title: Antithrombin III for critically ill patients: a systematic review with meta-analysis and trial sequential analysis.
abstract: OBJECTIVE
  Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties. We assessed the benefits and harms of AT III in critically ill patients.
  
  
  METHODS
  We searched from inception to 27 August 2015 in CENTRAL, MEDLINE, EMBASE, CAB, BIOSIS and CINAHL. We included randomized controlled trials (RCTs) irrespective of publication status, date of publication, blinding status, outcomes published or language.
  
  
  RESULTS
  We included 30 RCTs with a total of 3933 participants. The majority of included trials were at high risk of bias. Combining all trials, regardless of bias, showed no statistically significant effect of AT III on mortality (RR 0.95, 95% CI 0.88-1.03, I (2) = 0%, fixed-effect model, 29 trials, 3882 participants). Among those with severe sepsis and disseminated intravascular coagulation (DIC), AT III showed no impact on mortality (RR 0.95, 95% Cl 0.88-1.03, I (2) = 0%, fixed-effect model, 12 trials, 2858 participants). We carried out multiple subgroup and sensitivity analyses to assess the benefits and harms of AT III and to examine the impact of risk of bias. AT III significantly increased bleeding events (RR 1.58, 95% CI 1.35-1.84, I (2) = 0%, fixed-effect model, 11 trials, 3019 participants). However, for all other outcome measures and analyses, the results did not reach statistical significance.
  
  
  CONCLUSIONS
  There is insufficient evidence to support AT III substitution in any category of critically ill participants including those with sepsis and DIC. AT III did not show an impact on mortality, but increased the risk of bleeding.
authors: Department of Anaesthesia, Køge Sygehus, Copenhagen University Hospital, Copenhagen, Denmark. mikkel.allingstrup@gmail.com.|Department of Paediatric and Obstetric Anaesthesia, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. mikkel.allingstrup@gmail.com.
authors: Mikkel
authors: M
authors: Allingstrup
authors: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors: Jørn
authors: J
authors: Wetterslev
authors: Department of Paediatric and Obstetric Anaesthesia, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors: Frederikke B
authors: FB
authors: Ravn
authors: The Cochrane Anaesthesia, Critical and Emergency Care Group, University of Copenhagen Herlev Hospital, Herlev, Denmark.
authors: Ann Merete
authors: AM
authors: Møller
authors: Department of Paediatric and Obstetric Anaesthesia, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.|The Cochrane Anaesthesia, Critical and Emergency Care Group, University of Copenhagen Herlev Hospital, Herlev, Denmark.
authors: Arash
authors: A
authors: Afshari
mesh_terms: D000990:Antithrombin III / Q000627:therapeutic use*; D000991:Antithrombins / Q000627:therapeutic use*; D016638:Critical Illness / Q000401:mortality*; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D018805:Sepsis / Q000188:drug therapy / Q000401:mortality
chemical_list: D000991:Antithrombins; D000990:Antithrombin III
keywords: Antithrombin III; Bleeding; DIC; Multi organ failure; Sepsis; Septic shock