstructions during the inspiratory phase, suggesting its unique impact on airway stability. This obstruction was not observed with morphine. The fentanyl-induced obstructions were reversed by administering bronchodilators such as salbutamol and adrenaline. This suggests a possible therapeutic strategy for mitigating the adverse airway effects of fentanyl. Both drugs reduced the frequency of physiological sighs, a key mechanism to prevent alveolar collapse. However, fentanyl administration led to a complete cessation of sighs, while morphine only reduced their occurrence. Fentanyl-treated mice showed a significantly reduced ability to survive under hypoxic conditions compared to those administered morphine. This indicates that the impacts of hypoxaemia during opioid-induced respiratory depression can vary based on the opioid used.
(© 2023 The Authors. The Journal of Physiology © 2023 The Physiological Society.)
References: Anderson, T. M., Garcia, A. J., Baertsch, N. A., Pollak, J., Bloom, J. C., Wei, A. D., Rai, K. G., & Ramirez, J. M. (2016). A novel excitatory network for the control of breathing. Nature, 536(7614), 76-80.
Baertsch, N. A., Bush, N. E., Burgraff, N. J., & Ramirez, J. M. (2021). Dual mechanisms of opioid-induced respiratory depression in the inspiratory rhythm-generating network. eLife, 10, e67523.
Baldo, B. A., & Rose, M. A. (2022). Mechanisms of opioid-induced respiratory depression. Archives of Toxicology, 96(8), 2247-2260.
Baruah, U., Gaur, H., Saigal, D., & Pandey, D. (2022). Wooden chest syndrome: A curious case of fentanyl induced rigidity in adults. Indian Journal of Anaesthesiology, 66(12), 881-882.
Bateman, J. T., Saunders, S. E., & Levitt, E. S. (2023). Understanding and countering opioid-induced respiratory depression. British Journal of Pharmacology, 180(7), 813-828.
Bremer, P. T., Kimishima, A., Schlosburg, J. E., Zhou, B., Collins, K. C., & Janda, K. D. (2016). Combatting synthetic designer opioids: A conjugate vaccine ablates lethal doses of fentanyl class drugs. Angewandte Chemie (International ed in English), 55(11), 3772-3775.
Burgraff, N. J., Bush, N. E., Ramirez, J. M., & Baertsch, N. A. (2021). Dynamic rhythmogenic network states drive differential opioid responses in the. Journal of Neuroscience, 41(48), 9919-9931.
Burgraff, N. J., Phillips, R. S., Severs, L. J., Bush, N. E., Baertsch, N. A., & Ramirez, J. M. (2022). Inspiratory rhythm generation is stabilized by. Journal of Neurophysiology, 128(1), 181-196.
Cammarota, G., Vaschetto, R., Turucz, E., Dellapiazza, F., Colombo, D., Blando, C., Della Corte F, Maggiore SM, & Navalesi, P. (2011). Influence of lung collapse distribution on the physiologic response to recruitment maneuvers during noninvasive continuous positive airway pressure. Intensive Care Medicine, 37(7), 1095-1102.
Cao, M., Cardell, C. Y., Willes, L., Mendoza, J., Benjafield, A., & Kushida, C. (2014). A novel adaptive servoventilation (ASVAuto) for the treatment of central sleep apnea associated with chronic use of opioids. Journal of Clinical Sleep Medicine, 10(08), 855-861.
Dahan, A., Aarts, L., & Smith, T. W. (2010). Incidence, reversal, and prevention of opioid-induced respiratory depression. Anesthesiology, 112(1), 226-238.
El Baissari, M. C., Taha, S. K., & Siddik-Sayyid, S. M. (2014). Fentanyl-induced cough-pathophysiology and prevention. Middle East Journal of Anaesthesiology, 22(5), 449-456.
Filiatrault, M. L., Chauny, J. M., Daoust, R., Roy, M. P., Denis, R., & Lavigne, G. (2016). Medium increased risk for central sleep apnea but not obstructive sleep apnea in long-term opioid users: A systematic review and meta-analysis. Journal of Clinical Sleep Medicine, 12(04), 617-625.
Fu, M. J., Tsen, L. Y., Lee, T. Y., Lui, P. W., & Chan, S. H. (1997). Involvement of cerulospinal glutamatergic neurotransmission in fentanyl-induced muscular rigidity in the rat. Anesthesiology, 87(6), 1450-1459.
