title: Aprotinin and deep hypothermic circulatory arrest: there are no benefits even when appropriate amounts of heparin are given.
abstract: OBJECTIVE
  To evaluate retrospectively the effect of 'high-dose' aprotinin on blood losses, donor blood requirements and morbid events on patients undergoing ascending aorta and/or aortic arch procedures with the employ of deep hypothermic circulatory arrest (HCA).
  
  
  METHODS
  During the period 1987-1994, 39 patients underwent a thoracic aorta procedure with the employ of circulatory arrest; of these 18 (46.2%) were operated on during the period 1990-1994 and were given aprotinin intraoperatively following the 'high-dose' protocol (group I), while 21 (53.8%) who underwent surgery during the years 1987-1989, did not receive intraoperative aprotinin and served as historical controls (group II). Twenty-seven (69.2%) patients were male, 18 (46.2%) were operated on on an emergency basis, 15 (38.5%) were acute type A dissections, and two (5.1%) were redo-operations. Circulatory arrest times were not significantly different between the two groups (40 +/- 4 (S.E.) group I vs. 43 +/- 4 min group II, P = 0.62) likewise cardiopulmonary bypass (CPB) times (181 +/- 9 vs. 201 +/- 20 mm, P = 0.74) and the amount of heparin administered (32056 +/- 1435 vs. 31 691 +/- 1935 IU, P = 0.56).
  
  
  RESULTS
  Postoperative blood loss was comparable between the two groups (1213 +/- 243 (median 850) group I vs. 1528 +/- 377 (median 880) ml group II, P = 0.87), as well as the number of units of donor blood transfused (9.4 +/- 3.0 (median 6) vs. 9.9 +/- 3.6, (median 5) P = 0.87), and revisions for bleeding (2/18, 11.1% vs. 3/21, 14.3%, P = 0.77). In-hospital mortality rate was not statistically different (5/18, 27.7% group I vs. 6/21, 28.6% group II, P = 0.92). There were no significant differences between the two groups in myocardial infarction (2/18, 11.1% vs. 0/21, 0%, P = 0.21), and postoperative renal failure rates (3/18, 16.7% vs. 2/21, 9.5%, P = 0.65). On the other hand, there was a trend towards an increased incidence of permanent neurological deficit (5/18, 27.7% group I vs. 1/21, 4.8% group II, P = 0.07) and towards a more complicated postoperative course (perioperative renal failure and/or myocardial infarction and/or neurological deficit either transient or permanent) (8/18, 44.4% group I vs. 4/21, 19% group II, P = 0.09) in group I patients. Forward stepwise logistic regression analysis, performed on the whole group of patients, identified chronic obstructive pulmonary disease (P = 0.010, Odds ratio (OR) = 5.7), aprotinin use (P = 0.017, OR = 5.1), and the number of units of blood collected intraoperatively by the cellsaver (P = 0.045, OR = 1.3/unit) as independent predictors of complicated postoperative course in the whole group of patients. CPB time (P = 0.040, OR = 1.032/min), circulatory arrest time (P = 0.053, OR = 1.22/min), and overall donor blood units transfused (P = 0.067, OR = 1.37/unit) emerged as independent risk factors for in-hospital mortality at multivariate analysis.
  
  
  CONCLUSIONS
  Even when appropriate amounts of heparin are administered, 'high-dose' aprotinin probably is not an effective blood-sparing drug in deep HCA. Aprotinin should be employed cautiously in this clinical setting because of its possible correlation with an increased rate of postoperative morbid events.
authors.affiliation: Department of Cardiac Surgery, University of Milan, Centro Cardiologico, Fondazione I Monzino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Parolari
authors.forename: C
authors.initials: C
authors.lastname: Antona
authors.forename: F
authors.initials: F
authors.lastname: Alamanni
authors.forename: R
authors.initials: R
authors.lastname: Spirito
authors.forename: M
authors.initials: M
authors.lastname: Naliato
authors.forename: P
authors.initials: P
authors.lastname: Gerometta
authors.forename: V
authors.initials: V
authors.lastname: Arena
authors.forename: P
authors.initials: P
authors.lastname: Biglioli
mesh_terms: D000368:Aged; D000784:Aortic Dissection / Q000097:blood / Q000401:mortality / Q000601:surgery*; D017545:Aortic Aneurysm, Thoracic / Q000097:blood / Q000401:mortality / Q000601:surgery*; D007611:Aprotinin / Q000008:administration & dosage*; D016063:Blood Loss, Surgical / Q000503:physiopathology / Q000517:prevention & control*; D001803:Blood Transfusion; D002423:Cause of Death; D004305:Dose-Response Relationship, Drug; D005260:Female; D006324:Heart Arrest, Induced / Q000379:methods*; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000097:blood / Q000401:mortality / Q000601:surgery; D012086:Reoperation; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D006493:Heparin; D007611:Aprotinin