Frawley Geoff, Hallett Ben, Velkov Tony, Bjorksten Andrew
Department of Paediatric Anaesthesia and Pain Management, Royal Children's Hospital, Melbourne, Vic., Australia.
Department of Paediatrics, University of Melbourne, Parkville, Vic., Australia.
Paediatr Anaesth. 2016 Jun;26(6):575-81. doi: 10.1111/pan.12899. Epub 2016 Apr 7.
Infant spinal anesthesia with levobupivacaine has been promoted as a technique to reduce both the risk of postoperative apnea and exposure to volatile anesthesia. There is, however, no pharmacokinetic data to support the currently recommended doses.
Our aim was to determine whether infant levobupivacaine spinal anesthesia is associated with plasma concentrations consistent with a low risk of local anesthetic systemic toxicity.
This was an open-label pharmacokinetic safety and tolerability study of levobupivacaine spinal anesthesia in infants <55 weeks Post Menstrual Age undergoing lower abdominal surgery. Infants received a spinal anesthetic with levobupivacaine 1 mg·kg(-1) in the left lateral position.
Spinal anesthesia was successful in 25 (86.2%) of 29 infants (postmenstrual age 36-52 weeks; weight 2.2-4.7 kg). The median (IQR) total venous levobupivacaine plasma concentrations was 0.33 (0.25-0.42) μg·ml(-1) and unbound venous levobupivacaine was 19.5 (14.5-38) ng·ml(-1) . Median protein binding was 93.5 (91.4-96%). Alpha-1 acid glycoprotein concentrations were 0.25 (0.17-0.37) g·l(-1) and albumin concentrations were 29 (24-32) g·l(-1) .
Total plasma concentrations and unbound (free) concentration of levobupivacaine were consistently lower than concentrations reported in cases of pediatric local anesthetic toxicity. In a small number of infants requiring a repeat spinal of 1 mg·kg(-1) was also associated with acceptable total and free concentrations. We conclude that levobupivacaine at 1 mg·kg(-1) is associated with no systemic side effects in infants receiving awake spinal anesthesia.
左旋布比卡因用于婴儿脊髓麻醉已被推广为一种既能降低术后呼吸暂停风险又能减少挥发性麻醉剂暴露的技术。然而，目前尚无药代动力学数据支持当前推荐剂量。
我们的目的是确定婴儿左旋布比卡因脊髓麻醉是否与局部麻醉药全身毒性低风险一致的血浆浓度相关。
这是一项对月经后年龄小于55周接受下腹部手术的婴儿进行左旋布比卡因脊髓麻醉的开放标签药代动力学安全性和耐受性研究。婴儿在左侧卧位接受1mg·kg⁻¹左旋布比卡因的脊髓麻醉。
29例婴儿（月经后年龄36 - 52周；体重2.2 - 4.7kg）中有25例（86.2%）脊髓麻醉成功。左旋布比卡因总静脉血浆浓度中位数（IQR）为0.33（0.25 - 0.42）μg·ml⁻¹，未结合静脉左旋布比卡因浓度为19.5（14.5 - 38）ng·ml⁻¹。蛋白结合中位数为93.5（91.4 - 96%）。α-1酸性糖蛋白浓度为0.25（0.17 - 0.37）g·l⁻¹，白蛋白浓度为29（24 - 32）g·l⁻¹。
左旋布比卡因的总血浆浓度和未结合（游离）浓度始终低于儿科局部麻醉药毒性病例报告中的浓度。在少数需要重复1mg·kg⁻¹脊髓麻醉的婴儿中，总浓度和游离浓度也是可接受的。我们得出结论，1mg·kg⁻¹的左旋布比卡因在接受清醒脊髓麻醉的婴儿中无全身副作用。
