Aprotinin surgery

Aprotinin. Aprotinin is a naturally occurring serine protease inhibitor, has found widespread applications either by the intravenous route or as a component of biological sealants, because of its ability to decrease blood loss, and, as a consequence, transfusion requirements. Anaphylactic reactions are mediated by IgG and IgE antibodies. The risk of anaphylactic reactions has been estimated between 0.5 and 5.8% when used intravenously during cardiac surgery, and at 5 for 100,000 applications when used as a biologic sealant [25]. Patients previously treated with this drug present an increased risk and any new administration should be avoided for at least 6 months following an initial exposure [25]. 

Dietrich W, Ebell A, Busley R. Boulesteix AL Aprotinin and anaphylaxis analysis of 12,403 exposures to aprotinin in cardiac surgery. Ann Thorac Surg 2007 84 1144. 

Cardiopulmonary bypass, with extracorporeal circulation during cardiac artery bypass graft or heart valve replacement surgery, causes transient hemostatic defects in blood cells and perioperative bleeding. The protease inhibitor aprotinin (Trasylol) inhibits kalhkrein (coagulation phase) and plasmin (hbrinolysis) and protects platelets from mechanical injury. The overall effect after infusion is a decrease in bleeding. 

A meta-analysis of placebo-controlled trials of desmopressin in 702 cardiac surgery patients showed a significantly increased risk of myocardial infarction in treated patients (RR = 2.39, Cl = 1.02, 5.60) (30). Overall mortality was not different from placebo. Desmopressin was less efficacious in reducing perioperative blood loss than either aprotinin or lysine analogues. 

Aprotinin administration during surgery should follow heparin treatment to avoid any risk. Patients under the treatment of antifibrinolytic therapy should be treated cautiously when coadministering drugs affecting hemostasis and estrogens.229 Accumulation of albumin may occur in patients with impaired renal function if large volumes of albumin solutions are administered. 

Day JRS, Punjabi PP, Randi AM, Haskard DO, Landis RC, Taylor KM. Clinical inhibition of the seven-transmembrane thrombin receptor (PARI) by intravenous aprotinin during cardiothoracic surgery. Circulation 2004 110 2597-2600. 

Sedrakyan A, Treasure T, Elefteriades JA. Effect of aprotinin on clinical outcomes in coronary artery bypass graft surgery a systematic review and meta-analysis of randomized clinical trials. J. Thorac. Cardiovasc. Surg. 2004 128 442-448. 

The issue of whether the use of aprotinin is associated with an increased risk of vein graft thrombosis in cardiac bypass surgery has not been resolved (14,15). The use of... 

In a randomized, placebo-controUed, multicenter study of aprotinin in coronary artery bjrpass surgery, there was no increase in mortality or the incidence of myocardial infarction (20). 

As might be expected with a bovine protein, allergic reactions can occur, and repeated exposure can even result in anaphylactic reactions. In view of this, some have advocated a strategy of using aprotinin only if excessive bleeding is a problem after surgery (23). 

The sera of 150 patients who had undergone cardiac surgery and were receiving aprotinin for the first time have been studied before and after the operation. At 3.5 months after surgery, the prevalence of aprotinin-specific IgG antibodies was 33% (15/45) after local, 28% (13/46) after intravenous, and 69% (41/59) after combined exposure (33). The authors concluded that local administration of aprotinin induces a specific immune response and reinforces that of intravenous exposure they therefore recommended that any exposure in a patient should be documented. 

Royston D, Bidstrup BP, Taylor KM, Sapsford RN. Effect of aprotinin on need for blood transfusion after repeat open-heart surgery. Lancet 1987 2(8571) 1289-91. 

Lass M, Simic O, Ostermeyer J. Re-graft patency and clinical efficacy of aprotinin in elective bypass surgery. Cardiovasc Surg 1997 5(6) 604-7. 

Hayes A, Murphy DB, McCarroll M. The efficacy of singledose aprotinin 2 million KIU in reducing blood loss and its impact on the incidence of deep venous thrombosis in patients undergoing total hip replacement surgery. J Clin Anesth 1996 8(5) 357-60. 

Greilich PE, Okada K, Latham P, et al. Aprotinin but not e-aminocaproic acid decreases interleukin-10 after cardiac surgery with extracorporeal circulation-Randomized, double-blind, placebo-controlled study in patients receiving aprotinin and e-aminocaproic acid. Circulation 2001 104 (SuppI l) 265-269. 

By inhibiting fibrinolysis and preserving platelet function, aprotinin has been shown to reduce blood loss and transfusion requirements in cardiac surgery, lung, and liver transplantations, and surgery for hip replacement. Additional indications are hyperfibrinolytic hemostatic disorders and complications of thrombolytic therapies. In Europe, aprotinin has been in clinical use for about 40 years, but in the United States it has been approved for intravenous applications only since 1993 [M. Kunitz,... 

Three patients undergoing surgery who had received suxamethonium (succinyichoiine), alone or with tubocurarine, were given aprotinin intravenously in doses of 2500 to 12 000 KIU (kallikrein inactivator units) at the end of, or shortly after the operation, when spontaneous breathing had resumed. In each case respiration rapidly became inadequate and apnoea lasting periods of 7, 30 and 90 minutes occurred. Seven other cases have been reported elsewhere. ... 

In 2(X)7, aprotinin was temporarily withdrawn worldwide until results from the Canadian BART (Blood conservation using antifibrinolytics a randomized trial) study conducted in high-risk cardiac surgery patients was completed and evaluated. Sales of the drug were suspended in May 2008, but this suspension was lifted in Europe by the European Medicines Agency in February 2012. 

The use of aprotinin in patients undergoing surgery has been reported to increase the... 

In a prospective comparison of aprotinin (n = 1507) and aminocaproic add (n = 1830) in patients undergoing surgery, postoperative renal failure was significantly more common in the former (6.2% versus 2.7%) and at median 5.4-year follow-up (up to 12 years) mortality was higher (Kaplan-Meier failure rates 44% versus 24% at 8 years), with a stepwise relation between weight-based aprotinin dose and mortality [197 ]. 

In a non-randomized prospective study of 1188 patients who underwent cardiac surgery, the first 596 received aprotinin and the next 592 received tranexamic acid [198 ]. Postoperatively, in those who underwent primary valve surgery, tranexamic acid was associated with significantly higher incidences of seizures (4.6% versus 1.2%), persistent atrial fibrillation (7.9% versus 2.3%), and renal insufficiency (9.7% versus 1.7%). In those who underwent primary... 

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