Topical moistening of mastectomy wounds with diluted tranexamic acid to reduce bleeding: randomized clinical trial

K Ausen, A I Hagen, H S Østbyhaug, S Olafsson, B J Kvalsund, O Spigset, H Pleym, K Ausen, A I Hagen, H S Østbyhaug, S Olafsson, B J Kvalsund, O Spigset, H Pleym

Abstract

Background: Topical administration of tranexamic acid (TXA) may be an alternative to intravenous administration to reduce bleeding with a lower risk of systemic adverse events. The aim of this study was to investigate whether moistening a surgical wound with TXA before closure, leaving a thin film of drug only, would reduce postoperative bleeding.

Methods: This was a two-centre, stratified, parallel-group, placebo-controlled, double-blind RCT. Patients undergoing mastectomy with or without axillary lymph node clearance were randomized 1 : 1 to moistening of wound surface before closure with either 25 mg/ml TXA or 0·9 per cent sodium chloride (placebo). The primary endpoint was postoperative bleeding as measured by drain production in the first 24 h. Secondary endpoints were early haematoma, total drain production, postoperative complications and late aspirations of seroma within 3 months.

Results: Between 1 January 2016 and 31 August 2018, 208 patients were randomized. Two patients were converted to a different surgical procedure at surgery, and four did not receive the intervention owing to technical error. Thus, 202 patients were included in the study (101 in the TXA and 101 in the placebo group). TXA reduced mean drain production at 24 h (110 versus 144 ml; mean difference 34 (95 per cent c.i. 8 to 60) ml, P = 0·011). One patient in the TXA group had early haematoma compared with seven in the placebo group (odds ratio (OR) 0·13 (95 per cent c.i. 0·02 to 1·07); P = 0·057). There was no significant difference in postoperative complications between TXA and placebo (13 versus 10; OR 1·11 (0·45 to 2·73), P = 0·824) or need for late seroma aspirations (79 versus 67 per cent; OR 1·83 (0·91 to 3·68), P = 0·089).

Conclusion: Moistening the wound with TXA 25 mg/ml before closure reduces postoperative bleeding within the first 24 h in patients undergoing mastectomy. Registration number: NCT02627560 (https://clinicaltrials.gov).

© 2019 The Authors. BJS Open published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.

