右美托咪定在骨科手术中的应用进展
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摘要
右美托咪定为美托咪定的右旋对映体,是一种高选择性α2-肾上腺素能受体激动剂,具有多种药理特性,在麻醉领域得到了较充分的应用。骨科手术使患者受到的创伤以及术后疼痛与其他手术相比往往更严重,并发症也更多,甚至影响患者预后。由于右美托咪定具有镇静、镇痛、抗焦虑、抗炎、抗交感神经等作用,加之该药安全性高,对呼吸循环系统影响较小,近年其在骨科手术中的应用愈加广泛和深入。本文分别从镇痛、抗炎、镇静、术中唤醒、术后认知功能障碍、剂量与不良反应等方面介绍右美托咪定在骨科手术中的应用状况及研究进展,以期指导未来的临床应用和研究。
Dexmedetomidine, or 4-[(1 S)-1-(2, 3-dimethylphenyl)ethyl]-1 H-imidazole, with molecular formula C_(13) H_(16) N_2, is a highly selective alpha 2 adrenergic receptor agonist with multiple pharmacological properties and has been fully applied in the field of anesthesia. Orthopedic surgeries often result in more severe trauma and postoperative pain compared to other procedures, with more complications and even affecting prognosis of patients. Due to its sedative,analgesic, anti-anxiety, anti-inflammatory, and anti-sympathetic effects, dexmedetomidine has little impact on respiratory and circulatory systems. In recent years, the application of dexmedetomidine in orthopedic surgery has become more comprehensive and in-depth. This article introduces the application and research progress of dexmedetomidine in orthopedicsurgery including analgesia, anti-inflammation, sedation, intraoperative arousal, postoperative cognitive dysfunction, dosageand adverse reactions, hoping to guide further clinical applications and researches.
Dexmedetomidine, or 4-[(1 S)-1-(2, 3-dimethylphenyl)ethyl]-1 H-imidazole, with molecular formula C_(13) H_(16) N_2, is a highly selective alpha 2 adrenergic receptor agonist with multiple pharmacological properties and has been fully applied in the field of anesthesia. Orthopedic surgeries often result in more severe trauma and postoperative pain compared to other procedures, with more complications and even affecting prognosis of patients. Due to its sedative,analgesic, anti-anxiety, anti-inflammatory, and anti-sympathetic effects, dexmedetomidine has little impact on respiratory and circulatory systems. In recent years, the application of dexmedetomidine in orthopedic surgery has become more comprehensive and in-depth. This article introduces the application and research progress of dexmedetomidine in orthopedicsurgery including analgesia, anti-inflammation, sedation, intraoperative arousal, postoperative cognitive dysfunction, dosageand adverse reactions, hoping to guide further clinical applications and researches.
引文
[1]Weerink MAS,Struys MMRF,Hannivoort LN,et al.Clinical pharmacokinetics and pharmacodynamics of dexmedetomidine[J].Clin Pharmacokinet,2017,56(8):893-913.doi:10.1007/s40262-017-0507-7.
[2]吴新民,薛张纲,马虹,等.右美托咪定临床应用专家共识(2018)[J].临床麻醉学杂志,2018,34(8):820-823.Wu XM,Xue ZG,Ma H,et al.Expert consensus on the clinical application of dexmedetomidine(2018)[J].J Clin Anesthesiol,2018,34(8):820-823.doi:10.12089/jca.2018.08.024.
[3]Hall JE,Uhrich TD,Barney JA,et al.Sedative,amnestic,and analgesic properties of small-dose dexmedetomidine infusions[J].Anesth Analg,2000,90(3):699-705.
[4]Park SJ,Shin S,Kim SH,et al.Comparison of dexmedetomidine and fentanyl as an adjuvant to ropivacaine for postoperative epidural analgesia in pediatric orthopedic surgery[J].Yonsei Med J,2017,58(3):650-657.doi:10.3349/ymj.2017.58.3.650.
[5]Ortiz-Gómez JR,Perepérez-Candel M,Vázquez-Torres JM,et al.Postoperative analgesia for elective total knee arthroplasty under subarachnoid anesthesia with opioids:comparison between epidural,femoral block and adductor canal block techniques(with and without perineural adjuvants).A prospective,randomized,clinical trial[J].Minerva Anestesiol,2017,83(1):50-58.doi:10.23736/S0375-9393.16.11646-3.
[6]Cheah JW,Sing DC,Mclaughlin D,et al.The perioperative effects of chronic preoperative opioid use on shoulder arthroplasty outcomes[J].J Shoulder Elbow Surg,2017,26(11):1908-1914.doi:10.1016/j.jse.2017.05.016.
