Lord Héléne, Jean Nicole, Dumont Marc, Kassis Jeannine, Leblanc Martine
Hemodialysis Unit, Nephrology Division, Maisonneuve-Rosemont Hospital, University of Montreal, Canada.
Am J Nephrol. 2002 Jan-Feb;22(1):58-66. doi: 10.1159/000046675.
Low-molecular-weight heparins offer several advantages over standard heparins, but their use for maintenance hemodialysis has been limited in North America because of their higher cost. Our objective was to compare tinzaparin to standard heparin during maintenance hemodialysis over an 8-week period, in regard to the visual aspect of the extracorporeal circuit, filter reuse, bleeding and time for compression of vascular access at the end of hemodialysis session, nursing time devoted to anticoagulation administration, level of satisfaction of patients and nurses, and relative cost.
Thirty-two chronic hemodialysis adult patients with peripheral accesses were randomly divided into two groups in a cross-over design: tinzaparin for 4 weeks followed by standard heparin for 4 weeks, or vice versa. Hemodialysis was performed thrice weekly over 3.5-4 h using large surface reused filters. Standard heparin was administered as an initial bolus of 50-75 units per kilogram followed by an infusion to maintain an activated clotting time (ACTESTER) between 150 and 200 s and discontinued 30-45 min before the end of the session. The initial dose of tinzaparin was 3,500 IU anti-Xa for patients usually receiving 7,500 units or less of standard heparin, or 4,500 IU anti-Xa for patients receiving more than 7,500 units of standard heparin, and it was injected as a bolus in the arterial line at the beginning of hemodialysis. Dosage adjustments were made by increments or decrements of 500 IU.
A total of 6 patients did not require any adjustment in their dose of tinzaparin and remained at the initial dose, while the remaining 26 necessitated adjustments of the initial dose of tinzaparin: 20 patients required increments from the initial dose whereas 6 required reductions. For most patients, 27 of them, the standard heparin dose was kept at the same level throughout the study period (since it was their usual regimen and they were in stable medical conditions). According to the monitoring scale, the visual aspects of the tubing of the extracorporeal circuit and of the dialyzers at the end of the session were similar for both tinzaparin and standard heparin. The time of compression of the vascular access at the end of the hemodialysis sessions was not significantly different with tinzaparin than with standard heparin. However, as indicated below, most patients noted less bleeding (or oozing) from their access (during compression and thereafter, in the few hours after hemodialysis) with tinzaparin than with standard heparin. Clotting was observed more frequently in the arterial and venous bubble traps with tinzaparin than with standard heparin. The presence of clot(s) was observed in the arterial and venous bubble traps in, respectively, 18 +/- 12 and 10 +/- 6% of the sessions with tinzaparin, while in, respectively, 3 +/- 4 and 2 +/- 4% of the sessions with standard heparin (p < 0.005). Despite a tendency for a reduced reuse number of the dialyzers, the difference did not reach statistical significance. Among the 30 patients who completed the study, 2 reported excessive bleeding from their vascular access with tinzaparin whereas 8 reported such an excessive bleeding with standard heparin. The level of satisfaction of patients and nurses for tinzaparin was extremely good. The main reasons stated by the patients was reduced bleeding from their access after dialysis. The nurses preferred tinzaparin because of the simplicity and the rapidity of its administration, the lack of monitoring required, and the decreased bleeding/oozing tendency from the vascular access sites. The time spent for anticoagulation during a hemodialysis session was reported as 5 min with standard heparin (if no ACTESTER monitoring), 25-30 min with standard heparin (if ACTESTER monitoring required), and 1 min with tinzaparin. The cost analysis revealed that although tinzaparin is more than six times more expensive than standard heparin, the use of tinzaparin becomes similar to the use of standard heparin (USD 7.33 vs. USD 7.62 Canadian dollars for one hemodialysis session) if ACTESTER monitoring is performed (assuming that 22% of the sessions are routinely monitored and that one ACTESTER device is necessary for 8-10 dialysis stations, as applied in our unit).
Our experience with tinzaparin was positive: it represents a simple and easy way to offer anticoagulation during maintenance hemodialysis, it seems associated with less postdialysis bleeding, it saves precious nursing time and is widely appreciated by patients and staff.
低分子量肝素与普通肝素相比具有多种优势，但在北美，因其成本较高，在维持性血液透析中的应用受到限制。我们的目的是在为期8周的维持性血液透析期间，比较替扎肝素与普通肝素在体外循环的外观、滤器复用、出血情况、血液透析结束时血管通路压迫时间、抗凝给药所需护理时间、患者及护士满意度以及相对成本方面的差异。
32例有外周血管通路的慢性血液透析成年患者采用交叉设计随机分为两组：先使用替扎肝素4周，后使用普通肝素4周，或反之。使用大面积复用滤器，每周进行3次血液透析，每次3.5 - 4小时。普通肝素初始剂量为每千克50 - 75单位静脉推注，随后持续输注以维持活化凝血时间（ACTESTER）在150至200秒之间，并在透析结束前30 - 45分钟停用。替扎肝素的初始剂量：通常接受7500单位或更少普通肝素的患者为3500抗Xa国际单位，接受超过7500单位普通肝素的患者为4500抗Xa国际单位，在血液透析开始时作为静脉推注注入动脉管路。剂量调整以500国际单位的增量或减量进行。
共有6例患者无需调整替扎肝素剂量，维持初始剂量，其余26例需要调整替扎肝素初始剂量：20例患者需要增加初始剂量，6例需要减少。对于大多数患者（27例），整个研究期间普通肝素剂量保持在相同水平（因为这是他们的常规方案且病情稳定）。根据监测量表，血液透析结束时，替扎肝素和普通肝素在体外循环管路和透析器的外观方面相似。血液透析结束时血管通路压迫时间，替扎肝素与普通肝素相比无显著差异。然而，如下所述，大多数患者注意到与普通肝素相比，使用替扎肝素时其血管通路出血（或渗血）较少（在压迫期间及之后，血液透析后的数小时内）。与普通肝素相比，替扎肝素在动脉和静脉气泡捕集器中凝血更频繁。替扎肝素治疗期间，动脉和静脉气泡捕集器中出现凝血的比例分别为18±12%和10±6%，而普通肝素治疗期间分别为3±4%和2±4%（p<0.005）。尽管透析器复用次数有减少的趋势，但差异未达到统计学意义。在完成研究的30例患者中，2例报告使用替扎肝素时血管通路出血过多，而8例报告使用普通肝素时出血过多。患者和护士对替扎肝素的满意度非常高。患者给出的主要原因是透析后血管通路出血减少。护士更喜欢替扎肝素，因为其给药简单快捷，无需监测，且血管通路部位出血/渗血倾向降低。据报告，血液透析期间使用普通肝素进行抗凝的时间为5分钟（如果不进行ACTESTER监测），25 - 30分钟（如果需要ACTESTER监测），而使用替扎肝素为1分钟。成本分析显示，尽管替扎肝素比普通肝素贵六倍多，但如果进行ACTESTER监测（假设22%的透析疗程常规监测，且我们科室8 - 10个透析站需要一台ACTESTER设备），使用替扎肝素的成本与使用普通肝素相似（每次血液透析疗程分别为7.33加元和7.62加元）。
我们使用替扎肝素的经验是积极的：它是维持性血液透析期间提供抗凝的一种简单易行的方法，似乎与透析后出血减少有关，节省了宝贵的护理时间，并且受到患者和工作人员的广泛认可。
