Effects of local infiltration of analgesia and tranexamic acid in total knee replacements: safety and efficacy in reducing blood loss and comparability to intra-articular tranexamic acid

INTRODUCTION@#The use of periarticular (PA) tranexamic acid (TXA) and its efficacy in comparison with intra-articular (IA) TXA have not been well explored in the literature. This retrospective cohort study aimed to compare the effects of IA and PA TXA with analgesic components in reducing blood loss and improving immediate postoperative pain relief and functional outcomes in patients after unilateral primary total knee arthroplasty (TKA).@*METHODS@#A total of 63 patients underwent TKA, and they were divided into the IA TXA delivery group ( n = 42) and PA TXA delivery group ( n = 21). All patients were administered 1 g of TXA. They also received pericapsular infiltration consisting of 0.5 mL of adrenaline, 0.4 mL of morphine, 1 g of vancomycin, 1 mL of ketorolac and 15 mL of ropivacaine. Outcomes for blood loss and surrogate markers for immediate functional recovery were measured.@*RESULTS@#Of the 63 patients, 54% were female and 46% male. The mean drop in postoperative haemoglobin levels in the PA and IA groups was 2.0 g/dL and 1.6 g/dL, respectively, and this was not statistically significant ( P = 0.10). The mean haematocrit drop in the PA and IA groups was 6.1% and 5.3%, respectively, and this was also not statistically significant ( P = 0.58). The postoperative day (POD) 1 and discharge day flexion angles, POD 1 and POD 2 visual analogue scale (VAS) scores, gait distance on discharge and length of hospitalisation stay were largely similar in the two groups.@*CONCLUSION@#Our study showed that both IA and PA TXA with analgesic components were equally efficient in reducing blood loss and improving immediate postoperative pain relief and functional outcomes.

Clinical use of tranexamic acid: evidences and controversies

Abstract Tranexamic acid (TXA) significantly reduces blood loss in a wide range of surgical procedures and improves survival rates in obstetric and trauma patients with severe bleeding. Although it mainly acts as a fibrinolysis inhibitor, it also has an anti-inflammatory effect, and may help attenuate the systemic inflammatory response syndrome found in some cardiac surgery patients. However, the administration of high doses of TXA has been associated with seizures and other adverse effects that increase the cost of care, and the administration of TXA to reduce perioperative bleeding needs to be standardized. Tranexamic acid is generally well tolerated, and most adverse reactions are considered mild or moderate. Severe events are rare in clinical trials, and literature reviews have shown tranexamic acid to be safe in several different surgical procedures. However, after many years of experience with TXA in various fields, such as orthopedic surgery, clinicians are now querying whether the dosage, route and interval of administration currently used and the methods used to control and analyze the antifibrinolytic mechanism of TXA are really optimal. These issues need to be evaluated and reviewed using the latest evidence to improve the safety and effectiveness of TXA in treating intracranial hemorrhage and bleeding in procedures such as liver transplantation, and cardiac, trauma and obstetric surgery.

Avaliação do uso de múltiplas doses de ácido tranexâmico sobre a perda sanguínea na artroplastia total do joelho / Evaluation of the use of multiple doses of tranexamic acid on blood loss in total knee arthroplasty

