Beath S M, Nuttall G A, Fass D N, Oliver W C, Ereth M H, Oyen L J
Departments of Cardiovascular Anesthesiology and Anesthesiology, Mayo Graduate School of Medicine, Rochester, MN 55905, USA.
Anesth Analg. 2000 Aug;91(2):257-64. doi: 10.1097/00000539-200008000-00002.
Aprotinin is an effective but expensive drug used during cardiac surgery to reduce blood loss and transfusion requirements. Currently, aprotinin is administered to adults according to a fixed protocol regardless of the patient's weight. The purpose of this study was to determine aprotinin levels in patients receiving full- and half-dose aprotinin regimens by a simple functional aprotinin assay and to design a more individualized aprotinin dosage regimen for cardiac surgical patients. The mean plasma aprotinin concentration peaked 5 min after the initiation of cardiopulmonary bypass (full 401 +/- 92 KIU/mL, half 226 +/- 56 KIU/mL). The mean plasma aprotinin concentration after 60 min on cardiopulmonary bypass was less (full 236 +/- 81 KIU/mL, half 160 +/- 63 KIU/mL). There was large variation in the aprotinin concentration among patients. A statistically significant correlation was found between aprotinin concentration and patient weight (r(2) = 0.67, P < 0.05).
The current dosing schedule for aprotinin results in a large variation in aprotinin plasma concentrations among patients and a large variation within each patient over time. We combined the information provided by our study with that of a previous pharmacokinetic study to develop a potentially improved, weight-based, dosing regime for aprotinin.
抑肽酶是一种用于心脏手术以减少失血和输血需求的有效但昂贵的药物。目前,无论患者体重如何,抑肽酶均按照固定方案给予成人。本研究的目的是通过一种简单的功能性抑肽酶测定法确定接受全剂量和半剂量抑肽酶方案患者的抑肽酶水平,并为心脏手术患者设计更个体化的抑肽酶给药方案。体外循环开始后5分钟,血浆抑肽酶平均浓度达到峰值(全剂量401±92 KIU/mL,半剂量226±56 KIU/mL)。体外循环60分钟后的血浆抑肽酶平均浓度较低(全剂量236±81 KIU/mL,半剂量160±63 KIU/mL)。患者之间抑肽酶浓度存在较大差异。发现抑肽酶浓度与患者体重之间存在统计学显著相关性(r² = 0.67,P < 0.05)。
目前抑肽酶的给药方案导致患者之间抑肽酶血浆浓度差异较大,且每位患者体内随时间变化差异也较大。我们将本研究提供的信息与先前的药代动力学研究信息相结合,以制定一种可能改进的、基于体重的抑肽酶给药方案。