连续性肾脏替代治疗时枸橼酸药物代谢动力学数学模型的构建

Objective To establish a citrate pharmacokinetics model which is applied to evaluate the risk of citrate accumulation in patients with liver dysfunction in the continuous renal replacement treatment (CRRT) with regional citrate anticoagulation (RCA). Methods The source of citrate for extracorporeal anticoagulation, the body clearance and filter elimination of citrate, which were the three major citrate fluxes of systemic citrate level, were combined into a single-pool, first order kinetic equation. The data from a published clinical study of systemic citrate kinetics in the intensive care unit patients with or without liver cirrhosis were adapted and the citrate kinetic equation was applied to predict the risk of systemic citrate accumulation in patients with normal, impaired and absent liver clearance while different RCA-CRRT protocols were carried out. Results The single pool, first order citrate kinetic modeling equation was as follows:Csys=C(0)·e-[(clb+clf)·t/V]+G/CLb+CLf×(1-e-[(clb+clf)·t/V])There was excellent agreement between published citrate measurements and our predictions. Kinetic modeling showed that the plasma citrate concentration of patients with normal citrate body clearance was no more than 1 mmol/L during common RCA-CRRT. The model predicted that when the single pass fractional extraction of citrate on the artificial kidney was above 66％, systemic steady citrate concentration would be among the safe range even in patients of impaired body metabolism of citrate.Conclusions The citrate kinetic model of RCA-CRRT can predict the risk of systemic citrate accumulation and provide the basis for designing the safe RCA-protocols for the patients with impaired body clearance of citrate.     

主观综合性营养评估预测急性肾损伤患者的预后

目的 了解院内急性肾损伤（AKI）患者营养不良的情况;探讨主观综合性营养评估（SGA）分级与AKI患者预后的关系。 方法 前瞻性观察在复旦大学附属华山医院住院期间发生的AKI患者。在诊断AKI的24 h内进行营养评估,包括SGA评分、人体学测量和血清学营养指标。主要终点事件为90 d全因死亡。使用Cox回归模型校正混杂因素,分析SGA分级与AKI患者90 d全因死亡率的关系,并用Kaplan-Meier曲线和log-rank检验进行90 d生存分析。 结果 共 170例AKI患者入选。院内AKI患者中,营养正常（SGA评分A级）、中度营养不良（SGA评分B级）和重度营养不良（SGA评分C级）患者的比例分别为25.3%、51.8%和22.9%。3组的90 d全因死亡率分别为9.8%、34.9%和56.8%。经Cox回归模型校正混杂因素后,SGA评分差（B级和C级）患者的90 d全因死亡的风险比（HR）为SGA评分A级的4.0倍（95%CI 1.42~11.22,P = 0.008）。Kaplan-Meier生存曲线显示SGA分级越差,累积生存率越低（log-rank检验,P < 0.01）。 结论 SGA评分是AKI患者全因死亡的独立危险因素。对AKI患者及时进行SGA营养评估有重要意义。     

危重病评分系统预测急性肾损伤患者预后优于RIFLE分级

目的评价并比较序贯性脏器衰竭评分(sequential organ failure assessment,SOFA)、急性生理学与慢性健康状况评分(acute physiology and chronic health evaluation,APACHE)Ⅱ、简明急性生理学评分(simplified acute physiology score,SAPS)Ⅱ和Liano评分4种危重病评分系统及RIFLE标准对急性肾损伤(acute kidney injury,AKI)患者的预后评估价值。方法本研究为前瞻性、单中心研究,收集2008年12月到2009年11月复旦大学附属华山医院各种病因引起的AKI患者。AKI的诊断标准为RIFLE的肌酐标准,除外肾后性、肾小球性、肾血管性和间质性肾炎等引起的急性损伤。研究的主要终点是28d死亡率。比较存活组和死亡组的RIFLE分级、SOFA、APACHEⅡ、SAPSⅡ和Liano评分,并进行各种评分系统对死亡的ROC曲线分析,同时将4种评分方法根据RIFLE分级进行分层分析。结果共入选194例符合入选标准的AKI患者。存活组和死亡组的RIFLE分级、AKI病因、是否需要透析差异无统计学意义(P0.05)。死亡组的机械通气比例、SOFA、APACHEⅡ、SAPSⅡ和Liano评分显著高于存活组(P0.001)。SOFA、APACHEⅡ、SAPSⅡ和Liano评分预测死亡的受试者工作特性(ROC)曲线下面积分别为0.900、0.885、0.888、0.875(均P0.001),而RIFLE的ROC曲线下面积为0.566(P0.05)。按AKI的RIFLE级别进行分层分析时发现,4个评分方法在衰竭组(Fc)ROC曲线下面积最大,其中又以Liano评分最高。结论 RIFLE分级对AKI患者的预后无明显的判断价值,而危重病评分包括SOFA、APACHEⅡ、SAPSⅡ和Liano评分对AKI的预后具有良好的预测价值。     