A artroplastia total de joelho (ATJ) está relacionada a um sangramento peroperatório significativo que pode gerar complicações relacionadas à perda sanguínea e à hemotransfusão quando necessária. A administração intravenosa (IV) do ácido tranexâmico (ATX) tem apresentado bons resultados em reduzir a perda sanguínea visível em ATJ. O objetivo principal deste estudo foi avaliar o efeito do uso de múltiplas doses de ATX sobre a perda sanguínea na ATJ. De modo prospectivo e randomizado foram avaliados 60 participantes de ambos os sexos com idade superior a 50 anos, internados no INTO para realização de ATJ cimentada no período de agosto de 2017 a maio de 2018. Estes foram divididos em três grupos, com 20 pacientes cada, de acordo com a intervenção: Grupo I, composto por pacientes que receberam a dosagem IV de 15mg/kg de ATX 30 minutos antes da cirurgia e de 8/8 horas (h) por 24h no pósoperatório; Grupo II composto por pacientes que receberam ATX somente no pré-operatório na forma IV de 15mg/kg em dose única 30 minutos antes da cirurgia; Grupo III, controle, composto por pacientes que não receberam nenhuma dose de ATX. Em relação aos resultados, os grupos foram homogêneos em relação a sexo, idade, peso, hemoglobina (Hb) pré-operatória e volemia. Não houve diferença significativa entre os grupos I e II em relação ao grupo controle no que tange à queda de Hb em 24 e 48h. Em relação a perda sanguínea estimada em 24 e 48h, apenas o grupo II teve menor perda em relação ao grupo controle, apesar de as perdas nos grupos I e II não serem significativamente diferentes. Houve diferença significativa em relação à perda sanguínea avaliada pelo dreno nos grupos de intervenção, onde os grupos I e II apresentaram menor volume coletado em relação ao grupo III. Concluímos que o uso do ATX em uma e em múltiplas doses, utilizados nas ATJs realizadas com isquemia e revisão da hemostasia, se mostrou eficaz em reduzir as perdas visíveis aferidas no dreno. Contudo a utilização de múltiplas doses de ATX não se mostrou superior ao uso de uma única dose em reduzir a queda nos níveis pós-operatórios de Hb e em reduzir a perda sanguínea na ATJ. O uso de múltiplas doses não se correlacionou ao aumento de complicações tromboembólicas. Palavras-chave: Ácido tranexâmico, artroplastia total de joelho, osteoartrite de joelho, perda sanguínea

Total knee arthroplasty (TKA) is related to significant perioperative bleeding that can lead to complications related to blood loss and blood transfusion when necessary. Intravenous (IV) administration of tranexamic acid (ATX) has shown good results in reducing visible blood loss in TKA. The main objective of the study was to evaluate the effect of multiple-dose ATX use on blood loss in TKA. Prospectively and randomly, 60 participants of both sexes over 50 years of age, admitted to INTO for cemented TKA from August 2017 to May 2018, were evaluated. They were divided into three groups, with 20 patients each, according to the intervention: Group I, composed of patients who received the IV dose of 15mg / kg ATX 30 minutes before surgery and 8/8 hours (h) for 24h postoperatively; Group II consisted of patients receiving ATX only in the preoperative form IV of 15mg / kg in a single dose 30 minutes before surgery; Group III, control, composed of patients who received no dose of ATX. Regarding the results, the groups were homogeneous regarding gender, age, weight, preoperative hemoglobin (Hb) and blood volume. There was no significant difference between groups I and II in relation to the control group regarding the loss of Hb at 24 and 48h. Regarding the estimated blood loss at 24 and 48h, only group II had less loss compared to the control group, although the losses in groups I and II were not significantly different. There was a significant difference regarding the blood loss assessed by the drain in the intervention groups, where groups I and II had a smaller volume collected compared to group III. We conclude that the use of ATX in one and multiple doses, used in TKA performed with ischemia and revision of hemostasis, was effective in reducing the visible losses measured in the drain. However, the use of multiple doses of ATX was not superior to the use of a single dose in reducing the drop in postoperative Hb levels and reducing blood loss in TKA. The use of multiple doses did not correlate with increased thromboembolic complications

Antifibrinolytics in cardiac surgery.

