Anaphylactic reactions to aprotinin reexposure in cardiac surgery: relation to antiaprotinin immunoglobulin G and E antibodies.

BACKGROUND: Aprotinin, a serine proteinase inhibitor, reduces bleeding during cardiac surgery. As aprotinin is derived from bovine lung, it has antigenic properties. This investigation examined the incidence of anaphylactic reactions in patients reexposed to aprotinin and the relation to preformed antiaprotinin immunoglobulin (Ig)G and IgE antibodies. METHODS: This prospective observational study conducted at five centers in Germany evaluated patients undergoing repeat cardiac surgery reexposed to aprotinin between 1995 and 1996. Antiaprotinin IgG and IgE antibody measurements, using a noncommercial enzyme-linked immunosorbent assay and an immunofluorescence assay, respectively, were performed preoperatively and postoperatively. An anaphylactic reaction was defined as major changes from baseline within 10 min of aprotinin administration of systolic pressure 20% or greater, heart rate 20% or greater, inspiratory pressure greater than 5 cm H2O, or a skin reaction. RESULTS: In 121 cases (71 adults, 46 children), a mean aprotinin reexposure interval of 1,654 days (range, 16-7,136 days) was observed. Preoperative antiaprotinin IgG (optical density ratio > 3) and IgE antibodies (radioallergosorbent test [RAST] score < 3) were detected in 18 and 9 patients, respectively. High concentrations of each (IgG, optical density ratio > 10; IgE, RAST score > or = 3) were detected in five patients. Three patients (2.5%; 95% confidence interval, 0.51-7.1%) experienced an anaphylactic reaction after aprotinin exposure, followed by full recovery; these patients had reexposure intervals less than 6 months (22, 25, and 25 days) and the highest preoperative IgG concentrations of all patients (P < 0.05). Assay sensitivity was 100%, as no anaphylactic reactions occurred in IgG-negative patients (95% confidence interval, 0.0-3.1%); assay specificity was 98%. Preoperative IgE measurements were quantifiable in two of three reactive patients and in three nonreacting patients. CONCLUSIONS: Quantitative detection of antiaprotinin IgE and IgG lacks specificity for predictive purposes; however, quantitation of antiaprotinin IgG may identify patients at risk for developing an anaphylactic reaction to aprotinin reexposure.

Safety of virus inactivated antithrombin III concentrate antithrombin III immuno (AT III).

In a prospective clinical trial the risk of infection after application of virus inactivated antithrombin III concentrate ANTITHROMBIN III IMMUNO (AT III) was investigated in patients undergoing cardiovascular surgery. The study was conducted according to the recommendations of the International Committee on Thrombosis and Hemostasis (ICTH), with the exception that most patients required additional blood products as well as AT III. Twenty-seven patients were eligible to test for the risk of acquiring hepatitis B. Twenty-six patients could be evaluated in terms of hepatitis NANB transmission considering ALT-levels whereas 20 patients could be tested for anti-HCV one year after surgery. Samples from 78 patients could be monitored for anti-HIV-1. None of these patients showed any signs of infection. AT III IMMUNO seems to be an antithrombin III concentrate with low or absent infectivity.

Safety of vapour heated prothrombin complex concentrate (PCC) Prothromplex S-TIM 4.

The risk of infection after application of vapour heated prothrombin complex concentrate PROTHROMPLEX S-TIM 4 (PCC) was investigated in patients undergoing cardiovascular surgery. The study was conducted according to the recommendations of the International Committee on Thrombosis and Hemostasis (ICTH) with the exception that most patients required other blood products in addition to PCC. Twenty-One patients were eligible to test for the risk of acquiring hepatitis NANB (ALT-levels) and samples from 12 patients were available that could be screened for anti-HCV. Twenty patients qualified for evaluation of the risk of developing hepatitis B, and 67 patients qualified to test for HIV-1-Infection. None of these patients showed any signs of infection. Vapour heating of prothrombin complex concentrate seems to lower the risk of transmitting viral diseases considerably.

Blood transfusion requirements in coronary artery surgery with and without the activated clotting time (ACT) technique.

