Bayliff C D, Schwartz M L, Hardy B G
Clin Pharmacol Ther. 1985 Oct;38(4):457-61. doi: 10.1038/clpt.1985.204.
High-dose pentobarbital infusion has been advocated as an effective adjunct in controlling persistent intracranial hypertension after severe head trauma in patients refractory to conventional therapy. Pentobarbital disposition was assessed in 10 adults with severe nonpenetrating head injury after an intravenous loading dose of sodium pentobarbital, 10 mg/kg, infused over 1 hour, followed by a continuous infusion at 0.5 to 3.0 mg/kg/hr provided the cerebral perfusion pressure remained greater than 50 torr. Pharmacokinetic parameters of volume of distribution at steady state (Vss), total body clearance (CL), and t1/2 for the patients with trauma were statistically compared with similar estimates reported for seven adult subjects without head injury. On discontinuation of the pentobarbital infusion, serum concentrations in the patients followed a monoexponential decline with a mean (+/- SD) t1/2 and Vss that were significantly less than values reported for the control subjects (15.6 +/- 3.9 vs. 22.3 +/- 4.0 hours and 44.0 +/- 11.7 vs. 63.4 +/- 15.2 L, respectively). However, there was no significant difference between the mean pentobarbital CL of the patients (2.0 +/- 0.7 L/hr) and the subjects (2.0 +/- 0.4 L/hr). To our knowledge this is the first report on the disposition, elimination, and intrasubject variability of high-dose pentobarbital infusion in adult patients with head trauma.
大剂量戊巴比妥输注已被提倡作为一种有效的辅助手段，用于控制严重头部创伤后常规治疗无效患者的持续性颅内高压。对10例严重非穿透性头部损伤的成年人进行了戊巴比妥处置评估，静脉注射戊巴比妥钠负荷剂量10mg/kg，在1小时内输注完毕，随后以0.5至3.0mg/kg/小时持续输注，前提是脑灌注压保持大于50托。将创伤患者的稳态分布容积（Vss）、全身清除率（CL）和t1/2的药代动力学参数与7例无头部损伤的成年受试者报告的类似估计值进行统计学比较。在停止戊巴比妥输注后，患者血清浓度呈单指数下降，其平均（±标准差）t1/2和Vss显著低于对照受试者报告的值（分别为15.6±3.9小时对22.3±4.0小时和44.0±11.7升对63.4±15.2升）。然而，患者的平均戊巴比妥CL（2.0±0.7升/小时）与受试者（2.0±0.4升/小时）之间无显著差异。据我们所知，这是关于大剂量戊巴比妥输注在成年头部创伤患者中的处置、消除和个体内变异性的首份报告。
