Activity-guided antithrombin III therapy in severe surgical sepsis: efficacy and safety according to a retrospective data analysis.

Recent controlled studies that evaluated the efficacy of an adjuvant antithrombin (AT) III therapy in severe sepsis used a uniform AT-III dose and duration of therapy and did not adjust to the actual AT-III deficit. It was the aim of the present study to explore if surgical patients with severe sepsis might have a treatment benefit from an activity-guided AT-III therapy. We performed a retrospective cohort analysis using an intensive care unit (ICU) database. To examine the effect of AT-III on outcome and on red cell transfusion rate, multivariate generalized additive models (GAMs), Cox-type additive hazard regression models, and propensity score adjustments were used. Five hundred forty-five postoperative surgical patients requiring ICU therapy because of severe sepsis were analyzed. Antithrombin III was given to those patients believed to be at a high risk of dying. Antithrombin III therapy was guided by the individual AT-III activity and aimed at the maintenance of an activity of at least 100%. Antithrombin III supplementation was discontinued after the plasma AT-III activity had been persistently normal without simultaneous AT-III infusion. We found that patients receiving additional AT-III (n = 230) were sicker than those on standard therapy (n = 315; admission Acute physiology and chronic health evaluation II score, 19.8 +/- 7.3 vs. 17.9 +/- 7.1 [mean +/- SD]; P < 0.005). Correspondingly, 28-day mortality was higher in patients who had an additional AT-III therapy than in those on standard therapy (46.3% vs. 36.9%; P < 0.03), as was the number of red cell units transfused during ICU stay (21.5 +/- 26.7 vs. 9.3 +/- 12.1; P < 0.001). At multivariate analysis, there was no significant effect of AT-III therapy on 28-day mortality (GAM: odds ratio, 1.012; 95% confidence interval [CI], 0.651 - 1.573; P = 0.957) and 90-day survival time (Cox-type additive hazard regression: hazard ratio, 1.034; 95% CI, 0.779 - 1.387; P = 0.794). However, AT-III therapy was associated with a significantly higher frequency of red cell unit transfusion (GAM/zero-inflated Poisson: estimate, 1.26; 95% CI, 1.15 - 139; P < 0.001). Our results suggest that there seems to be no relevant effect of an activity-guided AT-III therapy on the prognosis of surgical patients with severe sepsis. However, transfusion frequency rises by AT-III therapy.

Independent determinants of early death in critically ill surgical patients.

Abnormalities in cardiocirculatory, respiratory, or coagulatory parameters are frequent after major surgery, but so far, no study has investigated their predictive value for early intensive care unit (ICU) mortality. We aimed to describe and quantify the relation between these parameters that are routinely determined on ICU admission and early death after complex surgery. Individual patient data were available from a local ICU database. We performed a retrospective observational cohort study using prospectively collected data from March 1, 1993, through February 28, 2005. A cohort of 4,214 cases who were admitted to the ICU immediately after operation was analyzed. We studied age, sex, number of red blood cell units transfused on admission day, and admission values for heart rate, systolic blood pressure, hemoglobin concentration, partial thromboplastin time, prothrombin time, respiratory function (Pao2/Fio2 ratio), and body temperature for their association with 4-day mortality. Effects were adjusted for the underlying disease and for disease severity during the first 24 h after admission. We used generalized additive models to fit continuous variables individually before combining them into the final generalized model. We found an independent linear association between the number of transfused red blood cell units, partial thromboplastin time, and body temperature with acute outcome. A smoothed model described the independent interaction between admission blood pressure and early death. Only values of less than 80 mmHg were associated with an increased risk of 4-day mortality. According to these results, bleeding complications after ICU admission should be treated aggressively to prevent early death of the patient. However, normotensive conditions do not seem to be required to prevent early mortality. Whether rapid rewarming may improve outcome needs further rigorous study.