Use Of Epsilon-aminocaproic Acid Research Articles

Effective hemostasis in children with Von Willebrand factor defects undergoing adenotonsillar procedures

Introduction Children with low von Willebrand factor (VWF) activity or type 1 von Willebrand disease (VWD) have increased risk of bleeding after adenotonsillar procedures and the optimal perioperative management to minimize bleeding is unknown. Aim To report the effectiveness and safety of an institutional protocol in minimizing postoperative bleeding in children with type 1 VWD or low VWF activity. Methods We conducted a retrospective chart review in children with type 1 VWD or low VWF activity treated via an institutional protocol that utilizes repeated doses of Desmopressin acetate (DDAVP, 1-deamino 8-D arginine- vasopressin) or VWF concentrate, brief hospitalization for observation and extended use of oral epsilon aminocaproic acid (EACA). Results From 2010 to 2017, 13 children underwent an adenotonsillar procedure and were treated with this protocol. Although 7.6% had minor immediate bleeding and 23% had minor delayed bleeding, no patients experienced major bleeding or required transfusion, additional surgery or other measures not specified by the protocol. Mild hyponatremia was observed in 80% of patients who received DDAVP. Conclusion Our institutional protocol specifying repeated dosing of DDAVP or VWF concentrate to sustain elevated VWF levels during periods of highest bleeding risk and extended use of EACA is effective at preventing major bleeding episodes after adenotonsillar procedures. However, this analysis raised safety concerns that prompted changes in the institutional protocol and highlight the need for further prospective studies to determine the optimal strategy for safely reducing bleeding complications in these patients.

The Effect of Epsilon-Aminocaproic Acid on the Development of Shunt-Dependent Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage: a Case-Control Study

The use of epsilon-aminocaproic acid (EACA) and other anti-fibrinolytic agents has been explored to prevent re-hemorrhage following subarachnoid hemorrhage (SAH) secondary to aneurysmal rupture. One reported complication includes increased rates of hydrocephalus (HCP) due to EACA administration. Herein, we present a single-institution case-control study investigating the relationship between EACA administration and the development of shunt-dependent HCP. All patients were managed by a single neurosurgeon at the University of Alabama at Birmingham (UAB) Medical Center who treated SAH patients with EACA. A power analysis was performed to determine the sample size, and 57 patients who required a ventriculoperitoneal shunt (VPS) for management of obstructive hydrocephalus after failing an external ventricular drain wean protocol were selected. Control patients with initial obstructive hydrocephalus who did not require VPS were matched by demographic factors. The overall rate of VPS placement was 44%; the odds ratio of VPS placement after treatment with EACA was 0.63. The presence of intraventricular hemorrhage or a poor clinical exam on presentation was closely associated with eventual placement of a VPS, with the odds ratio for a Fisher CT grade 4 hemorrhage being 13.89 and a clinical exam corresponding to a Hunt and Hess score of III and IV being 17.18 and 11.00, respectively. The administration of EACA does not appear to increase the incidence of shunt-dependent HCP following SAH and may therefore be employed if clinically needed. Intraventricular hemorrhage or a poor clinical exam on presentation does appear to increase the incidence of shunt-dependent HCP following SAH.

Blood loss and transfusion requirements with epsilon-aminocaproic acid use during cranial vault reconstruction surgery

ObjectiveTo determine whether epsilon-aminocaproic acid (EACA) load of 50 mg∙kg−1 before skin incision, and infusion of 25 mg∙kg−1∙h−1 until skin closure during cranial vault reconstruction (CVR) were associated with decreased estimated blood loss and transfusion requirements. BackgroundAntifibrinolytic medications decrease bleeding and transfusion requirements during cardiothoracic and orthopedic surgeries with high blood loss, but practical reductions in blood loss and transfusion requirements have not been consistently realized in children undergoing CVR. Current dosing recommendations are derived from adult extrapolations, and may or may not have clinical relevance. MethodRetrospective case-controlled study of 45 consecutive infants and children undergoing primary craniosynostosis surgery at Covenant Children's Hospital during years 2010-2014. Exclusion criteria included revision surgery, and chromosomal abnormalities associated with bleeding disorders. Blood loss and blood transfusion volumes as a percent of estimated blood volume were compared in the presence of EACA while controlling for age, suture phenotype, use of bone grafting, and length of surgery. Secondary outcomes measures included volume of crystalloid infused, length of hospital stay, and any postoperative intubation requirement. ResultsWhen analyzed based on length of surgery, EACA did reduce blood loss and blood transfusion (R2=0.19, P=.005 and R2=0.18, P=.010, respectively) with shorter surgeries. Conclusions and relevanceUsing a standardized dosing regimen of EACA during craniosynostosis surgery, we found statistical significance in blood loss and transfusion requirements in surgeries of the shortest duration. We suspect this may be due to our selected dosing regimen, which may be lower than recently recommended. This study contributes to the growing body of evidence supporting EACA in CVR for craniosynostosis.

