Aprotinin and deep hypothermic circulatory arrest: there are no benefits even when appropriate amounts of heparin are given

Eur J Cardiothorac Surg. 1997 Jan;11(1):149-56. doi: 10.1016/s1010-7940(96)01022-6.

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.

MeSH terms

  • Aged
  • Aortic Aneurysm, Thoracic / blood
  • Aortic Aneurysm, Thoracic / mortality
  • Aortic Aneurysm, Thoracic / surgery*
  • Aortic Dissection / blood
  • Aortic Dissection / mortality
  • Aortic Dissection / surgery*
  • Aprotinin / administration & dosage*
  • Blood Loss, Surgical / physiopathology
  • Blood Loss, Surgical / prevention & control*
  • Blood Transfusion
  • Cause of Death
  • Dose-Response Relationship, Drug
  • Female
  • Heart Arrest, Induced / methods*
  • Heparin / administration & dosage*
  • Humans
  • Male
  • Middle Aged
  • Postoperative Complications / blood
  • Postoperative Complications / mortality
  • Postoperative Complications / surgery
  • Reoperation
  • Retrospective Studies
  • Risk Factors
  • Survival Rate

Substances

  • Heparin
  • Aprotinin