|Year : 2015 | Volume
| Issue : 4 | Page : 479-482
Topical application of tranexamic acid versus systemic injection during coronary artery bypass graft surgery: a comparative study
Elham A Seiam1, Ayman M Kamaly1, Yaser M El-Nahass2, Abd El-Aziz A Abd El-Aziz MD 1, Amr M Masoud3
1 Department of Anesthesiology, Intensive Care, and Pain Management, Ain Shams University, Cairo, Egypt
2 Department of Cardiothoracic Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
3 Department of Anesthesiology at Cardiothoracic Academy, Ain Shams University Hospitals, Cairo, Egypt
|Date of Submission||27-Aug-2014|
|Date of Acceptance||18-Mar-2015|
|Date of Web Publication||29-Dec-2015|
Abd El-Aziz A Abd El-Aziz
Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain Shams University, 11371 Cairo
Source of Support: None, Conflict of Interest: None
Diffuse microvascular bleeding remains a common problem after myocardial revascularization with cardiopulmonary bypass.
The efficacy of locally administered tranexamic acid (topical application) was compared with systemically administered tranexamic acid to reduce postoperative bleeding after cardiopulmonary bypass in elective nonredo coronary artery bypass grafting (CABG).
The study included 60 patients of both sexes, aged between 35 and 65 years, and scheduled for elective CABG; patients were randomly assigned to two groups: group I (the intravenous tranexamic acid group; 30 patients) and group II (the topical tranexamic acid group; 30 patients). For each patient in each group, postoperative blood loss, number of units of packed red blood cells (RBCs) and fresh frozen plasma (FFP) transfused, frequency of resternotomy, duration of hospital and ICU stay, and mortality were recorded.
There were statistically significant differences between the two groups with regard to total postoperative blood loss and need for packed RBCs and FFP transfusion, being much greater in group I than in group II. There was no mortality in either group. Frequency of resternotomy was higher in group I than in group II, although the difference was statistically nonsignificant. The duration of hospital and ICU stay revealed no statistically significant differences between the two groups.
Intraoperative topical administration of tanexamic acid into the pericardial cavity before sternal closure during CABG surgery has reduced the incidence of postoperative blood loss and the need for postoperative packed RBCs and FFP transfusion.
Keywords: coronary artery bypass grafting, topical versus systemic, tranexamic acid
|How to cite this article:|
Seiam EA, Kamaly AM, El-Nahass YM, Abd El-Aziz AAA, Masoud AM. Topical application of tranexamic acid versus systemic injection during coronary artery bypass graft surgery: a comparative study. Ain-Shams J Anaesthesiol 2015;8:479-82
|How to cite this URL:|
Seiam EA, Kamaly AM, El-Nahass YM, Abd El-Aziz AAA, Masoud AM. Topical application of tranexamic acid versus systemic injection during coronary artery bypass graft surgery: a comparative study. Ain-Shams J Anaesthesiol [serial online] 2015 [cited 2020 Feb 21];8:479-82. Available from: http://www.asja.eg.net/text.asp?2015/8/4/479/172667
| Introduction|| |
Intraoperative and postoperative bleeding is one of the main complications in patients undergoing cardiopulmonary bypass (CPB) for cardiac surgery. During CPB, the blood is exposed to large foreign surfaces and materials, and to flow conditions normally not found in the circulation  .
In addition, use of homologous blood, pump prime fluids, and heparinization and reversal with protamine introduce complex changes in hemostasis. All of these factors affect the platelet function, coagulation, and the fibrinolytic system  .
A variety of hemostatic changes, such as platelet dysfunction, activation of blood coagulation despite anticoagulation with heparin, inactivation of clotting factors either by consumption or by residual effects of heparin after its neutralization by protamine, and hyperfibrinolysis due to an enhanced release of tissue-type plasminogen activator, have been reported  .
Various antifibrinolytic agents have been used to diminish post-bypass bleeding. These include e-aminocaproic acid, aprotinin (AP), and, most recently, tranexamic acid (TA)  .
Moreover, the application of TA into the chest before closure of the median sternotomy could remove plasminogen from the fibrin surface of clots, thereby inhibiting plasmin-induced degradation of fibrin. Thus, it might prevent the resolution of formed clots and lead to hemostasis by preserving their integrity  .
The aim of this study was to compare the efficacy of locally administered TA (topical application) with systemically administered TA to reduce postoperative bleeding after elective coronary artery bypass grafting (CABG).
| Patients and methods|| |
This comparative double-blinded study was conducted on 60 patients of both sexes, aged between 35 and 65 years, scheduled for elective CABG in the Cardiac Surgery Unit of Ain Shams University hospitals, from February 2010 to October 2012. Written informed consent was taken from all patients after obtaining approval from the ethics committee. Patients with a history of bleeding diathesis, history of thrombosis, heparin administration within the previous 48 h of surgery, NSAID intake within the last 3 days, renal dysfunction as determined by creatinine levels greater than 2 mg/dl, severe hepatic impairment, known allergy to TA, and patients scheduled for redo surgery were excluded from the study.
