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PubMed2000

The use of technologies to minimize exposure to perioperative allogeneic blood transfusion in elective surgery. A survey of Canadian hospitals.

BACKGROUND: Despite the growing medical and public interest in reducing exposure to allogeneic blood, little is known about the use of alternatives to allogeneic transfusion. This study was conducted to determine the availability of these technologies in Canadian hospitals and was undertaken under the auspices of the International Study of Peri-Operative Transfusion (ISPOT), a 10-country study of the effectiveness of, attitudes toward, and practices related to the use of alternatives to allogeneic transfusion. METHODS: A cross-sectional national mail survey of Canadian hospitals with greater than 50 medical/surgical beds. Chiefs of anesthesia, surgery, and the divisions of cardiac, orthopedic, vascular, and urology were initially mailed a brief postcard asking which of seven technologies were used in their center. This was then followed up with a one-page questionnaire asking how frequently the technologies were used, their thoughts on the appropriateness of the use of the technologies, barriers to their greater use, and reasons for nonuse of the technologies. RESULTS: Response rates to the postcard survey ranged from 70%-98%, depending on the technology and type of surgery, and ranged from 27%-53% for the follow-up questionnaire. All technologies were used most frequently in cardiac surgery. Aprotinin, tranexamic acid, aminocaproic acid, desmopressin, and cell salvage were reported used in over 70% of cardiac surgery centers. Of these, tranexamic acid and cell salvage were the only ones used routinely in some centers. Acute normovolemic hemodilution and erythropoietin were used in 45% and 20% of cardiac centers, respectively. The drugs were used in less than 15% of orthopedic, vascular, and urologic divisions, with the exception of desmopressin in urologic and vascular surgery and aminocaproic acid in urologic surgery. The techniques of cell salvage and acute normovolemic hemodilution were used in 30%-45% of these divisions, with the exception of cell salvage, which was used in less than 15% of urology units. In more than 60% of cases, the technologies were considered to be used "about right," although an important minority felt that they were underused. CONCLUSIONS: In general, alternatives to perioperative allogeneic transfusion were rarely used except in cardiac surgery.

Blood Loss, Surgical↗
PubMed1989

Cytoprotective effect of plasmin inhibitor on necrotizing agent-induced gastric lesions in rats.

We studied the effect of plasmin inhibitor on ethanol and ammonia-induced gastric mucosal lesions in rats using an ex vivo chamber. Tranexamic acid and aminocaproic acid significantly inhibited macroscopic gastric hemorrhagic necrosis and attenuated the decrease of gastric transmucosal potential difference induced by 50% ethanol and 1% ammonia. The protection of gastric mucosa afforded by tranexamic acid and aminocaproic acid was not affected by pretreatment with indomethacin (5 mg/kg). These results suggest that plasmin inhibitor plays an important role in the prevention of gastric deep necrosis following exposure of the stomach to a damaging agent.

Aminocaproic Acid↗
PubMed1976

Selective neuronal accumulation of omega-amino acids in the rabbit retina.

The uptakes of radioactive glycine, beta-alanine, GABA, delta-aminovaleric acid and epsilon-aminocaproic acid were studied in the rabbit retina in vivo and in vitro. Autoradiography demonstrated that the amino acids were mainly taken up and retained by certain cells of amacrine type. In the neurons, the omega-amino acids seem to be stored in a protected fashion. The uptake of delta-aminovaleric acid and epsilon-aminocaproic acid was temperature dependent, saturable, and of high-affinity type (with Km for delta-aminovaleric acid = 3.02 X 10(-5) M and for epsilon-aminocaproic acid 9.38 X 10(-5) M). The uptake of both delta-aminovaleric acid and epsilon-aminocaproic acid was competitively inhibited by GABA, but not by glycine or a number of other amino acids regarded as possible neurotransmitters. The uptakes of delta-aminolevulinic acid, taurine and alpha-amino-isobutyric acid were studied for comparison, but no selective neuronal uptake was observed. It is concluded that there are certain amacrine cells which selectively accumulate delta-amino acids such as beta-alanine, GABA, delta-aminovaleric acid and epsilon-aminocaproic acid. It seems possible that the mechanism accumulating GABA may also work with the other omega-amino acids. This opens the possibility that the omega-amino acids may serve as 'false neurotransmitters'.

