Efficacy and safety of preoperative preparation with Lugol's iodine solution in euthyroid patients with Graves' disease (LIGRADIS Trial): Study protocol for a multicenter randomized trial
José Luis Muñoz de Nova, Guzmán Franch-Arcas, Gina Paola Mejía-Abril, María Eugenia Flores-Ruiz, Nuria Muñoz-Pérez, Elena Pintos-Sánchez, Francisco Javier Guadarrama González, Álvaro Valdés de Anca, Enrique Mercader-Cidoncha, Aitor de la Quintana-Basarrate, Irene Osorio-Silla, Susana Ros-López, Lander Gallego-Otaegui, Elena Santos-Molina, Concepción Martínez-Nieto, Elena Gamborino-Caramés, Mariano Artés-Caselles, Leyre Lorente-Poch, Maitane García-Carrillo, Pablo Moreno-Llorente, Consuelo Marín-Velarde, Joaquín Ortega-Serrano, Juan Manuel Martos-Martínez, Oscar Vidal-Pérez, Patricia Luengo-Pierrard, Jesús María Villar-Del-Moral, José Luis Muñoz de Nova, Guzmán Franch-Arcas, Gina Paola Mejía-Abril, María Eugenia Flores-Ruiz, Nuria Muñoz-Pérez, Elena Pintos-Sánchez, Francisco Javier Guadarrama González, Álvaro Valdés de Anca, Enrique Mercader-Cidoncha, Aitor de la Quintana-Basarrate, Irene Osorio-Silla, Susana Ros-López, Lander Gallego-Otaegui, Elena Santos-Molina, Concepción Martínez-Nieto, Elena Gamborino-Caramés, Mariano Artés-Caselles, Leyre Lorente-Poch, Maitane García-Carrillo, Pablo Moreno-Llorente, Consuelo Marín-Velarde, Joaquín Ortega-Serrano, Juan Manuel Martos-Martínez, Oscar Vidal-Pérez, Patricia Luengo-Pierrard, Jesús María Villar-Del-Moral
Abstract
Background: Currently, both the American Thyroid Association and the European Thyroid Association recommend preoperative preparation with Lugol's Solution (LS) for patients undergoing thyroidectomy for Graves' Disease (GD), but their recommendations are based on low-quality evidence. The LIGRADIS trial aims to provide evidence either to support or refute the systematic use of LS in euthyroid patients undergoing thyroidectomy for GD.
Methods: A multicenter randomized controlled trial will be performed. Patients ≥18 years of age, diagnosed with GD, treated with antithyroid drugs, euthyroid and proposed for total thyroidectomy will be eligible for inclusion. Exclusion criteria will be prior thyroid or parathyroid surgery, hyperparathyroidism that requires associated parathyroidectomy, thyroid cancer that requires adding a lymph node dissection, iodine allergy, consumption of lithium or amiodarone, medically unfit patients (ASA-IV), breastfeeding women, preoperative vocal cord palsy and planned endoscopic, video-assisted or remote access surgery.Between January 2020 and January 2022, 270 patients will be randomized for either receiving or not preoperative preparation with LS. Researchers will be blinded to treatment assignment. The primary outcome will be the rate of postoperative complications: hypoparathyroidism, recurrent laryngeal nerve injury, hematoma, surgical site infection or death. Secondary outcomes will be intraoperative events (Thyroidectomy Difficulty Scale score, blood loss, recurrent laryngeal nerve neuromonitoring signal loss), operative time, postoperative length of stay, hospital readmissions, permanent complications and adverse events associated to LS.
Conclusions: There is no conclusive evidence supporting the benefits of preoperative treatment with LS in this setting. This trial aims to provide new insights into future Clinical Practice Guidelines recommendations.
Trial registration: ClinicalTrials.gov identifier: NCT03980132.
Keywords: Graves' disease; Hyperthyroidism; Lugol's solution; Thyroid surgery.
Conflict of interest statement
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:
© 2021 The Authors. Published by Elsevier Inc.
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References
- Kahaly G.J., Bartalena L., Hegedüs L., Leenhardt L., Poppe K., Pearce S.H. 2018 European thyroid association guideline for the management of graves' hyperthyroidism. Eur. Thyroid J. 2018;7(4):167–186.
- Zw L., Masterson L., Fish B., Jani P., Chatterjee K. Thyroid surgery for Graves ’ disease and Graves ’ ophthalmopathy. Cochrane Database Syst. Rev. 2015;25:CD010576.
- Plummer H.S. Results of administering iodine to patients having exophtalmic goiter. J. Am. Med. Assoc. 1923;80:1955.
- Whalen G., Sullivan M., Maranda L., Quinlan R., Larkin A. Randomized trial of a short course of preoperative potassium iodide in patients undergoing thyroidectomy for Graves' disease. Am. J. Surg. 2017;213(4):805–809.
- Yilmaz Y., Kamer K.E., Ureyen O., Sari E., Acar T., Karahalli O. The effect of preoperative Lugol's iodine on intraoperative bleeding in patients with hyperthyroidism. Ann. Med. Surg. 2016;9:53–57.
- Erbil Y., Ozluk Y., Giriş M., Salmaslioglu A., Issever H., Barbaros U. Effect of lugol solution on thyroid gland blood flow and microvessel density in the patients with Graves' disease. J. Clin. Endocrinol. Metab. 2007;92(6):2182–2189.
- Kaur S., Parr J.H., Ramsay I.D., Hennebry T.M., Jarvis K.J., Lester E. Effect of preoperative iodine in patients with Graves' disease controlled with antithyroid drugs and thyroxine. Ann. R. Coll. Surg. Engl. 1988;70(3):123–127.
- Coyle P.J., Mitchell J.E. Thyroidectomy: is Lugol's iodine necessary? Ann. R. Coll. Surg. Engl. 1982;64(5):334–335.
- Randle R.W., Bates M.F., Long K.L., Pitt S.C., Schneider D.F., Sippel R.S. Impact of potassium iodide on thyroidectomy for Graves' disease: implications for safety and operative difficulty. Surgery. 2018;163(1):68–72.
- Tsai C.-H., Kuo C.-Y., Yang P.-S., Cheng S.-P., Liu T.-P., Lee J.-J. Effects of preoperative iodine administration on thyroidectomy for hyperthyroidism: a systematic review and meta-analysis. Otolaryngol. Head Neck Surg. 2019;160(6):993–1002.
- Ross D.S., Burch H.B., Cooper D.S., Greenlee M.C., Laurberg P., Maia A.L. 2016 American thyroid association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016;26(10):1343–1421.
- Bartalena L., Burch H.B., Burman K.D., Kahaly G.J.A. 2013 European survey of clinical practice patterns in the management of Graves' disease. Clin. Endocrinol. 2016;84(1):115–120.
- Schneider D.F., Mazeh H., Oltmann S.C., Chen H., Sippel R.S. Novel thyroidectomy difficulty scale correlates with operative times. World J. Surg. 2014;38(8):1984–1989.
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