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1、右旋美托嘧啶的术后镇痛应用,南京大学医学院附属鼓楼医院麻醉科 顾小萍,镇痛 镇静 精准麻醉 可视化操作,麻醉医师，是舒适化医疗的主要参与者,刺激交感系统 增加心肌氧耗 延缓患者自主活动恢复 改变免疫系统 诱发慢性疼痛,术后镇痛，是舒适化医疗的重要组成,右旋美托咪啶:Dexmedetomidine,高效、高选择性和特异性的2受体激动剂 抑制交感神经活性 镇静、催眠和麻醉作用 镇痛作用,镇静作用,蓝斑是大脑内负责调解觉醒与睡眠的关键部位 蓝斑是下行延髓- 脊髓去甲肾上腺素能通路的起源，其在伤害性神经递质的调控中起重要作用,2-受体激动剂作用于去甲肾上腺素能神经元突触前膜2-受体，减少去甲肾上腺素释
2、放，从而产生镇静作用。,皮层,丘脑,中脑,延髓,镇痛作用的位点可能位于脊髓，脊髓中存在肾上腺素能下行抑制系统。2-受体激动剂激动脊髓背角2-受体，产生镇痛作用。,镇痛作用,对循环系统的影响,作用于中枢，抑制交感神经发放冲动，从而使血压下降、心率减慢。 作用于外周血管平滑肌的2B-受体，可使血管收缩，出现一过性的血压升高，小剂量缓慢注射可避免这一现象的出现。,对其它系统的影响,呼吸系统 无明显呼吸抑制 肾脏功能 利尿作用 内分泌系统 减少去甲肾上腺素、胰岛 素、皮质醇的释放。,DEX作为关节腔的注射用药在术后镇痛中的应用 DEX作为神经阻滞的复合用药在术后镇痛中的应用 DEX作为阿片类药物的辅助
3、用药术后镇痛中的应用,DEX在术后镇痛中的应用,DEX作为关节腔的注射用药在术后镇痛中的应用,Sixty patients ， double-blind placebo controlled . control group: i.v. 20ml saline and intra-articular 20ml saline the intra-articular group: i.v. 20ml saline and intra-articular 20ml saline+dexmedetomidine1ug/kg the i.v. group : i.v. 20ml saline+dexmed
4、etomidine1ug/kg and intra-articular 20ml saline.,significant reduction in pain scores for 6 h after operation in the intra-articular group but only for 1 h in the i.v. group. The time to first postoperative analgesic request was longer in the intra-articular group 312.0 (SD 120.7) min compared with
5、the control group 71.0 (50.1) min and the i.v. group 102.1 (54.4) min (P0.001). total diclofenac requirement was significantly lower in the intra-articular group 90.0 (46.2) mg than in the control group 165.0 (52.2) mg and in the i.v. group 129.3 (54.3) mg (P0.05).,Pain relief after Arthroscopic Kne
6、e Surgery: A comparison of intra-articular ropivacaine, fentanyl, and dexmedetomidine: A prospective, double-blinded, randomized controlled study. Manuar MB1, Majumdar S1, Das A2, Hajra BK1, Dutta S3, Mukherjee D1, Mitra T4, Kundu R4. Saudi J Anaesth. 2014 Apr;8(2):233-7.,MATERIALS AND METHODS: Marc
7、h 2008 to July 2010, in a prospective double-blinded fashion. Group A received 10 ml of 0.75% ropivacaine Group B received 50 g fentanyl Group C received 100 g of dexmedetomidine through the intra-articular route at the end of procedure. Pain assessed using visual analog scale and diclofenac sodium
8、given as rescue analgesia when VAS 4. Time of first analgesia request and total rescue analgesic used in 24 hours were calculated.,RESULTS: Time for requirement of first postoperative rescue analgesia in Group A was 380.61 22.973 min, in Group B was 326.82 17.131 min and in Group C was 244.09 20.096
9、 minutes. Total rescue analgesia requirement was less in Group A (1.394 0.496) compared to Group B (1.758 0.435) and Group C (2.546 0.546). Group A had higher mean VAS score at 6(th) and 24(th) postoperative hours. No side effects found among the groups.,CONCLUSION: intra-articular ropivacaine gives
10、 better postoperative pain relief increased time of first analgesic request decreased need of total postoperative analgesia compared to fentanyl and dexmedetomidine.,DEX作为神经阻滞的复合用药 药在术后镇痛中的应用,DEX作为阿片类药物的辅助用药在术后镇痛中的应用,There was also evidence of a decrease in pain intensity at 24 h; the weighted mean
