title: Heparin thromboprophylaxis in medical-surgical critically ill patients: a systematic review and meta-analysis of randomized trials.
abstract: OBJECTIVE
  Venous thromboembolism prevention during critical illness is a widely used quality metric. The objective of this systematic review was to systematically review the efficacy and safety of heparin thromboprophylaxis in medical-surgical patients in the ICU.
  
  
  METHODS
  We searched EMBASE, MEDLINE, the Cochrane Controlled Trials Register, Clinicaltrials.gov, and personal files through May 2012.
  
  
  METHODS
  Randomized trials in adult medical-surgical ICU patients comparing any heparin (unfractionated heparin or low-molecular-weight heparin) with each other or no anticoagulant prophylaxis, evaluating deep vein thrombosis, pulmonary embolism, major bleeding, or mortality.
  
  
  METHODS
  Independently, in duplicate, we abstracted trial characteristics, outcomes, and risk of bias.
  
  
  RESULTS
  Seven trials involved 7,226 patients. Any heparin thromboprophylaxis compared with placebo reduced rates of deep vein thrombosis (pooled risk ratio, 0.51 [95% CI, 0.41, 0.63]; p<0.0001; I=77%) and pulmonary embolism (risk ratio, 0.52 [95% CI, 0.28, 0.97]; p=0.04; I=0%) but not symptomatic deep vein thrombosis (risk ratio, 0.86 [95% CI, 0.59, 1.25]; p=0.43). Major bleeding (risk ratio, 0.82 [95% CI, 0.56, 1.21]; p=0.32; I=50%) and mortality (risk ratio, 0.89 [95% CI, 0.78, 1.02]; p=0.09; I=0%) rates were similar. Compared with unfractionated heparin, low-molecular-weight heparin reduced rates of pulmonary embolism (risk ratio, 0.62 [95% CI, 0.39, 1.00]; p=0.05; I=53%) and symptomatic pulmonary embolism (risk ratio, 0.58 [95% CI, 0.34, 0.97]; p=0.04) but not deep vein thrombosis (risk ratio, 0.90 [95% CI, 0.74, 1.08]; p=0.26; I=0%), symptomatic deep vein thrombosis (risk ratio, 0.87 [95% CI, 0.60, 1.25]; p=0.44; I=0%), major bleeding (risk ratio, 0.97 [95% CI, 0.75, 1.26]; p=0.83; I=0%), or mortality (risk ratio, 0.93 [95% CI, 0.82, 1.04]; p=0.20; I=31%).
  
  
  CONCLUSIONS
  Trial evidence to date suggests that any type of heparin thromboprophylaxis decreases deep vein thrombosis and pulmonary embolism in medical-surgical critically ill patients, and low-molecular-weight heparin compared with bid unfractionated heparin decreases pulmonary embolism and symptomatic pulmonary embolism. Major bleeding and mortality rates do not appear to be significantly influenced by heparin thromboprophylaxis in the ICU setting. Trial methodology, indirectness, and the heterogeneity and imprecision of some results temper inferences from this literature.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Waleed
authors.initials: W
authors.lastname: Alhazzani
authors.forename: Wendy
authors.initials: W
authors.lastname: Lim
authors.forename: Roman Z
authors.initials: RZ
authors.lastname: Jaeschke
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Murad
authors.forename: Jack
authors.initials: J
authors.lastname: Cade
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Cook
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D016638:Critical Illness; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006760:Hospitalization; D006801:Humans; D007362:Intensive Care Units; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight