Shalansky Stephen J, Vu Thanh, Pate Gordon E, Levin Adeera, Humphries Karin H, Webb John G
Pharmacy Department, St. Paul's Hospital, and Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Pharmacotherapy. 2005 Aug;25(8):1095-103. doi: 10.1592/phco.2005.25.8.1095.
Use of oral N-acetylcysteine for preventing radiographic contrast material-induced nephropathy (RCIN) has become widespread, despite conflicting results from clinical trials and meta-analyses. The variability in study results may reflect differences in baseline risks in study patients, hydration regimens, choice of contrast agent, definition of RCIN, and the oral dosage formulation of N-acetylcysteine used. Injectable N-acetylcysteine recently has become available in the United States. Although oral N-acetylcysteine regimens are typically administered during a 48-hour period, more rapid intravenous administration could offer an important advantage for urgent procedures such as coronary angiography. However, the three published studies in which intravenous N-acetylcysteine protocols were used have produced divergent results, likely because of substantially different dosage regimens. With few intravenous studies available, clinicians may look to more broadly studied oral regimens to estimate equivalent intravenous dosages. In the oral studies, however, a wide range of formulations were used, and the bioavailability of each product was uncertain. In addition, the intravenous route circumvents first-pass metabolism, resulting in less glutathione production, perhaps compromising the antioxidant effects of N-acetylcysteine administration. Overall, little evidence exists that any studied N-acetylcysteine protocol improves clinical outcomes in terms of reducing length of hospital stay, need for dialysis, or mortality. Furthermore, N-acetylcysteine may directly affect serum creatinine level, which all clinical trials to date have used as a primary outcome measure. If oral or intravenous N-acetylcysteine is used with the intention of preventing RCIN, more established preventive measures should not be overlooked, including adequate hydration with isotonic saline, avoidance of potentially nephrotoxic drugs, and use of iso-osmolar radiographic contrast media.
尽管临床试验和荟萃分析结果相互矛盾，但口服N-乙酰半胱氨酸预防造影剂肾病（RCIN）的应用已广泛普及。研究结果的差异可能反映了研究患者的基线风险、水化方案、造影剂选择、RCIN的定义以及所使用的N-乙酰半胱氨酸口服剂型的不同。注射用N-乙酰半胱氨酸最近在美国已可获得。虽然口服N-乙酰半胱氨酸方案通常在48小时内给药，但对于诸如冠状动脉造影等紧急手术，更快速的静脉给药可能具有重要优势。然而，已发表的三项使用静脉注射N-乙酰半胱氨酸方案的研究结果却不尽相同，这可能是由于剂量方案存在显著差异。由于可用的静脉注射研究较少，临床医生可能会参考更广泛研究的口服方案来估算等效的静脉注射剂量。然而，在口服研究中，使用了多种剂型，且每种产品的生物利用度尚不确定。此外，静脉途径绕过了首过代谢，导致谷胱甘肽生成减少，这可能会削弱N-乙酰半胱氨酸给药的抗氧化作用。总体而言，几乎没有证据表明任何已研究的N-乙酰半胱氨酸方案在缩短住院时间、减少透析需求或降低死亡率方面能改善临床结局。此外，N-乙酰半胱氨酸可能直接影响血清肌酐水平，而迄今为止所有临床试验均将其用作主要结局指标。如果使用口服或静脉注射N-乙酰半胱氨酸来预防RCIN，不应忽视更成熟的预防措施，包括用等渗盐水充分水化、避免使用潜在的肾毒性药物以及使用等渗造影剂。
