Meenks Sjoerd D, Foudraine Norbert A, Broen Kelly, le Noble Jos L M L, Janssen Paddy K C
Int J Clin Pharmacol Ther. 2020 Apr;58(4):223-229. doi: 10.5414/CP203640.
Low-molecular-weight heparins are frequently used to prevent venous thromboembolism. Vasopressor therapy may be associated with inadequate anti-factor Xa activity, thereby increasing the risk of venous thromboembolism. We aimed to assess the association between anti-factor Xa activity and norepinephrine dose in intensive care unit (ICU) patients treated with subcutaneous dalteparin for venous thromboembolism prophylaxis.
This was a prospective observational pilot study in adult ICU patients treated with dalteparin 5,000 IU subcutaneously once daily and norepinephrine > 0.25 µg/kg/min. Peak anti-factor Xa activity was monitored and dalteparin doses were adjusted following a predefined dose algorithm.
From November 2016 to April 2018, 32 patients were included. No correlation was found between norepinephrine dose and anti-factor Xa activity (r = -0.01, 95% confidence interval = -0.47 - 0.27, p = 0.57). Furthermore, following dalteparin 5,000 IU once daily, 28% of the patients showed anti-factor Xa activity < 0.10 IU/mL. Higher body mass index (BMI) (p < 0.001) but not patients' norepinephrine dose, age, or serum creatinine were risk factors for anti-factor Xa activity < 0.10 IU/mL. Dose increments to 7,500 IU once daily resulted in anti-factor Xa activity ≥ 0.10 IU/mL in all 5 patients (p = 0.043).
In this cohort of ICU patients, no association was found between norepinephrine dose and anti-factor Xa activity following subcutaneous dalteparin 5,000-IU administration once daily. Furthermore, nearly one-third of the patients showed anti-factor Xa activity below the target concentration for venous thromboembolism prophylaxis. Higher BMI was an independent risk factor for reduced anti-Xa activity.
低分子量肝素常用于预防静脉血栓栓塞。血管升压药治疗可能与抗Xa因子活性不足有关,从而增加静脉血栓栓塞的风险。我们旨在评估接受皮下注射达肝素预防静脉血栓栓塞的重症监护病房(ICU)患者中,抗Xa因子活性与去甲肾上腺素剂量之间的关联。
这是一项前瞻性观察性试点研究,研究对象为接受每日一次皮下注射5000 IU达肝素且去甲肾上腺素用量>0.25 μg/kg/min的成年ICU患者。监测抗Xa因子活性峰值,并按照预定义的剂量算法调整达肝素剂量。
2016年11月至2018年4月,共纳入32例患者。未发现去甲肾上腺素剂量与抗Xa因子活性之间存在相关性(r = -0.01,95%置信区间 = -0.47 - 0.27,p = 0.57)。此外,每日一次注射5000 IU达肝素后,28%的患者抗Xa因子活性<0.10 IU/mL。较高的体重指数(BMI)(p < 0.001)而非患者的去甲肾上腺素剂量、年龄或血清肌酐是抗Xa因子活性<0.10 IU/mL的危险因素。将剂量增至每日一次7500 IU后,所有5例患者的抗Xa因子活性均≥0.10 IU/mL(p = 0.043)。
在这一队列的ICU患者中,每日一次皮下注射5000 IU达肝素后,未发现去甲肾上腺素剂量与抗Xa因子活性之间存在关联。此外,近三分之一的患者抗Xa因子活性低于预防静脉血栓栓塞的目标浓度。较高的BMI是抗Xa活性降低的独立危险因素。