Furdui, A., da Silveira Scarpellini, C., & Montandon, G. (2023). Fentanyl-induced respiratory depression and locomotor hyperactivity are mediated by μ-opioid receptors expressed in somatostatin-negative neurons. eNeuro, 10(6), ENEURO.0035-23.2023.
Grell, F. L., Koons, R. A., & Denson, J. S. (1970). Fentanyl in anesthesia: A report of 500 cases. Anesthesia and Analgesia, 49(4), 523-532.
Grundy, D. (2015). Principles and standards for reporting animal experiments in The Journal of Physiology and Experimental Physiology. The Journal of Physiology, 593(12), 2547-2549.
Haouzi, P., & Tubbs, N. (2022). Effects of fentanyl overdose-induced muscle rigidity and dexmedetomidine on respiratory mechanics and pulmonary gas exchange in sedated rats. Journal of Applied Physiology, 132(6), 1407-1422.
Hess, D. R., & Bigatello, L. M. (2002). Lung recruitment: The role of recruitment maneuvers. Respiratory Care, 47(3), 308-317. ; discussion 317-308.
Hill, R., Santhakumar, R., Dewey, W., Kelly, E., & Henderson, G. (2020). Fentanyl depression of respiration: Comparison with heroin and morphine. British Journal of Pharmacology, 177(2), 254-265.
Hughes, S., & Smith, M. E. (1990). Opioid receptors in skeletal muscle of normal and dystrophic mice. Neuroscience Letters, 116(1-2), 29-33.
Kliewer, A., Gillis, A., Hill, R., Schmidel, F., Bailey, C., Kelly, E., Henderson, G., Christie, M. J., & Schulz, S. (2020). Morphine-induced respiratory depression is independent of β-arrestin2 signalling. British Journal of Pharmacology, 177(13), 2923-2931.
Koch, H., Caughie, C., Elsen, F. P., Doi, A., Garcia, A. J., Zanella, S., & Ramirez, J. M. (2015). Prostaglandin E2 differentially modulates the central control of eupnoea, sighs and gasping in mice. The Journal of Physiology, 593(1), 305-319.
Levitt, E. S., Abdala, A. P., Paton, J. F., Bissonnette, J. M., & Williams, J. T. (2015). μ opioid receptor activation hyperpolarizes respiratory-controlling Kölliker-Fuse neurons and suppresses post-inspiratory drive. The Journal of Physiology, 593(19), 4453-4469.
Li, P., & Yackle, K. (2017). Sighing. Current Biology, 27(3), R88-R89.
Lieske, S. P., Thoby-Brisson, M., Telgkamp, P., & Ramirez, J. M. (2000). Reconfiguration of the neural network controlling multiple breathing patterns: Eupnea, sighs and gasps. Nature Neuroscience, 3(6), 600-607.
Liu, S., Kim, D. I., Oh, T. G., Pao, G. M., Kim, J. H., Palmiter, R. D., Banghart, M. R., Lee, K. F., Evans, R. M., & Han, S. (2021). Neural basis of opioid-induced respiratory depression and its rescue. Proceedings of the National Academy of Sciences of the United States of America, 118(23), e2022134118.
Lui, P. W., Lee, T. Y., & Chan, S. H. (1989). Involvement of locus coeruleus and noradrenergic neurotransmission in fentanyl-induced muscular rigidity in the rat. Neuroscience Letters, 96(1), 114-119.
Mellen, N. M., Janczewski, W. A., Bocchiaro, C. M., & Feldman, J. L. (2003). Opioid-induced quantal slowing reveals dual networks for respiratory rhythm generation. Neuron, 37(5), 821-826.
Mendoza, J., Passafaro, R., Baby, S., Young, A. P., Bates, J. N., Gaston, B., & Lewis, S. J. (2013). L-Cysteine ethyl ester reverses the deleterious effects of morphine on, arterial blood-gas chemistry in tracheotomized rats. Respiratory Physiology & Neurobiology, 189(1), 136-143.
Miner, N. B., Schutzer, W. E., Zarnegarnia, Y., Janowsky, A., & Torralva, R. (2021). Fentanyl causes naloxone-resistant vocal cord closure: A platform for testing opioid overdose treatments. Drug and Alcohol Dependence, 227, 108974.