Cardiac surgery exerts a significant strain on the blood bank services and is a model example in which a multi-modal blood-conservation strategy is recommended. Significant bleeding during cardiac surgery, enough to cause re-exploration and/or blood transfusion, increases morbidity and mortality. Hyper-fibrinolysis is one of the important contributors to increased bleeding. This knowledge has led to the use of anti-fibrinolytic agents especially in procedures performed under cardiopulmonary bypass. Nothing has been more controversial in recent times than the aprotinin controversy. Since the withdrawal of aprotinin from the world market, the choice of antifibrinolytic agents has been limited to lysine analogues either tranexamic acid (TA) or epsilon amino caproic acid (EACA). While proponents of aprotinin still argue against its non-availability. Health Canada has approved its use, albeit under very strict regulations. Antifibrinolytic agents are not without side effects and act like double-edged swords, the stronger the anti-fibrinolytic activity, the more serious the side effects. Aprotinin is the strongest in reducing blood loss, blood transfusion, and possibly, return to the operating room after cardiac surgery. EACA is the least effective, while TA is somewhere in between. Additionally, aprotinin has been implicated in increased mortality and maximum side effects. TA has been shown to increase seizure activity, whereas, EACA seems to have the least side effects. Apparently, these agents do not differentiate between pathological and physiological fibrinolysis and prevent all forms of fibrinolysis leading to possible thrombotic side effects. It would seem prudent to select the right agent knowing its risk-benefit profile for a given patient, under the given circumstances.

A randomized prospective analysis of alteration of hemostatic function in patients receiving tranexamic acid and hydroxyethyl starch (130/0.4) undergoing off pump coronary artery bypass surgery.

Postoperative hemorrhagic complications is still one of the major problems in cardiac surgeries. It may be caused by surgical issues, coagulopathy caused by the side effects of the intravenous fluids administered to produce plasma volume expansion such as hydroxyl ethyl starch (HES). In order to thwart this hemorrhagic issue, few agents are available. Fibrinolytic inhibitors like tranexamic acid (TA) may be effective modes to promote blood conservation; but the possible complications of thrombosis of coronary artery graft, precludes their generous use in coronary artery bypass graft surgery. The issue is a balance between agents that promote coagulation and those which oppose it. Therefore, in this study we have assessed the effects of concomitant use of HES and TA. Thromboelastogram (TEG) was used to assess the effect of the combination of HES and TA. With ethical committee approval and patient's consent, 100 consecutive patients were recruited for the study. Surgical and anesthetic techniques were standardized. Patients fulfilling our inclusion criteria were randomly allocated into 4 groups of 25 each. The patients in group A received 20 ml/kg of HES (130/0.4), 10 mg/kg of T.A over 30 minutes followed by infusion of 1 mg/kg/hr over the next 12 hrs. The patients in group B received Ringer's lactate + TA at same dose. The patients in the Group C received 20 ml/kg of HES. Group D patients received RL. Fluid therapy was goal directed. Total blood loss was assessed. Reaction time (r), α angle, maximum amplitude (MA) values of TEG were assessed at baseline, 12, 36 hrs. The possible perioperative myocardial infraction (MI) was assessed by electrocardiogram (ECG) and troponin T values at the baseline, postoperative day 1. Duration on ventilator, length of stay (LOS) in the intensive care unit (ICU) were also assessed. The demographical profile was similar among the groups. Use of HES increased blood loss significantly (P < 0.05). Concomitant use of TA reduced blood loss when used along with HES. r value was prolonged at 12 hours in all the groups and α angle was reduced at 12 hours in all the groups, where as MA value was reduced at 12 th hour in the HES group compared to the baseline and increased in TA + HES group. These findings were statistically significant. No significant change in Troponin T values/ ECG, duration of ventilation and LOS ICU was observed. No adverse events was noticed in any of the four groups. HES (130/0.4) used at a dose of 20 ml/kg seems to produce coagulopathy causing increased blood loss perioperatively. Hemodilution produced by fluid therapy seems to produce Coagulopathy as observed by TEG parameters. Concomitant use of TA with HES appears to reverse these changes without causing any adverse effects in patients undergoing OPCAB surgery.

Risk factors associated with postoperative seizures in patients undergoing cardiac surgery who received tranexamic acid: A case-control study.

