Mariano Filippo, Leporati Marta, Carignano Paola, Stella Maurizio, Vincenti Marco, Biancone Luigi
Nefrologia, Dialisi e Trapianto U, Dipartimento di Medicina Generale e Specialistica, Citta' della Salute e della Scienza di Torino, Ospedale CTO, Via G. Zuretti 29, 10126, Turin, Italy.
Centro Regionale Antidoping e di Tossicologia "Alessandro Bertinaria", Orbassano, TO, Italy.
J Nephrol. 2015 Oct;28(5):623-31. doi: 10.1007/s40620-014-0143-3. Epub 2014 Sep 24.
Colistin pharmacokinetics data are scarce regarding patients undergoing renal replacement therapy (RRT), or even absent as in patients treated with sorbent technologies potentially capable of removing colistin by extensive absorption on many polymeric materials.
Twelve septic shock patients with acute kidney injury (AKI) undergoing RRT [continuous venovenous hemodiafiltration (CVVHDF) n = 7, coupled-plasma filtration adsorption-HF (CPFA-HF) n = 4, hemoperfusion n = 1] treated with colistin methanesulfonate at a dose of 4.5 × 10(6) U bid were studied. Colistin A (Col-A) and colistin B (Col-B) concentrations on plasma and effluent at time 0, 0.2, 1, 3, 6, 12, 24 and 48 h were determined by the liquid chromatography-tandem mass spectrometry method.
With CVVHDF the sieving coefficient was lower for Col-A, peaked early (0.40 for Col-A at 10 min, and 0.59 for Col-B at 3 h) and declined after 48 h (0.22 and 0.30 for Col-A and Col-B, respectively). Colistin's filter clearance showed a similar pattern, with the highest clearance value of 18.7 ml/min for Col-B at 1 h. With CPFA-HF after the cartridge the Col-A and Col-B levels were negligible (<0.2 mg/l) or not detectable. The sum of the effluent and cartridge clearances reached values of 30 and 40 ml/min for Col-A and Col-B, respectively. With hemoperfusion the postcartridge concentrations for Col-A and Col-B were about 30 % lower than those determined precartridge.
During CPFA-HF and CVVHDF, the extent of colistin removal is high, and patients should receive an unreduced dosage. However, due to risk of accumulation in long-term administration colistin plasma levels determination is recommended.
关于接受肾脏替代治疗(RRT)的患者,多黏菌素的药代动力学数据稀缺,而对于使用吸附技术治疗的患者,此类数据甚至不存在,因为吸附技术可能通过多种聚合材料的广泛吸附作用来清除多黏菌素。
研究了12例患有急性肾损伤(AKI)并接受RRT的感染性休克患者[持续静静脉血液透析滤过(CVVHDF)7例,配对血浆滤过吸附 - 血液滤过(CPFA - HF)4例,血液灌流1例],给予甲磺酸多黏菌素,剂量为4.5×10⁶ U,每日两次。采用液相色谱 - 串联质谱法测定0、0.2、1、3、6、12、24和48小时时血浆和流出液中的多黏菌素A(Col - A)和多黏菌素B(Col - B)浓度。
在CVVHDF过程中,Col - A的筛系数较低,峰值出现较早(Col - A在10分钟时为0.40,Col - B在3小时时为0.59),48小时后下降(Col - A和Col - B分别为0.22和0.30)。多黏菌素的滤过清除率呈现类似模式,Col - B在1小时时的最高清除率值为18.7 ml/min。在CPFA - HF过程中,经过滤器后Col - A和Col - B的水平可忽略不计(<0.2 mg/l)或无法检测到。流出液和滤器清除率之和,Col - A和Col - B分别达到30和40 ml/min。在血液灌流过程中,经过滤器后Col - A和Col - B的浓度比滤器前测定值低约30%。
在CPFA - HF和CVVHDF期间,多黏菌素的清除程度较高,患者应接受不减量的给药。然而,由于长期给药存在蓄积风险,建议测定多黏菌素血浆水平。