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右美托咪定在分娩镇痛中的研究进展
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Abstract:
近年来，随着国家生育政策的放开，越来越多产妇会面临分娩方式抉择。自然分娩的疼痛，确实会让不少女性继续选择剖宫产，因此，为了减少剖宫产率，确切可靠的优质分娩镇痛效果显得尤为重要。右美托咪定(Dexmedetomidine, DEX)具有镇静镇痛、抗寒颤、抗谵妄、抗焦虑、抗抑郁、减少麻醉药用量、轻度呼吸抑制等诸多优势，其安全性和有效性，以及能够给患者提供一定程度的舒适度，使其成为一种重要的硬膜外分娩镇痛麻醉佐剂，广泛应用于临床。本文就其药理学特性、对机体的影响以及在分娩镇痛领域的应用进展进行综述，旨在为分娩镇痛用药提供参考和依据。
In recent years, with the opening of the national fertility policy, more and more women will face the choice of childbirth mode. The pain of natural childbirth will indeed make many women continue to choose cesarean section; therefore, in order to reduce the rate of cesarean section, the exact and re-liable high-quality analgesic effect of childbirth is particularly important. Dexmedetomidine (DEX) has the advantages of sedation and analgesia, anti-shivering, anti-delirium, anti-anxiety, an-ti-depression, reduced narcotic dosage, mild respiratory depression, etc. Its safety and efficacy, as well as its ability to provide patients with a certain degree of comfort, make it as an important an-esthetic adjuvant widely used for epidural labor pain relief. This article reviews its pharmacological properties, effects on the body and its application in the field of labor analgesia, in order to provide reference and basis for labor analgesia.
| [1] | Van de Velde, M. and Carvalho, B. (2016) Remifentanil for Labor Analgesia: An Evidence-Based Narrative Review. In-ternational Journal of Obstetric Anesthesia, 25, 66-74. https://doi.org/10.1016/j.ijoa.2015.12.004 |
| [2] | Mo, J., et al. (2022) Association between Perinatal Pain and Postpartum Depression: A Systematic Review and Meta-Analysis. Jour-nal of Affective Disorders, 312, 92-99. https://doi.org/10.1016/j.jad.2022.06.010 |
| [3] | Deng, C.-M., et al. (2021) Neuraxial Labor Analgesia Is Associated with a Reduced Risk of Postpartum Depression: A Multicenter Prospective Cohort Study with Propensity Score Matching. Journal of Affective Disorders, 281, 342-350.
https://doi.org/10.1016/j.jad.2020.12.027 |
| [4] | Anim-Somuah, M., Smyth, R.M. and Jones, L. (2011) Epidural versus Non-Epidural or No Analgesia in Labour. Cochrane Database of Systematic Reviews, No. 12, Article No. CD000331.
https://doi.org/10.1002/14651858.CD000331.pub3 |
| [5] | Sia, A.T., Kwek, K. and Yeo, G.S. (2005) The in Vitro Effects of Clonidine and Dexmedetomidine on Human Myometrium. International Journal of Obstetric Anesthesia, 14, 104-107. https://doi.org/10.1016/j.ijoa.2004.11.004 |
| [6] | Wang, C., et al. (2017) Effect and Placental Transfer of Dexmedetomidine during Caesarean Section under Epidural Anaesthesia. Journal of International Medical Research, 45, 964-972. https://doi.org/10.1177/0300060517698330 |
| [7] | Ala-Kokko, T.I., et al. (1997) Transfer of Clonidine and Dexmedetomidine Across the Isolated Perfused Human Placenta. Acta Anaesthesiologica Scandinavica, 41, 313-319. https://doi.org/10.1111/j.1399-6576.1997.tb04685.x |
| [8] | Belleville, J.P. et al. (1992) Effects of Intravenous Dex-medetomidine in Humans: I. Sedation, Ventilation, and Metabolic Rate. Anesthesiology, 77, 1125-1133. https://doi.org/10.1097/00000542-199212000-00013 |
| [9] | Keating, G.M. (2015) Dexmedetomidine: A Review of Its Use for Sedation in the Intensive Care Setting. Drugs, 75, 1119-1130. https://doi.org/10.1007/s40265-015-0419-5 |
| [10] | Cruickshank, M., et al. (2016) Alpha-2 Agonists for Sedation of Mechanically Ventilated Adults in Intensive Care Units: A Systematic Review. Health Technology Assessment, 20, 1-117. https://doi.org/10.3310/hta20250 |
| [11] | Virtanen, R., Savola, J.M., Saano, V. and Nyman, L. (1988) Characterization of the Selectivity, Specificity and Potency of Medetomidine as an α2-Adrenoceptor Agonist. European Journal of Phar-macology, 150, 9-14.