[7]Rokhtabnak F,Ale Bouyeh MR,Seyed Siamdust A,et al.Comparison of the effects of intra-articular sole ropivacaine and combined ketorolac and ropivacaine for pain control after knee arthroscopy surgery[J].Br J Pain,2015,9(3):149-156.doi:10.1177/2049463714553312.
[8]Mitra S,Purohit S,Sharma M.Postoperative analgesia after wound infiltration with tramadol and dexmedetomidine as an adjuvant to ropivacaine for lumbar discectomies:a randomized-controlled clinical trial[J].J Neurosurg Anesthesiol,2017,29(4):433-438.doi:10.1097/ANA.0000000000000422.
[9]Hussain N,Grzywacz VP,Ferreri CA,et al.Investigating the efficacy of dexmedetomidine as an adjuvant to local anesthesia in brachial plexus block:a systematic review and Meta-analysis of 18randomized controlled trials[J].Reg Anesth Pain Med,2017,42(2):184-196.doi:10.1097/AAP.0000000000000564.
[10]Nguyen V,Tiemann D,Park E,et al.Alpha-2 Agonists[J].Anesthesiol Clin,2017,35(2):233-245.doi:10.1016/j.anclin.2017.01.009.
[11]Brummett CM,Hong EK,Janda AM,et al.Perineural dexmedetomidine added to ropivacaine for sciatic nerve block in rats prolongs the duration of analgesia by blocking the hyperpolarization-activated cation current[J].Anesthesiology,2011,115(4):836-843.doi:10.1097/ALN.0b013e318221fcc9.
[12]Andersen JH,Grevstad U,Siegel H,et al.Does dexmedetomidine have a perineural mechanism of action when used as an adjuvant to ropivacaine?:a paired,blinded,randomized trial in healthy volunteers[J].Anesthesiology,2017,126(1):66-73.doi:10.1097/ALN.0000000000001429.
[13]Li J,Wang H,Dong B,et al.Adding dexmedetomidine to ropivacaine for femoral nerve block inhibit local inflammatory response[J].Minerva Anestesiol,2017,83(6):590-597.doi:10.23736/S0375-9393.17.11430-6.
[14]Zhou H,Lu J,Shen Y,et al.Effects of dexmedetomidine on CD42a+/CD14+,HLADR+/CD14+and inflammatory cytokine levels in patients undergoing multilevel spinal fusion[J].Clin Neurol Neurosurg,2017,160:54-58.doi:10.1016/j.clineuro.2017.06.012.
[15]叶贵光,梁家新,莫振科,等.右美托咪定对下肢手术患者止血带诱发肢体缺血-再灌注损伤的影响[J].现代生物医学进展,2017,17(28):5578-5581.Ye GG,Liang JX,Mo ZK,et al.Effect of dexmedetomidine on the patients with lower limb surgery tourniquet induced limb ischemia-reperfusion injury[J].Prog Mod Biomed,2017,17(28):5578-5581.doi:10.13241/j.cnki.pmb.2017.28.041.
[16]He H,Zhou Y,Zhou Y,et al.Dexmedetomidine mitigates microglia-mediated neuroinflammation through upregulation of programmed cell death protein 1 in a rat spinal cord injury model[J].J Neurotraum,2018,35(21):2591-2603.doi:10.1089/neu.2017.5625.
[17]Chen J,Li H,Lim G,et al.Different effects of dexmedetomidine and midazolam on the expression of NR2B and GABAA-α1following peripheral nerve injury in rats[J].IUBMB Life,2018,70(2):143-152.doi:10.1002/iub.1713.
[18]Ng KT,Shubash CJ,Chong JS.The effect of dexmedetomidine on delirium and agitation in patients in intensive care:systematic review and meta-analysis with trial sequential analysis[J].Anaesthesia,2019,74(3):380-392.doi:10.1111/anae.14472.
[19]夏丽花,贺涛,伍国芳,等.右美托咪定在老年髋关节置换术中镇静及遗忘效果的临床观察[J].齐齐哈尔医学院学报,2017,38(18):2126-2128.Xia LH,He T,Wu GF,et al.Clinical observation of sedation and forgetting effect of dexmedetomidine in elderly hip replacement[J].J Qiqihar Med U,2017,38(18):2126-2128.
[20]Duan X,Coburn M,Rossaint R,et al.Efficacy of perioperative dexmedetomidine on postoperative delirium:systematic review and Meta-analysis with trial sequential analysis of randomised controlled trials[J].Br J Anaesth,2018,121(2):384-397.doi:10.1016/j.bja.2018.04.046.