Amino Acids↗
PubMed1996

Cost/benefit analysis of pharmacologic hemostasis.

BACKGROUND: Surgical bleeding with possible associated coagulopathies is a major source of morbidity and mortality. More than 27% of patients receive unnecessary blood or blood-product transfusions during cardiac operations. Analysis of the cost-benefit of pharmacologic hemostasis can be accomplished by relating all the components of cost, which include both direct and indirect costs to both direct and indirect benefits to the patient. METHODS: A significant reduction in transfusion requirements can be achieved by the systematic application of a clinical algorithm. An alternative is to use drugs that enhance hemostasis. Four such drugs commonly used are desmopressin acetate, tranexamic acid, epsilon-aminocaproic acid, and aprotinin. All these agents have been shown to successfully reduce bleeding and the need for transfusion. It appears that the order of efficacy (greatest to least) is aprotinin, tranexamic acid, epsilon-aminocaproic acid, and desmopressin acetate. RESULTS: Cost/benefit analysis associated with the use of these agents is complex. The direct costs of these drug treatments can be balanced against the costs related to blood and blood-product administration. Using epsilon-aminocaproic acid, blood used is valued at $30, whereas the drug treatment cost is less than $2. Aprotinin use results in costs of more than $500, with the drug costing $900. CONCLUSIONS: Improved hemostasis should also result in indirect cost savings from reduced operating room time, reduced intensive care unit and hospital stay, and the avoidance of reoperation for bleeding.

Aminocaproic Acid↗
PubMed2006

Do antifibrinolytics reduce allogeneic blood transfusion in orthopedic surgery?

Studies have shown that antifibrinolytic (aprotinin, tranexamic acid, epsilon-aminocaproic acid) reduce blood loss in orthopedic surgery. However, most lacked sufficient power to evaluate the efficacy and safety on clinical outcomes. This meta-analysis aims to evaluate whether intravenous antifibrinolytics, when compared with placebo, reduce perioperative allogeneic erythrocyte transfusion requirement in adults undergoing orthopedic surgery and whether it might increase the risk of venous thromboembolism. From MEDLINE, EMBASE, and the Cochrane Controlled Trials Register, the authors identified 43 randomized controlled trials in total hip and knee arthroplasty, spine fusion, musculoskeletal sepsis, or tumor surgery performed to July 2005 (for aprotinin, 23 trials with 1,268 participants; tranexamic acid, 20 with 1,084; epsilon-aminocaproic acid, 4 with 171). Aprotinin and tranexamic acid reduced significantly the proportion of patients requiring allogeneic erythrocyte transfusion according to a transfusion protocol. The odds ratio was 0.43 (95% confidence interval, 0.28-0.64) for aprotinin and 0.17 (0.11-0.24) for tranexamic acid. Results suggest a dose-effect relation with tranexamic acid. Epsilon-aminocaproic acid was not efficacious. Unfortunately, data were too limited for any conclusions regarding safety. Although the results suggest that aprotinin and tranexamic acid significantly reduce allogeneic erythrocyte transfusion, further evaluation of safety is required before recommending the use of antifibrinolytics in orthopedic surgery.

Adult↗
PubMed1997

[Drug or plant substances which antagonize venoms or potentiate antivenins].

