Department of Paediatric Anaesthesia and Pain Management, Royal Children's Hospital Melbourne Australia, Parkville, Vic., Australia.
Critical Care and Neurosciences Theme, Murdoch Children's Research Institute, Parkville, Vic., Australia.
Paediatr Anaesth. 2021 Jun;31(6):655-664. doi: 10.1111/pan.14170. Epub 2021 Apr 18.
Pharmacokinetic simulation was used to characterize levobupivacaine disposition after regional anesthetic rescue for failed spinal anesthesia in neonates and infants.
Population pharmacokinetics of levobupivacaine were estimated after spinal blockade in a cohort of neonates and infants (n = 25, postnatal age 5-18 weeks, gestation 21-41 weeks, weight 2.4-6 kg). Total levobupivacaine concentrations were assayed 3-4 times in the first hour after spinal levobupivacaine 1 mg kg administration. Parameters were estimated using nonlinear mixed-effects models and supported by priors. Covariates included postnatal age and total body weight. Parameter estimates were used to simulate total levobupivacaine concentrations after a primary spinal levobupivacaine 1 mg kg with rescue caudal levobupivacaine 1.5-2.5 mg kg .
A one-compartment model with a mature clearance 21.5 L h 70 kg (CV 47.3%) and central volume 189 L 70 kg (CV 37%) adequately described time-concentration profiles. Clearance maturation was described using a maturation half-time of 11.5 weeks postnatal age. The absorption half-time for spinal levobupivacaine was 2.6 min (CV 56.8%). The upper (97.5% prediction) for peak concentrations after rescue caudal levobupivacaine were 1.5 mg kg , 2 mg kg , and 2.5 mg kg was 2.05 mg L , 2.5 mg L , and 2.9 mg L respectively.
Total bupivacaine concentrations greater than 2.5 mg L are associated with neurotoxicity in adults. Predicted concentrations after either a repeat spinal or a caudal rescue dose of levobupivacaine 1.5 mg kg 1 h after spinal levobupivacaine administration are below the neurotoxic concentration threshold.
通过药代动力学模拟来描述新生儿和婴儿因脊髓麻醉失败而进行区域性麻醉补救后左布比卡因的处置情况。
对 25 例新生儿和婴儿（出生后年龄 5-18 周，胎龄 21-41 周，体重 2.4-6 公斤）进行脊髓阻滞后的群体药代动力学研究。在给予左布比卡因 1 毫克/公斤后 1 小时内，3-4 次检测总左布比卡因浓度。使用非线性混合效应模型进行参数估计，并提供先验知识。协变量包括产后年龄和总体重。使用参数估计值模拟初次脊髓给予左布比卡因 1 毫克/公斤后，用 1.5-2.5 毫克/公斤的骶骨左布比卡因进行补救的总左布比卡因浓度。
一个具有成熟清除率 21.5 L/h/70 kg（CV 47.3%）和中央容积 189 L/70 kg（CV 37%）的单室模型可以很好地描述时间-浓度曲线。清除率成熟度用出生后 11.5 周的成熟半衰期来描述。脊髓左布比卡因的吸收半衰期为 2.6 分钟（CV 56.8%）。骶骨左布比卡因补救后，峰浓度的上（97.5%预测）值分别为 1.5 毫克/公斤、2 毫克/公斤和 2.5 毫克/公斤，分别为 2.05 毫克/升、2.5 毫克/升和 2.9 毫克/升。
成人中，总布比卡因浓度大于 2.5 毫克/升与神经毒性有关。在给予左布比卡因 1 毫克/公斤后 1 小时再次给予脊髓或骶骨补救剂量 1.5 毫克/公斤后，预测的浓度低于神经毒性浓度阈值。