Figures

Figure 1
Figure 1
CONSORT diagram for the study

References

    1. Society of Thoracic Surgeons Blood Conservation Guideline Task Force , Ferraris VA, Brown JR, Despotis GJ, Hammon JW, Reece TB et al 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg 2011; 91: 944–982.
    1. Murkin JM. Lessons learned in antifibrinolytic therapy: the BART trial. Semin Cardiothorac Vasc Anesth 2009; 13: 127–131.
    1. Ker K, Prieto‐Merino D, Roberts I. Systematic review, meta‐analysis and meta‐regression of the effect of tranexamic acid on surgical blood loss. Br J Surg 2013; 100: 1271–1279.
    1. Ker K, Roberts I. Tranexamic acid for surgical bleeding. BMJ 2014; 349: g4934.
    1. Lecker I, Wang DS, Whissell PD, Avramescu S, Mazer CD, Orser BA. Tranexamic acid‐associated seizures: causes and treatment. Ann Neurol 2016; 79: 18–26.
    1. Sharma V, Katznelson R, Jerath A, Garrido‐Olivares L, Carroll J, Rao V et al The association between tranexamic acid and convulsive seizures after cardiac surgery: a multivariate analysis in 11 529 patients. Anaesthesia 2014; 69: 124–130.
    1. Takagi H, Ando T, Umemoto T; All‐Literature Investigation of Cardiovascular Evidence (ALICE) group . Seizures associated with tranexamic acid for cardiac surgery: a meta‐analysis of randomized and non‐randomized studies. J Cardiovasc Surg (Torino) 2017; 58: 633–641.
    1. Gerstein NS, Kelly SP, Brierley JK. Yet another tranexamic acid‐related thrombotic complication. J Cardiothorac Vasc Anesth 2016; 30: e21–e22.
    1. Myers SP, Kutcher ME, Rosengart MR, Sperry JL, Peitzman AB, Brown JB et al Tranexamic acid administration is associated with an increased risk of posttraumatic venous thromboembolism. J Trauma Acute Care Surg 2019; 86: 20–27.
    1. Ausen K, Pleym H, Liu J, Hegstad S, Nordgård HB, Pavlovic I et al Serum concentrations and pharmacokinetics of tranexamic acid after two means of topical administration in massive weight loss skin‐reducing surgery. Plast Reconstr Surg 2019; 143: 1169e–1178e.
    1. Montroy J, Hutton B, Moodley P, Fergusson NA, Cheng W, Tinmouth A et al The efficacy and safety of topical tranexamic acid: a systematic review and meta‐analysis. Transfus Med Rev 2018; 32: 165–178.
    1. Nouraei SM. What are the optimal dose of administration and time of drainage for topical tranexamic acid in patients undergoing cardiac surgery? Korean J Thorac Cardiovasc Surg 2017; 50: 477–478.
    1. Ker K, Beecher D, Roberts I. Topical application of tranexamic acid for the reduction of bleeding. Cochrane Database Syst Rev 2013; (7)CD010562.
    1. Li J, Zhang Z, Chen J. Comparison of efficacy and safety of topical versus intravenous tranexamic acid in total hip arthroplasty: a meta‐analysis. Medicine (Baltimore) 2016; 95: e4689.
    1. Lin C, Qi Y, Jie L, Li HB, Zhao XC, Qin L et al Is combined topical with intravenous tranexamic acid superior than topical, intravenous tranexamic acid alone and control groups for blood loss controlling after total knee arthroplasty: a meta‐analysis. Medicine (Baltimore) 2016; 95: e5344.
    1. Ausen K, Fossmark R, Spigset O, Pleym H. Randomized clinical trial of topical tranexamic acid after reduction mammoplasty. Br J Surg 2015; 102: 1348–1353.
    1. Kuroi K, Shimozuma K, Taguchi T, Imai H, Yamashiro H, Ohsumi S et al Pathophysiology of seroma in breast Cancer. Breast Cancer 2005; 12: 288–293.
    1. van Bemmel AJ, van de Velde CJ, Schmitz RF, Liefers GJ. Prevention of seroma formation after axillary dissection in breast cancer: a systematic review. Eur J Surg Oncol 2011; 37: 829–835.
    1. NTNU. Randomisation [accessed 15 February 2019].
    1. Oertli D, Laffer U, Haberthuer F, Kreuter U, Harder F. Perioperative and postoperative tranexamic acid reduces the local wound complication rate after surgery for breast cancer. Br J Surg 1994; 81: 856–859.
    1. Biomath. Paired t‐test [accessed 15 January 2012].
    1. Ker K, Edwards P, Perel P, Shakur H, Roberts I. Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta‐analysis. BMJ 2012; 344: e3054.
    1. Knight H, Banks J, Muchmore J, Ives C, Green M. Examining the use of intraoperative tranexamic acid in oncoplastic breast surgery. Breast J 2019; 25: 1047–1049.
    1. Wolter A, Scholz T, Pluto N, Diedrichson J, Arens‐Landwehr A, Liebau J. Subcutaneous mastectomy in female‐to‐male transsexuals: optimizing perioperative and operative management in 8 years clinical experience. J Plast Reconstr Aesthet Surg 2018; 71: 344–352.
    1. Kuroi K, Shimozuma K, Taguchi T, Imai H, Yamashiro H, Ohsumi S et al Effect of mechanical closure of dead space on seroma formation after breast surgery. Breast Cancer 2006; 13: 260–265.
    1. Chen CY, Hoe AL, Wong CY. The effect of a pressure garment on post‐surgical drainage and seroma formation in breast cancer patients. Singapore Med J 1998; 39: 412–415.
    1. O'Hea BJ, Ho MN, Petrek JA. External compression dressing versus standard dressing after axillary lymphadenectomy. Am J Surg 1999; 177: 450–453.
    1. Cox S, Cole M, Mankarious S, Tawil N. Effect of tranexamic acid incorporated in fibrin sealant clots on the cell behavior of neuronal and nonneuronal cells. J Neurosci Res 2003; 72: 734–746.
    1. Lishko VK, Novokhatny VV, Yakubenko VP, Skomorovska‐Prokvolit HV, Ugarova TP. Characterization of plasminogen as an adhesive ligand for integrins alphaMbeta2 (Mac‐1) and alpha5beta1 (VLA‐5). Blood 2004; 104: 719–726.
    1. Peterson H, Sundbeck A. Mechanisms behind the inhibiting effect of tranexamic acid on tumour growth and spread In Metastasis Developments in Oncology, Hellman K, Hilgard P, Eccles S. (eds), vol. 4. Springer: Dordrecht, 1980.
    1. Eikebrokk TA, Vassmyr BS, Ausen K, Gravastrand C, Spigset O, Pukstad B. Cytotoxicity and effect on wound re‐epithelialization after topical administration of tranexamic acid. BJS Open 2019; 3: 840–851.
    1. Furtmüller R, Schlag MG, Berger M, Hopf R, Huck S, Sieghart W et al Tranexamic acid, a widely used antifibrinolytic agent, causes convulsions by a gamma‐aminobutyric acid(A) receptor antagonistic effect. J Pharmacol Exp Ther 2002; 301: 168–173.
    1. Pellegrini A, Giaretta D, Chemello R, Zanotto L, Testa G. Feline generalized epilepsy induced by tranexamic acid (AMCA). Epilepsia 1982; 23: 35–45.
    1. Schlag MG, Hopf R, Redl H. Convulsive seizures following subdural application of fibrin sealant containing tranexamic acid in a rat model. Neurosurgery 2000; 47: 1463–1467.
    1. Mahmoud K, Ammar A. Accidental intrathecal injection of tranexamic acid. Case Rep Anesthesiol 2012; 2012: 646028.

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