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Canadian Journal of Anaesthesia

, Volume 40, Issue 7, pp 625–631 | Cite as

Low-dose aprotinin infusion is not clinically useful to reduce bleeding and transfusion of homologous blood products in high-risk cardiac surgical patients

  • Jean-François Hardy
  • Jean Desroches
  • Sylvain Belisle
  • Jean Perrault
  • Michel Carrier
  • Danielle Robitaille
Reports of Investigation

Abstract

A high-dose regimen of aprotinin 5–6 million KIU is effective in reducing bleeding and the need for homologous blood products (HBP) associated with cardiopulmonary bypass (CPB). These high doses aim at achieving plasmin and plasma kallikrein concentrations which in vitro are inhibitory but, theoretically, smaller doses could suffice in vivo. Also, aprotinin is an expensive drug, so efficiency requires using the smallest effective dose. Therefore, the efficacy of prophylactic aprotinin 1 million KIU (the maximal dose approved currently) was evaluated in a patient population at high risk of bleeding and of being transfused. Forty-one patients undergoing reoperation or a complex surgical procedure were included in a prospective, randomized, placebo-controlled, double-blind study. Before skin incision, a bolus of 200,000 KIU aprotinin was administered in 20 min, followed by an infusion of 100,000 KIU· hr−1 over eight hours. Control patients received an equal volume of saline. Dryness of the operative field, chest drainage, transfusion of HBP, haemoglobin concentrations, and coagulation variables (including bleeding time) were compared. There were no differences between aprotinin and placebo-treated patients for all clinical and laboratory variables. The apparent ineffectiveness of aprotinin may be explained by the use of an insufficient dose, by a different protocol of administration (e.g., no bolus in CPB prime), or by the inability of aprotinin to decrease bleeding and transfusions any further. Also, the number of patients studied does not exclude the possibility of a Type II error. However, based on the small differences observed, we conclude that low-dose aprotinin infusion is not useful clinically to reduce chest drainage and transfusions in a patient population at high risk of being exposed to HBP.

Key words

anaesthesia: cardiac blood: coagulation antifibrinolytics, aprotinin surgery: cardiovascular, cardiopulmonary bypass 

Résumé

Une posologie élevée d’aprotinine de 5–6 millions KIU diminue le saignement et le besoin de produits sanguins homologues utilisés pour la circulation extracorporelle (CEC). Ces doses élevées visent l’atteinte de concentrations de plasmine et de kallicréine plasmatique efficaces in vitro, mais théoriquement, de plus faibles doses devraient suffire in vivo. De plus, l’aprolinine est une produit coûteux et il est normal qu’on n’utilise que la plus petite dose efficace. C’est dans ce contexte que l’efficacité de l’aprolinine prophylactique 1 million KIU (la dose maximale actuellement approuvée) est évaluée sur une population à haut risque d’hémorragies et de transfusions subséquentes. Quarante-et-un patients soumis à une ré-opération ou à une intervention cardiaque complexe sont inclus dans une étude prospective à double aveugle, randomisée et contrôlée avec placebo. Avant l’incision de la peau, un bolus de 200000 KIU d’aprotinine est administré en 20 min, suivi d’une perfusion de 100 000 KIU · hr−1 répartie sur huit heures. Le groupe contrôle reçoit du soluté physiologique en volume égal. La quantité de sang du champ opératoire, l’importance des pertes par les drains thoraciques, les transfusions de produit sanguins homologues, la concentration de l’hémoglobine et les épreuves de coagulation (temps de saignement inclus) sont comparés. On ne trouve pas de différences entre le groupe aprotinine et le groupe placebo pour tous les paramètres cliniques et de laboratoire. L’inefficacité apparente de l’aprotinine peut s’expliquer par l’utilisation d’une dose insuffisante, par un protocole d’administration différent (v.g. absence de bolus dans l’amorce de CEC), ou par l’incapacité de l’aprotinine à diminuer encore plus le saignement et le besoin de transfusions. De plus le nombre de patients étudiés n’exclut pas la possibilité d’une erreur de type II. Toutefois, sur la base des différences minimes observées, nous concluons que l’aprotinine à faible dose en perfusion n’est pas utile cliniquement pour diminuer les pertes par les drains thoraciques et la quantité de sang transfusée chez une population de patients très susceptible de recevoir des produits de sang homologue.

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Copyright information

© Canadian Anesthesiologists 1993

Authors and Affiliations

  • Jean-François Hardy
    • 1
  • Jean Desroches
    • 1
  • Sylvain Belisle
    • 1
  • Jean Perrault
    • 4
  • Michel Carrier
    • 2
  • Danielle Robitaille
    • 3
  1. 1.Department of AnaesthesiaUniversity of Montreal, Montreal Heart InstituteMontreal
  2. 2.Department of SurgeryUniversity of Montreal, Montreal Heart InstituteMontreal
  3. 3.Department of HaematologyUniversity of Montreal, Montreal Heart InstituteMontreal
  4. 4.Research CentretUniversity of Montreal, Montreal Heart InstituteMontreal

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