Antithrombin III for critically ill patients

Afshari A, Wetterslev J, Brok J, Møller AM

Published Online:

December 8, 2010

Insufficient evidence is available from randomized controlled trials to support the use of antithrombin III to improve the survival of critically ill patients. Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties. In the present systematic review we set out to assess the benefits and harms of its use in critically ill patients. We identified 20 randomized trials comparing AT III versus placebo or no intervention. We could not identify a clear beneficial effect of AT III on our predefined outcomes, overall or among various types of patients or subgroups. The number of bleeding events was increased with AT III and we conclude that there is a need for a large scale clinical trial with low risk of bias to assess the benefits and harms of this intervention in patients who are not also given heparin.

Abstract (click to read)

Background:

Critical illness is associated with uncontrolled inflammation and vascular damage which can result in multiple organ failure and death. Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties but the efficacy and any harmful effects of AT III supplementation in critically ill patients are unknown.

Objectives:

To assess the benefits and harms of AT III in critically ill patients.

Search strategy:

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); MEDLINE; EMBASE; Science Citation Index Expanded; International Web of Science; CINAHL; LILACS; and the Chinese Biomedical Literature Database (up to November 2006). We contacted authors and manufacturers in the field.

Selection criteria:

We included all randomized clinical trials, irrespective of blinding or language, that compared AT III with no intervention or placebo in critically ill patients.

Data collection and analysis:

Our primary outcome measure was mortality. We each independently abstracted data and resolved any disagreements by discussion. We presented pooled estimates of the intervention effects on dichotomous outcomes as relative risks (RR) with 95% confidence intervals (CI). We performed subgroup analyses to assess risk of bias, the effect of AT III in different populations (sepsis, trauma, obstetric, and paediatric patients), and the effect of AT III in patients with or without the use of concomitant heparin. We assessed the adequacy of the available number of participants and performed a trial sequential analysis to establish the implications for further research.

Main results:

We included 20 randomized trials with a total of 3458 participants; 13 of these trials had high risk of bias. When we combined all trials, AT III did not statistically significantly reduce overall mortality compared with the control group (RR 0.96, 95% CI 0.89 to 1.03; no heterogeneity between trials). A total of 32 subgroup and sensitivity analyses were carried out. Analyses based on risk of bias, different populations, and the role of adjuvant heparin gave insignificant differences. AT III reduced the multiorgan failure score among survivors in an analysis involving very few patients. AT III increased bleeding events (RR 1.52, 95% CI 1.30 to 1.78).

Authors' conclusions:

AT III cannot be recommended for critically ill patients based on the available evidence. A randomized controlled trial of AT III, without adjuvant heparin, with prespecified inclusion criteria and good bias protection is needed.

This record should be cited as:

Afshari A, Wetterslev J, Brok J, Møller AM. Antithrombin III for critically ill patients. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD005370. DOI: 10.1002/14651858.CD005370.pub2

Assessed as up to date:

November 4, 2006

Find the research

Get full text at The Cochrane Library

Primary Review Group:

Anaesthesia Group

Health topics:

Anaesthesia & pain control > Post-anaesthetic unit/intensive care unit > Sepsis & critical care

Infectious disease > Sepsis & critical care

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Antithrombin III for critically ill patients

More like this

Copyright © 2011 - The Cochrane Collaboration