https://doi.org/10.1016/0014-2999(88)90744-3 |
| [12] | Anttila, M., Penttil？, J., Helminen, A., Vuorilehto, L. and Scheinin, H. (2003) Bioavailability of Dexmedetomidine after Extravascular Doses in Healthy Subjects. British Journal of Clinical Pharmacology, 56, 691-693.
https://doi.org/10.1046/j.1365-2125.2003.01944.x |
| [13] | Panzer, O., Moitra, V. and Sladen, R.N. (2011) Pharma-cology of Sedative-Analgesic Agents: Dexmedetomidine, Remifentanil, Ketamine, Volatile Anesthetics, and the Role of Peripheral Mu Antagonists. Anesthesiology Clinics, 29, 587-605. https://doi.org/10.1016/j.anclin.2011.09.002 |
| [14] | Rodrigues, A.D. and Roberts, E.M. (1997) The in Vitro Interac-tion of Dexmedetomidine with Human Liver Microsomal Cytochrome P4502D6 (CYP2D6). Drug Metabolism and Disposition, 25, 651-655. |
| [15] | Philipp, M., Brede, M. and Hein, L. (2002) Physiological Significance of α2-Adrenergic Receptor Subtype Diversity: One Receptor Is Not Enough. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 283, R287-R295. https://doi.org/10.1152/ajpregu.00123.2002 |
| [16] | Iirola, T., et al. (2011) Pharmacokinetics of Prolonged Infusion of High-Dose Dexmedetomidine in Critically Ill Patients. Critical Care, 15, Ar-ticle No. R257. https://doi.org/10.1186/cc10518 |
| [17] | Iirola, T., et al. (2012) Population Pharmacokinetics of Dex-medetomidine during Long-Term Sedation in Intensive Care Patients. British Journal of Anaesthesia, 108, 460-468. https://doi.org/10.1093/bja/aer441 |
| [18] | V？litalo, P.A., et al. (2013) Population Pharmacokinetics of Dexmedetomi-dine in Critically Ill Patients. Clinical Drug Investigation, 33, 579-587. https://doi.org/10.1007/s40261-013-0101-1 |
| [19] | Nelson, L.E., et al. (2003) The α2-Adrenoceptor Agonist Dexme-detomidine Converges on an Endogenous Sleep-Promoting Pathway to Exert Its Sedative Effects. Anesthesiology, 98, 428-436.
https://doi.org/10.1097/00000542-200302000-00024 |
| [20] | Nacif-Coelho, C., Correa-Sales, C., Chang, L.L. and Maze, M. (1994) Perturbation of Ion Channel Conductance Alters the Hypnotic Response to the α2-Adrenergic Agonist Dexmedetomidine in the Locus Coeruleus of the Rat. Anesthesiology, 81, 1527-1534. https://doi.org/10.1097/00000542-199412000-00029 |
| [21] | Ebert, T.J., Hall, J.E., Barney, J.A., Uhrich, T.D. and Colinco, M.D. (2000) The Effects of Increasing Plasma Concentrations of Dexmedetomidine in Humans. Anesthesiology, 93, 382-394.
https://doi.org/10.1097/00000542-200008000-00016 |
| [22] | Giovannitti, J.J., Thoms, S.M. and Crawford, J.J. (2015) Alpha-2 Adrenergic Receptor Agonists: A Review of Current Clinical Applications. Anesthesia Progress, 62, 31-39. https://doi.org/10.2344/0003-3006-62.1.31 |
| [23] | Panzer, O., Moitra, V. and Sladen, R.N. (2009) Pharmacology of Sedative-Analgesic Agents: Dexmedetomidine, Remifentanil, Ketamine, Volatile Anesthetics, and the Role of Peripheral Mu Antagonists. Critical Care Clinics, 25, 451-469.
