Venous thromboembolism in critically ill patients

Andrew F. Shorr; Mark D. Williams

doi:10.1160/TH08-07-0468

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 101(01): 139-144
DOI: 10.1160/TH08-07-0468

Wound Healing and Inflammation/Infection

Schattauer GmbH

Venous thromboembolism in critically ill patients

Observations from a randomized trial in sepsis

Authors

Andrew F. Shorr

¹Pulmonary and Critical Care Department, Washington Hospital Center, Washington, DC, USA
Mark D. Williams

²Lilly Research Laboratories, Indianapolis, Indiana, USA

Abstract

Summary

Venous thromboembolism (VTE) is a central concern in the intensive care unit (ICU). However, little is known about both current practices for VTE prevention in the ICU and the risk for VTE in persons with severe sepsis and septic shock. XPRESS was a randomized, double-blind, placebo-controlled trial of prophylactic heparin in patients with severe sepsis and higher disease severity who were treated with drotrecogin alfa (activated) (DAA). Subjects were randomized to unfractionated heparin, low-molecular-weight heparin, or placebo during the DAA infusion period. All patients underwent ultrasonography between days 4-6 to screen for VTE. We assessed baseline utilization of VTE prophylaxis along with application of these methods after completion of the DAA infusion. The study included 1,935 subjects and, prior to enrollment approximately half were given no form of prophylaxis. By day 6, 5% of subjects developed a VTE, and the rate of VTE did not vary based on type of heparin administered. The vast majority of VTE detected by day 6 were clinically silent. Of factors analyzed, history of VTE was the only variable independently associated with development of a VTE (odds ratio, 3.66, 95% confidence interval 1.77–7.56, p=0.005). Strikingly, patients who were initially receiving heparin prophylaxis prior to enrollment but who then had this discontinued because of randomization to placebo suffered more VTE that persons continuing on some form of heparin. Despite multiple guidelines, physicians do not uniformly prescribe VTE prophylaxis. Nonetheless, early VTE occurs even in persons given DAA. Most VTE in critically ill patients are clinically silent.

Keywords

Deep-vein thrombosis - heparin - prevention - pulmonary embolism - sepsis

Full Text

References

References
1 Geerts W, Selby R. Prevention of venous thromboembolism in the ICU. Chest 2003; 124: 357S-363S.
2 Rocha AT, Tapson VF. Venous thromboembolism in intensive care patients. Clin Chest Med 2003; 24: 103-122.
3 Cook D, Crowther M, Meade M. et al. Deep venous thrombosis in medical-surgical critically ill patients: prevalence, incidence, and risk factors. Crit Care Med 2005; 33: 1565-1571.
4 Ibrahim EH, Iregui M, Prentice D. et al. Deep vein thrombosis during prolonged mechanical ventilation despite prophylaxis. Crit Care Med 2002; 30: 771-774.
5 Patel R, Cook DJ, Meade MO. et al. Burden of illness in venous thromboembolism in critical care: a multicenter observational study. J Crit Care 2005; 20: 341-347.
6 Cook D, Douketis J, Crowther MA. et al. The diagnosis of deep venous thrombosis and pulmonary embolism in medical-surgical intensive care unit patients. J Crit Care 2005; 20: 314-319.
7 Dellinger RP, Carlet JM, Masur H. et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004; 32: 858-873.
8 Levi M, Levy M, Williams MD. et al. Prophylactic heparin in patients with severe sepsis treated with drotrecogin alfa (activated). Am J Respir Crit Care Med 2007; 176: 483-490.
9 Cited at http://www.ihi.org/IHI/Topics/CriticalCare/IntensiveCare/Measures/, accessed 25 Nov. 2007.
10 Cited at http://www.jointcommission.org/NR/rdonlyres/D6BD8CA-53F3D-47A4-8F72-79D242360494/0/DVT080604.pdf, accessed 25 Nov. 2007.
11 Geerts W, Cook D, Selby R. et al. Venous thromboembolism and its prevention in critical care. J Crit Care 2002; 17: 95-104.
12 Tapson VF, Decousus H, Pini M. et al. Venous thromboembolism prophylaxis in acutely ill hospitalized medical patients: findings from the International Medical Prevention Registry on Venous Thromboembolism. Chest 2007; 132: 936-945.
13 Holley AB, Moores LK, Jackson JL. Provider preferences for DVT prophylaxis. Thromb Res 2006; 117: 563-568.
14 Granger CB, Miller JM, Bovill EG. et al. Rebound increase in thrombin generation and activity after cessation of intravenous heparin in patients with acute coronary syndromes. Circulation 1995; 91: 1929-1935.
15 Di Nisio M, Bijsterveld NR, Meijers JC. et al. Effects of clopidogrel on the rebound hypercoagulable state after heparin discontinuation in patients with acute coronary syndromes. J Am Coll Cardiol 2005; 46: 1582-1583.