Harvey B, Johnson T N, Yeomanson D, Mulla H, Mayer A P
1Paediatric Intensive Care, Sheffield Children's Hospital, Sheffield, UK.
Perfusion. 2014 Jan;29(1):32-8. doi: 10.1177/0267659113497497. Epub 2013 Jul 17.
During continuous venoveno haemofiltration (CVVH), extracorporeal drug clearance is dependant on blood flow, ultrafiltration rate, albumin binding, and the drug's molecular weight and volume of distribution. Drug doses are adjusted assuming reduced drug clearance by the renal system and CVVH. High volume haemofiltration, pre-dilution and different filter membranes can greatly alter drug clearance. Consequently, assessing the adequacy of cephalosporin dosing during CVVH is complex; under- or overdosing may occur. We studied the pharmacokinetic properties of ceftriaxone during CVVH in vitro. Renaflow filters were used to model 6, 20 and 50 kg patients. Each circuit and reservoir was prepared with a known volume of Hartmann's solution, human albumin solution 4.5% or blood. Pump speed and exchange rate were standardised for weight. Haemosol BO was used as the replacement fluid with 70% pre-dilution. Following paired sampling from the circuit and ultrafiltrate fluid, ceftriaxone was injected into the circuit. Paired samples were taken up to 720 minutes. Ceftraxione concentrations were determined using high performance liquid chromatography (HPLC). Maximum circuit concentrations (Cmax) at 2 minutes for albumin were 3.5, 2.65 and 4.85 mg/l, for blood were 4.5, 6.5 and 5.55 mg/l and for Hartmann's were 1.65, 2.95 and 3.65 mg/l for 6 kg, 20 kg and 50 kg models. The sieving coefficients (Sc) from blood (ratio of mean concentrations in the ultrafiltrate/circuits samples) were 0.31 and 0.51 with T1/2 (the half life) 62 and 20 minutes in the 6 kg and the 20 kg circuits, respectively. The data suggest in an in vitro model of ceftriaxone is rapidly cleared during CVVH. Albumin circuits had the lowest Sc and longest terminal T1/2, reflecting protein binding of the drug and suggest ceftriaxone clearance may be more rapid in hypoalbuminaemic patients. The Cmax was lower in the Hartmann circuits, possibly reflecting precipitation of the drug with calcium in this solution.
在持续静脉-静脉血液滤过（CVVH）过程中，体外药物清除取决于血流量、超滤率、白蛋白结合率以及药物的分子量和分布容积。假定肾脏系统和CVVH导致药物清除率降低，据此调整药物剂量。高容量血液滤过、预稀释和不同的滤器膜可极大改变药物清除率。因此，评估CVVH期间头孢菌素给药的充足性很复杂；可能会出现给药不足或过量的情况。我们在体外研究了CVVH期间头孢曲松的药代动力学特性。使用Renaflow滤器模拟6、20和50千克的患者。每个循环回路和储液器都用已知体积的哈特曼溶液、4.5%人白蛋白溶液或血液配制。泵速和置换率根据体重进行标准化。使用Haemosol BO作为预稀释度为70%的置换液。从循环回路和超滤液中进行配对采样后，将头孢曲松注入循环回路。在长达720分钟的时间内采集配对样本。使用高效液相色谱法（HPLC）测定头孢曲松浓度。对于6千克、20千克和50千克模型，白蛋白组在2分钟时的最大循环回路浓度（Cmax）分别为3.5、2.65和4.85毫克/升，血液组分别为4.5、6.5和5.55毫克/升，哈特曼溶液组分别为1.65、2.95和3.65毫克/升。血液组的筛系数（Sc，超滤液/循环回路样本中平均浓度的比值）分别为0.31和0.51，6千克和20千克循环回路中的半衰期（T1/2）分别为62分钟和20分钟。数据表明，在体外模型中，CVVH期间头孢曲松被快速清除。白蛋白循环回路的Sc最低，终末T1/2最长，反映了药物的蛋白结合情况，并提示低白蛋白血症患者中头孢曲松的清除可能更快。哈特曼溶液循环回路中的Cmax较低，可能反映了该溶液中药物与钙的沉淀。