Dendroaspis jamesoni (Elapidae) and Echis oceliatus (Viperidae) are responsible for most of severe evenomation in Cameroon. Toxicity of venoms of these two species has been measured using mice according to the method of Spearman & Kàrber. The effect on experimental envenomation of various drugs (atropine, promethazine, neostigmine, hydrocortisone, pentosane sulfuric polyester, heparin, tranexamic acid and aminocaproic acid) and plant extracts (Schumanniophyton magnificum, Bidens pilosa, Securidaca longepedunculata and Garcinia lucida) has been observed associated or not with the antivenom lpser Afrique (SAV). The venom of D. jamesoni contains neurotoxins agonizing and antagonising acetylcholine. The toxicity of the venom did not depend on the route of injection. Atropine, promethazine, neostigmine and hydrocortisone protected animals against a venom dose up to 2 LD50. Moreover, atropine and promethazine potentiated the SAV. Similar results have been obtained with extracts from S. magnificum and B. pilosa. The venom of E. ocellatus induces haemorrhage and necrosis. The toxicity increased by 3-fold when the venom was injected through intravenous or intraperitoneal route, compared to intramuscular route. Pentosane sulfuric polyester and tranexamic acid protected mice against doses up to 3 LD50. Pentosane sulfuric polyester, hydrocortisone, heparin and aminocaproic acid increased the SAV protective titre by 50%. However, tried plant extracts weakly antagonised the venom and did not potentiate the SAV.

Aminocaproates↗
PubMed2006

The role of antifibrinolytic agents in gynecologic cancer surgery.

OBJECTIVE: To compare the effects of crystalloid and colloid solutions, tranexamic acid and epsilon-aminocaproic acid on the need for allogenic blood transfusion and on coagulation and fibrinolysis parameters. METHODS: We conducted the study in the Anesthesiology and Reanimation Department of Hacettepe University Medical Faculty, Ankara, Turkey between March 2004 and April 2005. The study included 105 patients, classified by the American Society of Anesthesiology as physical status groups I-II, undergoing gynecologic cancer treatment. We divided them into 5 groups: group I (crystalloid) received crystalloid solutions, group II (colloid) received colloid solutions, group III (tranexamic acid) received 10 mg x kg(-1) tranexamic acid, and group 5 (epsilon-aminocaproic acid) received 100 mg x kg(-1) epsilon-aminocaproic acid. All patients bleeding amount was measured and recorded perioperatively, and at the 12th and 24th hours postoperatively. We then evaluated the patients' hemoglobin, hematocrit, activated thromboplastin time, international normalized ration, fibrinogen, and thrombocyte count and symptoms of pulmonary embolism. RESULTS: In comparing the amount of bleeding, the bleeding in the tranexamic acid group was 30.8% less than the crystalloid group (p<0.05), 33.3% less than the colloid group (p<0.05), and 23.9% less than the epsilon-aminocaproic acid group (p<0.05). CONCLUSION: When the negative effects of blood transfusions were considered, tranexamic acid administration can be recommended for decreasing the need for blood transfusion in gynecologic cancer surgery.

Aminocaproic Acid↗
PubMed1988

The effect of antifibrinolytic agents on wound healing.

The effect on the tensile strength of healing wounds of 2 of the most commonly used antifibrinolytic substances, tranexamic acid and epsilon-aminocaproic acid, has been studied in white rats. 2 symmetrical linear lines were made on the dorsal skin, in 1 of which was injected 1 ml of the test solution. The incisions were closed with interrupted sutures, and after 7 days the animal was sacrificed, the wound excised and its tensile strength determined. The results showed tranexamic acid (1 ml of a solution containing 100 mg/ml) to have a positive effect on wound healing, whereas epsilon-aminocaproic acid (1 ml of a solution containing 400 mg/ml) had a negative effect. When both agents were compared in the same animal, wounds in tissue injected with tranexamic acid had a higher tensile strength than those made in tissue pre-treated with epsilon-aminocaproic acid. Even compared at the same ionic strength, similar results were obtained. It is clear from this investigation that, unlike epsilon-aminocaproic acid, tranexamic acid has a positive effect on wound healing, and that this effect is not due to the antifibrinolytic properties, as both are powerful fibrinolytic inhibitors.

Aminocaproates↗
PubMed1992

Effects of antifibrinolytic agents on the life span of fibrin sealant.