Peri-operative blood-loss after total hip arthroplasty can be significantly reduced with topical application of epsilon-aminocaproic acid.

To evaluate the peri-operative blood loss with the use of epsilon-aminocaproic acid (ε-ACA) in total hip arthroplasty (THA). One hundred sixty patients treated with THA were followed; 5g ε-ACA diluted in 100ml normal saline was applied intra-operatively. Eighty patients not receiving ε-ACA (non ε-ACA group) and eighty patients receiving ε-ACA (ε-ACA group) were compared regarding blood loss, need of transfusion, and thrombo-embolic complications. Blood loss (mean ± SD) for the non ε-ACA group was 1678 ± 515ml and for the ε-ACA group 1403 ± 417ml (p < 0.05). In the non ε-ACA group 23 patients needed blood transfusions compared to ten patients in the ε-ACA group (p < 0.05). Cost savings were $284.39 per patient. No patient in either group developed a thrombo-embolic complication. This study demonstrates a significant reduction in peri-operative blood loss after THA with topically applied ε-ACA. The application of ε-ACA reduced costs by lowering transfusion rates and did not increase thrombo-embolic events. ε-ACA is safe and effective in reducing blood loss and cost-efficient in THA.

O uso do ácido epsilon amino caproico intra-alveolar para o controle do sangramento pós-exodontia em pacientes anticoagulados

When patients on anticoagulants are submitted to dental extractions, there is risk of postoperative bleeding. The maintenance of anticoagulant therapy has been indicate donce the INR is within the therapeutic levels. Additional resources for bleeding control like the use of epsilon amino caproic acid (EACA) may be adopted. The objective of this study was to report a series of cases of tooth extractions followed by the intra-alveolar use of EACA, in patients using anticoagulants with INR ? 3.0. From 25 tooth extractions, only one patient needed professional intervention to control postoperative bleeding. The results suggest that the use of intra-alveolar EACA, associated with routine post-surgical care, may contribute to hemostasis in patients using anticoagulants.

An Examination of Aneurysm Rerupture Rates with Epsilon Aminocaproic Acid

Epsilon aminocaproic acid (EACA) has been used in the past to prevent cerebral aneurysm rerupture. Recent studies have indicated that short-term treatment with EACA can lower rebleeding rates without significantly increasing ischemic or thrombotic complications or permanent shunt rates. The goal of this study is to determine the efficacy of EACA in the prevention of aneurysm rerupture at a high volume subarachnoid hemorrhage center. We conducted a retrospective study of 355 consecutive subarachnoid hemorrhage patients over a 2-year period under our current protocol for EACA use. Patients were divided by presentation time to our institution and whether the patient received EACA. The primary endpoints of the study were rebleeding rates, ischemic complications, thrombotic complications, vasospasm, shunt rates, and outcomes. Rerupture rates were reduced by half in the entire pool of patients on EACA after controlling for Hunt and Hess Scores and Fisher Scores. In patients who received early aneurysm treatment, this effect persisted but was non-statistically significant due to the small numbers of reruptures. In addition, there was no evidence to suggest that EACA increased ischemic or thrombotic complications, vasospasm, or VPS rates. In patients presenting earlier than 24 h to our institution, there was a non-significant trend toward worse outcomes after EACA use. This trend was reversed in patients arriving after 24 h. There is evidence to suggest that EACA is protective from aneurysm rerupture without significant ischemic or thrombotic complications when used for less than 72 h. However, if the aneurysm is treated, this effect is modest indicating that early aneurysm treatment remains the gold standard for rerupture prevention.

