Antithrombin III for critically ill patients

Abstract

Our primary outcome measure was mortality. Two authors each independently abstracted data and resolved any disagreements by discussion. We presented pooled estimates of the intervention effects on dichotomous outcomes as risk ratios (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, obstetrics, and paediatrics), 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 trial sequential analysis (TSA) to establish the implications for further research. Main resultsWe included 30 RCTs with a total of 3933 participants (3882 in the primary outcome analyses).Combining all trials, regardless of bias, showed no statistically significant effect of AT III on mortality with a RR of 0.95 (95% CI 0.88 to 1.03), I² statistic = 0%, fixed-effect model, 29 trials, 3882 participants, moderate quality of evidence). For trials with low risk of bias the RR was 0.96 (95% Cl 0.88 to 1.04, I² statistic = 0%, fixed-effect model, 9 trials, 2915 participants) and for high risk of bias RR 0.94 (95% Cl 0.77 to 1.14, I² statistic = 0%, fixed-effect model, 20 trials, 967 participants).For participants with severe sepsis and DIC the RR for mortality was non-significant, 0.95 (95% Cl 0.88 to 1.03, I² statistic = 0%, fixed-effect model, 12 trials, 2858 participants, moderate quality of evidence).We conducted 14 subgroup and sensitivity analyses with respect to the different domains of risk of bias, but detected no statistically significant benefit in any subgroup analyses.Our secondary objective was to assess the benefits and harms of AT III. For complications specific to the trial intervention the RR was 1.26 (95% Cl 0.83 to 1.92, I² statistic = 0%, random-effect model, 3 trials, 2454 participants, very low quality of evidence). For complications not specific to the trial intervention, the RR was 0.71 (95% Cl 0.08 to 6.11, I² statistic = 28%, random-effects model, 2 trials, 65 participants, very low quality of evidence). For complications other than bleeding, the RR was 0.72 ( 95% Cl 0.42 to 1.25, I² statistic = 0%, fixed-effect model, 3 trials, 187 participants, very low quality of evidence). Eleven trials investigated bleeding events and we found a statistically significant increase, RR 1.58 (95% CI 1.35 to 1.84, I² statistic = 0%, fixed-effect model, 11 trials, 3019 participants, moderate quality of evidence) in the AT III group. The amount of red blood cells administered had a mean difference (MD) of 138.49 (95% Cl -391.35 to 668.34, I² statistic = 84%, random-effect model, 4 trials, 137 participants, very low quality of evidence). The effect of AT III in patients with multiple organ failure (MOF) was a MD of -1.24 (95% Cl -2.18 to -0.29, I² statistic = 48%, random-effects model, 3 trials, 156 participants, very low quality of evidence) and for patients with an Acute Physiology and Chronic Health Evaluation score (APACHE) at II a...

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

“…However, a phase III clinical trial of high-dose antithrombin for adults with sepsis and septic shock as well as systematic reviews of antithrombin for critically ill patients did not demonstrate any beneficial effect on overall mortality. Antithrombin was associated with an increased risk of bleeding [340,341]. Although post hoc subgroup analyses of patients with sepsis associated with DIC showed better survival in patients receiving antithrombin, this agent cannot be recommended until further clinical trials are performed.…”

ROLE OF ANTITHROMBIN IN DIAGNOSTICS AND INTENSIVE THERAPY OF ACUTE DIC-SYNDROME (review of literature and evidence of actual clinical practice)

“…Однако следует отметить, что у пациентов с массивными травмами сочетание концентрата АТ III с гепарином не только не дало дополни-тельных преимуществ по сравнению с АТ III, но и потребовало достоверно большего объема переливания крови, что объясняется повышен-ной кровоточивостью при комбинированной терапии [23].…”

“…В дальнейшем этим же автором было продолжено изучение влияния введения концентрата АТ III на смерт-ность у пациентов с ДВС крови. В рандомизи-рованном контролируемом исследовании на 170 пациентах (85 пациентов -введение кон-центрата АТ III при его исходной активности ниже 80%, 85 пациентов -введение гепарина по 300 МЕ/час при постоянной его инфузии) было показано снижение смертности в группе АТ III (13%) против контроля (31%, р < 0,005) [14,15,23].…”

“…в 1999 г., [23]. Влиянию концентрата АТ III на проявления органной дисфункции у пациентов с шоком было посвящено рандомизированное плацебо-контролируемое исследование Inthorn D. и со-авт.…”

“…Сходные результаты, свиде-тельствующие о целесообразности примене-ния концентрата антитромбина III в подобных ситуациях, были также продемонстрированы Hinshaw LB в 1990 г. О позитивном влиянии те-рапии с применением концентрата антитром-бина III на состояние пациентов с травмой, отягощенной развитием ДВС-синдрома, также указывали в 2004 г. Miniello S. и соавт. [23].…”