A prospective comparison of three argatroban treatment regimens during hemodialysis in end-stage renal disease

被引:107
作者
Murray, PT
Reddy, BV
Grossman, EJ
Hammes, MS
Trevino, S
Ferrell, J
Tang, I
Hursting, MJ
Shamp, TR
Swan, SK
机构
[1] Univ Chicago, Nephrol Sect, Chicago, IL USA
[2] Clin Sci Consulting, Potomac, MD USA
[3] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA
[4] DaVita Clin Res, Minneapolis, MN USA
关键词
argatroban; anticoagulation; hemodialysis; end-stage renal disease;
D O I
10.1111/j.1523-1755.2004.66022.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background. We prospectively evaluated 3 treatment regimens of argatroban, a direct thrombin inhibitor, for providing adequate, safe anticoagulation in patients with end- stage renal disease (ESRD) during hemodialysis. Methods. In this randomized, 3- way crossover study, ESRD patients underwent hemodialysis sessions of 3- or 4- hour duration using high- flux membranes and each of 3 argatroban treatment regimens (A: 250-mug/ kg bolus, with an additional 250- mug/ kg bolus allowed; B: 250-mug/ kg bolus followed by 2-mug/ kg/ min infusion; C: steady- state, 2-mug/ kg/ min infusion initiated 4 hours before dialysis). Pharmacodynamic effects including activated clotting times (ACTs); hemodialysis efficacy including single-pool Kt/ V, urea reduction ratio (URR), and circuit flow; and safety through a 3- day follow- up were monitored. Argatroban pharmacokinetic parameters including dialytic clearance were evaluated during regimen C. Results. Thirteen patients completed 38 hemodialysis sessions (1 patient withdrew consent after 2 sessions). Mean +/- SD ACTs increased from 131 +/- 14 seconds at baseline to 153 +/- 24, 200 +/- 30, and 197 +/- 33 seconds, respectively, after 60 minutes of hemodialysis using regimens A, B, and C. Across regimens, mean Kt/ Vs (1.5- 1.6) and URRs (70%- 73%) were comparable. No dialyzer was changed; 1 session was shortened 15 minutes because of circuit clot formation. Systemic argatroban clearance increased similar to20% during hemodialysis, without clinically significantly affecting ACTs. Upon argatroban discontinuation, ACTs and plasma argatroban decreased concurrently (elimination half- life, 35 +/- 6 min). No thrombosis, bleeding, serious adverse events, or clinically significant changes in vital signs or routine laboratory measures occurred. Conclusion. Argatroban, administered by each treatment regimen, provides safe, adequate anticoagulation to enable successful hemodialysis in ESRD patients. Argatroban dialytic clearance by high- flux membranes is clinically insignificant.
引用
收藏
页码:2446 / 2453
页数:8
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