Antifibrinolytic agents are used during cardiac surgery to minimize bleeding and reduce exposure to blood products. Several reports suggest that tranexamic acid (TA) can induce seizure activity in the postoperative period. To examine factors associated with postoperative seizures in patients undergoing cardiac surgery who received TA. University-affiliated hospital. Case-control study. Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) between January 2008 and December 2009 were identified. During this time, all patients undergoing heart surgery with CPB received TA. Cases were defined as patients who developed seizures that required initiation of anticonvulsive therapy within 48 h of surgery. Exclusion criteria included subjects with preexisting epilepsy and patients in whom the convulsive episode was secondary to a new ischemic lesion on brain imaging. Controls who did not develop seizures were randomly selected from the initial cohort. From an initial cohort of 903 patients, we identified 32 patients with postoperative seizures. Four patients were excluded. Twenty-eight cases and 112 controls were analyzed. Cases were more likely to have a history of renal impairment and higher preoperative creatinine values compared with controls (1.39 ± 1.1 vs. 0.98 ± 0.02 mg/dL, P = 0.02). Significant differences in the intensive care unit, postoperative and total lengths of stay were observed. An association between high preoperative creatinine value and postoperative seizure was identified. TA may be associated with the development of postoperative seizures in patients with renal dysfunction. Doses of TA should be reduced or even avoided in this population.

Antifibrinolíticos e cirurgia cardíaca com circulação extracorpórea / Antifibrinolytics and cardiac surgery with cardiopulmonary bypass

JUSTIFICATIVA E OBJETIVOS: A cirurgia cardíaca é a especialidade cirúrgica que com mais freqüência está associada a sangramento, coagulopatia e necessidade de derivados de sangue. Os agentes farmacológicos aprotinina, ácido epsilon-aminocapróico e ácido tranexâmico são os mais utilizados para auxiliar na hemostasia dos pacientes submetidos à circulação extracorpórea. O objetivo deste trabalho foi apresentar a fisiopatologia do sangramento em cirurgia cardíaca e a atual situação dos antifibrinolíticos quanto à sua eficácia e complicações quando usados nesses procedimentos, dando maior ênfase ao ácido tranexâmico e à aprotinina. CONTEUDO: São discutidos os mecanismos pelos quais a circulação extracorpórea provoca alteração na hemostasia e de que maneira os antifibrinolíticos agem para diminuir o sangramento e o uso de sangue alogênico em cirurgia cardíaca. É dada ênfase ao problema do tromboembolismo que pode ocorrer com o emprego desses antifibrinolíticos, com revisão da literatura. CONCLUSÃO: A fibrinólise é um dos principais fatores relacionados com o aumento do sangramento em cirurgia cardíaca com circulação extracorpórea. A inibição da fibrinólise, juntamente com a preservação da função plaquetária, é, provavelmente, o mecanismo pelo qual os antifibrinolíticos diminuem o sangramento. O emprego desses fármacos reduz o sangramento em cirurgia cardíaca com circulação extracorpórea num percentual que pode chegar a 50 por cento. Com relação à preocupação com o tromboembolismo, os ácidos tranexâmico e epsilon-aminocapróico são opções que oferecem maior segurança que a aprotinina.

BACKGROUND AND OBJECTIVES: Cardiac surgery is the surgical subspecialty most often associated with bleeding, bleeding disorders, and the need of blood products. Agents such as aprotinin, episilon-aminocaproic acid, and tranexamic acid are frequently used to aid the hemostasis of patients undergoing cardiopulmonary bypass. The objective of this report is to present the physiopathology of bleeding during cardiac surgeries and the current role of antifibrinolytics regarding their efficacy and complications when used in those procedures, with emphasis on tranexamic acid and aprotinin. CONTENTS: The mechanisms of changes in hemostasis caused by cardiopulmonary bypass, how antifibrinolytics decrease bleeding, and the use of alogenic blood in cardiac surgery are discussed. A review of the literature emphasizes the thromboembolism secondary to the use of those antifibrinolytics. CONCLUSION: Fibrinolysis is one of the main factors related with increased bleeding during cardiac surgery with cardiopulmonary bypass. Inhibition of fibrinolysis associated with the preservation of platelet function is, probably, the mechanism by which anti-fibrinolytics decrease bleeding. Those agents reduce bleeding in up to 50 percent in cardiac surgeries with cardiopulmonary bypass. Tranexamic acid and episilon-aminocaproic acid are safer than aprotinin in the prevention of thromboembolism.