11、difference was -0.7 cm (-1.2 to -0.1) on a 10-cm visual analog scale with clonidine and -0.6 cm (-0.9 to -0.2) with dexmedetomidine. There was also evidence of a decrease in pain intensity at 12 h; the weighted mean difference was -1.5 cm (-2.1 to -1.0) on a 10-cm visual analog scale with clonidine
12、and -1.4 cm (-2.7 to -0.2) with dexmedetomidine at 1h .,The incidence of early nausea was decreased with both (number needed to treat, approximately nine).,Clonidine increased the risk of intraoperative (number needed to harm, approximately nine) andpostoperative hypotension (number needed to harm,
13、20). Dexmedetomidine increased the risk of postoperative bradycardia (number needed to harm, three). R,CONCLUSIONS: Perioperative systemic 2 agonists decrease postoperative opioid consumption, pain intensity, and nausea. Recovery times are not prolonged. Common adverse effects are bradycardia and ar
14、terial hypotension. The impact of 2 agonists on chronic pain or hyperalgesia remains unclear because valid data are lacking.,METHODS: double-blinded, randomized, controlled study, 100 women undergoing abdominal total hysterectomy were allocated Group M： receive either morphine 1 mg /ml Group D: morp
15、hine 1 mg/ ml plus dexmedetomidine 5 ug /ml postoperative i.v. PCA, which was programmed to deliver 1 ml per demand with a 5 min lockout interval and no background infusion. Cumulative PCA requirements pain intensities cardiovascular and respiratory variables PCA-related adverse events were recorded
16、 for 24 h after operation.,Compared with Group M, patients in Group D required 29% less morphine during the 0-24 h postoperative period and reported significantly lower pain levels from the second postoperative hour onwards and throughout the study,decreases in heart rate from presurgery baseline at
17、 1, 2, and 4 h after operation were significantly greater in Group D (by a range of 5-7 beats min(-1) respectively).,decreases in mean blood pressure from presurgery baseline at 1, 2, and 4 h after operation were significantly greater in Group D (by a range of 10-13%, respectively).,Whereas levels o
18、f sedation were similar between the groups at each observational time point, The 4-24 h incidence of nausea was significantly lower in Group D (34% vs 56.3%, P0.05). There was no bradycardia, hypotension, oversedation, or respiratory depression,CONCLUSIONS: The addition of dexmedetomidine to i.v. PC
19、A morphine resulted in superior analgesia significant morphine sparing less morphine-induced nausea devoid of additional sedation and untoward haemodynamic changes.,PATIENTS: One hundred and twenty parturients (American Society of Anesthesiologists class 1 or 2) scheduled for elective caesarean deli
20、very under spinal anaesthesia randomly allocated into three groups (n = 40 each). INTERVENTIONS: Group 1: physiological saline bolus after delivery and sufentanil PCA, Group 2: dexmedetomidine bolus (0.5 g kg) after delivery and sufentanil PCA Group 3: dexmedetomidine bolus (0.5 g kg) after delivery
21、 and sufentanil with dexmedetomidine PCA (background infusion of 0.045 g kg h with a bolus of 0.07 g kg),PTh and PTTh were significantly increased 1 h after drug administration in groups 2 (1.59 0.45, 2.57 0.46 mA) and 3 (1.74 0.37, 2.56 0.48 mA) compared with group 1 (1.49 0.49, 2.42 0.62 mA) (P 0.
