Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients
Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients
复制标题
DOI：
10.1097/01.ccm.0000084871.76568.e6
复制
发表时间：
2003-10-01
影响因子：
8.8
通讯作者：
Gangl, A
中科院分区：
文献类型：
--
作者：
Kramer, L;Bauer, E;Gangl, A
目的：研究柠檬酸纳在重症患者中的药代动力学和代谢情况，确定在肝功能障碍（肝硬化、肝肾综合征）情况下柠檬酸蓄积的风险。
设计：前瞻性队列研究。
地点：维也纳大学医院内科四系重症监护病房。
患者：连续入选的重症肝硬化患者（n = 16）和非肝硬化患者（n = 16）。
干预措施：输注柠檬酸纳（0.5 mmol·kg⁻¹·h⁻¹）和氯化钙（0.17 mmol·kg⁻¹·h⁻¹）2小时，分析系列动脉血样本。
测量及主要结果：非肝硬化重症患者的柠檬酸总体清除率正常，但肝硬化患者显著降低（710对340 mL/min，p = 0.008）。肝硬化患者的柠檬酸峰值浓度和随时间变化的浓度分别增加了65%和114%（p < 0.001）；分布容积相似。净代谢变化在数量上相似，但肝硬化患者的pH值和血浆碳酸氢盐浓度上升较慢。未发现与柠檬酸相关的副作用。标准肝功能检测无法预测柠檬酸清除率，肾功能以及急性生理与慢性健康状况评分Ⅱ对其无明显影响。
结论：这项针对重症患者柠檬酸药代动力学和代谢的首次系统性研究通过证实肝硬化患者柠檬酸清除率降低，确认了肝脏柠檬酸代谢的重要作用。药代动力学数据可为重症患者临床使用柠檬酸抗凝提供依据。只要调整剂量并监测离子钙，柠檬酸抗凝即使在失代偿性肝硬化患者中似乎也是可行的。本研究中两组间柠檬酸输注的代谢后果无差异，但在长时间输注时可能更显著。
Objectives. To investigate pharmacokinetics and metabolism of sodium citrate in critically ill patients. To determine the risk of citrate accumulation in the setting of liver dysfunction (cirrhosis, hepatorenal syndrome).Design, Prospective cohort study.Setting. Intensive Care Unit, Department of Medicine IV, University Hospital Vienna.Patients. Consecutive critically ill cirrhotic (n = 16) and non-cirrhotic patients (n = 16).Interventions. Infusion of sodium citrate (0.5 mmol.kg(-1).hr(-1)) and calcium chloride (0.17 mmol.kg(-1).hr(-1)) for 2 hrs. Analysis of serial arterial blood samples.Measurements and Main Results: Total body clearance of citrate was normal in noncirrhotic critically ill patients but significantly reduced in cirrhotic patients (710 vs. 340 mL/min, p = .008). Citrate peak concentrations and concentration over time were increased by 65% and 114% in cirrhotic patients (p < .001), respectively; volumes of distribution were similar. Net metabolic changes were quantitatively similar, with pH and plasma bicarbonate concentrations increasing more slowly in cirrhotic patients. No citrate-related side effects were noted. Citrate clearance could not be predicted by standard liver function tests and was not appreciably influenced by renal function and Acute Physiology and Chronic Health Evaluation 11 scores.Conclusions: This first systematic study on citrate pharmacokinetics and metabolism in critically ill patients confirms a major role of hepatic citrate metabolism by demonstrating reduced citrate clearance in cirrhotic patients. Pharmacokinetic data could provide a basis for the clinical use of citrate anticoagulation in critically ill patients. Provided dose adaptation and monitoring of ionized calcium, citrate anticoagulation seems feasible even in patients with decompensated cirrhosis. Metabolic consequences of citrate infusion were not different between groups in this study but may be more pronounced in prolonged infusion.