Control of anticoagulation during cardiopulmonary bypass (CPB) with the automated activated whole blood clotting time (ACT) and reversal of heparin after CPB using a computerized ACT dose-response curve method resulted in significant reductions of blood transfusion requirements, surgical time, and protamine doses in 150 patients undergoing coronary artery bypass grafting procedures (ACT group) as compared to 200 patients for whom a standard fixed dose protocol for heparin and protamine was used (control patients). Mean transfusion requirements were 1,938 +/- 60 SEM ml whole blood and 853 +/- 48.3 SEM ml red blood cells for control patients and 1,397 +/- 59 SEM ml whole blood (P less than 0.001) and 695 +/- 34 SEM ml red blood cells (P less than 0.01) in the ACT group. ACT group patients also required less protamine with 26.2 +/- 0.60 SEM ml Protamine 1,000 (Roche) as compared to 33.9 +/- 0.49 SEM ml for control patients (P less than 0.001) but more heparin with 31,440 +/- 783 SEM I.U. versus 26,760 +/- 263 SEM I.U. (P less than 0.001). Surgical time decreased from 321 +/- 5.5 SEM min for control patients to 289 +/- 5.4 SEM min for ACT group patients (P less than 0.001).

[Individual heparin and protamine dosage in heart surgery]. / Individuelle Heparin- und Protamindosierung in der Herzchirurgie.

Several methods of heparin administration before and heparin neutralization after cardiopulmonary bypass (CPB) have been proposed, based on individual dose-response curves of the activated clotting time (ACT). We investigated the use of a regression line, established from simultaneous double determinations of the ACT before and after serial doses of heparin (240 and 360 IU/kg), calculated by computer to determine the doses of heparin and protamine needed. Administration of protamine doses calculated from ACT measurements at termination of CPB in 31 patients resulted in ACT measurements which were not significantly different from pre-heparin levels, however. ACT values after 360 IU/kg heparin varied widely. Among 351 patients studied 62.9% had ACT values greater than 450 s, 27,9% had ACT values between 450 and 350 s, and 9.1% had ACT values less than 350 s. Our studies produced an interesting finding. Mean ACT values of women after both doses of heparin were significantly smaller (p less than 0.0000) (359.7 +/- 6 s, n = 144 and 452.4 +/- 9 s, n = 160) than those of men (393.8 +/- 3.7 s, n = 501 and 501.0 +/- 5.1 s, n = 549).

Contractility and ultrastructure of cardiac muscle of guinea pigs treated with diphtheria toxin.

The development of tension and the ultrastructure of cardiac papillary muscle of normal guinea pigs were compared to guinea pigs receiving lethal doses of diphtheria toxin. The maximal isometric force of the papillary muscles at various levels of resting tension indicated no significant difference between the control and the diphtheritic animals. Neither did the sarcomere lengths of papillary muscles, fixed at various levels of tension, show any significant difference between these two groups. Electronmicroscopy in diphtheritic animals showed intact myofilaments but marked dilatation of the T and L system as well as pathologic fat deposits adjacent to the subsarcolemma and the T system. The results, therefore, suggest that diphtheria toxin acts on the T and L system, but does not affect structure and function of the myofilaments in the acute stage of diphtheria intoxication.

Effect of the H2-receptor antagonists (burimamide and metiamide) on gastric secretion stimulated by histamine and its methyl derivatives.

This study was done to determine the comparative effectiveness of burimamide and metiamide as antagonists of gastric secretion stimulated by histamine and its methyl derivatives, Nalpha-methylhistamine, N-alpha,N-alpha-dimethylhistamine and 4-methylhistamine, in dogs with vagally denervated (Heidenhain pouches) and vagally innervated gastric mucosal septal pouches (Pavlov-type pouches). The secretagogues were always given by continuous i.v. infusion to produce steady states of secretory activity in the fasted conscious dogs; the antagonists were given by either rapid "bolus" i.v. injection or continuous i.v. infusion. With bolus injections, both antagonists promptly inhibited the secretion produced by histamine and its methyl derivatives. When control secretory rates were similar, 40 mumol of burimamide per kg and 4 mumol of metiamide per kg produced the same degree of inhibition. When the antagonists were also given by continuous i.v. infusion, the difference between them was greater, metiamide being 15 to 17 times more potent than burimamide. The effectiveness of the antagonists was not changed by vagal denervation. Symptoms of toxicity to burimamide developed at doses in excess of 30 mumol/kg/hr; none occurred with doses of metiamide ranging from 1.8 to 7.5 mumol/kg/hr.