Uso tópico de agente antifibrinolítico na redução do sangramento após revascularização cirúrgica do miocárdio

Antifibrinolytic agents reduce bleeding after cardiac surgery, but there are adverse effects after their systemic use. These effects are avoided by topical application of antifibrinolytic agents in pericardial cavity. We compared the effects of topically applied epsilon-aminocaproic acid (EACA) and placebo on postoperative bleeding and transfusion requirements after coronary artery bypass surgery. In this single center prospective, randomized, double-blind trial, 53 patients were randomized into two groups to receive EACA (24 g in 250 ml of saline solution) or placebo (250 ml of saline solution) before sternal closure. Groups were comparable with respect to all preoperative and intraoperative variables. Postoperative bleeding, transfusion requirements and hematologic parameters were evaluated. Postoperative bleeding within first 24 hours (h) period (EACA group 154.66+/-74.64 x Placebo group 220.21+/-136.42 ml; P=0.031) showed statistically significant inter-group difference, within 48 h (EACA group 259.14+/-420.07 x Placebo group 141.67+/-142.58 ml; P=0.614), as well as cumulative blood loss (EACA group 832.07+/-576.86 x Placebo group 827.50+/-434.12 ml; P=0.975), not showed statistically inter-group differences. Inter-group difference of blood product requirements was statistically significant (EACA group 185.90+/-342.07 x Placebo group 439.42+/-349.07 ml; P=0.016). Laboratory analyses showed no differences between the two groups postoperative (hematologic characteristics: hemoglobin (g/dl)- EACA group 9.18+/-0.92 x Placebo group 8.85+/-1.48 g/dL; P=0.11; hematocrit (%)-EACA group 28.15+/-3.35 x Placebo group 26.67+/-4.15%; P=0.06). Topical use of epsilon aminocaproic acid reduces postoperative bleeding in the first 24 hours and requirements of blood transfusion after coronary artery bypass graft surgery.

Epsilon-aminocaproic acid (EACA).

Epsilon-aminocaproic acid (EACA) is a synthetic inhibitor of the plasmin-plasminogen system. It is the only potent antifibrinolytic agent which is commercially available in the United States. Effective blood levels of the drug are readily obtainable with either oral or intravenous administration, with very high levels of the drug being found in the urine since the drug is greatly concentrated during excretion. EACA has been used in numerous clinical situations to control bleeding and has been claimed to be an effective agent in subarachnoid hemorrhage, genitourinary bleeding from many causes, and in dental surgery in hemophiliacs. It may also be effective in several less well studied situations such as prophylaxis of bleeding episodes in hemophiliacs, control of menorrhagia, gastrointestinal bleeding, obstetrical bleeding and in bleeding following cardiac and thoracic surgery. Major side effects from EACA include hypotension, cardiac arrhythmias, rhabdomyolysis, and generation of thrombi. The incidence of thrombotic events secondary to the inhibition of the fibrinolytic system by EACA is unknown, but may be particularly increased in those patients who have some underlying predisposition to develop thrombosis. The potential benefit from the use of EACA must be weighed against the possible serious complications, particularly the development of widespread thrombi.

The efficacy and safety of ɛ‐aminocaproic acid treatment in patients with cirrhosis and hyperfibrinolysis

Patients with decompensated cirrhosis are at risk for hyperfibrinolysis; this is potentially fatal. epsilon-aminocaproic acid has been used to treat patients with hyperfibrinolysis; however, the data about its benefit in the setting of cirrhosis are minimal. To analyse the efficacy of epsilon-aminocaproic acid and its safety in cirrhotic patients with hyperfibrinolysis. All patients with an abnormal euglobin lysis time who were admitted to Rancho Los Amigos Medical Center from 1 January 2001 to 31 December 2002 were included in the study. Their medical records were reviewed and analysed. There were 60 cirrhotic patients with shortened euglobin lysis time. Fifty-two patients received epsilon-aminocaproic acid. Of the 52 patients, seven had one or more bleeding episodes with the subcutaneous or soft tissue bleeding as the most common indication for epsilon-aminocaproic acid use. Of the 37 patients, 34 (92%) had improvement or resolution of their bleeding. Only two (3%) patients had epsilon-aminocaproic acid treatment discontinued because of minor side effects, rash and lightheadedness. There were no thromboembolic complications of treatment. epsilon-aminocaproic acid was found to be effective and safe for treatment of hyperfibrinolysis in patients with cirrhosis.