利尿剂临床应用的新进展

利尿剂从开始使用至今已有40多年的历史,目前仍广泛地用于临床。当今对利尿剂的临床评价已逐步走上循证医学轨道,以大量的临床试验、荟萃分析评价利尿剂的效果以及对疾病发展、预后的影响和不良反应。本文阐述利尿剂在临床常见疾病中应用的进展、利尿剂的不良反应和新型利尿剂的研究进展。     

甘露醇是脑外伤患者发生急性肾损伤的独立危险因素

目的 探讨脑外伤患者发生急性肾损伤(AKI)的危险因素,并评价甘露醇在其中的作用。 方法 回顾性分析2006年1月至2008年12月间复旦大学华山医院神经外科急救中心收治的脑外伤患者AKI的发生情况,AKI诊断采用RIFLE分期标准。采用Logistic回归分析脑外伤患者发生AKI的危险因素,建立脑外伤患者AKI发生的预测模型,并运用接受者操作特性(ROC)曲线及曲线下面积评价该模型对预测脑外伤患者并发AKI的敏感性和特异性。采用倾向性得分匹配法（PSM）进一步分析甘露醇对脑外伤患者发生AKI的影响。 结果 共入选符合标准的脑外伤患者171例,其中AKI组53例,非AKI组118例。患者平均年龄（45.92±16.50）岁。单因素分析结果显示,年龄、高血压、急诊手术、系统性炎性反应综合征（SIRS）、Glasgow昏迷评分、序贯器官衰竭评估（SOFA）评分、SOFA呼吸评分、SOFA凝血评分、SOFA心血管评分、机械通气天数、红细胞悬液累计输注总量、血浆累计输注总量、呋塞米累计总剂量、托拉塞米累计总剂量、甘露醇累计总剂量是脑外伤患者发生AKI的危险因素。多因素Logistic回归分析显示,SOFA评分（OR=1.516,95%CI 1.222~1.881,P < 0.01）、托拉塞米累计总剂量（OR=0.016,95%CI 1.002~1.031,P = 0.016）、甘露醇累计总剂量（OR=2.687,95%CI 1.062~6.800,P = 0.037）是脑外伤患者发生AKI的独立危险因素。运用ROC曲线及曲线下面积评价由SOFA评分、托拉塞米累计总剂量和甘露醇累计总剂量3个变量组成的多因素Logistic回归模型对脑外伤患者发生AKI预测的敏感性和特异性,结果显示ROC曲线下面积为0.901（P < 0.01）,提示该模型对预测脑外伤患者AKI的发生具有良好的敏感性和特异性。倾向性得分匹配法分析结果显示甘露醇总剂量是脑外伤患者发生AKI的独立危险因素。 结论 AKI是脑外伤患者住院期间常见的并发症。SOFA评分、托拉塞米累计总剂量、甘露醇总剂量是脑外伤患者发生AKI的独立危险因素。     

