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Ann Thorac Surg 1995;59:877-879
© 1995 The Society of Thoracic Surgeons

Aprotinin Reduces Blood Loss in Lung Transplant Recipients

The Toronto Lung Transplant Program, The Toronto Hospital, University of Toronto, Toronto, Ontario, Canada

Accepted for publication January 4, 1995.

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
After early experience with perioperative bleeding in sequential single-lung transplant recipients, aprotinin was introduced in an attempt to reduce this complication and the attendant morbidity. Records of sequential single-lung transplantations (n = 33) performed between January 1989 and November 1991 were reviewed to assess the impact of aprotinin on perioperative blood loss and blood product requirements. Recipients were divided according to whether or not they required cardiopulmonary bypass. In patients requiring cardiopulmonary bypass (n = 15), mean estimated postoperative blood loss was 3,000 +/- 500 mL in those who did not receive aprotinin (n = 4) compared with 1,177 +/- 253 mL in those who received aprotinin (n = 11) (p < 0.05). An average of 8.0 +/- 0.7 units of packed red blood cells were administered to patients not receiving aprotinin compared with 3.1 +/- 0.7 units to those who received aprotinin (p < 0.05). Requirements for fresh frozen plasma were similar in each group. There were no differences in blood loss or blood product replacement in the group not undergoing cardiopulmonary bypass (n = 18). Therefore, we conclude that aprotinin decreases postoperative blood loss and blood product requirements in patients undergoing sequential single-lung transplantation under cardiopulmonary bypass.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Excessive perioperative bleeding may increase morbidity and mortality in any surgical procedure including transplantation. Over time, improvements in surgical technique and expertise have served to reduce technical complications and perioperative bleeding during lung transplantation. One such modification has been the change from en-bloc double-lung transplantation to sequential single-lung transplants (SSLTs) [1]. Although this shift in operative technique has lessened the likelihood of cardiopulmonary bypass (CPB) and consequent heparinization, a proportion of lung transplant procedures still will involve CPB.

Aprotinin was introduced because of continuing concerns over perioperative bleeding in SSLT recipients. Aprotinin reduces bleeding through inhibition of kallikrein, thereby reducing tissue-plasminogen activator release [2]. Aprotinin previously has been reported to be beneficial in reducing bleeding in patients who undergo repeat open heart operations and those who take aspirin [3, 4].

To assess operative outcome after the introduction of aprotinin we reviewed operative records retrospectively and sought to evaluate whether aprotinin has been associated with reduced operative blood loss and reduced need for blood product replacement.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
A retrospective review of operative and medical records of all SSLTs performed by The Toronto Lung Transplant Program between January 1989 and November 1991 was conducted. Patients who had received tranexamic acid were excluded. A standard anesthetic technique was used in all cases. The operative procedure has been described previously [5]. Procedures were divided according to the need for CPB and for the administration of aprotinin. Aprotinin was administered during induction of anesthesia (1 million KIU), at the time of CPB (2 million KIU), and during CPB (500,000 KIU per hour of CPB). Systemic anticoagulation for CPB was established by intravenous bolus infusion of heparin (300 to 400 international units/kg). The level of anticoagulation during CPB was monitored by repeated (every 20 minutes) measurements of activated clotting times. Baseline activated clotting time before heparinization was established in each patient with a bypass target range for activated clotting time of 480 to 650 seconds. Bolus infusions of 5,000 to 10,000 international units of heparin were given for activated clotting time levels of 525 seconds or greater. After cessation of CPB, anticoagulation was reversed by bolus infusion of protamine sulfate (1 mg/100 international units of heparin given). Activated clotting time levels were monitored until baseline levels were reached with additional protamine sulfate administered as required. In the intensive care unit, postoperative surveillance of anticoagulation continued with hourly monitoring of prothrombin time and partial thromboplastin time until stable baseline levels were reached.

Postoperative bleeding was estimated from amounts recorded from the wound drainage system and weight of sponges used during the operative procedure. Blood product replacement over the first 24 hours was recorded.