Epsilon Aminocaproic Acid (EACA) Reduces Transfusion Requirements in Patients with Thrombocytopenic Hemorrhage.

EACA is an antifibrinolytic drug that has been used to control hemorrhage by stabilizing thrombus. It has been used in thrombocytopenic patients largely on an empiric basis, based on small case series reports with randomized trials lacking. Use of this drug has been limited secondary to concerns about the side effects. We reviewed our experience with EACA to help determine safety and efficacy. We conducted a computer database search of all patients who were prescribed EACA at the Cleveland Clinic Foundation from 1997 to 2003. We then analyzed patients older than 18 years with hemorrhage and thrombocytopenia of less than 75,000/μl. We excluded patients undergoing prophylactic EACA use during cardiac, urologic or orthopedic surgery. 75 patients were identified. Their median age was 55years (Range 23–84 years). There were 38 Males and 37 Females. Underlying diagnoses included Acute Myelogenous Leukemia (N=35), Myelodysplastic syndrome (N=9), Non Hodgkins Lymphoma (N=9), and others (N=22). 33 had hematopoietic stem cell transplants (24 Allogeneic of whom 19 had Graft Versus Host Disease and 9 Autologous). The source of bleeding included Mucosal membranes (N=30), Gastrointestinal (N=27), Genitourinary (N=5), Pulmonary (N=4), Uterine (N=3), Venous catheter associated (N=3) and Central Nervous System (N=3). Alloimmunization or refractoriness to platelet transfusion was identified in 32 (43%) patients. The median platelet count at the initiation of EACA was 6,000/μl (Range 1,000–62,000/μl), the median duration of EACA administration was 10 days (Range 1–216 days), the median average dose was 6 grams/day (Range 2–24 grams/day). Bleeding completely stopped in 50 patients (67%), decreased in 13 (17%) and did not stop in 12 (16%). Red blood cell transfusions were decreased in 46(61%) patients. Prior to EACA, patients were on an average receiving 1.6 +/− 0.7 platelet unit transfusions per day (Range 0–3 Units/day). Subsequent to EACA, patients received 1.0 +/− 0.7 transfusions per day for the duration of time they received EACA (Range 0–3 Units/day). The average decrease in daily transfusion needs was 0.5 +/− 0.6 units (median 0.5 units, range 0.2–3 unit decrease. p<0.001). Adverse events attributable to EACA included worsening of liver function tests in 5 patients (All with underlying GVHD), genitourinary clots requiring discontinuation of the drug in 3 patients, cardiac arrhythmia in 2 patients (Atrial Fibrillation & sinus bradycardia), and elevated creatinine in 1 patient. Neither Disseminated intravascular coagulation (DIC) nor Deep venous Thrombosis (DVT) was observed while on the drug. We conclude that EACA is an effective drug in the treatment of thrombocytopenic hemorrhage with an overall response rate of 84%. EACA reduces transfusion requirements with manageable side effects. Further study of EACA is warranted as a treatment for thrombocytopenic hemorrhage.

