Wendy Lim1, Maureen Meade, Francois Lauzier, Ryan Zarychanski, Sangeeta Mehta, Francois Lamontagne, Peter Dodek, Lauralyn McIntyre, Richard Hall, Diane Heels-Ansdell, Robert Fowler, Menaka Pai, Gordon Guyatt, Mark A Crowther, Theodore E Warkentin, P J Devereaux, Stephen D Walter, John Muscedere, Margaret Herridge, Alexis F Turgeon, William Geerts, Simon Finfer, Michael Jacka, Otavio Berwanger, Marlies Ostermann, Ismael Qushmaq, Jan O Friedrich, Deborah J Cook. 1. 1Department of Medicine, McMaster University, Hamilton, ON, Canada. 2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada. 3Research Center of the CHU de Québec, Population Health and Optimal Health Practices Research Unit, Québec, QC, Canada. 4Division of Critical Care, Department of Medicine, Québec, QC, Canada. 5Section of Critical Care, Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada. 6Section of Hematology/Medical Oncology, Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada. 7Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada. 8Division of Critical Care, Department of Medicine, Centre de Recherche Clinique Étiene-Le Bel, Université de Sherbrooke, Sherbrooke, QC, Canada. 9Division of Critical Care Medicine and Center for Health Evaluation and Outcome Sciences, St. Paul's Hospital and University of British Columbia, Vancouver, BC, Canada. 10Department of Critical Care, University of Ottawa, Ottawa, ON, Canada. 11Department of Anesthesia, Queen Elizabeth II Health Sciences Centre, 12Department of Critical Care, Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada. 13Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada. 14Department of Medicine, Queen's University, Kingston, ON, Canada. 15Department of Anesthesiology, Québec, QC, Canada. 16Department of Medicine, University of Toronto, Toronto, ON, Canada. 17Malcolm Fisher Department of Intensive Care Medicine, Royal North Shore Hospital, Sydney, Australia. 18The George Institute for Global Health, University of Sydney, Sydney, Australia. 19Department of Critical Care, University of Alberta, Edmonton, AB, Canada. 20Department of Anesthesia, University of Alberta, Edmonton, AB, Canada. 21Department of Medicine, Research Institute-HCor, Hospital do Coracao, Sao Paolo, Brazil. 22Department of Intensive Care Medicine, Guys
Abstract
OBJECTIVES: To identify risk factors for failure of anticoagulant thromboprophylaxis in critically ill patients in the ICU. DESIGN: Multivariable regression analysis of thrombosis predictors from a randomized thromboprophylaxis trial. SETTING: Sixty-seven medical-surgical ICUs in six countries. PATIENTS: Three thousand seven hundred forty-six medical-surgical critically ill patients. INTERVENTIONS: All patients received anticoagulant thromboprophylaxis with low-molecular-weight heparin or unfractionated heparin at standard doses. MEASUREMENTS AND MAIN RESULTS: Independent predictors for venous thromboembolism, proximal leg deep vein thrombosis, and pulmonary embolism developing during critical illness were assessed. A total of 289 patients (7.7%) developed venous thromboembolism. Predictors of thromboprophylaxis failure as measured by development of venous thromboembolism included a personal or family history of venous thromboembolism (hazard ratio, 1.64; 95% CI, 1.03-2.59; p = 0.04) and body mass index (hazard ratio, 1.18 per 10-point increase; 95% CI, 1.04-1.35; p = 0.01). Increasing body mass index was also a predictor for developing proximal leg deep vein thrombosis (hazard ratio, 1.25; 95% CI, 1.06-1.46; p = 0.007), which occurred in 182 patients (4.9%). Pulmonary embolism occurred in 47 patients (1.3%) and was associated with body mass index (hazard ratio, 1.37; 95% CI, 1.02-1.83; p = 0.035) and vasopressor use (hazard ratio, 1.84; 95% CI, 1.01-3.35; p = 0.046). Low-molecular-weight heparin (in comparison to unfractionated heparin) thromboprophylaxis lowered pulmonary embolism risk (hazard ratio, 0.51; 95% CI, 0.27-0.95; p = 0.034) while statin use in the preceding week lowered the risk of proximal leg deep vein thrombosis (hazard ratio, 0.46; 95% CI, 0.27-0.77; p = 0.004). CONCLUSIONS: Failure of standard thromboprophylaxis using low-molecular-weight heparin or unfractionated heparin is more likely in ICU patients with elevated body mass index, those with a personal or family history of venous thromboembolism, and those receiving vasopressors. Alternate management or incremental risk reduction strategies may be needed in such patients.
RCT Entities:
OBJECTIVES: To identify risk factors for failure of anticoagulant thromboprophylaxis in critically ill patients in the ICU. DESIGN: Multivariable regression analysis of thrombosis predictors from a randomized thromboprophylaxis trial. SETTING: Sixty-seven medical-surgical ICUs in six countries. PATIENTS: Three thousand seven hundred forty-six medical-surgical critically ill patients. INTERVENTIONS: All patients received anticoagulant thromboprophylaxis with low-molecular-weight heparin or unfractionated heparin at standard doses. MEASUREMENTS AND MAIN RESULTS: Independent predictors for venous thromboembolism, proximal leg deep vein thrombosis, and pulmonary embolism developing during critical illness were assessed. A total of 289 patients (7.7%) developed venous thromboembolism. Predictors of thromboprophylaxis failure as measured by development of venous thromboembolism included a personal or family history of venous thromboembolism (hazard ratio, 1.64; 95% CI, 1.03-2.59; p = 0.04) and body mass index (hazard ratio, 1.18 per 10-point increase; 95% CI, 1.04-1.35; p = 0.01). Increasing body mass index was also a predictor for developing proximal leg deep vein thrombosis (hazard ratio, 1.25; 95% CI, 1.06-1.46; p = 0.007), which occurred in 182 patients (4.9%). Pulmonary embolism occurred in 47 patients (1.3%) and was associated with body mass index (hazard ratio, 1.37; 95% CI, 1.02-1.83; p = 0.035) and vasopressor use (hazard ratio, 1.84; 95% CI, 1.01-3.35; p = 0.046). Low-molecular-weight heparin (in comparison to unfractionated heparin) thromboprophylaxis lowered pulmonary embolism risk (hazard ratio, 0.51; 95% CI, 0.27-0.95; p = 0.034) while statin use in the preceding week lowered the risk of proximal leg deep vein thrombosis (hazard ratio, 0.46; 95% CI, 0.27-0.77; p = 0.004). CONCLUSIONS: Failure of standard thromboprophylaxis using low-molecular-weight heparin or unfractionated heparin is more likely in ICU patients with elevated body mass index, those with a personal or family history of venous thromboembolism, and those receiving vasopressors. Alternate management or incremental risk reduction strategies may be needed in such patients.
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