Does sugammadex suppress allergic inflammation due to rocuronium in animal model of rat?

Main Article Content

Serdar Yeşiltaş
Zeynep Nur Orhon
Hasan Cakır
Mahmut Dogru
Melek Gura Celik

Keywords

Anaphylaxis; inflammation; lung; rat; rocuronium; sugammadex

Abstract

Introduction and Objectives: There are a few reports in the literature about the successful use of sugammadex in the treatment of hypersensitivity reactions caused by rocuronium; however, the pathophysiological mechanism is still unknown. This study aims to investigate the changes caused by rocuronium in the lung and the effect of sugammadex on these changes with bio-chemical, light microscopic and immunohistochemical parameters on a rat model.
Materials and Methods: For the study, 28-male Sprague-Dawley rats were randomly divided, seven of each, into four groups. Group C (control) received only 0. 9 % NaCl without any drug. Group R received rocuronium alone 1mg/kg. Group S received sugammadex alone 96 mg/kg. Group RS received rocuronium 1mg/kg and sugammadex 96 mg/kg. After 24 h later, the ani-mals were sacrificed and their tissues were removed. Biochemical (IgE/CRP), light microscopic and immunohistochemical findings were recorded.
Results: Immunoglobulin E and CRP levels, peribronchial, alveolar septal lymphocytic infiltra-tion, thickening of the alveolar membranes and bleeding sites in Group R were significantly higher than all the other groups. In Group RS, while these parameters were significantly lower than that of Group R and Group S, it was significantly higher than that of Group C. Total mast cells and tryptase-positive mast cells counts were significantly higher in Group R than in all other groups. In Group RS, these parameters were statistically lower than that of Group R and Group S, but higher than that of Group C.
Conclusions: This study shows that allergic inflammatory changes due to rocuronium in the lungs of rats are reduced with sugammadex. These results support cases of anaphylaxis due to rocuronium which improved with sugammadex.