Reply to Mcmullin et al

I thank McMullin et al for the opportunity to allay their concerns and thereby avoid perpetuating suboptimal polycythaemia vera (PV) management. First, with respect to bone marrow examination as a diagnostic test for PV, bone marrow morphology is no surrogate for clonality, and marrow morphology cannot distinguish PV from its companion myeloproliferative disorders. Furthermore, a cytogenetic abnormality will be present in only 25% of PV patients at diagnosis (Najfeld et al, 2002). As there are many potential causes for erythrocytosis other than PV, one can estimate that bone marrow examinations on 10 patients would be needed to obtain one with a cytogenetic abnormality, hardly a cost-effective endeavour. Furthermore, some PV patients have normal marrow morphology at diagnosis (Ellis et al, 1986). Finally, contrary to the contention of McMullin et al, the presence of myelofibrosis at diagnosis, like a cytogenetic abnormality, has no prognostic significance (Ellis et al, 1986). Second, the specious reasoning employed by McMullin et al to justify treating asymptomatic thrombocytosis in PV supports my contention that no other medical condition has caused more otherwise astute clinicians to suspend disbelief than thrombocytosis. The haematocrit, not the platelet count, is the major determinant of blood viscosity and the high thrombosis rate in the phlebotomy arm of the Polycythemia Vera Study Group (PVSG) trial (PVSG-01) was the direct result of inadequate phlebotomy therapy. Importantly, neither the PVSG (Berk et al, 1986) nor others (i.e. Wehmeier et al, 1991) have found a correlation between the platelet count and thrombosis in PV, and antiplatelet therapy was no panacea against thrombosis either. It is also bogus to cite survival data for untreated PV patients to justify platelet count reduction. There are no published data demonstrating that platelet count reduction prolongs survival in PV or even in essential thrombocytosis. Third, with respect to phlebotomy causing myelofibrosis, McMullin et al unfortunately have citation amnesia. Myelofibrosis is part of the natural history of PV and there are five studies, including one from the UK (Messinezy et al, 1985), that refute the contention that it is a phlebotomy stigma; certainly hydroxyurea could not prevent it. McMullin et al should also ponder why phlebotomy would cause myelofibrosis in a disease in which marrow function is autonomous but not in a disease such as haemochromatosis, where it is not. Fourth, with respect to hydroxyurea, I would remind McMullin et al that the introduction of cytotoxic agents to control bone marrow function in PV has inevitably been associated with recognition of their leukaemogenicity. There is a growing literature that suggests hydroxyurea may be no different (Weinfeld et al, 1994; Sterkers et al, 1998) and in the absence of proof of its safety, its use should be restricted to situations where its benefits outweigh its risks. Fifth, with respect to the use of epsilon aminocaproic acid (EACA), McMullin et al should not be averse to learning new treatment strategies for PV. Extreme thrombocytosis is associated with a reduction in large von Willebrand factor multimers (Budde et al, 1993). EACA has been used for decades to reduce mucous membrane bleeding in von Willebrand's disease and is useful for controlling bleeding in PV, for the same reason. Sixth, I fail to understand what could be controversial about keeping the haematocrit less than 0·36 during pregnancy in PV. Normally during pregnancy, the plasma volume expands disproportionately to the red cell mass, producing the so-called ‘physiological anaemia’. Therefore, a normal haematocrit in a pregnant PV patient must indicate the presence of an expanded red cell mass. To ignore this is to place both the patient and her fetus at risk of thrombosis, and ignoring that risk, not the removal of it, is what should be controversial. Finally, I am pleased that McMullin et al and I have a common ground for agreement as I never suggested that anagrelide should be employed during pregnancy.

Furosemide: progress in understanding its diuretic, anti-inflammatory, and bronchodilating mechanism of action, and use in the treatment of respiratory tract diseases.