[21]Lee C,Lee CH,Lee G,et al.The effect of the timing and dose of dexmedetomidine on postoperative delirium in elderly patients after laparoscopic major non-cardiac surgery:a double blind randomized controlled study[J].J Clin Anesth,2018,47:27-32.doi:10.1016/j.jclinane.2018.03.007.
[22]Shin HJ,Koo BW,Bang SU,et al.Intraoperative dexmedetomidine sedation reduces the postoperative agitated behaviour in elderly patients undergoing orthopaedic surgery compared to the propofol sedation[J].Minerva Anestesiol,2017,83(10):1042-1050.doi:10.23736/S0375-9393.17.11794-3.
[23]Sanders RD,Maze M.Contribution of sedative-hypnotic agents to delirium via modulation of the sleep pathway[J].Can J Anaesth,2011,58(2):149-156.doi:10.1007/s12630-010-9421-2.
[24]Zaal IJ,Slooter AJ.Delirium in critically ill patients:epidemiology,pathophysiology,diagnosis and management[J].Drugs,2012,72(11):1457-1471.doi:10.2165/11635520-000000000-00000.
[25]Lu J,Chen G,Zhou H,et al.Effect of parecoxib sodium pretreatment combined with dexmedetomidine on early postoperative cognitive dysfunction in elderly patients after shoulder arthroscopy:a randomized double blinded controlled trial[J].J Clin Anesth,2017,41:30-34.doi:10.1016/j.jclinane.2017.06.004.
[26]Su X,Meng ZT,Wu XH,et al.Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery:a randomised,double-blind,placebo-controlled trial[J].Lancet,2016,388(10054):1893-1902.doi:10.1016/S0140-6736(16)30580-3.
[27]Chen Z,Dai N,Lin S,et al.Impact of dexmedetomidine on intraoperative wake-up tests in patients undergoing spinal surgery[J].J Perianesth Nurs,2018,33(4):448-452.doi:10.1016/j.jopan.2016.07.009.
[28]Shukry M,Miller JA.Update on dexmedetomidine:use in nonintubated patients requiring sedation for surgical procedures[J].Ther Clin Risk Manag,2010,6:111-121.
[29]Kang R,Jeong JS,Yoo JC,et al.Effective dose of intravenous dexmedetomidine to prolong the analgesic duration of interscalene brachial plexus block:a single-center,prospective,double-blind,randomized controlled trial[J].Reg Anesth Pain Med,2018,43(5):488-495.doi:10.1097/AAP.0000000000000773.
[30]Abdulatif M,Fawzy M,Nassar H,et al.The effects of perineural dexmedetomidine on the pharmacodynamic profile of femoral nerve block:a dose-finding randomised,controlled,double-blind study[J].Anaesthesia,2016,71(10):1177-1185.doi:10.1111/anae.13603.
[31]Rahimzadeh P,Faiz SHR,Imani F,et al.Comparative addition of dexmedetomidine and fentanyl to intrathecal bupivacaine in orthopedic procedure in lower limbs[J].BMC Anesthesiol,2018,18(1):62.doi:10.1186/s12871-018-0531-7.
[32]Hong B,Jung C,Jo Y,et al.Sedation with dexmedetomidine prolongs the analgesic duration of brachial plexus block:a randomised controlled trial[J].Anaesth Crit Care Pain Med,2018,pii:S2352-5568(18)30139-5.doi:10.1016/j.accpm.2018.08.006.
[33]Bicer C,Esmaoglu A,Akin A,et al.Dexmedetomidine and meperidine prevent postanaesthetic shivering[J].Eur JAnaesthesiol,2006,23(2):149-153.doi:10.1017/S0265021505002061.
[2]吴新民,薛张纲,马虹,等.右美托咪定临床应用专家共识(2018)[J].临床麻醉学杂志,2018,34(8):820-823.Wu XM,Xue ZG,Ma H,et al.Expert consensus on the clinical application of dexmedetomidine(2018)[J].J Clin Anesthesiol,2018,34(8):820-823.doi:10.12089/jca.2018.08.024.
[3]Hall JE,Uhrich TD,Barney JA,et al.Sedative,amnestic,and analgesic properties of small-dose dexmedetomidine infusions[J].Anesth Analg,2000,90(3):699-705.
[4]Park SJ,Shin S,Kim SH,et al.Comparison of dexmedetomidine and fentanyl as an adjuvant to ropivacaine for postoperative epidural analgesia in pediatric orthopedic surgery[J].Yonsei Med J,2017,58(3):650-657.doi:10.3349/ymj.2017.58.3.650.
