 |
|
Prophylaxis Against Deep Vein Thrombosis in Critically Ill Patients With Severe Renal Insufficiency With the Low-Molecular-Weight Heparin DalteparinAn Assessment of Safety and Pharmacodynamics: The DIRECT Study
James Douketis, MD, FRCPC;
Deborah Cook, MD, MSc, FRCPC;
Maureen Meade, MD, FRCPC;
Gordon Guyatt, MD, FRCPC;
William Geerts, MD, FRCPC;
Yoanna Skrobik, MD, FRCPC;
Martin Albert, MD, FRCPC;
John Granton, MD, FRCPC;
Paul Hébert, MD, FRCPC;
Guiseppe Pagliarello, MD, FRCSC;
John Marshall, MD, FRCSC;
Robert Fowler, MD, FRCPC;
Andreas Freitag, MD, FRCPC;
Christian Rabbat, MD, FRCPC;
David Anderson, MD, FRCPC;
Nicole Zytaruk, MSc;
Diane Heels-Ansdell, MSc;
Mark Crowther, MD, MSc, FRCPC; for the Canadian Critical Care Trials Group
Arch Intern Med. 2008;168(16):1805-1812.
Background Use of low-molecular-weight heparins is avoided in patients with renal insufficiency because of concerns about an excessive anticoagulant effect and increased bleeding risk. To challenge this premise, we evaluated if deep vein thrombosis (DVT) prophylaxis with dalteparin sodium confers an excessive anticoagulant effect in critically ill patients with severe renal insufficiency.
Methods We conducted a multicenter, single-arm clinical trial of DVT prophylaxis with dalteparin sodium, 5000 IU once daily in critically ill patients with a creatinine clearance lower than 30 mL/min (to convert to milliliters per second, multiply by 0.0167). Bioaccumulation was defined by a trough anti-Xa level higher than 0.40 IU/mL, measured twice weekly. The pharmacodynamic properties of dalteparin were assessed by serial anti-Xa levels measured on days 3, 10, and 17.
Results We enrolled 156 patients with a mean (SD) creatinine clearance of 18.9 (6.5) mL/min; 18 were excluded because they died or were discharged before testing (n = 3) or had prevalent DVT (n = 15). Of 138 patients included, the median (interquartile range [IQR]) duration of dalteparin exposure was 7 (4-12) days. In 120 patients who had at least 1 trough anti-Xa level (427 total measurements), no patient had bioaccumulation (0%; 95% confidence interval [CI]: 0%-3.0%); the median (IQR) trough anti-Xa level was undetectable (<0.10 IU/mL [<0.10 to <0.10 IU/mL]). Based on serial measurements, peak anti-Xa levels were 0.29 to 0.34 IU/mL and trough levels were lower than 0.06 IU/mL. Deep vein thrombosis occurred in 7 of 138 patients (5.1%; 95% CI, 2.5%-10.1%); major bleeding occurred in 10 patients (7.2%; 95% CI, 4.0%-12.8%), all with trough anti-Xa levels of 0.18 IU/mL or lower.
Conclusion In critically ill patients with severe renal insufficiency, DVT prophylaxis with dalteparin sodium, 5000 IU once daily, is not associated with an excessive anticoagulant effect due to drug bioaccumulation and is unlikely to contribute to bleeding.
Trial Registration clinicaltrials.gov Identifier: NCT00138099
Author Affiliations: Departments of Medicine (Drs Douketis, Cook, Meade, Guyatt, Freitag, Rabbat, and Crowther) and Clinical Epidemiology and Biostatistics (Drs Douketis, Cook, Meade, and Guyatt and Mss Zytaruk and Heels-Ansdell), McMaster University, Hamilton, Ontario, Canada; Department of Medicine (Drs Geerts, Granton, and Fowler), Interdepartmental Divisions of Critical Care (Drs Granton, Marshall, and Fowler) and Surgery (Dr Marshall), University of Toronto, Toronto, Ontario, Canada; Department of Medicine, Université de Montréal, Montréal, Quebec, Canada (Drs Skrobik and Albert); Department of Critical Care, University of Ottawa, Ottawa, Ontario, Canada (Drs Hébert and Pagliarello); and Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada (Dr Anderson).
 CiteULike  Connotea  Delicious  Digg  Facebook  Reddit  Technorati  Twitter
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Parenteral Anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines
Garcia et al.
Chest 2012;141:e24S-e43S.
ABSTRACT
| FULL TEXT
Venous Thromboembolic Disease
Streiff et al.
J Natl Compr Canc Netw 2011;9:714-777.
FULL TEXT
Deep Vein Thrombosis and Stress Ulcer Prophylaxis in the Intensive Care Unit
Goodwin and Hoffman
Journal of Pharmacy Practice 2011;24:78-88.
ABSTRACT
| FULL TEXT
Dosing Low Molecular Weight Heparins in Kidney Disease
Saltiel
Journal of Pharmacy Practice 2010;23:205-209.
ABSTRACT
An Official ATS/ERS/ESICM/SCCM/SRLF Statement: Prevention and Management of Acute Renal Failure in the ICU Patient: An International Consensus Conference in Intensive Care Medicine
Brochard et al.
Am. J. Respir. Crit. Care Med. 2010;181:1128-1155.
ABSTRACT
| FULL TEXT
Preventing venous thromboembolism in long-term care residents: Cautious advice based on limited data
PAI and DOUKETIS
Cleveland Clinic Journal of Medicine 2010;77:123-130.
ABSTRACT
| FULL TEXT
Coagulopathy in Critically III Patients: Part 2-Soluble Clotting Factors and Hemostatic Testing
Wheeler and Rice
Chest 2010;137:185-194.
ABSTRACT
| FULL TEXT
Low-Molecular-Weight Heparins in Renal Impairment and Obesity: Available Evidence and Clinical Practice Recommendations Across Medical and Surgical Settings
Nutescu et al.
The Annals of Pharmacotherapy 2009;43:1064-1083.
ABSTRACT
| FULL TEXT
Update in Critical Care 2008
Fowler et al.
Am. J. Respir. Crit. Care Med. 2009;179:743-758.
FULL TEXT
Prevention of venous thromboembolism: consensus, controversies, and challenges
Selby and Geerts
ASH Education Book 2009;2009:286-292.
ABSTRACT
| FULL TEXT
Prevention of Deep Venous Thrombosis in Patients with Renal Failure
JWatch Oncology and Hematology 2008;2008:2-2.
FULL TEXT
Low-Molecular-Weight Heparin for DVT Prophylaxis in Patients with Renal Insufficiency
JWatch General 2008;2008:2-2.
FULL TEXT
|