The patients were then randomly allocated into two groups. Group I (the intravenous TA group: 30 patients) and group II (the topical TA group: 30 patients). In group I, patients received 30 mg/kg of TA in three divided doses (each diluted in 20 ml of normal saline) at three time points as follows: 10 mg/kg immediately after induction, 10 mg/kg immediately after going on CPB, and 10 mg/kg after separation from CPB and reversal of protamine. In group II, patients received 2 g of TA diluted in 250 ml normal saline solution at room temperature in the pericardial cavity before closure of the sternum. In addition to the above, patients received three boluses of normal saline (20 ml each) at three time points: (a) immediately after induction, (b) immediately after going on CPB, and (c) after separation from CPB and reversal of protamine.
Anesthesia in both groups was induced with fentanyl 3-5 mg/kg and thiopental 3 mg/kg and maintained with boluses of fentanyl 100-200 mg and midazolam 2.5 mg. Muscle paralysis was secured with pancuronium bromide 0.1 mg/kg. Intraoperative monitoring included the following: five-lead ECG, pulse oximetery, capnography, temperature, central venous pressure, invasive blood pressure, activated clotting time, arterial blood gases, hemoglobin (Hb), and hematocrit (Hct).
Statistical analysis of data was performed with an HP computer using the statistical package for social sciences, version 13, for Windows (SPSS Corp., Chicago, Illinois, USA) as follows: variables were described as mean ± SD, range, numbers, and percentages; qualitative variables were compared by means of the c2 -test; the Mann-Whitney test was used to compare two groups as regards quantitative variables (parametric and nonparametric). For all tests a P (probability) value less than 0.05 was considered statistically significant and a P value less than 0.01 was considered highly significant.
| Results|| |
As regards age, sex, body weight, and preoperative Hb and Hct levels of patients, no statistically significant difference was found between the two groups (P > 0.05) [Table 1].
As regards postoperative Hb and Hct levels, there were statistically significant differences between the two groups, with lower values in the systemic group than in the topical group [Table 2].
There was a statistically significant difference between the two groups regarding total postoperative blood loss, which was much greater in the systemic group than in the topical group [Table 3].
Also, there was a statistically significant difference as regards the proportion of patients transfused with packed RBCs and fresh frozen plasma (FFP), being higher in the systemic group than in the topical group [Table 4].
There were no statistically significant differences between the studied groups as regards morbidity, mortality, resternotomy, and duration of hospital and ICU stay [Table 5].
| Discussion|| |
In the current study, total postoperative blood loss was significantly lower in the topical group (338.7 ± 66 ml) when compared with the systemic group (419 ± 71.9 ml) and this corresponds to a 19% decrease in the total amount of bleeding. Regarding the transfusion of packed RBCs in the ICU, only three patients (10%) in the topical group required transfusion, compared with 11 patients (36.6%) in the systemic group; this difference was statistically significant. Regarding FFP transfusion in the ICU, only six patients (20%) in the topical group required transfusion, in comparison with 50% (15 patients) in the systemic group; this difference also reached a statistically significant value.
There was no mortality in either group; and comparison of hospital stay and ICU stay revealed no statistically significant difference between the two groups.
Regarding the frequency of resternotomy for bleeding, only three patients (5%) in the systemic group required resternotomy versus only one patient (1.6%) in the topical group. However, this difference was not statistically significant.
Our results are in accordance with the trial conducted by De bonis et al.  , who studied postoperative blood loss with the topical use of TA in 40 patients undergoing primary coronary surgery who were randomly assigned to group 1 (the TA group) and group 2 (the placebo group). TA could not be detected in any of the blood samples blindly collected from 24 patients to verify whether any systemic absorption of the drug had occurred.
Also, our results are in accordance with those published by Abul-Azm and Abdullah  , who studied postoperative blood loss with the topical use of TA in 100 patients undergoing different open heart surgeries. During the first postoperative 24 h, cumulative blood loss was significantly higher in the placebo group compared with the TA group. More blood transfusions were administered to the placebo group as compared with the TA group.
The results of the current study are comparable to the results of Baric et al.  , who evaluated postoperative blood loss with the topical use of antifibrinolytics. In their study, 300 patients were assigned to three groups to receive AP, TA, or placebo topically before sternal closure. Postoperative bleeding within the first 12 h showed statistically significant intergroup differences. Bleeding rates were significantly higher in the placebo group compared with the groups treated with antifibrinolytic agents (AP and TA groups). Although the TA group showed the lowest values, no statistically significant differences between TA and AP groups were found. Intergroup differences in blood products requirements were not statistically significant.