Accumulated experimental and clinical data suggest that adrenocorticosteroids and/or endogenous ouabain-like substances may play an important role in the mechanism of furosemide diuretic action. It was reported that the drug is highly bound in the adrenals, lungs, kidney, spleen, and liver. In patients with liver cirrhosis, furosemide exerted a markedly decreased natriuretic effect compared with normal subjects, and the plasma levels of circulating endothelin and atrial natriuretic factor (ANF) were significantly elevated. In neonates, after administration of furosemide, the urinary excretion of endothelin-1 and aldosterone increased markedly, and it is known that endothelin may release ANF and aldosterone in a dose-dependent manner. Furosemide was used to stimulate zona glomerulosa, whereas ANF decreased the production of steroids in zona glomerulosa and fasciculata cell culture owing to stimulation by various factors. Because the concomitant use of ANF and furosemide appeared to be diuretically effective in newborns after cardiac surgery, one may suggest that furosemide competes with ANF for its effects on the adrenals. Furosemide administered by inhalation exerted a protective effect on allergic and perennial nonallergic rhinitis and was effective in preventing the postsurgical recurrence of nasal polyposis. The drug can also be used as an antiasthmatic agent. In preterm ventilator-dependent infants with chronic lung disease, aerosolized furosemide improved pulmonary function with no marked effect on diuresis. In adults and children with asthma, furosemide exerted a protective effect against bronchoconstriction induced by several indirect stimuli similar to that of disodium cromoglycate or nedocromil. Aerosolized furosemide had a preventive effect also on bronchoconstriction induced by inhaled lysine acetylsalicylate in patients with aspirin-sensitive asthma. In high-dose beclomethasone-dependent asthma, inhaled lysine acetylsalicylate and furosemide exerted a mutually potentiating antiasthmatic activity, allowing considerable sparing of the inhaled steroid. It is proposed that this effect may be explained by the corticosteroid-sparing action of lysine released from the lysine acetylsalicylate molecule because similar beneficial effects were also obtained after the concomitant use of epsilon-aminocaproic acid (whose chemical structure is almost the same as that of lysine) and prednisone. Furosemide exhibited an anti-inflammatory effect through inhibition of production and release of cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha from peripheral mononuclear cells, which may have a beneficial effect on local inflamed tissue imbalance in the ratio of different cytokines, thus improving the sensitivity of target cells to endogenous glucocorticosteroids.

Adjuvant use of e-aminocaproic acid (Amicar) in the endovascular treatment of cranial arteriovenous fistulae

We report our experience with the use of the antifibrinolytic agent epsilon-aminocaproic acid (EACA), Amicar, as an adjuvant to endovascular treatment of cranial arteriovenous fistulae. We also review applications of antifibrinolytic agents to neurovascular disorders and discuss the mechanism of action, dosing strategy, contraindications, and possible complications associated with the use of EACA. We identified 13 patients with cranial arteriovenous fistulae (five direct carotid cavernous fistulae [CCF], seven dural arteriovenous fistulae [DAVF], and one vein of Galen malformation) who received EACA as an adjunct to endovascular treatment. In all cases embolic coils were the primary embolic agent. We reviewed the modes of initial endovascular therapy and angiographic findings immediately thereafter and the response to EACA. Two direct CCF and two DAVF were completely thrombosed on follow-up angiography, and two DAVF demonstrated diminished flow after EACA therapy. Seven fistulae did not respond to EACA. Four of eight tightly coiled fistulae thrombosed, while none of five loosely coiled fistulae thrombosed. None of four cases with a residual fistula separate from the coil mass underwent thrombosis with EACA, while four of nine cases without a separate fistula thrombosed. There was no morbidity related to EACA therapy. EACA may thus be useful as an adjunct to endovascular treatment of cranial arteriovenous fistulae. Loose or incomplete coil packing of the fistula predicts a poor response to EACA therapy.

Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion.

