title: Reheparinisation requirements after cardiopulmonary bypass in patients treated with aprotinin.
abstract: OBJECTIVE
  To determine reheparinisation requirements following protamine neutralisation after the discontinuation of cardiopulmonary bypass in a group of patients receiving "low dose" aprotinin compared with a control group.
  
  
  METHODS
  Randomised, placebo controlled study.
  
  
  METHODS
  Regional cardiothoracic unit within a district general hospital.
  
  
  METHODS
  20 patients were consecutively allocated to one of two groups. All patients had a primary elective aortocoronary bypass operation using standard anaesthetic techniques and no patient was withdrawn from the study.
  
  
  METHODS
  Aprotinin group patients (n = 9) received aprotinin (1 x 10(6) kallikrein inactivator units (KIU)) as an intravenous bolus after the induction of anaesthesia, and 1 x 10(6) KIU was added to the pump prime. Control group patients (n = 11) received 0.9% saline placebo.
  
  
  METHODS
  Activated clotting time (ACT), heparin concentration, and heparin dose response (HDR) measured before, during, and after bypass. The HDR is an accurate method to determine the patients' in vitro response to heparin and is used to predict the dose of heparin required to attain an ACT of 400 seconds.
  
  
  RESULTS
  Activated clotting times were similar in the two groups for the duration of the study. Heparin concentrations were zero in all patients before heparin administration and after protamine neutralisation. During bypass there was no difference between the groups. The median heparin dose response was the same in the two groups before the administration of heparin, but after the neutralisation of heparin with protamine after the discontinuation of bypass the HDR was significantly higher in the aprotinin group for up to one hour (median of 2.9 IU/ml v 1.25 in the control group at 10 minutes after protamine neutralisation, P < 0.01; 2.5 v 1.45 at 30 minutes, P < 0.05; and 2.9 v 1.6 at one hour, P < 0.001).
  
  
  CONCLUSIONS
  Heparin requirements were nearly doubled in patients treated with aprotinin, who required reheparinisation for up to one hour after protamine. This relative "heparin resistance" cannot be explained by the presence of excessive protamine. Aprotinin may be a substrate for the N-carboxypeptidase that destroys protamine, thus indirectly enhancing and prolonging the activity of protamine.
authors.affiliation: Department of Anaesthetics, Guy's Hospital, London.
authors.forename: C R
authors.initials: CR
authors.lastname: Bailey
authors.forename: A R
authors.initials: AR
authors.lastname: Fisher
authors.forename: A K
authors.initials: AK
authors.lastname: Wielogorski
mesh_terms: D007611:Aprotinin / Q000008:administration & dosage*; D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D011446:Prospective Studies; D014914:Whole Blood Coagulation Time
chemical_list: D006493:Heparin; D007611:Aprotinin