title: Acidosis induced by carbon dioxide insufflation decreases heparin potency: a risk factor for thrombus formation.
abstract: BACKGROUND
  Since the introduction of CO2insufflation during open heart surgery in our hospital, we incidentally observed thrombus formation in the dissected heart, in the pericardium and in the cardiotomy reservoir of the cardiopulmonary bypass system. Furthermore, we measured very high levels of pCO2, causing severe acidosis, in stagnant blood in the pericardium and cardiotomy reservoir.
  
  
  OBJECTIVE
  In this in vitro study, we assessed the influence of acidosis and hypothermia on heparin potency and thrombin formation.
  
  
  METHODS
  We assessed heparin potency in function of pH (pH 5.0-7.4) and temperature (24-37°C) by comparing the activated partial thromboplastin time in platelet-poor plasma between samples with and without unfractionated heparin. We measured thrombin formation in platelet-poor plasma by means of fluorescent, calibrated, automated thrombography in function of pH (pH 5.0-7.4) and temperature (24-37°C). The parameters of interest were the endogenous thrombin potential and the peak amount of thrombin generation.
  
  
  RESULTS
  The major finding of this study is the significant decrease in the efficiency of unfractionated heparin in delaying thrombus formation at acidotic (pH 5.0-7.0) conditions (p=0.034-0.05). Furthermore, we found that thrombin formation is significantly increased at hypothermic (24-34°C) conditions (p=<0.001-0.01).
  
  
  CONCLUSIONS
  Based on the results of our in-vitro study, we conclude that acidosis may lead to a decreased heparin potency. Acidosis, as induced by CO2insufflation, may predispose patients to incidental thrombus formation in stagnant blood in the open thorax and in the cardiotomy reservoir. Hypothermia might further increase this risk. Therefore, we recommend reconsidering the potential advantages and disadvantages of using CO2insufflation during cardiopulmonary bypass.
authors: 1 Department of Extracorporeal Circulation, St. Antonius Hospital, Nieuwegein, The Netherlands.
authors: Karin A M
authors: KA
authors: Gorter
authors: 1 Department of Extracorporeal Circulation, St. Antonius Hospital, Nieuwegein, The Netherlands.
authors: Marco C
authors: MC
authors: Stehouwer
authors: 2 Department of Cardiovascular Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands.
authors: Bart P
authors: BP
authors: Van Putte
authors: 3 Department of Anesthesiology, St. Antonius Hospital, Nieuwegein, The Netherlands.
authors: Eline A
authors: EA
authors: Vlot
authors: 4 Department of Clinical Chemistry and Hematology, University Medical Centre Utrecht, The Netherlands.
authors: Rolf T
authors: RT
authors: Urbanus
mesh_terms: D000138:Acidosis / Q000097:blood* / Q000209:etiology; D000925:Anticoagulants / Q000494:pharmacology* / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D001784:Blood Gas Analysis; D002245:Carbon Dioxide / Q000097:blood*; D006493:Heparin / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007036:Hypothermia, Induced / Q000009:adverse effects / Q000379:methods; D007327:Insufflation / Q000009:adverse effects* / Q000379:methods; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000209:etiology* / Q000517:prevention & control
chemical_list: D000925:Anticoagulants; D002245:Carbon Dioxide; D006493:Heparin
keywords: CO2 insufflation; acidosis; blood coagulation; heparin; thrombin