Central Annals of Otolaryngology and Rhinology

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

*Corresponding authorBarbara Pittore, Otorhinolaryngology Department, C.T.O, Hospital, Via Cattaneo, 09016 Iglesias, Italy, Tel: 39-338-9658-541; Fax: 39-0781-392-2675; E

Submitted: 12 August 2015

Accepted: 28 August 2015

Published: 31 August 2015

Copyright© 2015 Pittore et al.

OPEN ACCESS

Keywords•Tonsillectomy•Tranexamic Acid•Morbidity•Bleeding

Research Article

Tranexamic Acid in the Management of the Post Adeno-Tonsillectomy PhaseBarbara Pittore1*, Carlo Loris Pelagatti2, Lisa Fraser3, Mauro Cau2, Francesco Deiana2, and Giovanni Sotgiu4

1Department of Otorhinolaryngology, C.T.O Hospital, Italy2Department of Otorhinolaryngology, S. Francesco Hospital, Italy3Department of Otorhinolaryngology, University Hospital Southampton NHS Foundation Trust, UK4Department of Biomedical Sciences, University of Sassari-Research, Medical Education 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.

ABBREVIATIONSSD: Standard Deviation; COM: Chronic Otitis Media; TA:

Tranexamic Acid

INTRODUCTIONTranexamic 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 adeno-tonsillectomy procedures (e.g., diathermy [13], noose tie [14], ultrasonic armonic scalpel [15] and drugs such as TA [16-

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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 METHODSBetween 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

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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 DISCUSSIONOut 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 followed-up 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)

DISCUSSIONBleeding is the main complication in otorhinolaryngological

surgery, in particular in oral and nasal surgery [22, 23]. Adeno-tonsillectomy 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 adeno-tonsillectomy 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.

CONCLUSIONWe 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.

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(2015) Tranexamic Acid in the Management of the Post Adeno-Tonsillectomy Phase. Ann Otolaryngol Rhinol 2(9): 1060.

Cite this article

ACKNOWLEDGEMENTSThank 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.

REFERENCES1. Dunn CJ, Goa KL. Tranexamic acid: a review of its use in surgery and

other indications. Drugs. 1999; 57: 1005-1032.

2. Longstaff C. Studies on the mechanisms of action of aprotinin and tranexamic acid as plasmin inhibitors and antifibrinolytic agents. Blood Coagul Fibrinolysis. 1994; 5: 537-542.

3. Grassin-Delyle S, Couturier R, Abe E, Alvarez JC, Devillier P, Urien S. A practical tranexamic acid dosing scheme based on population pharmacokinetics in children undergoing cardiac surgery. Anesthesiology. 2013; 118: 853-862.

4. Esfandiari BR, Bistgani MM, Kabiri M. Low dose tranexamic acid effect on post-coronary artery bypass grafting bleeding. Asian Cardiovasc Thorac Ann. 2013; 21: 669-674.

5. Makwana J, Paranjape S, Goswami J. Antifibrinolytics in liver surgery. Indian J Anaesth. 2010; 54: 489-495.

6. Martin JG, Cassatt KB, Kincaid-Cinnamon KA, Westendorf DS, Garton AS, Lemke JH3. Topical administration of tranexamic acid in primary total hip and total knee arthroplasty. J Arthroplasty. 2014; 29: 889-894.

7. Sarny S, Ossimitz G, Habermann W, Stammberger H. Hemorrhage following tonsil surgery: a multicenter prospective study. Laryngoscope. 2011; 121: 2553-2560.

8. Bhattacharyya N, Kepnes LJ. Revisits and postoperative hemorrhage after adult tonsillectomy. Laryngoscope. 2014; 124: 1554-1556.

9. Goldman JL, Baugh RF, Davies L, Skinner ML, Stachler RJ, Brereton J, et al. Mortality and major morbidity after tonsillectomy: etiologic factors and strategies for prevention. Laryngoscope. 2013; 123: 2544-2553.

10. Alexander DW, Graff TD, Kelley E. Factors in tonsillectomy mortality. Arch Otolaryngol. 1965; 82: 409-411.

11. Davies DD. Anaesthetic mortality in tonsillectomy and adenoidectomy. Br J Anaesth. 1964; 36: 110-114.

12. Aydin S, Taskin U, Altas B, Erdil M, Senturk T, Celebi S, Oktay MF. Post-tonsillectomy morbitities: a randomized, prospective controlled

clinical trial of cold dissection versus thermal welding tonsillectomy. J Laryngol Otol 2014; 128: 163-165.

13. Sharp JF, Rogers MJ, Riad M, Kerr AI. Combined study to assess the role of calcium alginate swabs and ligation of the inferior tonsillar pole in the control of intra-operative blood loss during tonsillectomy. J Laryngol Otol. 1991; 105: 191-194.

14. Sood S, Corbridge R, Powles J, Bates G, Newbegin CJ. Effectiveness of the ultrasonic harmonic scalpel for tonsillectomy. Ear Nose Throat J. 2001; 80: 514-516, 518.

15. Vitale W. Initial notes on the use of AMCHA (trans-4-aminomethylcyclohexancarbonic acid) in otorhinolaryngologic surgery. Minerva Otorinolaringol. 1971; 21: 224-228.

16. Mazauric FX, Boudon A, Rheingold C. [Value of tranexamic acid in extracapsular tonsillectomy in adults]. JFORL J Fr Otorhinolaryngol Audiophonol Chir Maxillofac. 1973; 22: 165-168.

17. Falbe-Hansen J Jr, Jacobsen B, Lorenzen E. Local application of an antifibrinolytic in tonsillectomy. A double-blind study. J Laryngol Otol. 1974; 88: 565-568.

18. Castelli G, Vogt E. [Result of an antifibrinolytic treatment using tranexamic acid for the reduction of blood-loss during and after tonsillectomy]. Schweiz Med Wochenschr. 1977; 107: 780-784.

19. George A, Kumar R, Kumar S, Shetty S. A randomized control trial to verify the efficacy of pre-operative intra venous tranexamic Acid in the control of tonsillectomy bleeding. Indian J Otolaryngol Head Neck Surg. 2011; 63: 20-26.

20. Brum MR, Miura MS, Castro SF, Machado GM, Lima LH, Lubianca Neto JF. Tranexamic acid in adenotonsillectomy in children: a double-blind randomized clinical trial. Int J Pediatr Otorhinolaryngol. 2012; 76: 1401-1405.

21. Albirmawy OA, Saafan ME, Shehata EM, Basuni AS, Eldaba AA. Topical application of tranexamic acid after adenoidectomy: a double-blind, prospective, randomized, controlled study. Int J Pediatr Otorhinolaryngol. 2013; 77: 1139-1142.

22. Chan CC, Chan YY, Tanweer F. Systematic review and meta-analysis of the use of tranexamic acid in tonsillectomy. Eur Arch Otorhinolaryngol. 2013; 270: 735-748.

23. Krings JG, Kallogjeri D, Wineland A, Nepple KG, Piccirillo JF, Getz AE. Complications of primary and revision functional endoscopic sinus surgery for chronic rhinosinusitis. Laryngoscope 2014, 124; 838-845.