Fibrin sealant, a biologic glue consisting of fibrinogen and thrombin, has been used in a variety of surgical procedures. The usefulness of fibrin sealant may be prolonged by the addition of antifibrinolytic agents. This study compared the efficacy of transexamic acid (30 mg/ml), epsilon-aminocaproic acid (25 mg/ml), and aprotinin (3000 KIU/ml) to provide data on the choice of an appropriate antifibrinolytic agent for use with fibrin sealant. By use of a modified in vitro plasma euglobulin lysis time (hours), all agents were found to be superior (n = 10 for each agent, P < 0.05, analysis of variance for completely randomized design followed by Dunnett's test for multiple comparisons) to control. Lysis times (mean +/- SE) were (control) 50.9 +/- 0.5, (tranexamic acid) 402.6 +/- 25.4, (epsilon-aminocaproic acid) 433.5 +/- 21.2, and (aprotinin) 393.9 +/- 26.0. Using the in vivo implantation of fibrin sealant supplemented with 125I-fibrinogen in the rat peritoneum significant improvement in percentage clot (mean +/- SE) remaining was found (P < 0.05, analysis for repeated measures followed by tests for multiple comparisons) under the following conditions: at 3 hr by weight (n = 15), tranexamic acid (70.13 +/- 2.02%) was superior to aprotinin (61.22 +/- 2.21%) and control (61.28 +/- 2.36%); at 3 hr by radioactivity counts (n = 19), tranexamic acid (76.29 +/- 0.75%) was superior to epsilon-aminocaproic acid (72.52 +/- 1.28%) and aprotinin (73.84 +/- 0.78%); at 72 hr by radioactivity counts (n = 10), aprotinin (27.30 +/- 2.45%) was superior to epsilon-aminocaproic acid 19.76 +/- 3.09% and control (20.38 +/- 3.01%). These data suggest the early (3-hr) superiority of tranexamic acid as an inhibitor of plasminogen activation and the late (72-hr) effectiveness of aprotinin as an inhibitor of plasmin. The possibility of a synergistic effect of tranexamic acid and aprotinin is suggested.

Adhesives↗
PubMed1997

Drugs to minimize perioperative blood loss in cardiac surgery: meta-analyses using perioperative blood transfusion as the outcome. The International Study of Peri-operative Transfusion (ISPOT) Investigators.

UNLABELLED: Concern about the side effects of allogeneic red blood cell transfusion has increased interest in methods of minimizing perioperative transfusion. We performed meta-analyses of randomized trials evaluating the efficacy and safety of aprotinin, desmopressin, tranexamic acid, and epsilon-aminocaproic acid in cardiac surgery. All identified randomized trials in cardiac surgery were included in the meta-analyses. The primary outcome was the proportion of patients who received at least one perioperative allogeneic red cell transfusion. Sixty studies were included in the meta-analyses. The largest number of patients (5808) was available for the meta-analysis of aprotinin, which significantly decreased exposure to allogeneic blood (odds ratio [OR] 0.31, 95% confidence interval [CI] 0.25-0.39; P < 0.0001). The efficacy of aprotinin was not significantly different regardless of the type of surgery (primary or reoperation), aspirin use, or reported transfusion threshold. The use of aprotinin was associated with a significant decrease in the need for reoperation because of bleeding (OR 0.44, 95% CI 0.27-0.73; P = 0.001). Desmopressin was not effective, with an OR of 0.98 (95% CI 0.64-1.50; P = 0.92). Tranexamic acid significantly decreased the proportion of patients transfused (OR 0.50, 95% CI 0.34-0.76; P = 0.0009). Epsilon-aminocaproic acid did not have a statistically significant effect on the proportion of patients transfused (OR 0.20, 95% CI 0.04-1.12; P = 0.07). There were not enough patients to exclude a small but clinically important increase in myocardial infarction or other side effects for any of the medications. We conclude that aprotinin and tranexamic acid, but not desmopressin, decrease the number of patients exposed to perioperative allogeneic transfusions in association with cardiac surgery. IMPLICATIONS: Aprotinin, desmopressin, tranexamic acid, and epsilon-aminocaproic acid are used in cardiac surgery in an attempt to decrease the proportion of patients requiring blood transfusion. This meta-analysis of all published randomized trials provides a good estimate of the efficacy of these medications and is useful in guiding clinical practice. We conclude that aprotinin and tranexamic acid, but not desmopressin, decrease the exposure of patients to allogeneic blood transfusion perioperatively in relationship to cardiac surgery.

