Singelyn François J, Verheyen Cees C P M, Piovella Franco, Van Aken Hugo K, Rosencher Nadia
Department of Anesthesiology, Clinical Center, Soyaux, France.
Anesth Analg. 2007 Dec;105(6):1540-7, table of contents. doi: 10.1213/01.ane.0000287677.95626.60.
The benefit-risk ratio of extended fondaparinux therapy has not been assessed in patients undergoing major lower limb joint arthroplasty. Few data on the concomitant use of fondaparinux and continuous neuraxial or deep peripheral nerve blockade are available. We performed a prospective intervention study in patients undergoing major orthopedic surgery primarily designed to assess the efficacy of fondaparinux when drug administration was withheld for 48 h to permit removal of a neuraxial or deep peripheral nerve catheter. The safety and efficacy of extended fondaparinux therapy for the prevention of venous thromboembolism were also evaluated.
Patients received a daily subcutaneous injection of 2.5 mg fondaparinux for 3 to 5 wk postoperatively. In patients with a neuraxial or deep peripheral nerve catheter, the catheter was removed 36 h after the last fondaparinux dose. The next fondaparinux dose was administered 12 h after catheter removal. The primary end points were symptomatic venous thromboembolism and major bleeding up to 4-6 wk after surgery.
We recruited 5704 patients. A neuraxial or deep peripheral nerve catheter was inserted in 1553 (27%) patients and 78 (1.4%) patients, respectively. The rate of venous thromboembolism was 1.0% (54 of 5387). There was no difference between patients without (1.1%) or with (0.8%) a catheter (the upper limit of the 95% confidence interval of the odds ratio, 1.49, being below the predetermined noninferiority margin of 1.75). The incidence of major bleeding was 0.8% (42 of 5382). No neuraxial or perineural hematoma was reported.
Once-daily subcutaneous injection of 2.5 mg fondaparinux given for 3 to 5 wk was effective and safe for prevention of venous thromboembolism after major orthopedic surgery. Temporary discontinuation of fondaparinux for 48 h permitted safe removal of a neuraxial or deep peripheral nerve catheter without decreasing thromboprophylatic efficacy.
在接受下肢大关节置换术的患者中，尚未评估延长使用磺达肝癸钠治疗的获益风险比。关于磺达肝癸钠与持续神经轴索或深部周围神经阻滞联合使用的数据很少。我们对接受大型骨科手术的患者进行了一项前瞻性干预研究，主要目的是评估在停用药物48小时以允许拔除神经轴索或深部周围神经导管后磺达肝癸钠的疗效。还评估了延长使用磺达肝癸钠预防静脉血栓栓塞的安全性和有效性。
患者术后3至5周每天皮下注射2.5mg磺达肝癸钠。对于留置神经轴索或深部周围神经导管的患者，在最后一剂磺达肝癸钠给药36小时后拔除导管。在拔除导管12小时后给予下一剂磺达肝癸钠。主要终点是术后4至6周内有症状的静脉血栓栓塞和大出血。
我们招募了5704例患者。分别有1553例（27%）和78例（1.4%）患者插入了神经轴索或深部周围神经导管。静脉血栓栓塞发生率为1.0%（5387例中的54例）。未留置导管的患者（1.1%）和留置导管的患者（0.8%）之间无差异（优势比的95%置信区间上限为1.49，低于预先设定的非劣效性界值1.75）。大出血发生率为0.8%（5382例中的42例）。未报告神经轴索或神经周围血肿。
术后3至5周每天一次皮下注射2.5mg磺达肝癸钠对于预防大型骨科手术后的静脉血栓栓塞有效且安全。暂时停用磺达肝癸钠48小时可安全拔除神经轴索或深部周围神经导管，而不降低血栓预防效果。
