Heparin in Severe Sepsis

The Heparin in Severe Sepsis Research Program

The Heparin in Severe Sepsis Research Program, initiated by Dr Megan Robertson, involved a point prevalence study, an inception cohort study and a pilot study.

The point prevalence study involved collection of information about current Venous Thromboembolism (VTE) prophylaxis practice in critically ill patients at 30 sites throughout Australia and New Zealand. Information on all intensive care patients was collected on a single day (9 May 2007), with 505 patients recruited. This study was published in March 2010.

The inception cohort study involved assessing the specific utilisation of Unfractioned Heparin (UFH) and Low-Molecular-Weight Heparin (LMWH) in patients with severe sepsis over a 28 day period. This study recruited patient at 28 sites, with 255 patients recruited. Data analysis has been completed and a manuscript is being prepared.

The pilot study aimed to determine the feasibility of performing a large multi-centre randomised blinded study to determine if low-dose UFH reduces all-cause 90-day mortality in Intensive Care Unit (ICU) patients with severe sepsis and to determine the incidence of complications associated with low-dose UFH treatment in this patient group. The pilot study was conducted in 4 sites and was closed due to a lack of feasible recruitment in May 2008.

Findings: The point prevalence study found that, of the 502 patients included in the survey, 431 of these (86%) received VTE prophylaxis. Of these, 64% (276/431) received pharmacological prophylaxis and 80% (345/431) received mechanical prophylaxis, with 44% (190/431) receiving both. Of those receiving pharmacological prophylaxis, unfractionated heparin was used in 74%, and enoxaparin (low molecular weight heparin) in 23%. Contraindications to pharmacological prophylaxis were reported in 122 patients. Overall, pharmacological prophylaxis was administered to 87% of potentially suitable patients.

In the pilot study, 103 patients met inclusion criteria of whom only 6 were randomised into the study. The most frequent reason for exclusion (28% of excluded patients) was severe renal impairment (creatinine clearance less than 30 ml/min) which was a contraindication to the use of fondaparinux. 10% of excluded patients were receiving full anticoagulation and therefore ineligible for the study. 13 patients who were eligible for the study could not be randomised because they met criteria outside of available pharmacy support hours. This pilot study demonstrated that a large scale heparin versus fondaparinux study is not feasible in the ANZ ICU population.

Publications: The publications relating to this study include:

Robertson MS, Nichol AD, Higgins AM, Bailey MJ, Presneill JJ, Cooper DJ, Webb SA, McArthur C, MacIsaac CM and the VTE Point Prevalence Investigators for the Australian and New Zealand Intensive Care Research Centre (ANZIC-RC) and the Australian and New Zealand Intensive Care Society Clinical Trials Group (ANZICS CTG). Venous thromboembolism prophylaxis in the critically ill: a point prevalence survey of current practice in Australian and New Zealand intensive care units. Criti Care Resusc; March 2010; 12(1): 9-15.

Collaborators: The Heparin in Severe Sepsis project was conducted in collaboration with Melbourne Health.

Endorsement: The Heparin in Severe Sepsis project was endorsed by the ANZICS-CTG.