Tranexamic Acid in the Management of the Post Adeno-Tonsillectomy Phase

Objective: To evaluate if oral Tranexamic Acid can decrease the proportion of individuals with secondary bleeding in the post-operative adeno-tonsillectomy phase. Study design: Observational, retrospective epidemiological study. Setting: San Francesco Hospital, Nuoro, Italy Patients and methods: Over 20 months 236 children underwent elective adeno-tonsillectomy for chronic tonsillitis and/or otitis media and/or adenotonsillar hypertrophy. Two groups of patients were identified: the first one included 149 patients who took oral Tranexamic Acid (20 mg/Kg daily) for 10 days in the postoperative period, whereas the second one was characterized by 87 patients who did not take Tranexamic Acid. Results: Only 6/236 (2.54%) cases of secondary bleeding were reported; 3/149 (2.01%) belonged to the group taking Tranexamic Acid, whereas 3/87 (3.44%; p-value: 0.5) belonged to the group not exposed to Tranexamic Acid. They were admitted and followed-up for 48 hours; no surgical interventions were performed. Conclusion: Oral Tranexamic Acid did not significantly decrease the proportion of post-adenotonsillectomy bleeding episodes in our cohort. New prospective, randomized, controlled trials are needed to test the effectiveness of that drug in the management of post-adenotonsillectomy hemorrhages episodes. ABBREVIATIONS SD: Standard Deviation; COM: Chronic Otitis Media; TA: Tranexamic Acid INTRODUCTION Tranexamic acid (TA) is a drug used for treating and preventing bleeding [1]. TA is a synthetic derivative of the amino acid lysine [2]. It is an antifibrinolytic that competitively inhibits the activation of plasminogen to plasmin, a molecule responsible for the degradation of fibrin, by binding to specific sites of both plasminogen and plasmin [2]. The latter molecule is a protein that forms the framework of blood clots [2]. TA is frequently used in surgical interventions characterized by a high risk of blood loss such as in cardiac [3], vascular [4], liver [5], and large orthopedic procedures [6]. It is estimated that hemorrhages occur in 2-5% [7,8] of the patients following a tonsillectomy, representing the most common and serious complication [9]. While the majority of those events are self-limiting, a minority needs to be surgically treated [8]. Although extremely rare, sudden severe hemorrhage may occur and can result in death [10-12]. Post tonsillectomy mortality ranges from 1 per 10.000 individuals [10] to 1 per 28.000 [12], with approximately 16% caused by hemorrhages [9, 10,12]. Several methods has been used to prevent and reduce the frequency and the amount of bleeding during and after adenotonsillectomy procedures (e.g., diathermy [13], noose tie [14], ultrasonic armonic scalpel [15] and drugs such as TA [16Central Pittore et al. (2015) Email: Ann Otolaryngol Rhinol 2(9): 1060 (2015) 2/4 20]). The role of TA in the management of hemorrhages is still controversial, as discussed by Chan CC et al in a recent systematic review and meta-analysis [21]. Aim of this study was to retrospectively compare a group of pediatric patients who post-operatively took TA with a second group of children who did not take TA, in order to evaluate a proportional difference in terms of post-operative bleeding. MATERIALS AND METHODS Between January 2012 and September 2013, 236 pediatric patients underwent elective adeno-tonsillectomy for chronic tonsillitis and/or otitis media and/or adenotonsillar hypertrophy at the Otorhinolaryngology Department of the San Francesco Hospital, Nuoro, Italy. The patients were classified into two groups; the first one included 149 patients who took orally TA (dosage: 10 mg/Kg twice daily) for 10 days in the post-operative period, whereas the second group of 87 patients was not treated with TA. Oral antibiotics were prescribed to all individuals consecutively selected for this observational