Aminocaproic Acid↗
PubMed2000

Improved purification of the membrane-bound hydrogenase-sulfur-reductase complex from thermophilic archaea using epsilon-aminocaproic acid-containing chromatography buffers.

A hydrogenase-sulfur reductase (SR) complex was purified from membrane preparations of the extremely thermophilic, acidophilic archaeon Acidianus ambivalens using a combination of sucrose density gradient centrifugation and column chromatography (FPLC). All chromatographic steps were performed in the presence of 0.5% epsilon-aminocaproic acid resulting in the elution of the SR complex as a sharp peak. In contrast, chromatography using buffers without epsilon-aminocaproic acid, or in the presence of detergents, were not successful. The purified A. ambivalens SR complex consisted of at least four subunits with relative molecular masses of 110000, 66000, 39000 and 29000, respectively. A similar procedure was applied to purify the membrane-bound hydrogenase from Thermoproteus neutrophilus, a non-related extremely thermophilic but neutrophilic archaeon, which consisted of only two subunits with relative molecular masses of 66000 and 39000, respectively.

Aminocaproic Acid↗
PubMed1983

Epsilon-aminocaproic acid-induced myopathy. A case report.

The prolonged administration of epsilon-aminocaproic acid (EACA) resulted in the development of severe proximal myopathy associated with high plasma creatine kinase values, rhabdomyolysis, myoglobinuria, and mild hyperbilirubinaemia. Withdrawal of the drug led to spontaneous resolution of the clinical and biochemical syndrome. Structural and enzyme studies of a biopsy specimen of the involved skeletal muscle supported the presence of subclinical myopathy. The mechanism whereby EACA produces its toxicity in muscle may in part be due to inhibition of cathepsin D, but the possibility that other proteases are involved has not been excluded. The fact that this clinical syndrome is rare despite the widespread use of EACA may be because it only occurs in subjects with a subclinical skeletal muscle disorder which is unmasked by the drug.

Adult↗
PubMed1992

The effect of warm heart surgery on postoperative bleeding.

The effects of normothermic systemic perfusion (35 degrees to 37 degrees C; n = 73) were compared with those of moderately hypothermic systemic perfusion (25 degrees to 29 degrees C; n = 73) with respect to blood loss, transfusion requirements, and platelet levels in 146 patients undergoing isolated, primary coronary artery bypass grafting. In addition, most patients were given an antifibrinolytic medication during operation as follows: tranexamic acid (10 gm intravenously; n = 63), epsilon-aminocaproic acid (15 gm intravenously; n = 63), or no drug as a control. (n = 20). Normothermic patients tended to bleed less at 24 hours (warm, 864 +/- 42 ml and cold, 918 +/- 68 ml), but these differences were not statistically significant. Patients receiving either tranexamic acid or epsilon-aminocaproic acid, regardless of perfusion temperature, bled less after 6, 12, and 24 hours than did cold control patients (p less than 0.05). Warm control patients also bled less than did cold control patients after 6 or 12 hours (p less than 0.05), and neither drug further reduced blood loss in these patients. Circulating platelet levels were better preserved in patients receiving either tranexamic acid or epsilon-aminocaproic acid and in patients with warm perfusion and no drug than in cold control patients. Normothermic systemic perfusion, tranexamic acid, and epsilon-aminocaproic acid each reduced postoperative blood loss and preserved platelets.

Aminocaproic Acid↗