Concerns regarding the safety of transfused blood have prompted re-consideration of the use of allogeneic (blood from an unrelated donor) blood transfusion. To assess the effects of the anti-fibrinolytic drugs aprotinin, tranexamic acid, and epsilon aminocaproic acid, on peri-operative red blood cell (RBC) transfusion. We searched MEDLINE (to May 1998), EMBASE (to December 1997), web sites of international health technology assessment agencies (to May 1998). References in identified trials and review articles were checked and authors contacted to identify any additional studies. Randomised controlled trials of anti-fibrinolytic drugs in adults scheduled for non-urgent surgery. Two reviewers independently assessed trial quality and extracted data. We found 61 trials of aprotinin (7027 participants). Aprotinin reduced the rate of RBC transfusion by a relative 30% (RR=0.70: 95%CI: 0.64 to 0.76). The average absolute risk reduction (ARR) was 20.4% (95%CI: 15.6% to 25.3%). On average, aprotinin use saved 1.1 units of RBC (95%CI: 0.69 to 1.47) in those requiring transfusion. Aprotinin also significantly reduced the need for re-operation due to bleeding (RR=0.40: 95%CI: 0.25 to 0.66). We found 18 trials of tranexamic acid (TXA) (1,342 participants). TXA reduced the rate of RBC transfusion by a relative 34% (RR=0.66: 95%CI: 0.54 to 0.81). This represented an ARR of 17.2% (95%CI: 8.7% to 25.7%). TXA use resulted in a saving of 1.03 units of RBC (95%CI: 0.67 to 1.39) in those requiring transfusion. We found four trials of epsilon aminocaproic acid (EACA) (208 participants). EACA use resulted in a statistically non-significant reduction in RBC transfusion (RR=0.48: 95%CI: 0.19 to 1.19). Comparisons between agents Eight trials made 'head-to-head' comparisons between TXA and aprotinin. There was no significant difference between the two drugs in the rate of RBC transfusion: RR=1.21 (95%CI: 0.83 to 1.76) for TXA compared to aprotinin. Adverse Effects Aprotinin did not seem to be associated with an excess risk of adverse effects, including thrombo-embolic events (thrombosis RR=0.64: 95%CI: 0.31 to 1.31) and renal failure (RR=1.19: 95%CI: 0.79 to 1.79). Fewer data were available for TXA and EACA. From this review it appears that aprotinin reduces the need for red cell transfusion, and the need for re-operation due to bleeding, without serious adverse effects. However, there was significant heterogeneity in trial outcomes, and some evidence of publication bias. Similar trends were seen with TXA and EACA, although the data were rather sparse. The poor evaluation of these latter drugs is unfortunate as results suggest they may be equally as effective as aprotinin, but are significantly cheaper. The evidence reviewed here supports the use of aprotinin in cardiac surgery. Further small trials of this drug are not warranted. Future trials should be large enough to compare the efficacy and cost-effectiveness of aprotinin with that of TXA and EACA.

A multicenter trial of 6-aminocaproic acid (Amicar) in the prevention of bleeding in infants on ECMO

Background/Purpose: Intracranial hemorrhage (ICH), is a major source of morbidity and the leading cause of death in neonates treated with extracorporeal membrane oxygenation (ECMO). Anecdotal reports have suggested that epsilonaminocaproic acid (EACA) can decrease the risk of ICH. The purpose of this study was to evaluate, in a multiinstitutional, prospective, randomized, blinded fashion, the effect of EACA on the incidence of hemorrhagic complications in neonates receiving ECMO. Methods: All neonates (except congenital diaphragmatic hernia) who met criteria for ECMO at three institutions were eligible for enrollment. EACA (100 mg/kg) or placebo was given at the time of cannulation followed by 25 mg/kg/h for 72 hours. Bleeding complications, transfusion requirements, and thrombotic complications were recorded. Post-ECMO imaging included head ultrasound scan computed tomography (CT) scan, and duplex ultrasound scan of the inferior vena cava and renal vessels. Results: Twenty-nine neonates were enrolled (EACA, 13 and placebo, 16). Five (17.2%) patients had a significant (grade 3 or larger) ICH. There was no statistical difference in the incidence of significant ICH in patients who received EACA (23%) versus placebo (12.5%). Septic patients accounted for all of the ICH in the EACA group. Thrombotic complications (aortic thrombus and SVC syndrome) developed in two patients from the placebo group. There was no difference in thrombotic circuit complications between groups. Conclusions: Our results suggest that the use of EACA in neonates receiving ECMO is safe but may not decrease the overall incidence of hemorrhagic complications.

C1 esterase inhibitor deficiency, airway compromise, and anesthesia.

C1 esterase inhibitor deficiency, airway compromise, and anesthesia.

