Antithrombin supplementation for anticoagulation during continuous hemofiltration in critically ill patients with septic shock: a case-control study

Abstract

Introduction: Acquired antithrombin III (AT) deficiency may induce heparin resistance and premature membrane clotting during continuous renal replacement therapy (CRRT). The purpose of this study was to evaluate the effect of AT supplementation on filter lifespan in critically ill patients with septic shock requiring CRRT.

Methods: We conducted a retrospective case-control analysis based on a 4-year observational study with prospectively collected data in two medical intensive care units in a university hospital. In all, 106 patients with septic shock underwent CRRT during the study period (55 during 2001 to 2002 and 51 during 2003 to 2004). Of these, 78 had acquired AT deficiency (plasma level below 70%) at onset of renal supportive therapy, 40 in the first 2-year period and 38 in the last 2-year period. In the latter intervention period, patients received AT supplementation (50 IU/kg) during CRRT each time that plasma AT activity, measured once daily, fell below 70%.

Results: In a case-control analysis of the 78 patients with acquired AT deficiency, groups were similar for baseline characteristics, except in severity of illness as assessed by a higher Simplified Acute Physiology Score (SAPS) II after 2002. In comparison with controls, cases had a significantly greater AT level after AT supplementation, but not at baseline, and a smaller number of episodes of clots, without excess bleeding risk. The median hemofilter survival time was longer in the AT group than in the heparin group (44.5 versus 33.4 hours; p = 0.0045). The hemofiltration dose, assessed by the ratio of delivered to prescribed ultrafiltration, increased during intervention. AT supplementation was independently associated with a decrease in clotting rate, whereas femoral angioaccess and higher SAPS II were independent predictors of filter failure. However, mortality did not differ between periods, in the control period the observed mortality was significantly higher than predicted by the SAPS II score, unlike in the treatment period.

Conclusion: In sepsis patients requiring CRRT and with acquired AT deficiency, anticoagulation with unfractionated heparin plus AT supplementation prevent premature filter clotting and may contribute to improving outcome, but the cost-effectiveness of AT remains to be determined.

Figure 1

Receiver operating characteristic (ROC) curve for antithrombin in a group of septic shock patients (n = 55) who underwent continuous renal replacement therapy in the intensive care unit from January 2001 to December 2002. The ROC curve was generated by plotting sensitivity against (100 – specificity) for each value of AT. A threshold value of 70% with the highest sensitivity and specificity (88.9% and 87.9%, respectively) was set to predict filter clotting. The area under the curve is 0.886.

Figure 2

Study flow chart.

Figure 3

Survival curves of filters in patients with an AT of less than 70% according to AT supplementation (period 2) or not (period 1). The estimated hazard ratio was 2.15 (95% confidence interval 1.29 to 4.02).