https://doi.org/10.1016/j.ccc.2009.04.004 |
| [24] | Zhang, Z., et al. (2015) Neuronal Ensembles Sufficient for Recovery Sleep and the Sedative Actions of α2 Adrenergic Agonists. Nature Neuroscience, 18, 553-561. https://doi.org/10.1038/nn.3957 |
| [25] | Bekker, A. and Sturaitis, M.K. (2005) Dexmedetomidine for Neurological Surgery. Neurosurgery, 57, 1-10.
https://doi.org/10.1227/01.NEU.0000163476.42034.A1 |
| [26] | Hall, J.E., et al. (2000) Sedative, Amnestic, and An-algesic Properties of Small-Dose Dexmedetomidine Infusions. Anesthesia & Analgesia, 90, 699-705. https://doi.org/10.1097/00000539-200003000-00035 |
| [27] | Jun, J.H., Kim, K.N., Kim, J.Y. and Song, S.M. (2017) The Effects of Intranasal Dexmedetomidine Premedication in Children: A Systematic Review and Meta-Analysis. Cana-dian Journal of Anesthesia, 64, 947-961.
https://doi.org/10.1007/s12630-017-0917-x |
| [28] | Doze, V.A., Chen, B.-X. and Maze, M. (1989) Dexmedetomidine Produces a Hypnotic-Anesthetic Action in Rats via Activation of Central Alpha-2 Adrenoceptors. Anesthesiology, 71, 75-79.
https://doi.org/10.1097/00000542-198907000-00014 |
| [29] | Blaudszun, G., Lysakowski, C., Elia, N. and Tramèr, M.R. (2012) Effect of Perioperative Systemic α2 Agonists on Postoperative Morphine Consumption and Pain Intensity: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Anesthesiology, 116, 1312-1322. https://doi.org/10.1097/ALN.0b013e31825681cb |
| [30] | Venn, R.M., et al. (1999) Preliminary UK Experience of Dexmedetomidine, a Novel Agent for Postoperative Sedation in the Intensive Care Unit. Anaesthesia, 54, 1136-1142. https://doi.org/10.1046/j.1365-2044.1999.01114.x |
| [31] | Li, Z., et al. (2015) A Randomised Controlled Trial to Evaluate the Effectiveness of Intrathecal Bupivacaine Combined with Different Adjuvants (Fentanyl, Clonidine and Dexmedetomidine) in Caesarean Section. Drug Research, 65, 581-586.
https://doi.org/10.1055/s-0034-1395614 |
| [32] | Li, Y.Z., Jiang, Y., Lin, H. and Yang, X.P. (2019) Subarachnoid and Epidural Dexmedetomidine for the Prevention of Post-Anesthetic Shivering: A Meta-Analysis and Systematic Review. Drug Design, Development and Therapy, 13, 3785-3798. https://doi.org/10.2147/DDDT.S204411 |
| [33] | Lawhead, R.G., Blaxall, H.S. and Bylund, D.B. (1992) α-2A Is the Predominant α-2 Adrenergic Receptor Subtype in Human Spi-nal Cord. Anesthesiology, 77, 983-991. https://doi.org/10.1097/00000542-199211000-00022 |
| [34] | Kanazi, G.E., et al. (2006) Effect of Low-Dose Dexmedetomidine or Clonidine on the Characteristics of Bupivacaine Spinal Block. Acta Anaesthesiologica Scandinavica, 50, 222-227. https://doi.org/10.1111/j.1399-6576.2006.00919.x |
| [35] | Zhang, X., Wang, D., Shi, M. and Luo, Y. (2017) Efficacy and Safety of Dexmedetomidine as an Adjuvant in Epidural Analgesia and Anesthesia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Clinical Drug Investigation, 37, 343-354. https://doi.org/10.1007/s40261-016-0477-9 |
| [36] | Zhao, Y., Xin, Y., Liu, Y., Yi, X. and Liu, Y. (2017) Effect of Epidural Dexmedetomidine Combined with Ropivacaine in Labor Analgesia: A Randomized Double-Blinded Controlled Study. The Clinical Journal of Pain, 33, 319-324.