Mondal, S., Ghosh, S., Bhattacharya, S., Choudhury, B., Mallick, S., & Prasad, A. (2015). Comparison between dexmedetomidine and fentanyl on intubation conditions during awake fiberoptic bronchoscopy: A randomized double-blind prospective study. Journal of Anaesthesiology Clinical Pharmacology, 31(2), 212-216.
Montandon, G., Ren, J., Victoria, N. C., Liu, H., Wickman, K., Greer, J. J., & Horner, R. L. (2016). G-protein-gated inwardly rectifying potassium channels modulate respiratory depression by opioids. Anesthesiology, 124(3), 641-650.
Mubashir, T., Nagappa, M., Esfahanian, N., Botros, J., Arif, A. A., Suen, C., Wong, J., Ryan, C. M., & Chung, F. (2020). Prevalence of sleep-disordered breathing in opioid users with chronic pain: A systematic review and meta-analysis. Journal of Clinical Sleep Medicine, 16(6), 961-969.
Nicholson, B., & Verma, S. (2004). Comorbidities in chronic neuropathic pain. Pain Medicine, 5(Suppl 1), S9-S27.
Niesters, M., Overdyk, F., Smith, T., Aarts, L., & Dahan, A. (2013). Opioid-induced respiratory depression in paediatrics: A review of case reports. British Journal of Anaesthesia, 110(2), 175-182.
O'Donnell, J. K., Halpin, J., Mattson, C. L., Goldberger, B. A., & Gladden, R. M. (2017). Deaths involving fentanyl, fentanyl analogs, and U-47700 - 10 States, July-December 2016. Mmwr Morbidity and Mortality Weekly Report, 66(43), 1197-1202.
Palkovic, B., Marchenko, V., Zuperku, E. J., Stuth, E. A. E., & Stucke, A. G. (2020). Multi-level regulation of opioid-induced respiratory depression. Physiology, 35(6), 391-404.
Pergolizzi, J. V., Webster, L. R., Vortsman, E., Ann LeQuang, J., & Raffa, R. B. (2021). Wooden chest syndrome: The atypical pharmacology of fentanyl overdose. Journal of Clinical Pharmacy and Therapeutics, 46(6), 1505-1508.
Prekupec, M. P., Mansky, P. A., & Baumann, M. H. (2017). Misuse of novel synthetic opioids: A deadly new trend. Journal of Addiction Medicine, 11(4), 256-265.
Ramirez, J. M. (2014). The integrative role of the sigh in psychology, physiology, pathology, and neurobiology. Progress in Brain Research, 209, 91-129.
Ramirez, J. M., Burgraff, N. J., Wei, A. D., Baertsch, N. A., Varga, A. G., Baghdoyan, H. A., Lydic, R., Morris K. F., Bolser, D. C., & Levitt, E. S. (2021). Neuronal mechanisms underlying opioid-induced respiratory depression: Our current understanding. Journal of Neurophysiology, 125(5), 1899-1919.
Ramirez, J. M., Vlemincx, E., Baertsch, N. A., & Severs, L. J. (2022). The sigh and related behaviors. Handbook of Clinical Neurology, 188, 357-372.
Ren, J., Ding, X., Funk, G. D., & Greer, J. J. (2009). Ampakine CX717 protects against fentanyl-induced respiratory depression and lethal apnea in rats. Anesthesiology, 110(6), 1364-1370.
Rosal, N. R., Thelmo, F. L., Tzarnas, S., DiCalvo, L., Tariq, S., & Grossman, C. (2021). Wooden chest syndrome: A case report of fentanyl-induced chest wall rigidity. Journal of Investigative Medicine High Impact Case Reports, 9, 23247096211034036.
Saunders, S. E., & Levitt, E. S. (2020). Kölliker-Fuse/Parabrachial complex mu opioid receptors contribute to fentanyl-induced apnea and respiratory rate depression. Respiratory Physiology & Neurobiology, 275, 103388.
Scamman, F. L. (1983). Fentanyl-O2-N2O rigidity and pulmonary compliance. Anesthesia and Analgesia, 62(3), 332-334.