Data are expressed as means +/- standard error. Data were compared by an unpaired t test. Differences were considered statistically significant at p less than 0.05.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
A total of 34 SSLT procedures between January 1989 and November 1991 were reviewed. Fifteen patients received aprotinin. The 18 patients who did not receive aprotinin received transplants before those who did. One operative procedure was excluded as an accurate assessment of blood loss was not possible from the operative records. Fifteen patients required CPB, and 18 did not. Eleven of 15 patients undergoing CPB received aprotinin. Patients are listed according to their underlying disease in Table 1. In patients requiring CPB, mean estimated postoperative blood loss was 3,000 +/- 500 mL in those who did not receive aprotinin compared with 1,177 +/- 253 mL in those who received aprotinin (p < 0.05) (Table 2). An average of 8.0 +/- 0.7 units of packed red blood cells were administered to patients not receiving aprotinin compared with 3.1 +/- 0.7 units to those who received aprotinin (p < 0.05). In addition, more platelets were given to patients not receiving aprotinin (7.0 +/- 2.4 versus 0 units; p < 0.05). No differences were noted in requirement for fresh frozen plasma. With regard to the patients not undergoing CPB, there were no differences in blood loss or blood product replacement between the 3 patients receiving aprotinin and the 15 not receiving aprotinin (see Table 2).

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment References

We specifically restricted the analysis to subjects who had undergone virtually identical procedures (SSLT) and have not included data with en bloc double-lung and single-lung transplantation. Improvements in technique or surgical expertise may account for less blood loss as all subjects receiving aprotinin received transplants subsequent to those who did not. However, we believe that this is unlikely as the study was restricted to those undergoing similar procedures, the time frame was relatively short (34 months), and all patients were operated on by only two experienced lung transplant surgeons. Furthermore, in the CPB group of patients receiving aprotinin, a higher proportion of patients had cystic fibrosis as the cause of end-stage lung disease (9/11 versus 2/4). As pleural complications are relatively common in patients with cystic fibrosis, a higher rate of blood loss compared with the other causes of end-stage lung disease might have been expected but was not seen.

Reduced blood loss may be an inconsequential measure of morbidity. There are no studies in the transplant literature documenting whether reducing blood replacement requirements leads to improved allograft function or decreased mortality. It is possible the implied improved hemostasis may lessen operative time and the time on CPB, if required. Another potential benefit of reducing blood loss and subsequent need for replacement is the reduction in risk of exposure to blood-transmitted infectious agents. However, the cost of aprotinin is $278.00 Canadian per million KIU whereas the estimated cost of packed red blood cells and platelets according to the Canadian Red Cross is between $35 and $40 per unit. As with all medical therapy, the potential benefit must be weighed against the dollar cost. It may be that equivalent benefit may occur with less expensive antifibrinolytic agents such as tranexamic acid.

In summary, we have shown that SSLT recipients who required CPB and received aprotinin had an approximately 50% reduction in blood loss and perioperative blood product requirements when compared with similar patients not given aprotinin. Aprotinin did not decrease blood loss or transfusion requirements when CPB was not used. As it is often difficult to be certain which transplant recipient will not require CPB, it seems reasonable to administer aprotinin to all patients undergoing SSLT.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Address reprint requests to Dr Kesten, Western Division, The Toronto Hospital, 399 Bathurst St, Edith Cavell Wing 4-009, Toronto, ON, Canada M5T 2S8.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 

1. Kaiser LR, Pasque MK, Trulock EP, Low DE, Dresler CM, Cooper JD. Bilateral sequential lung transplantation: the procedure of choice for double-lung replacement. Ann Thorac Surg 1991;52:438–46.[Abstract]
2. Fritz H, Wunderer G. Biochemistry and applications of aprotinin, the kallikrein inhibitor from bovine organs. Arzneimittelforsch 1983;33:479–94.[Medline]
3. Royston D, Bidstrup BP, Taylor KM, Sapsford RN. Effect of aprotinin on need for blood transfusion after repeat open-heart surgery. Lancet 1987;2:1289–91.[Medline]
4. Bidstrup BP, Royston D, McGuiness C, Sapsford RN. Aprotinin in aspirin-treated patients. Perfusion 1990;5(Suppl):77–81.
5. Pasque MK, Cooper JD, Kaiser LR, Haydock DA, Triantafillou A, Trulock EP. Improved technique for bilateral lung transplantation: rationale and initial clinical experience. Ann Thorac Surg 1990;49:785–91.[Abstract]
6. Neuhaus P, Bechstein WO, Lefebre B, Blumhardt G, Slama K. Effect of aprotinin on intraoperative bleeding and fibrinolysis in liver transplantation. Lancet 1989;2:924–5.[Medline]
7. Royston D. Aprotinin therapy in heart and heart-lung transplantation. J Heart Lung Transplant 1993;12:S19–25.[Medline]

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Janet R. Maurer Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kesten, S. Articles by Maurer, J. R. Search for Related Content PubMed PubMed Citation Articles by Kesten, S. Articles by Maurer, J. R.