连续性肾脏替代治疗时枸橼酸药物代谢动力学数学模型的构建

目的 构建连续性肾脏替代治疗（CRRT）时枸橼酸药物代谢动力学数学模型,并运用该模型预测肝功能异常患者进行局部枸橼酸抗凝（RCA）-CRRT时发生枸橼酸蓄积的风险。 方法 将体外枸橼酸输注速度、体内枸橼酸药物动力学、体外枸橼酸透析清除动力学等影响血浆枸橼酸浓度的参数综合,构建一个服从一室模型、一级消除动力学的枸橼酸药物代谢动力学数学模型。运用模型采用文献报道的肝硬化和非肝硬化危重患者体内枸橼酸药物代谢动力学参数,预测枸橼酸代谢正常、肝功能损害及肝衰竭的患者在实施不同CRRT治疗方案时发生枸橼酸蓄积的风险。 结果 枸橼酸药物代谢动力学数学模型： 。由模型得到的血浆枸橼酸浓度预测值与文献报道的实测浓度拟合理想。根据模型推算,体内枸橼酸清除正常的患者在接受RCA-CRRT时,血浆枸橼酸浓度始终﹤1 mmol/L;当CRRT抽提分数高于66%时,肝功能异常患者体内枸橼酸稳态浓度将低于中毒浓度。 结论 枸橼酸药物代谢动力学模型可预测危重患者在实施RCA-CRRT时发生枸橼酸蓄积的风险,并为体内枸橼酸代谢清除障碍的患者选择合适安全的RCA-CRRT方案提供理论依据。     

连续性肾脏替代治疗时枸橼酸药物代谢动力学数学模型的构建

Objective To establish a citrate pharmacokinetics model which is applied to evaluate the risk of citrate accumulation in patients with liver dysfunction in the continuous renal replacement treatment (CRRT) with regional citrate anticoagulation (RCA). Methods The source of citrate for extracorporeal anticoagulation, the body clearance and filter elimination of citrate, which were the three major citrate fluxes of systemic citrate level, were combined into a single-pool, first order kinetic equation. The data from a published clinical study of systemic citrate kinetics in the intensive care unit patients with or without liver cirrhosis were adapted and the citrate kinetic equation was applied to predict the risk of systemic citrate accumulation in patients with normal, impaired and absent liver clearance while different RCA-CRRT protocols were carried out. Results The single pool, first order citrate kinetic modeling equation was as follows:Csys=C(0)·e-[(clb+clf)·t/V]+G/CLb+CLf×(1-e-[(clb+clf)·t/V])There was excellent agreement between published citrate measurements and our predictions. Kinetic modeling showed that the plasma citrate concentration of patients with normal citrate body clearance was no more than 1 mmol/L during common RCA-CRRT. The model predicted that when the single pass fractional extraction of citrate on the artificial kidney was above 66％, systemic steady citrate concentration would be among the safe range even in patients of impaired body metabolism of citrate.Conclusions The citrate kinetic model of RCA-CRRT can predict the risk of systemic citrate accumulation and provide the basis for designing the safe RCA-protocols for the patients with impaired body clearance of citrate.     

选择性粒细胞吸附装置治疗重症急性肾损伤的研究

目的初步观察选择性粒细胞吸附装置(selective cytopheretic device,SCD)联合连续性静静脉血液滤过(continuous veno-venous hemofiItration,CVVH)治疗重症急性肾损伤(acute kidney injury,AKI)患者的疗效,并观察不良事件的发生情况.方法本研究重症AKI的定义为临床诊断为缺血性或肾毒性急性肾小管坏死,同时至少有1个肾外器官衰竭或存在脓毒血症.入选者除给予标准的重症监护治疗外,还同时接受SCD联合CVVH治疗.历史对照组为改善急性肾脏疾病照护计划(the program to improve care in acute renal disease,PICARD)研究中年龄和序贯器官衰竭评分(sequential organ failure assessment,SOFA)评分匹配的患者.主要终点事件为院内全因死亡.其他观察指标包括尿量变化及不良反应情况.使用Cox回归模型校正混杂因素,分析SCD联合CVVH治疗模式的疗效是否优于常规CVVH治疗.结果共入选9例重症AKI患者.SCD联合CVVH治疗组院内全因死亡率为22.2%,显著低于历史对照组(77.8%)(X2=5.247,P=0.027).在校正年龄、SOFA评分、平均尿量变化等混杂因素后,Cox回归模型显示,SCD联合CVVH的疗效优于常规CVVH治疗(T=-2.596,P=0.0222).治疗7d后,SCD治疗组平均尿量从基线值约500ml/d升高至2000ml/d以上.研究过程中,患者仅有数例轻度不良反应,无严重不良事件发生.结论 SCD可通过灭活激活的白细胞而调控机体免疫反应,最终降低重症AKI患者的死亡率.SCD安全性良好.     

局部枸橼酸抗凝在连续性肾脏替代治疗中的应用进展

自20世纪90年代,局部枸橼酸抗凝(regional citrate anticoagulation,RCA)最早被应用于持续动静脉血液滤过治疗[1],目前对于伴有出凝血功能