Intensive Care Medicine

, Volume 41, Issue 7, pp 1209–1219 | Cite as

Thromboprophylaxis with low molecular weight heparin versus unfractionated heparin in intensive care patients: a systematic review with meta-analysis and trial sequential analysis

  • Sigrid BeitlandEmail author
  • Irene Sandven
  • Lill-Kristin Kjærvik
  • Per Morten Sandset
  • Kjetil Sunde
  • Torsten Eken
Systematic Review



To compare benefits and harms of low molecular weight heparin (LMWH) versus unfractionated heparin (UFH) as thromboprophylaxis in intensive care unit (ICU) patients.


We conducted a systematic review with meta-analysis and trial sequential analysis (TSA) of randomised controlled trials (RCTs) comparing LMWH with UFH as thromboprophylaxis in adult ICU patients. We searched Ovid Medline, PubMed, Embase, Cochrane Library, UpToDate, Guidelines International Network, PROSPERO and the metaRegister of Controlled Trials through 3 December 2014. Random effects risk ratios (RR) and 95 % confidence intervals (CI) were derived for the endpoints deep vein thrombosis (DVT), pulmonary embolism (PE), major bleeding, mortality and net clinical benefit (any DVT, any PE, major bleeding and/or mortality).


Eight RCTs (5567 patients) were included, whereof two were considered to have overall low risk of bias. Pooled analyses showed that LMWH compared with UFH reduced the risk of any DVT (RR 0.84, 95 % CI 0.71–0.98, p = 0.03) and resulted in a net clinical benefit (RR 0.90, 95 % CI 0.83–0.97, p = 0.01). There was no statistically significant difference in the risk of any PE (RR 0.65, 95 % CI 0.41–1.03, p = 0.06), major bleeding (RR 0.99, 95 % CI 0.77–1.28, p = 0.96) or mortality (RR 0.93, 95 % CI 0.78–1.12, p = 0.43). TSA supported the results of the conventional analysis on the outcome net clinical benefit but not on risk of any DVT.


Evidence from this systematic review revealed a beneficial effect of LMWH compared with UFH when used as thromboprophylaxis in ICU patients.


Haemorrhage Critical illness Venous thrombosis Heparin Pulmonary embolism Venous thromboembolism 



The authors are grateful to Marie Isachsen for performing the literature search and documenting the search strategy, and to Kjetil Gundro Brurberg for helpful input on the result presentation.

Conflicts of interest

The authors declare that they have no competing interests.

Supplementary material

134_2015_3840_MOESM1_ESM.doc (2.4 mb)
Supplementary material 1 (DOC 2409 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2015

Authors and Affiliations

  • Sigrid Beitland
    • 1
    • 2
    Email author
  • Irene Sandven
    • 3
  • Lill-Kristin Kjærvik
    • 2
  • Per Morten Sandset
    • 1
    • 4
  • Kjetil Sunde
    • 1
    • 2
  • Torsten Eken
    • 2
  1. 1.Institute of Clinical MedicineUniversity of OsloOsloNorway
  2. 2.Department of AnaesthesiologyOslo University HospitalOsloNorway
  3. 3.Oslo Centre for Biostatistics and Epidemiology, Research Support ServicesOslo University HospitalOsloNorway
  4. 4.Department of HaematologyOslo University HospitalOsloNorway

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