22、05).,实验结果1,Sufentanil consumption in group 3 was 43.9 19.2g, significantly lower than in group 1 (54.5 23.9 g) and group 2 (56.3 20.6 g) (P 0.05).,Compared with group 3, VAS was increased at 4, 8 and 24 h after surgery in groups 1 and 2 (P 0.05); there was no difference between groups 1 and 2,实验结果2,
23、*,*,*,实验结果3,Proc (Bayl Univ Med Cent). 2014 Jan;27(1):3-10.,METHODS: Thirty-eight thoracotomy patients were administered dexmedetomidine intraoperatively and overnight postoperatively and then randomized to receive placebo or dexmedetomidine titrated from 0.1 to 0.5 gkgh(-1) the day following surger
24、y for up to 24 hours on a telemetry floor. Opioids via a patient-controlled analgesia pump were available for both groups, and vital signs including transcutaneous carbon dioxide, pulse oximetry, respiratory rate, and pain and sedation scores were monitored. .,The dexmedetomidine group used 41% less
25、 opioids but achieved pain scores equal to those of the placebo group.,The mean respiratory rate and oxygen saturation were similar in the two groups.,Mild hypercarbia occurred in both groups, but periods of significant respiratory depression were noted only in the placebo group.,Significant hypoten
26、sion was noted in one patient in the dexmedetomidine group in conjunction with concomitant administration of a beta-blocker agent. The placebo group reported a higher number of opioid-related adverse events.,结果4,*,*,Evaluation of dexmedetomidine and postoperative pain management in patients with ado
27、lescent idiopathic scoliosis: conclusions based on a retrospective study at a tertiary pediatric hospital. Jones JS1, Cotugno RE, Singhal NR, Soares N, Semenova J, Nebar S, Parke EJ, Shrader MW, Hotz J. Pediatr Crit Care Med. 2014 Jul;15(6):e247-52.,结果4,*,*,DESIGN: This was a retrospective chart rev
28、iew. Patients were separated into two groups: those that received opioid via patient-controlled analgesia pain therapy alone those that received opioid via patient-controlled analgesia pain therapy with dexmedetomidine. PATIENTS: One hundred sixty-three children with adolescent idiopathic scoliosis.
29、,*,*,MEASUREMENTS AND MAIN RESULTS: Measurements included patient demographics, American Society of Anesthesiologists Physical Status Classification System, levels of spinal fusion, length of hospital stay, complications, numeric pain scores, opioid requirement, elastomeric pain pump use, length of
30、time until ambulation, adverse effects, and naloxone use. Data were collected through the first 72 hours of the perioperative period. One hundred six patients received opioids via patient-controlled analgesia therapy with dexmedetomidine and 57 received opioids via patient-controlled analgesia alone
31、. Within the groups, there were 46 patients who received local anesthetic infusions via elastomeric pumps in the patient-controlled analgesia with dexmedetomidine group and 16 patients had pumps in the patient-controlled analgesia-alone group. There was no overall difference in postoperative use of
32、morphine (or equivalents) between the two groups. However, the use of elastomeric pain pumps demonstrated a statistically significant decrease in mean overall opioid consumption (42.6 mg vs 63.1 mg, p 0.001).,*,*,CONCLUSIONS: There was no difference in opioid use related to dexmedetomidine on any po
33、stoperative day. The only variable showing a significant opioid sparing effect was the use of local anesthetic infusions via elastomeric pumps. Using continuous local anesthetic infusions instead of dexmedetomidine could eliminate the need for ICU admission, require shorter hospital stays, and reduc
34、e costs while still providing safe and effective pain control.,*,*,Comparison of patient-controlled analgesia with and without dexmedetomidine following spine surgery in children. Sadhasivam S1, Boat A, Mahmoud M. J Clin Anesth. 2009 Nov;21(7):493-501,*,*,DESIGN: Retrospective comparison. SETTING: U
35、niversity-affiliated childrens hospital. MEASUREMENTS: The medical charts of 131 children with idiopathic scoliosis (IS) and NMS who had major spine surgery were reviewed. Out of 131, postoperatively 94 children received PCA with morphine alone (PCA group) and the remaining 37 children received PCA
36、morphine and dexmedetomidine infusion at 0.4 mcg/kg/hour for 24 hours (PCA + Dex group). Preoperative, intraoperative, and postoperative morphine use data were collected.,*,*,MAIN RESULTS: Intraoperative use of morphine was similar in children with IS and NMS. However, patients with IS used more mor
37、phine than patients with NMS on the first, second and third postoperative days in both groups. In children with IS, use of morphine on the second postoperative day was significantly higher in the PCA + Dex group (73 mg 50.5, 110.5) than the PCA alone group (54 mg 36, 69, P = 0.03). The overall frequ
38、ency of all perioperative complications was more in the PCA alone group (40% vs. 32%) than the PCA + Dex group.,*,*,CONCLUSION: Postoperative 24-hour dexmedetomidine infusion as an adjunct to PCA with opioids might have a morphine-sparing effect as evidenced by the increase in morphine use on postoperative day 2 after the dexmedetomidine infusion was stopped.,DEX具有的镇静、镇痛、抗焦虑、抗交感兴奋作用且对呼吸系统的抑制作用轻微，其在围麻醉期的应用越来越广。 关注DEX的临床优越性的同时，其尚未明确的作用机制及安全剂量范围仍需探索，有关副作用仍需提防，以便为临床应用提供更好的基础。,展 望,谢谢,