title: Bivalirudin for Alternative Anticoagulation in Extracorporeal Membrane Oxygenation: A Systematic Review.
abstract: BACKGROUND
  Extracorporeal membrane oxygenation (ECMO) offers therapeutic options in refractory respiratory and/or cardiac failure. Systemic anticoagulation with heparin is routinely administered. However, in patients with heparin-induced thrombocytopenia or heparin resistance, the direct thrombin inhibitor bivalirudin is a valid option and has been increasingly used for ECMO anticoagulation. We aimed at evaluating its safety and its optimal dosing for ECMO.
  
  
  METHODS
  Systematic web-based literature search of PubMed and EMBASE performed via National Health Service Library Evidence and manually, updated until January 30, 2016.
  
  
  RESULTS
  The search revealed 8 publications relevant to the topic (5 case reports). In total, 58 patients (24 pediatrics) were reported (18 received heparin as control groups). Bivalirudin was used with or without loading dose, followed by infusion at different ranges (lowest 0.1-0.2 mg/kg/h without loading dose; highest 0.5 mg/kg/h after loading dose). The strategies for monitoring anticoagulation and optimal targets were dissimilar (activated partial thromboplastin time 45-60 seconds to 42-88 seconds; activated clotting time 180-200 seconds to 200-220 seconds; thromboelastography in 1 study).
  
  
  CONCLUSIONS
  Bivalirudin loading dose was not always used; infusion range and anticoagulation targets were different. In this systematic review, we discuss the reasons for this variability. Larger studies are needed to establish the optimal approach with the use of bivalirudin for ECMO.
authors.affiliation: 1 Department of Anesthesia and Intensive Care, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Palermo, Italy.|2 School of Anaesthesia and Intensive Care, University of Catania, Catania, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Sanfilippo
authors.affiliation: 3 Department of Anaesthesiology, Ruhr-University Bochum, University Hospital Knappschaftskrankenhaus, Bochum, Germany.|4 Critical Care Research Group, The Prince Charles Hospital and The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Sven
authors.initials: S
authors.lastname: Asmussen
authors.affiliation: 4 Critical Care Research Group, The Prince Charles Hospital and The University of Queensland, Brisbane, Queensland, Australia.|5 Department of Anaesthesiology and Intensive Care Medicine, Philipps University, Marburg, Germany.
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Maybauer
authors.affiliation: 1 Department of Anesthesia and Intensive Care, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Palermo, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Santonocito
authors.affiliation: 4 Critical Care Research Group, The Prince Charles Hospital and The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: John F
authors.initials: JF
authors.lastname: Fraser
authors.affiliation: 6 Department of Anaesthesiology and Pain Therapy, Inselspital, Bern University Hospital, Bern, Switzerland.
authors.forename: Gabor
authors.initials: G
authors.lastname: Erdoes
authors.affiliation: 4 Critical Care Research Group, The Prince Charles Hospital and The University of Queensland, Brisbane, Queensland, Australia.|5 Department of Anaesthesiology and Intensive Care Medicine, Philipps University, Marburg, Germany.|7 Cardiothoracic Anaesthesia and Intensive Care, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom.
authors.forename: Marc O
authors.initials: MO
authors.lastname: Maybauer
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage*; D000991:Antithrombins / Q000008:administration & dosage*; D002648:Child; D015199:Extracorporeal Membrane Oxygenation / Q000379:methods*; D006333:Heart Failure / Q000628:therapy; D006629:Hirudins / Q000008:administration & dosage*; D006801:Humans; D010446:Peptide Fragments / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012131:Respiratory Insufficiency / Q000628:therapy; D013921:Thrombocytopenia / Q000628:therapy; D015912:Thrombolytic Therapy / Q000379:methods
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C074619:bivalirudin
keywords: ECMO; HIT; cardiopulmonary bypass; direct thrombin inhibitor; heparin-induced thrombocytopenia