Department of Pharmacy, Harper University Hospital, Detroit, Michigan.
Department of Pharmacy, Detroit Receiving Hospital, Detroit, Michigan.
Pharmacotherapy. 2017 Oct;37(10):1241-1248. doi: 10.1002/phar.2014.
Pharmacologic options for venous thromboembolism (VTE) prophylaxis are often limited in critically ill patients due to thrombocytopenia and multisystem organ dysfunction. Fondaparinux offers potential advantages in the critically ill; however, it is currently contraindicated in severe renal dysfunction (SRD). We evaluated anti-factor Xa levels in critically ill patients with SRD who were receiving an extended interval dosing regimen of fondaparinux for VTE prophylaxis.
A prospective, single-arm, interventional study was conducted at two academic hospitals of the Detroit Medical Center. Eligible patients were in the intensive care unit, had an estimated creatinine clearance of less than 30 ml/minute, and had either acute kidney injury or end-stage renal disease; several patients were taking renal replacement therapy. Fondaparinux was administered at an extended interval dosing regimen of 2.5 mg subcutaneously every 48 hours. Fondaparinux peak and trough anti-factor Xa levels were obtained. Lower extremity venous duplex studies were performed at baseline and study completion to assess for deep vein thrombosis (DVT), and patients were monitored for bleeding complications.
Thirty-two patients were enrolled. Patients received a median of four doses (interquartile range two to five) of fondaparinux. Fondaparinux peak (n=98) and trough (n=86) anti-factor Xa levels were 0.36 ± 0.18 mg/L and 0.17 ± 0.11 mg/L (mean ± SD), respectively, and were similar to levels reported in patients with normal renal function receiving conventional once-daily dosing. No lower extremity DVTs or suspected VTE events occurred. Two (6%) patients had significant bleeding events.
In critically ill patients with SRD, an extended interval fondaparinux dosing regimen of 2.5 mg every 48 hours for VTE prophylaxis achieved peak and trough anti-factor Xa levels similar to those reported in noncritically ill patients with normal renal function receiving once-daily fondaparinux. This regimen offers an alternative for patients with SRD when heparinoids must be avoided.
由于血小板减少症和多系统器官功能障碍，重症患者的静脉血栓栓塞症（VTE）预防的药物选择往往受到限制。磺达肝素钠在重症患者中具有潜在优势；然而，目前其在严重肾功能不全（SRD）中被禁用。我们评估了在接受磺达肝素钠延长间隔给药方案预防 VTE 的 SRD 重症患者中的抗 Xa 因子水平。
在底特律医疗中心的两家学术医院进行了一项前瞻性、单臂、干预性研究。符合条件的患者在重症监护病房，估计肌酐清除率<30ml/min，患有急性肾损伤或终末期肾病；一些患者正在接受肾脏替代治疗。磺达肝素钠以每 48 小时皮下注射 2.5mg 的延长间隔给药方案给药。获得磺达肝素钠的峰值和谷值抗 Xa 因子水平。在基线和研究完成时进行下肢静脉双功超声检查以评估深静脉血栓形成（DVT），并监测患者出血并发症。
共纳入 32 名患者。患者接受了中位数为 4 剂（四分位间距 2-5 剂）的磺达肝素钠治疗。磺达肝素钠的峰值（n=98）和谷值（n=86）抗 Xa 因子水平分别为 0.36±0.18mg/L 和 0.17±0.11mg/L（平均值±标准差），与肾功能正常接受常规每日一次给药的患者报告的水平相似。未发生下肢 DVT 或疑似 VTE 事件。有 2 名（6%）患者发生严重出血事件。
在 SRD 的重症患者中，磺达肝素钠延长间隔给药方案（每 48 小时 2.5mg）用于 VTE 预防可达到与肾功能正常接受每日一次磺达肝素钠治疗的非重症患者报告的相似的峰值和谷值抗 Xa 因子水平。当必须避免肝素类药物时，该方案为 SRD 患者提供了一种替代方案。