JUSTIFICATIVA Y OBJETIVOS: La cirugía cardiaca es la especialidad quirúrgica que más frecuentemente está asociada al sangramiento, cuagulopatía y con necesidad de derivados de sangre. Los agentes farmacológicos aprotinina, ácido epsilon-aminocapróico y el ácido tranexámico son los más utilizados para auxiliar en la hemostasia de los pacientes sometidos a la circulación extracorpórea. El objetivo de este trabajo fue presentar la fisiopatología del sangramiento en cirugía cardiaca y la actual situación de los antifibrinolíticos en cuanto a su eficacia y complicaciones cuando usados en estos procedimientos dando más énfasis al ácido tranexámico y a la aprotinina. CONTENIDO: Son discutidos los mecanismos por los cuales la circulación extracorpórea provoca alteración en la hemostasia y de que manera los antifibrinolíticos actúan para disminuir el sangramiento y el uso de sangre alogénica en cirugía cardiaca. Se le da énfasis al problema del trombo embolismo que puede ocurrir con el uso de esos antifibrinolíticos, con revisión de la literatura. CONCLUSIONES: La fibrinólisis es uno de los principales factores relacionados con el aumento del sangramiento en cirugía cardiaca con circulación extracorpórea. La inhibición de la fibrinólisis, conjuntamente con la preservación de la función plaquetaria es probablemente el mecanismo por el cual los antifibrinolíticos disminuyen el sangramiento. El uso de esos fármacos reduce el sangramiento en cirugía cardiaca con circulación extracorpórea en un porcentaje que puede alcanzar el 50 por ciento. Con relación a la preocupación con el trombo embolismo, el ácido tranexámico y el ácido epsilon-aminocapróico son opciones que ofrecen una mayor seguridad que la aprotinina.

Emprego do ácido tranexâmico para controle de sangramento em cirurgia de revascularizaçäo miocárdica / Use of tranexamic acid for bleeding control in myocardial revascularization

Objetivo - Comparar 2 grupos de pacientes submetidos a revascularizaçäo miocárdica, quanto ao emprego do antifibrinolítico ácido tranexâmico e sua efetividade em diminuir o sangramento pós-operatório e as possíveis complicaçöes de seu uso. Métodos - Análise prospectiva de 2 grupos de 80 pacientes. Grupo A - sem uso de antifibrinolítico (dez/91 a maio/92). Quantificaçäo da drenagem e quantidade de sangue ou derivados infundidos no período de 12h bem como as complicaçöes em cada grupo. Resultados - Mortalidade hospitalar: grupo A - 3,8 por cento; grupo b - 2,5 por cento. Drenagem de 12h: grupo A - 602 + ou - 547ml e grupo B - 260 + ou - 260ml, (p<0,001). Infusäo de sangue: grupo A - 1.782 + ou - 1.163 e grupo B - 1.105 + ou - 839ml, (p<0,001). Complicaçöes: grupo A - 2 casos com infarto agudo do miocárdio (IAM) intra-operatório, 1 icterícia; grupo B - 1 IAM intra-operatório, 1 revisäo hemostasia, 1 icterícia, 1 insuficiência renal, 2 infecçäp esterma;. 1 crise convulsiva. Tempo médio de permanência hospitalar de 10 dias (ambos os grupos). Conclusäo - O ácido tranexâmico foi efetivo em diminuir o sangramento e o volume de sangue infundido em cirurgia de revascularizaçäo miocárdica