Central Annals of Otolaryngology and Rhinology

Research Article *Corresponding author Barbara Pittore, Otorhinolaryngology Department, C.T.O, Hospital, Via Cattaneo, 09016 Iglesias, Italy, Tranexamic Acid in the Tel: 39-338-9658-541; Fax: 39-0781-392-2675; E

Submitted: 12 August 2015 Management of the Post Adeno- Accepted: 28 August 2015 Published: 31 August 2015 Tonsillectomy Phase Copyright © 2015 Pittore et al. Barbara Pittore1*, Carlo Loris Pelagatti2, Lisa Fraser3, Mauro Cau2, Francesco Deiana2, and Giovanni Sotgiu4 OPEN ACCESS 1 Department of Otorhinolaryngology, C.T.O Hospital, Italy Keywords 2 Department of Otorhinolaryngology, S. Francesco Hospital, Italy • Tonsillectomy 3 Department of Otorhinolaryngology, University Hospital Southampton NHS Foundation • Tranexamic Acid Trust, UK • Morbidity 4 Department of Biomedical Sciences, University of Sassari-Research, Medical Education • Bleeding and Professional Development, Ital

Abstract 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 post- operative 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 vascular [4], liver [5], and large orthopedic procedures [6]. SD: Standard Deviation; COM: Chronic Otitis Media; TA: It is estimated that hemorrhages occur in 2-5% [7,8] of Tranexamic Acid the patients following a tonsillectomy, representing the most common and serious complication [9]. While the majority of INTRODUCTION those events are self-limiting, a minority needs to be surgically Tranexamic acid (TA) is a drug used for treating treated [8]. Although extremely rare, sudden severe hemorrhage and preventing bleeding [1]. TA is a synthetic derivative of the may occur and can result in death [10-12]. Post tonsillectomy mortality ranges from 1 per 10.000 individuals [10] to 1 per inhibits the activation of plasminogen to plasmin, a molecule 28.000 [12], with approximately 16% caused by hemorrhages [9, amino acid lysine [2]. It is an antifibrinolytic that competitively 10,12]. sites of both plasminogen and plasmin [2]. Several methods has been used to prevent and reduce the responsible for the degradation of fibrin, by binding to specific The latter molecule is a protein that forms the framework of frequency and the amount of bleeding during and after adeno- blood clots [2]. TA is frequently used in surgical interventions tonsillectomy procedures (e.g., diathermy [13], noose tie [14], characterized by a high risk of blood loss such as in cardiac [3], ultrasonic armonic scalpel [15] and drugs such as TA [16-

Cite this article: (2015) Tranexamic Acid in the Management of the Post Adeno-Tonsillectomy Phase. Ann Otolaryngol Rhinol 2(9): 1060. Pittore et al. (2015) Email: Central

20]). The role of TA in the management of hemorrhages is still tympanometry, baseline bloods, electrocardiography and controversial, as discussed by Chan CC et al in a recent systematic anesthesiological assessment. review and meta-analysis [21]. Exclusion criteria for surgical intervention were: previous Aim of this study was to retrospectively compare a group of history of bleeding or spontaneous hematoma, altered pediatric patients who post-operatively took TA with a second coagulation tests, evidence of hematopoietic, cardiovascular, group of children who did not take TA, in order to evaluate a hepatic, renal, neurologic, psychiatric or auto-immune diseases. proportional difference in terms of post-operative bleeding. All 236 patients underwent tonsillectomy by bipolar MATERIALS AND METHODS diathermy technique (using 20-25 Watt) connected to an irrigation system (0.45% saline solution) to decrease the Between January 2012 and September 2013, 236 pediatric diathermy injury in the tonsillar bed. Of the 236 adenoidectomies, patients underwent elective adeno-tonsillectomy for chronic 55 were performed endoscopically (0° degree - 2.7-4 mm rigid tonsillitis and/or otitis media and/or adenotonsillar hypertrophy at the Otorhinolaryngology Department of the San Francesco and a Vision elect HD monitor [Stryker]) using adenotome, and Hospital, Nuoro, Italy. 181scope were [Karl performed Storz] with traditionally a 1188 Hight by Definition mouth using camera adenotome, [Stryker] curette and Juracz forceps. In both cases the hemostasis was included 149 patients who took orally TA (dosage: 10 mg/Kg controlled with an angled bipolar (20-25 Watt). twiceThe daily) patients for 10 were days classified in the post-operative into two groups; period, the first whereas one Analysis the second group of 87 patients was not treated with TA. Oral antibiotics were prescribed to all individuals consecutively Descriptive analysis of the demographic, epidemiological, selected for this observational study (amoxicillin+ clavulanic acid; and clinical variables was carried out (tables 4). Variables were in case of allergy to penicillin clarithromycin was administered) collected using an ad-hoc electronic-form. Fisher exact test was performed to statistically compare differences between those they were treated with paracetamol for analgesia. treated with TA VS. those non treated with TA. STATA statistical for the first 10 days following the surgical procedure; in addition software (Stata Corp, Stata Statistical Software Release 9, College Pre-operative evaluation included an otolaryngologist Station, TX, USA, 2005) was used to carry out descriptive and examination consisting of anterior and posterior rhinoscopy with a inferential analyses. flexible nasendoscope to assess the grade of adenoid hypertrophy, 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:

