Peutrell J M, Holder K, Gregory M
Royal Hospital for Sick Children, St Michael's Hill, Bristol.
Br J Anaesth. 1997 Feb;78(2):160-2. doi: 10.1093/bja/78.2.160.
The maximum recommended dose for extradural infusions of bupivacaine in children older than 1 month is 0.5 mg kg-1 h-1 but there are few specific reports of the associated blood concentrations during infusions in babies. Toxic symptoms can occur in children at plasma concentrations of bupivacaine as low as 2 micrograms ml-1. We attempted to measure venous plasma concentrations of total and free bupivacaine in babies aged 3-12 months during extradural infusions given at a rate commonly used in our hospital. We studied eight babies (mean age 33 weeks; mean weight 7.8 kg). After a mean initial dose of 1.2 mg kg-1 (range 1.1-1.3 mg kg-1), bupivacaine was infused at a mean rate of 0.38 (0.36-0.39) mg kg-1 h-1 for a mean of 31 (4-44) h. Blood was obtained at 4, 8, 16, 24, 32 and 40 h after starting the infusion and plasma separated by centrifugation. Total plasma bupivacaine concentration was measured using high pressure liquid chromatography (HPLC). Plasma concentrations of total bupivacaine were mostly less than 2 micrograms ml-1. One baby had a concentration of 2.02 micrograms ml-1 at 32 h and showed clear evidence of accumulation of bupivacaine. Babies can accumulate bupivacaine and achieve plasma concentrations above the threshold for toxic side effects, despite infusion rates below the currently accepted maximum. The samples size in our study was small but we believe an extradural infusion rate of 0.375 mg kg-1 h-1 is probably an absolute maximum for babies younger than 12 months.
1个月以上儿童布比卡因硬膜外输注的最大推荐剂量为0.5毫克/千克/小时,但关于婴儿输注期间相关血药浓度的具体报道很少。布比卡因血浆浓度低至2微克/毫升时,儿童就可能出现中毒症状。我们试图测量我院常用速率进行硬膜外输注时,3至12个月婴儿静脉血浆中总布比卡因和游离布比卡因的浓度。我们研究了8名婴儿(平均年龄33周;平均体重7.8千克)。平均初始剂量为1.2毫克/千克(范围1.1 - 1.3毫克/千克)后,布比卡因以平均速率0.38(0.36 - 0.39)毫克/千克/小时输注,平均输注31(4 - 44)小时。输注开始后4、8、16、24、32和40小时采集血液,离心分离血浆。使用高压液相色谱法(HPLC)测量血浆总布比卡因浓度。血浆总布比卡因浓度大多低于2微克/毫升。一名婴儿在32小时时浓度为2.02微克/毫升,显示出布比卡因蓄积的明确证据。尽管输注速率低于目前公认的最大值,婴儿仍可蓄积布比卡因并使血浆浓度高于毒性副作用阈值。我们研究的样本量较小,但我们认为对于12个月以下的婴儿,硬膜外输注速率0.375毫克/千克/小时可能是绝对最大值。