The results of the current study are also in accordance with the results of the trial conducted by Fawzy et al.  on 38 patients scheduled for primary isolated CABG. During the first 24 h postoperatively, cumulative blood loss was significantly less in the TA group compared with the placebo group. There was no significant difference in postoperative packed RBC transfusion between the two groups. Significantly less platelet transfusion was required in the TA group (median zero unit) than in the placebo group (median two units). Apart from re-exploration for excessive surgical bleeding in one patient in the TA group, no difference was found in morbidity or mortality between the two groups. The authors concluded that there was significant reduction in postoperative blood loss in the first 24 h after surgery (37%) with the maximum reduction in the third hour (66%).
The results of the current study are also in accordance with the results of Brown et al.  , who conducted a meta-analysis to compare AP, aminocaproic acid, and TA with placebo, head to head, in eight clinical outcomes from 138 trials. All agents were effective in significantly reducing blood loss and the proportion of patients transfused with packed RBCs over placebo. Only high-dose AP reduced the rate of re-exploration. There were no significant risks or benefits for any agent with respect to mortality, stroke, myocardial infarction, or renal failure. However, high-dose AP significantly increased the risk for renal dysfunction. Compared head to head, high-dose AP demonstrated significant reduction in total blood loss over aminocaproic acid and TA. There were no significant differences in any agent when compared head to head on other outcomes.
The results of the current study are comparable to the results of Henry et al.  . In 61 trials on AP (7027 participants), they found that AP had reduced the rate of RBC transfusion by 30% and had also significantly reduced the need for reoperation due to bleeding. In 18 trials of TA (1342 participants), they found that TA use has reduced the rate of RBC transfusion by 34% and has resulted in a saving of 1.03 units of RBCs in those requiring transfusion. In four trials of epsilon aminocaproic acid (208 participants), they found that epsilon aminocaproic acid use resulted in a statistically nonsignificant reduction in RBC transfusion.
In contrast to our findings, Yasim et al.  did not find a statistically significant reduction in postoperative bleeding after topical application of AP and TA in 30 patients undergoing open heart surgery with CPB who were randomized into three groups (AP, TA, and placebo).
In contrast to our findings, Isgro et al.  conducted a study on 97 patients, in which AP was given systemically to 49 patients and was applied topically to 48 patients by spraying the substance on the target area (pericardium). Their results suggest that there is no difference between the perioperative application of systemically given AP and locally applied AP.
| Conclusion|| |
The current study demonstrated that topical administration of TA during cardiac surgery can reduce postoperative blood loss and the need for transfusion (both packed RBCs and FFP).
| Acknowledgements|| |
Conflicts of interest
| References|| |
Linden MD. The hemostatic defect of cardiopulmonary bypass. J Thromb Thrombolysis 2003; 16:129-147.
Despotis GJ, Avidan MS, Hogue CW Jr. Mechanisms and attenuation of hemostatic activation during extracorporeal circulation. Ann Thorac Surg 2001; 72:S1821-S1831.
Yahya U, Salim B, Hikmet K. Levels of protein C and protein S, tissue-plasminogen activator, and fibrinogen during cardiopulmonary bypass. Turk J Med Sci 2007; 37:345-350.
Khalil PN, Ismail M, Kalmar P, von Knobelsdorff G, Marx G. Activation of fibrinolysis in the pericardial cavity after cardiopulmonary bypass. Thromb Haemost 2004; 92:568-574.
Yasim A, Asik R, Atahan E. Effects of topical applications of aprotinin and tranexamic acid on blood loss after open heart surgery. Anadolu Kardiyol Derg 2005; 5:36-40.
De Bonis M, Cavaliere F, Alessandrini F, Lapenna E, Santarelli F, Moscato U, et al
. Topical use of tranexamic acid in coronary artery bypass operations: a double-blind, prospective, randomized, placebo-controlled study. J Thorac Cardiovasc Surg 2000; 119:575-580.
Abul-Azm A, Abdullah KM. Effect of topical tranexamic acid in open heart surgery. Eur J Anaesthesiol 2006; 23:380-384.
Baric D, Biocina B, Unic D, Sutlic Z, Rudez I, Vrca VB, et al
. Topical use of antifibrinolytic agents reduces postoperative bleeding: a double-blind, prospective, randomized study. Eur J Cardiothorac Surg 2007; 31:366-371.
Fawzy H, Elmistekawy E, Bonneau D, Latter D, Errett L Can local application of tranexamic acid reduce post-coronary bypass surgery blood loss? A randomized controlled trial. J Cardiothorac Surg 2009; 4:25.
Brown JR, Birkmeyer NJ, O'Connor GT. Meta-analysis comparing the effectiveness and adverse outcomes of antifibrinolytic agents in cardiac surgery. Circulation 2007; 115:2801-2813.
Henry DA, Carless PA, Moxey AJ, O'Connell D, Stokes BJ, McClelland B, et al
. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev 2007; 4:CD001886.
Isgro F, Stanisch O, Kiessling AH, Gürler S, Hellstern P, Saggau W. Topical application of aprotinin in cardiac surgery. Perfusion 2002; 17:347-351.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]