Severs, L. J., Vlemincx, E., & Ramirez, J. M. (2022). The psychophysiology of the sigh: I: The sigh from the physiological perspective. Biological Psychology, 170, 108313.
Shoemaker, A., Steelman, K., Srbu, R., & Bell, H. J. (2020). Disparity in the effect of morphine on eupnea and gasping in anesthetized spontaneously breathing adult rats. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 319(5), R526-R540.
Somerville, N. J., O'Donnell, J., Gladden, R. M., Zibbell, J. E., Green, T. C., Younkin, M., Ruiz, S., Babakhanlou-Chase, H., Chan, M., Callis, B. P., Kuramoto-Crawford, J., Nields, H. M., Walley, A. Y. (2017). Characteristics of fentanyl overdose - Massachusetts, 2014-2016. MMWR Morbidity and Mortality Weekly Report, 66(14), 382-386.
Streisand, J. B., Bailey, P. L., LeMaire, L., Ashburn, M. A., Tarver, S. D., Varvel, J., & Stanley, T. H. (1993). Fentanyl-induced rigidity and unconsciousness in human volunteers. Incidence, duration, and plasma concentrations. Anesthesiology, 78(4), 629-634.
Sun, X., Thörn Pérez, C., Halemani, D. N., Shao, X. M., Greenwood, M., Heath, S., Feldman, J. L., Kam, K. (2019). Opioids modulate an emergent rhythmogenic process to depress breathing. eLife, 8, e50613.
Torralva, R., & Janowsky, A. (2019). Noradrenergic mechanisms in fentanyl-mediated rapid death explain failure of naloxone in the opioid crisis. Journal of Pharmacology and Experimental Therapeutics, 371(2), 453-475.
van der Schier, R., Roozekrans, M., van Velzen, M., Dahan, A., & Niesters, M. (2014). Opioid-induced respiratory depression: Reversal by non-opioid drugs. F1000Prime Rep, 6, 79.
Viemari, J. C., Garcia, A. J., Doi, A., Elsen, G., & Ramirez, J. M. (2013). β-Noradrenergic receptor activation specifically modulates the generation of sighs in vivo and in vitro. Frontiers in Neural Circuits, 7, 179.
Walker, J. M., Farney, R. J., Rhondeau, S. M., Boyle, K. M., Valentine, K., Cloward, T. V., & Shilling, K. C. (2007). Chronic opioid use is a risk factor for the development of central sleep apnea and ataxic breathing. Journal of Clinical Sleep Medicine, 03(05), 455-461.
Wei, A. D., & Ramirez, J. M. (2019). Presynaptic mechanisms and KCNQ potassium channels modulate opioid depression of respiratory drive. Frontiers in Physiology, 10, 1407.
Zawilska, J. B. (2017). An expanding world of novel psychoactive substances: Opioids. Frontiers in Psychiatry, 8, 110.
Zebraski, S. E., Kochenash, S. M., & Raffa, R. B. (2000). Lung opioid receptors: Pharmacology and possible target for nebulized morphine in dyspnea. Life Sciences, 66(23), 2221-2231.
معلومات مُعتمدة: HL154558 United States HL NHLBI NIH HHS; HL090554 United States HL NHLBI NIH HHS; HL126523 United States HL NHLBI NIH HHS; HL144801 United States HL NHLBI NIH HHS; HL145004 United States HL NHLBI NIH HHS; R01 HL151389 United States HL NHLBI NIH HHS; P01 HL144454 United States HL NHLBI NIH HHS; R01 HL144801 United States HL NHLBI NIH HHS; HL151389 United States HL NHLBI NIH HHS; HL166317 United States HL NHLBI NIH HHS
فهرسة مساهمة: Keywords: breathing; control of breathing; opioid
المشرفين على المادة: 76I7G6D29C (Morphine)
UF599785JZ (Fentanyl)
0 (Analgesics, Opioid)
0 (Bronchodilator Agents)
QF8SVZ843E (Albuterol)
YKH834O4BH (Epinephrine)
تواريخ الأحداث: Date Created: 20231001 Date Completed: 20231023 Latest Revision: 20240613
رمز التحديث: 20240613
DOI: 10.1113/JP285163
PMID: 37778015
قاعدة البيانات: MEDLINE
الوصف
تدمد:1469-7793
DOI:10.1113/JP285163