Berk S I, Grunwald A, Pal S, Bodenheimer M M
College of Pharmacy, St. John's University, Jamaica, New York.
Am J Cardiol. 1993 Aug 15;72(5):393-6. doi: 10.1016/0002-9149(93)91128-5.
Patients admitted to the coronary care unit who received both intravenous nitroglycerin and heparin were studied to evaluate heparin dosage requirements. Physicians ordered all nitroglycerin and heparin doses as well as coagulation studies without knowledge of this study. Activated partial thromboplastin time (APTT) values obtained during steady-state heparin administration were considered therapeutic if the ratio of APTT/APTT-baseline was > or = 1.5. Sixty patients with myocardial infarction or unstable angina were included in the study. The initial therapeutic heparin dose of 1,014 +/- 151 units/hour produced an APTT ratio of 2.0 +/- 0.5. At the time of the initial therapeutic dose, the nitroglycerin dose was 110 +/- 108 micrograms/min. There was a significant correlation between the initial therapeutic dose and both total (r = 0.56; p = 0.0001) and lean (r = 0.26; p < 0.05) body weight. Comparison of patients with nitroglycerin doses < and > or = 100 micrograms/min revealed a significant difference in the initial therapeutic dose (971 +/- 147 vs 1,077 +/- 136 U/hour, p < 0.01), but not the initial therapeutic dose standardized to total body weight (14.0 +/- 2.5 vs 13.5 +/- 2.7 U/kg/hour). Similarly, analysis of variance revealed a significant difference in the initial therapeutic dose (p < 0.05), but not the initial therapeutic dose standardized to weight among 5 different nitroglycerin dosage ranges (10 to 533 micrograms/min). Neither aspirin use, thrombolytic therapy nor decreasing or discontinuing the nitroglycerin dose significantly affected heparin requirements. Thus, contrary to prior reports, clinically significant heparin resistance induced by nitroglycerin was not found.
对入住冠心病监护病房且接受静脉注射硝酸甘油和肝素的患者进行研究,以评估肝素的剂量需求。医生在不知道本研究的情况下开出所有硝酸甘油和肝素的剂量以及凝血研究医嘱。在肝素稳态给药期间获得的活化部分凝血活酶时间(APTT)值,如果APTT/APTT基线比值≥1.5,则被认为是治疗有效的。该研究纳入了60例心肌梗死或不稳定型心绞痛患者。初始治疗性肝素剂量为1014±151单位/小时,APTT比值为2.0±0.5。在初始治疗剂量时,硝酸甘油剂量为110±108微克/分钟。初始治疗剂量与总体重(r = 0.56;p = 0.0001)和瘦体重(r = 0.26;p < 0.05)之间存在显著相关性。比较硝酸甘油剂量<100微克/分钟和≥100微克/分钟的患者,发现初始治疗剂量存在显著差异(971±147 vs 1077±136单位/小时,p < 0.01),但按总体重标准化后的初始治疗剂量无显著差异(分别为14.0±2.5 vs 13.5±2.7单位/千克/小时)。同样,方差分析显示初始治疗剂量存在显著差异(p < 0.05),但在5个不同硝酸甘油剂量范围(10至533微克/分钟)内按体重标准化后的初始治疗剂量无显著差异。阿司匹林的使用、溶栓治疗以及硝酸甘油剂量的减少或停用均未显著影响肝素需求。因此,与先前的报道相反,未发现硝酸甘油诱导的具有临床意义的肝素抵抗。