[5]Ortiz-Gómez JR,Perepérez-Candel M,Vázquez-Torres JM,et al.Postoperative analgesia for elective total knee arthroplasty under subarachnoid anesthesia with opioids:comparison between epidural,femoral block and adductor canal block techniques(with and without perineural adjuvants).A prospective,randomized,clinical trial[J].Minerva Anestesiol,2017,83(1):50-58.doi:10.23736/S0375-9393.16.11646-3.
[6]Cheah JW,Sing DC,Mclaughlin D,et al.The perioperative effects of chronic preoperative opioid use on shoulder arthroplasty outcomes[J].J Shoulder Elbow Surg,2017,26(11):1908-1914.doi:10.1016/j.jse.2017.05.016.
[7]Rokhtabnak F,Ale Bouyeh MR,Seyed Siamdust A,et al.Comparison of the effects of intra-articular sole ropivacaine and combined ketorolac and ropivacaine for pain control after knee arthroscopy surgery[J].Br J Pain,2015,9(3):149-156.doi:10.1177/2049463714553312.
[8]Mitra S,Purohit S,Sharma M.Postoperative analgesia after wound infiltration with tramadol and dexmedetomidine as an adjuvant to ropivacaine for lumbar discectomies:a randomized-controlled clinical trial[J].J Neurosurg Anesthesiol,2017,29(4):433-438.doi:10.1097/ANA.0000000000000422.
[9]Hussain N,Grzywacz VP,Ferreri CA,et al.Investigating the efficacy of dexmedetomidine as an adjuvant to local anesthesia in brachial plexus block:a systematic review and Meta-analysis of 18randomized controlled trials[J].Reg Anesth Pain Med,2017,42(2):184-196.doi:10.1097/AAP.0000000000000564.
[10]Nguyen V,Tiemann D,Park E,et al.Alpha-2 Agonists[J].Anesthesiol Clin,2017,35(2):233-245.doi:10.1016/j.anclin.2017.01.009.
[11]Brummett CM,Hong EK,Janda AM,et al.Perineural dexmedetomidine added to ropivacaine for sciatic nerve block in rats prolongs the duration of analgesia by blocking the hyperpolarization-activated cation current[J].Anesthesiology,2011,115(4):836-843.doi:10.1097/ALN.0b013e318221fcc9.
[12]Andersen JH,Grevstad U,Siegel H,et al.Does dexmedetomidine have a perineural mechanism of action when used as an adjuvant to ropivacaine?:a paired,blinded,randomized trial in healthy volunteers[J].Anesthesiology,2017,126(1):66-73.doi:10.1097/ALN.0000000000001429.
[13]Li J,Wang H,Dong B,et al.Adding dexmedetomidine to ropivacaine for femoral nerve block inhibit local inflammatory response[J].Minerva Anestesiol,2017,83(6):590-597.doi:10.23736/S0375-9393.17.11430-6.
[14]Zhou H,Lu J,Shen Y,et al.Effects of dexmedetomidine on CD42a+/CD14+,HLADR+/CD14+and inflammatory cytokine levels in patients undergoing multilevel spinal fusion[J].Clin Neurol Neurosurg,2017,160:54-58.doi:10.1016/j.clineuro.2017.06.012.
[15]叶贵光,梁家新,莫振科,等.右美托咪定对下肢手术患者止血带诱发肢体缺血-再灌注损伤的影响[J].现代生物医学进展,2017,17(28):5578-5581.Ye GG,Liang JX,Mo ZK,et al.Effect of dexmedetomidine on the patients with lower limb surgery tourniquet induced limb ischemia-reperfusion injury[J].Prog Mod Biomed,2017,17(28):5578-5581.doi:10.13241/j.cnki.pmb.2017.28.041.
[16]He H,Zhou Y,Zhou Y,et al.Dexmedetomidine mitigates microglia-mediated neuroinflammation through upregulation of programmed cell death protein 1 in a rat spinal cord injury model[J].J Neurotraum,2018,35(21):2591-2603.doi:10.1089/neu.2017.5625.
[17]Chen J,Li H,Lim G,et al.Different effects of dexmedetomidine and midazolam on the expression of NR2B and GABAA-α1following peripheral nerve injury in rats[J].IUBMB Life,2018,70(2):143-152.doi:10.1002/iub.1713.
