The authors of this Cochrane review conclude that antithrombin (AT) III cannot be recommended for critically ill patients based on the available evidence. A randomised controlled trial of AT III, without adjuvant heparin, with prespecified inclusion criteria and good bias protection is needed. The primary outcome measure used in the review was mortality. The review included 20 randomised controlled trials with a total of 3458 participants; 13 of these trials had high risk of bias. When the authors 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).

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