THE NON HEMOSTATIC LIABILITIES OF EPSILON-AMINOCAPROIC ACID

Introduction. The pandemic use of epsilon-aminocaproic acid (EACA) has the potential to cause intraoperative hyperkalemia [1] and renal dysfunction [2] in the setting of cardiopulmonary bypass (CPB). We hypothesize that EACA causes intraoperative hyperkalemia but the renal impairment in fact lasts into the postoperative period. Therefore we conducted a retrospective investigation into adult cardiopulmonary bypass patients, comparing those who received EACA to those who did not. Methods. This IRB approved, retrospective, chart review evaluated cardiopulmonary bypass records, anesthesia records and laboratory data in 435 consecutive patients requiring cardiopulmonary bypass surgery during July and August 1996 and April and May 1997. (Except for the introduction of epsilon-aminocaproic acid into routine use, there were no other changes in clinical practice, cardiopulmonary bypass technique or personnel.) Data collected:-patient demographics; surgery; surgeon; use of epsilon aminocaproic acid; preoperative and highest serum K during CPB; preoperative, day 2 and highest postoperative serum creatinine; intraoperative urine output; CPB and aortic cross clamp times and volumes of CPB prime and cardioplegia. 160 patients were excluded for incomplete data; use of aprotinin; administration of insulin, furosemide or potassium; aortic cross clamp times <30 minutes or > 120 minutes and cardioplegia over 3 liters. Patients were divided into two groups on the basis of receiving EACA or not. The unpaired t-test and Fishers Exact test were used for statistical comparison between the groups, p< 0.05 significant. Results. EACA was administered to 145 (53%) patients. There were no differences in demographics, preoperative or cardiopulmonary factors between the two groups (Table 1, Table 2). Both groups had significantly increased intraoperative K+ compared to their baseline K+ (p<0.05). However, compared to the No EACA group, those patients who were given EACA had significantly higher serum potassium levels during CPB (range 3.5-6.7 mg/dL) c.f. (range 4.3-7.8 mg/dL), p<0.05. The postoperative serum creatinine in the EACA group was significantly greater than both its baseline value (p<0.05) and the No EACA postoperative creatinine (p<0.05). There was no difference between the preoperative and postoperative serum creatinine in the No EACA group.Table 1Table 2Discussion. Under conditions of this study, EACA administration is associated with intraoperative hyperkalemia and persistent renal dysfunction. We have recently reported that EACA induces subtle changes in intraoperative renal tubular function in cardiac patients [2]. This study demonstrates that the use of intraoperative EACA affects cellular shifts of potassium with subsequent hyperkalemia and influences renal performance leading to postoperative renal impairment.

Reduction of bleeding after heart operations through the prophylactic use of epsilon-aminocaproic acid

Excessive postoperative bleeding after heart operations continues to be a source of morbidity. This prospective double-blind study evaluated epsilon-aminocaproic acid as an agent to reduce postoperative bleeding and investigated its mode of action. One hundred three patients were randomly assigned to receive either 30 gm epsilon-aminocaproic acid (51 patients) or an equivalent volume of placebo (52 patients). In a subset of these patients (14 epsilon-aminocaproic acid, 12 placebo), tests of platelet function and fibrinolysis were performed. Results: By multivariate analysis, three factors were associated with decreased blood loss in the first 24 hours after operation: epsilon-aminocaproic acid versus placebo (647 ml versus 839 ml, p = 0.004), surgeon 1 versus all other surgeons (582 ml versus 978 ml, p = 0.002), and no intraaortic balloon versus intraaortic balloon pump use (664 ml versus 1410 ml, p = 0.02). No significant differences in platelet function could be demonstrated between the two groups. Inhibited fibrinolysis, as reflected by less depression of the euglobulin clot lysis and no rise in d-dimer levels, was significant in the epsilon-aminocaproic acid group compared with the placebo group. Conclusion: The intraoperative use of epsilon-aminocaproic acid reduces postoperative cardiac surgical bleeding. (J T HORAC C ARDIOVASC S URG 1996;112:1098-107)

Fatal aortic thrombosis in a neonate during infusion of epsilon-aminocaproic acid

Hemorrhagic complications are common in patients placed on extracorporeal life support (ECLS), especially in those who have additional risk factors. Several centers use epsilon-aminocaproic acid (EACA) in their high-risk ECLS patients in an attempt to decrease the incidence of such complications, despite the fact that no controlled trials have been performed examining the risks and benefits of its use. The authors report the case of a neonate who had fatal aortic thrombosis during EACA administration. Also included is a discussion of the use of EACA in patients who require cardiopulmonary bypass.

Prophylactic epsilon-aminocaproic acid (EACA) administration minimizes blood replacement therapy during cardiac surgery.

Prophylactic epsilon-aminocaproic acid (EACA) administration minimizes blood replacement therapy during cardiac surgery.