[18]Ng KT,Shubash CJ,Chong JS.The effect of dexmedetomidine on delirium and agitation in patients in intensive care:systematic review and meta-analysis with trial sequential analysis[J].Anaesthesia,2019,74(3):380-392.doi:10.1111/anae.14472.
[19]夏丽花,贺涛,伍国芳,等.右美托咪定在老年髋关节置换术中镇静及遗忘效果的临床观察[J].齐齐哈尔医学院学报,2017,38(18):2126-2128.Xia LH,He T,Wu GF,et al.Clinical observation of sedation and forgetting effect of dexmedetomidine in elderly hip replacement[J].J Qiqihar Med U,2017,38(18):2126-2128.
[20]Duan X,Coburn M,Rossaint R,et al.Efficacy of perioperative dexmedetomidine on postoperative delirium:systematic review and Meta-analysis with trial sequential analysis of randomised controlled trials[J].Br J Anaesth,2018,121(2):384-397.doi:10.1016/j.bja.2018.04.046.
[21]Lee C,Lee CH,Lee G,et al.The effect of the timing and dose of dexmedetomidine on postoperative delirium in elderly patients after laparoscopic major non-cardiac surgery:a double blind randomized controlled study[J].J Clin Anesth,2018,47:27-32.doi:10.1016/j.jclinane.2018.03.007.
[22]Shin HJ,Koo BW,Bang SU,et al.Intraoperative dexmedetomidine sedation reduces the postoperative agitated behaviour in elderly patients undergoing orthopaedic surgery compared to the propofol sedation[J].Minerva Anestesiol,2017,83(10):1042-1050.doi:10.23736/S0375-9393.17.11794-3.
[23]Sanders RD,Maze M.Contribution of sedative-hypnotic agents to delirium via modulation of the sleep pathway[J].Can J Anaesth,2011,58(2):149-156.doi:10.1007/s12630-010-9421-2.
[24]Zaal IJ,Slooter AJ.Delirium in critically ill patients:epidemiology,pathophysiology,diagnosis and management[J].Drugs,2012,72(11):1457-1471.doi:10.2165/11635520-000000000-00000.
[25]Lu J,Chen G,Zhou H,et al.Effect of parecoxib sodium pretreatment combined with dexmedetomidine on early postoperative cognitive dysfunction in elderly patients after shoulder arthroscopy:a randomized double blinded controlled trial[J].J Clin Anesth,2017,41:30-34.doi:10.1016/j.jclinane.2017.06.004.
[26]Su X,Meng ZT,Wu XH,et al.Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery:a randomised,double-blind,placebo-controlled trial[J].Lancet,2016,388(10054):1893-1902.doi:10.1016/S0140-6736(16)30580-3.
[27]Chen Z,Dai N,Lin S,et al.Impact of dexmedetomidine on intraoperative wake-up tests in patients undergoing spinal surgery[J].J Perianesth Nurs,2018,33(4):448-452.doi:10.1016/j.jopan.2016.07.009.
[28]Shukry M,Miller JA.Update on dexmedetomidine:use in nonintubated patients requiring sedation for surgical procedures[J].Ther Clin Risk Manag,2010,6:111-121.
[29]Kang R,Jeong JS,Yoo JC,et al.Effective dose of intravenous dexmedetomidine to prolong the analgesic duration of interscalene brachial plexus block:a single-center,prospective,double-blind,randomized controlled trial[J].Reg Anesth Pain Med,2018,43(5):488-495.doi:10.1097/AAP.0000000000000773.
[30]Abdulatif M,Fawzy M,Nassar H,et al.The effects of perineural dexmedetomidine on the pharmacodynamic profile of femoral nerve block:a dose-finding randomised,controlled,double-blind study[J].Anaesthesia,2016,71(10):1177-1185.doi:10.1111/anae.13603.
[31]Rahimzadeh P,Faiz SHR,Imani F,et al.Comparative addition of dexmedetomidine and fentanyl to intrathecal bupivacaine in orthopedic procedure in lower limbs[J].BMC Anesthesiol,2018,18(1):62.doi:10.1186/s12871-018-0531-7.
[32]Hong B,Jung C,Jo Y,et al.Sedation with dexmedetomidine prolongs the analgesic duration of brachial plexus block:a randomised controlled trial[J].Anaesth Crit Care Pain Med,2018,pii:S2352-5568(18)30139-5.doi:10.1016/j.accpm.2018.08.006.
[33]Bicer C,Esmaoglu A,Akin A,et al.Dexmedetomidine and meperidine prevent postanaesthetic shivering[J].Eur JAnaesthesiol,2006,23(2):149-153.doi:10.1017/S0265021505002061.