study (amoxicillin+ clavulanic acid; in case of allergy to penicillin clarithromycin was administered) for the first 10 days following the surgical procedure; in addition they were treated with paracetamol for analgesia. Pre-operative evaluation included an otolaryngologist examination consisting of anterior and posterior rhinoscopy with a flexible nasendoscope to assess the grade of adenoid hypertrophy, tympanometry, baseline bloods, electrocardiography and anesthesiological assessment. Exclusion criteria for surgical intervention were: previous history of bleeding or spontaneous hematoma, altered coagulation tests, evidence of hematopoietic, cardiovascular, hepatic, renal, neurologic, psychiatric or auto-immune diseases. All 236 patients underwent tonsillectomy by bipolar diathermy technique (using 20-25 Watt) connected to an irrigation system (0.45% saline solution) to decrease the diathermy injury in the tonsillar bed. Of the 236 adenoidectomies, 55 were performed endoscopically (0° degree 2.7-4 mm rigid scope [Karl Storz] with a 1188 Hight Definition camera [Stryker] and a Vision elect HD monitor [Stryker]) using adenotome, and 181 were performed traditionally by mouth using adenotome, curette and Juracz forceps. In both cases the hemostasis was controlled with an angled bipolar (20-25 Watt). Analysis Descriptive analysis of the demographic, epidemiological, and clinical variables was carried out (tables 4). Variables were collected using an ad-hoc electronic-form. Fisher exact test was performed to statistically compare differences between those treated with TA VS. those non treated with TA. STATA statistical software (Stata Corp, Stata Statistical Software Release 9, College Station, TX, USA, 2005) was used to carry out descriptive and inferential analyses. Table 1: Demographic, epidemiological and clinical characteristics of 236 Sardinian children. Variables Age, mean (SD), years 5.1 (2.1) Male, n (%) 138 (58.5) Adenoid/tonsil hypertrophy, n (%) 165 (69.9) Surgical intervention: endoscopic adeno-tonsillectomy, n (%) 55 (23.3) Allergy to penicillin, n (%) 2 (66.7) Post-surgical intervention antibiotic therapy, n (%) 87 (36.9) Primary bleeding, n (%) 3 (1.3) Secondary bleeding, n (%) 6 (2.5) Occurrence of the secondary bleeding, mean (SD), days 10.7 (2.7) Duration of the surgical intervention, mean (SD), minutes 40.6 (14.1) Abbreviations: SD: Standard Deviation Table 2: Demographic, epidemiological and clinical characteristics of 236 Sardinian children, stratified by gender. Variables Female Male p-value Age, mean (SD), years 5.3 (2.0) 5.1 (2.2) 0.54 Adenoid/tonsil hypertrophy, n (%) 70 (71.4) 95 (68.8) 0.67 Allergy to penicillin, n (%) 0 (0.0) 2 (100.0) 0.08 Post-surgical intervention antibiotic therapy, n (%) 61 (62.2) 88 (63.8) 0.81 Primary bleeding, n (%) 1 (1.0) 2 (1.5) 0.08 Secondary bleeding, n (%) 1 (1.0) 5 (3.6) 0.21 Occurrence of the secondary bleeding, mean (SD), days 8 (0.0) 11.2 (2.6) Duration of the surgical intervention, mean (SD), minutes 40.7 (15.6) 40.6 (13.1) 0.92 Central Pittore et al. (2015) Email: Ann Otolaryngol Rhinol 2(9): 1060 (2015) 3/4 Table 3: Demographic, epidemiological and clinical characteristics of 236 Sardinian children, stratified by diagnosis. Variables Adenoid/tonsil hypertrophy Adenoid/tonsil hypertrophy + COM p-value Age, mean (SD), years 5.4 (2.2) 4.6 (2.0) 0.005 Male, n (%) 95 (57.6) 43 (60.6) 0.67 Allergy to penicillin, n (%) 1 (100.0) 1 (50.0) 0.39 Post-surgical intervention antibiotic therapy, n (%) 101 (61.2) 48 (67.6) 0.35 Primary bleeding, n (%) 2 (1.2) 1 (1.4) 0.90 Secondary bleeding, n (%) 5 (3.0) 1 (1.4) 0.47 Occurrence of the secondary bleeding, mean (SD), days 10.8 (3.0) 10.0 (0.0) Duration of the surgical intervention, mean (SD), minutes 37.1 (13.7) 48.6 (11.8) <0.001 Abbreviations: SD: Standard Deviation; COM: Chronic Otitis Media Table 4: Demographic, epidemiological and clinical characteristics