School of Pharmacy, Pharmacy Australia Centre of Excellence, University of Queensland, Brisbane, QLD, Australia.
Pharmacy Department, Princess Alexandra Hospital, Brisbane, QLD, Australia.
Int J Clin Pharm. 2020 Apr;42(2):462-473. doi: 10.1007/s11096-020-01004-5. Epub 2020 Mar 5.
Background The effect of obesity on the pharmacokinetics and pharmacodynamics of unfractionated heparin is not clearly understood, therefore to reduce the risk of bleeding, maximal dose (capped) nomograms are often used. This can lead to inadequate anticoagulation and increased mortality and morbidity. In Queensland, Australia, statewide nomograms recommend total-body-weight-based dosing, with capped initial bolus and maintenance doses. Objective To determine if current practices for unfractionated heparin dosing leads to inadequate anticoagulation in obese patients. Setting Princess Alexandra Hospital, Queensland, Australia. Method A retrospective audit of unfractionated heparin dosing in 200 patients divided into cohorts of; < 100 kg (defined as non-obese), 100-124.9 kg, 125-150 kg and > 150 kg, Main outcomes measured Mean maintenance doses in U/h and U/kg/h required to achieve two consecutive therapeutic activated partial thromboplastin times' and the corresponding time to achieve this endpoint. Results The mean ± standard deviation maintenance doses required to achieve two consecutive therapeutic activated partial thromboplastin times' in U/h were 1229 ± 316, 1673 ± 523, 2031 ± 596 and 2146 ± 846, and in U/kg/h were 16 ± 4.1, 15.1 ± 4.8, 14.9 ± 4.2 and 11.6 ± 4.2 for the weight cohorts respectively. The median time (inter-quartile range) to therapeutic activated partial thromboplastin times' for obese patients was 39 (21.5-56) h. Conclusions Our results suggest inadequate dosing in obese patients. We recommend the use of larger absolute doses (U/h) of nfractionated heparin but reduced uncapped total body weight-based doses-(U/kg/h) as patient weight increases.
背景 肥胖对未分级肝素的药代动力学和药效学的影响尚不清楚,因此为了降低出血风险,常使用最大剂量(封顶)剂量图。这可能导致抗凝不足,并增加死亡率和发病率。在澳大利亚昆士兰州,全州剂量图建议根据总体重进行给药,初始推注和维持剂量封顶。目的 确定目前使用未分级肝素给药方案是否会导致肥胖患者抗凝不足。地点 澳大利亚昆士兰州亚历山德拉公主医院。方法 对 200 名患者的未分级肝素给药情况进行回顾性审核,患者分为<100kg(定义为非肥胖)、100-124.9kg、125-150kg 和>150kg 四个队列。主要观察指标 达到两个连续治疗性激活部分凝血活酶时间(aPTT)所需的平均维持剂量(U/h)和 U/kg/h,以及达到该终点所需的相应时间。结果 达到两个连续治疗性 aPTT 所需的平均维持剂量(U/h)分别为 1229±316、1673±523、2031±596 和 2146±846,U/kg/h 分别为 16±4.1、15.1±4.8、14.9±4.2 和 11.6±4.2。肥胖患者达到治疗性 aPTT 的中位时间(四分位间距)为 39(21.5-56)小时。结论 我们的结果表明肥胖患者的剂量不足。我们建议使用更大的未分级肝素绝对剂量(U/h),但随着患者体重增加,减少无封顶的基于总体重的剂量(U/kg/h)。