VariablesDemographic, epidemiological and clinical characteristics of 236 Sardinian children,Female stratified by gender.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

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Table 3: Adenoid/tonsil Adenoid/tonsil VariablesDemographic, epidemiological and clinical characteristics of 236 Sardinian children, stratified by diagnosis. p-value hypertrophy hypertrophy + COM 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:

VariablesDemographic, epidemiological and clinical characteristics of 236Antibiotics Sardinian +children, TA stratified byAntibiotics post-surgical therapy. 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 the risk of post-tonsillectomy bleeding [21]. Castelli G et al [18] Out of 236 adeno-tonsillectomies only 6 cases of secondary reduced the mean blood loss, but it did not significantly decrease bleeding (2.54%) were diagnosed; 3/149 (2.01%) were in the reduction of blood loss during the operation and in the post group treated with TA and 3/87 (3.44%) in the second group not surgicalconducted period a randomized after the studyadministration showing statistically of TA. George significant A et al exposed to TA (Tables 1-4). They were admitted and followed- up for 48 hours; however, a new surgical intervention was not needed to manage any bleeding episodes. Before their discharge, bleeding[19] evaluated reduction; the efficacy on the ofother intra-venous hand, following TA prescription the same instudy the they started TA, which was administered for ten days. design,pre-operative Brum MRphase: et al they [20] demonstrated did not prove a the statistically effectiveness significant of TA. No major or minor adverse events attributable to TA were In our cohort TA was used orally in the post-operative phase for a noted. period of 10 days: the decreased rate of secondary hemorrhages bleeding between the two groups of patients (p-value=0.5) compared with the group not treated with TA. Unfortunately, There was no statistically significant reduction in the rate of itin was those not exposedpossible to to evaluate TA was the not amount statistically of blood significant loss in our if DISCUSSION cohort. TA can also be used topically as described by Albirmawy Bleeding is the main complication in otorhinolaryngological OA et al [21]. surgery, in particular in oral and nasal surgery [22, 23]. Adeno- tonsillectomy is a common Ear Nose Throat surgical procedure. that the use of TA to prevent and reduce the frequency of bleeding Despite technological advances of surgical techniques [17], episodesOn the after basis adeno-tonsillectomy of the current scientific is still evidence, controversial. it can be stated bleeding due to tonsillectomy still remains the major cause of morbidity associated with the above-mentioned procedure [9]. CONCLUSION Only a few papers described the role of TA in the post adeno- tonsillectomy phase; it is interesting to note that the application proportions of bleeding between those pediatric patients of TA varied in the mode of delivery, dosage and timing of takingWe and found not taking no statistically TA orally. significantTherefore, further differences prospective, in the administration [18-20]. Chan CC et al in their systematic review randomized, controlled studies are required to better and meta-analysis included seven papers of potentially relevant understand the role of TA in preventing secondary hemorrhages in adenotonsillectomy. impact in our study [22]. It was proved that TA significantly Ann Otolaryngol Rhinol 2(9): 1060 (2015) 3/4 Pittore et al. (2015) Email: Central

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