J Korean Med Sci.  2016 Nov;31(11):1828-1837. 10.3346/jkms.2016.31.11.1828.

Pharmacological and Mechanical Thromboprophylaxis in Critically Ill Patients: a Network Meta-Analysis of 12 Trials

• Park J
• Lee JM
• Lee JS
• Cho YJ

• KMID: 2470282
• DOI: http://doi.org/10.3346/jkms.2016.31.11.1828

Abstract

Thromboprophylaxis for venous thromboembolism is widely used in critically ill patients. However, only limited evidence exists regarding the efficacy and safety of the various thromboprophylaxis techniques, especially mechanical thromboprophylaxis. Therefore, we performed meta-analysis of randomized controlled trials (RCTs) that compared the overall incidence of deep vein thrombosis (DVT) for between unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and intermittent pneumatic compression (IPC) in critically ill patients. A Bayesian random effects model for multiple treatment comparisons was constructed. The primary outcome measure was the overall incidence of DVT at the longest follow-up. The secondary outcome measure was the incidence of major bleeding, as defined by the original trials. Our analysis included 8,622 patients from 12 RCTs. The incidence of DVT was significantly lower in patients treated with UFH (OR, 0.45; 95% CrI, 0.22-0.83) or LMWH (OR, 0.38; 95% CrI, 0.18-0.72) than in patients in the control group. IPC was associated with a reduced incidence of DVT compared to the control group, but the effect was not statistically significant (OR, 0.50; 95% CrI, 0.20-1.23). The risk of DVT was similar for patients treated with UFH and LMWH (OR, 1.16; 95% CrI, 0.68-2.11). The risk of major bleeding was similar between the treatment groups in medical critically ill patients and also in critically ill patients with a high risk of bleeding. In critically ill patients, the efficacy of mechanical thromboprophylaxis in reducing the risk of DVT is not as robust as those of pharmacological thromboprophylaxis.

Keyword

Deep Vein Thrombosis; Venous Thrombosis; Meta-Analysis

MeSH Terms

Anticoagulants/*therapeutic use
Bayes Theorem
Critical Illness
Databases, Factual
Heparin/*therapeutic use
Heparin, Low-Molecular-Weight/*therapeutic use
Humans
Incidence
Intermittent Pneumatic Compression Devices
Odds Ratio
Venous Thromboembolism/*prevention & control
Venous Thrombosis/epidemiology/etiology
Anticoagulants
Heparin, Low-Molecular-Weight
Heparin

Figure

• 

  Fig. 1 Flow diagram of trial selection and network plot of the meta-analysis. (A) The flow diagram follows the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). (B) Network plot of meta-analysis model: each treatment is represented by a node; the size of the node is proportional to the sample size randomized to each group and the thickness of the line connecting the nodes is proportional to the total randomized sample size in each pair-wise comparison. LMWH = low-molecular-weight heparin, IPC = intermittent pneumatic compression, UFH = unfractionated heparin.

• 

  Fig. 2 Comparative efficacy of thromboprophylaxis interventions in the prevention of deep vein thrombosis (DVT). (A) Estimated odds ratios (ORs) and 95% credible intervals (CrIs) for DVT from network meta-analysis for different thromboprophylaxis interventions, according to a Bayesian network meta-analysis with random effects model. The circles and horizontal lines indicate pair-wise OR and 95% CrI, respectively. (B) Rank probability of each treatment arm for the risk of DVT. The number on the horizontal axis is the possible rank of each treatment, from best to worst according to the outcome. The size of each bar corresponds to the probability of each treatment being at a specific rank. LMWH = low-molecular-weight heparin, IPC = intermittent pneumatic compression, UFH = unfractionated heparin.

• 

  Fig. 3 Analysis of consistency and heterogeneity in the network meta-analysis model for the risk of deep vein thrombosis. LMWH = low-molecular-weight heparin, IPC = intermittent pneumatic compression, UFH = unfractionated heparin.

• 

  Fig. 4 Comparative safety of thromboprophylaxis interventions for the risk of major bleeding. (A) Estimated odds ratios (ORs) and 95% credible intervals (CrIs) for major bleeding from eight trials reporting the incidence of major bleeding. (B) Estimated OR and 95% CrI for major bleeding from four trials that included medical critically ill patients with a standard risk of bleeding. (C) Estimated OR and 95% CrI for major bleeding from four trials that included surgical or trauma critically ill patients with a high risk of bleeding. The circles and horizontal lines indicate Bayesian ORs and 95% CrIs, respectively.

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