丙泊酚在产科麻醉中应用的争议和进展（黄绍强）课件

丙泊酚在产科麻醉中应用 的争议和进展 复旦大学附属妇产科医院麻醉科 黄绍强 产品说明书 n孕妇及产科患者 （流产者除外） 丙泊酚在孕期使用的安全性尚未证实，故 本品不应用于孕期妇女 丙泊酚可通过胎盘屏障，可能会引起新生 儿抑郁，因此本品不应用于产科麻醉 禁用禁用 Miller麻醉学（第6版） n产科全麻诱导的标准： 硫贲妥钠45mg/kg、司可林11.5mg/kg快 速诱导 产妇低血压危机时，以氯胺酮11.5mg/kg 代替硫贲妥钠 现状 n丙泊酚自1986年上市后迅速在麻醉各个领 域得到广泛的应用 n硫贲妥钠无药？ n相当多的医院产科全麻使用丙泊酚诱导 n国内外情况大致相当 矛盾矛盾 该怎样来看待该怎样来看待 丙泊酚在产科丙泊酚在产科 麻醉中的应用麻醉中的应用 ？ 主要内容 n丙泊酚在产科病人的药代动力学 胎盘转运 n丙泊酚在产科全麻中应用的评价 对新生儿的影响正反双方的证据 对子宫平滑肌的影响 在特殊产妇的应用 n丙泊酚辅助椎管内麻醉的应用 清醒镇静 抗恶心呕吐 预防和处理瘙痒 丙泊酚的胎盘转运 nPropofol crossed the placenta, as demonstrated by concentrations found in UV in phase 1 (0.13-0.75 g/ml ) in phase 2 (0.78-1.37 g/ml ) nAt delivery, UV : MV 0.70 +/- 0.06 for phase 1 0.76 +/- 0.10 for phase 2 nUA : UV 1.09 +/- 0.04 for phase 1 0.70 +/- 0.05 for phase 2 Dailland P, et al. Anesthesiology. 1989;71(6):827 UA血药浓度明显低于成人丙泊酚单次诱导后再清醒的血药浓度（1.07g/ml） UA血药浓度稍高于UV血药浓度，提示胎儿组织中的丙泊酚再分布 持续输注时UA血药浓度总低于UV，反映胎儿对丙泊酚的持续摄取和代谢 NHP只有UA的1/10，说明药物在新生儿体内迅速代谢清除 通过乳汁摄入到新生儿体内然后作用于新生儿的药量与经胎盘作用于新生 儿的药量相比可以忽略不计 丙泊酚全麻诱导 对新生儿的影响 n在PubMed上检索到以英文发表在主流杂 志上的RCT 11个 对Apgar评分的影响：11个RCT 对神经学和适应能力评分（NACS）的影 响：7个RCT 对Apgar评分的影响 n与硫贲妥钠相似： Moore J, et al. Anaesthesia. 1989, 44(9):753-7. Valtonen M, et al. Anaesthesia. 1989, 44(9):758-62. Gin T, et al. Anaesth Intensive Care. 1990, 18(2):175-9. Gregory MA, et al. Can J Anaesth. 1990, 37(5):514-20. Yau G, et al. Anaesthesia. 1991, 46(1):20-3. Siafaka I, et al. Clin Exp Obstet Gynecol. 1992, 19(2):93-6. Gin T, et al. Br J Anaesth. 1993, 70(3):311-6. Abboud TK, et al. Acta Anaesthesiol Scand. 1995, 39(2):205-9. n较硫贲妥钠低： Celleno D, et al. Br J Anaesth. 1989, 62(6):649-54. Capogna G, et al. Int J Obstet Anesth. 1991, 1(1):19-23. Celleno D, et al. J Clin Anesth. 1993, 5(4):284-8. 对Apgar评分的影响正反两方证据的比较 文献编号病例数平均剂量 正方：1212.15 2162.5 3202 4102 6mg/Kg.h输 注 5202 6mg/Kg.h输 注 6102.3 7302 8372 反方：1202.8 2282.5 3302.4 对NACS评分的影响 n与硫贲妥钠相似： Gregory MA, et al. Can J Anaesth. 1990, 37(5):514-20. Capogna G, et al. Int J Obstet Anesth. 1991, 1(1):19-23. Gin T, et al. Br J Anaesth. 1993, 70(3):311-6. Abboud TK, et al. Acta Anaesthesiol Scand. 1995, 39(2):205-9. n较硫贲妥钠低： Celleno D, et al. Br J Anaesth. 1989, 62(6):649-54. Yau G, et al. Anaesthesia. 1991, 46(1):20-3 Celleno D, et al. J Clin Anesth. 1993, 5(4):284-8. 对NACS评分的影响正反两方证据的比较 文献编号病例数平均剂量 正方：1102 6mg/Kg.h输 注 2282.5 3302 4372 反方：1202.8 2202 6mg/Kg.h输 注 3302.4 丙泊酚药效学的评价 nCompared with thiopentone propofol reduces the cardiovascular response to laryngoscopy and tracheal intubation. Maternal recovery from anesthesia may be marginally quicker. Neonatal outcome is satisfactory although one group of researchers has consistently preferred thiopentone to propofol. nCompared with inhalational agents infusions of propofol do not offer any significant advantages for the maintenance of anesthesia and the risk of neonatal depression is potentially greater. nAlthough propofol has no major advantages to justify it replacing thiopentone for the induction of anesthesia in pregnancy, propofol does give satisfactory results and should be available as an alternative. Gin T. Acta Anaesthesiol Sin. 1994，32(2):127 nA controversies meeting of the Obstetric Anaesthetists Association in March 2003 revealed only 25% support for the motion proposing it as the induction agent of choice. nThis, however, is a considerable increase from a 1997 survey of the same organization indicating that 95% n离体时游离的异丙酚0. 5 g/ml 约相当于人体内9 10 g/ml 的浓度 异丙酚在临床血药浓度范围内 不抑制人妊娠子宫平滑肌的收缩、不增加出血量 与瑞芬太尼联合用于剖宫产 n瑞芬太尼0.5 g/kg静注后以0.20 g/kg.min持续输 注 n以血浆浓度5 g /mL进行丙泊酚靶控输注诱导， 司可林辅助插管后丙泊酚靶浓度降至2.5 g/mL n产妇的血流动力学维持非常稳定 n尽管10例中有6例新生儿出现抑制，但只需简短 地面罩通气即可很快恢复，无需纳洛酮和气管 插管 nUA pH was 7.20 in all infants. Van de Velde M, et al. Int J Obstet Anesth. 2004,13:153 四川医学，2006 ，27 (10 )：1046 在特殊产妇的应用 nInt J Obstet Anesth. 2007;16(2):155. Caesarean section using total intravenous anaesthesia in a patient with Ebsteins anomaly complicated by supraventricular tachycardia. nJ Clin Anesth. 2004;16(3):217. Anesthesia for cesarean section in a patient with spinal muscular atrophy. nBr J Anaesth. 2001;86(1):135. Use of remifentanil in a patient with peripartum cardiomyopathy requiring Caesarean section. nActa Anaesthesiol Belg. 2001;52(2):207. Target controlled infusion of remifentanil and propofol for cesarean section in a patient with multivalvular disease and severe pulmonary hypertension. nJ Clin Anesth. 1998;10(3):242. Propofol anesthesia for cesarean section successfully managed in a patient with moyamoya disease. nInt J Obstet Anesth. 1997;6(1):59. Total intravenous anaesthesia for caesarean section in a patient with Marfans syndrome. n在这些病例报道中 ，新生儿抑制有的 没有发生，有的发 生了但比较轻微， 经简单的处理很快 就恢复 n最重要的是产妇的 血流动力学维持平 稳，保证了这些合 并严重心脑血管疾 病的母亲的安全 辅助脊麻清醒镇静 nLow dose propofol infusion technique (3 mg/kg/h following 0.3 mg/kg bolus) in 37 Cesarean parturients were evaluated, compared with another 33 parturients under spinal anesthesia without any sedatives. nRESULTS: The induction to delivery time was 32.6 min. Satisfactory conscious sedation was shown without increasing the incidence of post-spinal hypotension and hypoxemia compared with non -sedative group. The plasma propofol concentrations in the mean time of delivery in MV and UV were 0.86 and 0.33 g /ml, respectively. UV concentration neither correlated with infusion time nor exceeded the maternal venous concentration. The Apgar scores as well as UV blood gas analyses did not differ significantly between two groups. Cheng YJ, Acta Anaesthesiol Sin. 1997 Jun;35(2):79 预防和处理 椎管内吗啡引起的瘙痒 n剖宫产脊麻时0.2mg吗啡鞘内给药可以进行有效 的术后镇痛，但同时会引起产妇的瘙痒 n亚催眠剂量的丙泊酚（10mg）能有效地处理这 种副反应，但在胎儿娩出后立即静注并不能预 防术后瘙痒的发生 Warwick JP, et al. Anaesthesia. 1997;52(3):270-5 Beilin Y, et al. Anesth Analg. 1998;86(2):310-3. 丙泊酚20mg能有效地预防 椎管内吗啡引起的瘙痒 Br J Anaesth. 2006 ;96(6):796 预防产妇恶心呕吐 最小有效剂量： n80 patients received either placebo or propofol at three different doses immediately after clamping of the umbilical cord nThe rate of patients experiencing no emetic symptoms in an intraoperative, postdelivery period was 45% with propofol 0.5 mg/kg .h 80% with propofol 1.0 mg/kg .h 80% with propofol 2.0 mg/kg.h 40% with placebo Fujii Y, et al. Obstet Gynecol. 2002;99:75. 丙泊酚的止吐机制 n丙泊酚可增加大脑伏隔核的多巴胺浓度 n早期认为止吐作用与脑内多