of 236 Sardinian children, stratified by post-surgical therapy. Variables Antibiotics + TA Antibiotics p-value Age, mean (SD), years 5.2 (2.2) 5.1 (2.0) 0.87 Male, n (%) 88 (59.1) 50 (57.5) 0.81 Allergy to penicillin, n (%) 0 (0.0) 2 (100.0) 0.08 Adenoid/tonsil hypertrophy, n (%) 101 (67.8) 64 (73.6) 0.35 Primary bleeding, n (%) 3 (2.0) 0 (0.0) 0.18 Secondary bleeding, n (%) 3 (2.0) 3 (3.5) 0.50 Occurrence of the secondary bleeding, mean (SD), days 12.0 (2.7) 9.3 (2.3) 0.26 Duration of the surgical intervention, mean (SD), minutes 38.8 (13.7) 43.7 (14.4) 0.009 Abbreviations: SD: Standard Deviation; TA: Tranexamic Acid RESULTS AND DISCUSSION Out of 236 adeno-tonsillectomies only 6 cases of secondary bleeding (2.54%) were diagnosed; 3/149 (2.01%) were in the group treated with TA and 3/87 (3.44%) in the second group not exposed to TA (Tables 1-4). They were admitted and followedup for 48 hours; however, a new surgical intervention was not needed to manage any bleeding episodes. Before their discharge, they started TA, which was administered for ten days. No major or minor adverse events attributable to TA were noted. There was no statistically significant reduction in the rate of bleeding between the two groups of patients (p-value=0.5) DISCUSSION Bleeding is the main complication in otorhinolaryngological surgery, in particular in oral and nasal surgery [22, 23]. Adenotonsillectomy is a common Ear Nose Throat surgical procedure. Despite technological advances of surgical techniques [17], bleeding due to tonsillectomy still remains the major cause of morbidity associated with the above-mentioned procedure [9]. Only a few papers described the role of TA in the post adenotonsillectomy phase; it is interesting to note that the application of TA varied in the mode of delivery, dosage and timing of administration [18-20]. Chan CC et al in their systematic review and meta-analysis included seven papers of potentially relevant impact in our study [22]. It was proved that TA significantly reduced the mean blood loss, but it did not significantly decrease the risk of post-tonsillectomy bleeding [21]. Castelli G et al [18] conducted a randomized study showing statistically significant reduction of blood loss during the operation and in the post surgical period after the administration of TA. George A et al [19] evaluated the efficacy of intra-venous TA prescription in the pre-operative phase: they demonstrated a statistically significant bleeding reduction; on the other hand, following the same study design, Brum MR et al [20] did not prove the effectiveness of TA. In our cohort TA was used orally in the post-operative phase for a period of 10 days: the decreased rate of secondary hemorrhages in those exposed to TA was not statistically significant if compared with the group not treated with TA. Unfortunately, it was not possible to evaluate the amount of blood loss in our cohort. TA can also be used topically as described by Albirmawy OA et al [21]. On the basis of the current scientific evidence, it can be stated that the use of TA to prevent and reduce the frequency of bleeding episodes after adeno-tonsillectomy is still controversial. CONCLUSION We found no statistically significant differences in the proportions of bleeding between those pediatric patients taking and not taking TA orally. Therefore, further prospective, randomized, controlled studies are required to better understand the role of TA in preventing secondary hemorrhages in adenotonsillectomy. Central Pittore et al. (2015) Email: Ann Otolaryngol Rhinol 2(9): 1060 (2015) 4/4 (2015) Tranexamic Acid in the Management of the Post Adeno-Tonsillectomy Phase. Ann Otolaryngol Rhinol 2(9): 1060. Cite this article ACKNOWLEDGEMENTS Thank you to Ms Lisa Fraser who presented this study at the International Congress of the European Society of Pediatric Otorhinolaryngology (ESPO), 31 May-03 June 2014, Ireland, Dublin.