Bivalirudin versus unfractionated heparin for prevention of hemofilter occlusion during continuous renal replacement therapy.
OBJECTIVE
To evaluate the safety and efficacy of bivalirudin compared with heparin for preventing hemofilter occlusion during continuous venovenous hemofiltration (CVVH).


METHODS
Prospective, randomized, double-blind study.


METHODS
University-affiliated hospital.


METHODS
Ten critically ill adults (median age 58 yrs, 70% male) with acute renal failure who, without anticoagulation, experienced hemofilter survival time of 24 hours or less during CVVH.


METHODS
Patients were randomized to receive bivalirudin 2 mg/hour (five patients) or heparin 400 units/hour (five patients) administered prefilter into the extracorporeal circuit.


RESULTS
Patients had a median Acute Physiology and Chronic Health Evaluation (APACHE) II score of 24, Sequential Organ Failure Assessment (SOFA) score of 11, and reduced antithrombin activity (75.5 units/dl). Baseline characteristics were not significantly different between groups. Study drug was administered in 40 hemofilters (18 from bivalirudin-treated patients, 22 from heparin-treated patients). The primary efficacy outcome was hemofilter survival time, defined as the interval of time between commencement of CVVH with a new extracorporeal circuit (hemofilter) and hemofilter failure. Compared with no anticoagulation, the addition of bivalirudin or heparin significantly improved hemofilter survival time (mean ± SD 10 ± 5 hrs with no anticoagulation vs 22 ± 18 hrs with anticoagulation, p=0.0005). Hemofilter survival time was significantly increased in patients receiving bivalirudin versus those receiving heparin (29.6 ± 20.7 vs 16.5 ± 13.6 hrs, p=0.045). Independent predictors of hemofilter survival were use of bivalirudin therapy and increased antithrombin III activity. No patients randomized to bivalirudin experienced any bleeding or thrombosis events; one patient who received heparin developed alveolar hemorrhage, and one developed a lower extremity deep vein thrombosis.


CONCLUSIONS
Compared with heparin, bivalirudin was more efficacious in prolonging hemofilter survival time and was well tolerated. Additional studies of bivalirudin for prevention of hemofilter occlusion during continuous renal replacement therapy are warranted.
Department of Clinical Pharmacy, School of Pharmacy, University of Colorado, Aurora, Colorado 80045, USA. ty.kiser@ucdenver.edu
Tyree H
TH
Kiser
Robert
R
MacLaren
Douglas N
DN
Fish
Kathryn L
KL
Hassell
Isaac
I
Teitelbaum
D058186:Acute Kidney Injury / Q000628:therapy*; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D000991:Antithrombins / Q000008:administration & dosage / Q000009:adverse effects; D016638:Critical Illness; D004311:Double-Blind Method; D005260:Female; D006440:Hemofiltration / Q000379:methods*; D006493:Heparin / Q000008:administration & dosage* / Q000009:adverse effects; D006629:Hirudins / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D013997:Time Factors
D000925:Anticoagulants; D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D006493:Heparin; C074619:bivalirudin