https://doi.org/10.1097/AJP.0000000000000411 |
| [37] | Li, L., Yang, Z. and Zhang, W. (2021) Epidural Dexme-detomidine for Prevention of Intrapartum Fever during Labor Analgesia: A Randomized Controlled Trial. Pain and Therapy, 10, 391-400.
https://doi.org/10.1007/s40122-020-00215-y |
| [38] | Pang, R.-Y., et al. (2022) Comparison of Epidural Dexme-detomidine to Fentanyl in Reducing Ropivacaine Dose in Programmed Intermittent Epidural Bolus Plus Patient Con-trolled Epidural Analgesia During Labor: A Randomized, Double-Blind, Controlled Study. Frontiers in Medicine, 9, Ar-ticle 935643. https://doi.org/10.3389/fmed.2022.935643 |
| [39] | Zhang, T., Yu, Y., Zhang, W. and Zhu, J. (2019) Comparison of Dexmedetomidine and Sufentanil as Adjuvants to Local Anesthetic for Epidural Labor Analgesia: A Randomized Controlled Trial. Drug Design, Development and Therapy, 13, 1171-1175. https://doi.org/10.2147/DDDT.S197431 |
| [40] | Zhang, W. and Li, C. (2018) EC50 of Epidural Ropivacaine Combined with Dexmedetomidine for Labor Analgesia. The Clinical Journal of Pain, 34, 950-953. https://doi.org/10.1097/AJP.0000000000000613 |
| [41] | Chen, X., Cai, M., Lei, X.F. and Yu, J. (2021) Obesity De-creases the EC50 of Epidural Ropivacaine When Combined with Dexmedetomidine for Labor Analgesia. Expert Review of Clinical Pharmacology, 14, 1051-1056.
https://doi.org/10.1080/17512433.2021.1929924 |
| [42] | Li, G., et al. (2020) Combination of Sufentanil, Dexme-detomidine and Ropivacaine to Improve Epidural Labor Analgesia Effect: A Randomized Controlled Trial. Experimental and Therapeutic Medicine, 20, 454-460.
https://doi.org/10.3892/etm.2020.8730 |
| [43] | Jain, A., Mittal, A., Sharma, S. and Deep, A. (2022) Comparative Evaluation of Intrathecal Dexmedetomidine and Fentanyl as an Adjuvant for Combined Spinal-Epidural Analgesia for Labor. Anesthesia: Essays and Researches, 16, 197-202. https://doi.org/10.4103/aer.aer_73_22 |
| [44] | Li, G., Wang, H., Qi, X., Huang, X. and Li, Y. (2021) Intrathecal Dexmedetomidine Improves Epidural Labor Analgesia Effects: A Randomized Controlled Trial. Journal of International Medical Research, 49, Article ID: 300060521999534.
https://doi.org/10.1177/0300060521999534 |
| [45] | 吴新民, 等. 右美托咪定临床应用专家共识[J]. 临床麻醉学杂志, 2018, 34(8): 820-823. |
| [46] | Abdalla, W., Ammar, M.A. and Tharwat, A.I. (2015) Combination of Dexmedetomi-dine and Remifentanil for Labor Analgesia: A Double-Blinded, Randomized, Controlled Study. Saudi Journal of Anaes-thesia, 9, 433-438.
https://doi.org/10.4103/1658-354X.159470 |
| [47] | Palanisamy, A., Klickovich, R.J., Ramsay, M., Ouyang, D.W. and Tsen, L.C. (2009) Intravenous Dexmedetomidine as an Adjunct for Labor Analgesia and Cesarean Delivery Anesthesia in a Parturient with a Tethered Spinal Cord. International Journal of Obstetric Anesthesia, 18, 258-261. https://doi.org/10.1016/j.ijoa.2008.10.002 |