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References

1. Michavila Gomez AV, Belver Gonzalez MT, Alvarez NC, Giner Muñoz MT, Hernando Sastre V, Porto Arceo JA, Induráin BV. Drug allergy work group of the Spanish Society of Paediatric Allergy, Immunology (SEICAP) perioperative anaphylactic reactions: review and procedure protocol in paediatrics. Allergol Immunopathol (Madr). 2015;43(2):203-14. https://doi. org/10.1016/j.aller.2013.07.012.
2. Kemp HI, Cook TM, Thomas M, Harper NJN. UK anaesthetists’ perspectives and experiences of severe perioperative anaphylaxis: NAP6 baseline survey. Br J Anaesth. 2017;119(1):132-9. https://doi.org/10.1093/bja/aex124
3. Savic LC, Kaura V, Yusaf M, Hammond-Jones AM, Jackson R, Howell S, et al. Anaesthetic Audit and Research Matrix of Yorkshire. Incidence of suspected perioperative anaphylaxis: A multicenter snapshot study. J Allergy Clin Immunol Pract. 2015;3(3):454-5. https://doi.org/10.1016/j.jaip.2014.12.016
4. Dong SW, Mertes PM, Petitpain N, Hasdenteufel F, Malinovsky JM. GERAP. Hypersensitivity reactions during anesthesia. Results from the ninth French survey (2005-2007). Minerva Anestesiol. 2012;78(8):868-78.
5. Florvaag E, Johansson SG, Oman H, Venemalm L, Degerbeck F, Dybendal T, et al. Prevalence of IgE antibod-ies to morphine. Relation to the high and low incidences of NMBA anaphylaxis in Norway and Sweden, respectively. Acta Anaesthesiol Scand. 2005;49(4):437-44. https://doi. org/10.1111/j.1399-6576.2004.00591.x
6. Mirakhur RK. Safety aspects of non-depolarizing neuromuscular blocking agents with special reference to rocuronium bromide. Eur J Anaesthesiol Suppl. 1994;9:133-40.
7. Bevan DR. Newer neuromuscular blocking agents. Pharmacol Toxicol. 1994;74(1):3-9. https://doi.org/10.1111/j. 1600-0773.1994.tb01065.x
8. Sadleir PH, Clarke RC, Bunning DL, Platt PR. Anaphylaxis to neuromuscular blocking drugs: incidence and cross-reactivity in Western Australia from 2002 to 2011. Br J Anaesth. 2013;110(6):981-7. https://doi.org/10.1093/bja/aes506
9. Schaller SJ, Fink H. Sugammadex as a reversal agent for neuromuscular block: an evidence-based review. Core Evid. 2013;8:57-67. https://doi.org/10.2147/CE.S35675
10. Czarnetzki C, Tassonyi E, Lysakowski C, Elia N, Tramèr MR. Efficacy of sugammadex for the reversal of moderate and deep rocuronium-induced neuromuscular block in patients pretreated with intravenous magnesium: a randomized con-trolled trial. Anesthesiology. 2014;121(1):59-67. https://doi. org/10.1097/ALN.0000000000000204
11. McDonnell NJ, Pavy TJ, Green LK, Platt PR. Sugammadex in the management of rocuronium-induced anaphylaxis. Br J Anaesth. 2011;106(2):199-201. https://doi.org/10.1093/bja/aeq366
12. De La Cruz I, Errando C, Calaforra S. Treatment of anaphylaxis to rocuronium with sugammadex: a case report with bronchospasm as the only symptom. Turk J Anaesthesiol Reanim. 2019;47(1):69-72. https://doi.org/10.5152/TJAR.2019.21298
13. Kawano T, Tamura T, Hamaguchi M, Yatabe T, Yamashita K, Yokoyama M. Successful management of rocuronium-induced anaphylactic reactions with sugammadex: a case report. J Clin Anesth. 2012;24(1):62-4. https://doi.org/10.1016/j. jclinane.2011.04.015
14. Takazawa T, Tomita Y, Yoshida N, Tomioka A, Horiuchi T, Nagata C, Orihara M, et al. Three suspected cases of sugammadex-induced anaphylactic shock. BMC Anesthesiol. 2014;14:92. https://doi.org/10.1186/1471-2253-14-92
15. Min KC, Woo T, Assaid C, McCrea J, Gurner DM, Sisk CM, et al. Incidence of hypersensitivity and anaphylaxis with sugamma-dex. J Clin Anesth. 2018;47:67-73.https://doi.org/10.1016/j. jclinane.2018.03.018
16. Ho G, Clarke RC, Sadleir PH, Platt PR. The first case report of anaphylaxis caused by the inclusion complex of rocuronium and sugammadex. A A Case Rep. 20161;7(9):190-2. https://doi. org/10.1213/XAA.0000000000000382
17. Ebo DG, Baldo BA, Van Gasse AL, Mertens C, Elst J, Sermeus L, et al. Anaphylaxis to sugammadex-rocuronium inclusion complex: an IgE-mediated reaction due to allergenic changes at the sugammadex primary rim. J Allergy Clin Immunol Pract. 2020;8(4):1410-5. https://doi.org/10.1016/j.jaip.2019.11.018.
18. Tomak Y, Yılmaz A, Bostan H, Tümkaya L, Altuner D, Kalkan Y, et al. Effects of sugammadex and rocuronium mast cell number and degranulation in rat liver. Anaesthesia. 2012;67(10):1101-4. https://doi.org/10.1111/j.1365-2044.2012.07264.x
19. Kalkan Y, Tumkaya L, Bostan H, Tomak Y, Altuner D, Yilmaz A, et al. Effect of sugammadex on rocuronium induced changes in pancreatic mast cells. Toxicol Ind Health. 2015;31(8):738-46. https://doi.org/10.1177/0748233713484654
20. Elieh Ali Komi D, Wöhrl S, Bielory L. Mast cell biology at molecular level: a comprehensive review. Clin Rev Allergy Immunol. 2020;58(3):342-65. https://doi.org/10.1007/s12016-019-08769-2.
21. McNeil HP, Gotis-Graham I. Human mast cell subsets--distinct functions in inflammation? Inflamm Res. 2000;49(1):3-7. https://doi.org/10.1007/PL00012386
22. Schwartz LB. Mast cells and their role in urticaria. J Am Acad Dermatol. 1991;25:190-203; 203-4. https://doi.org/10.1016/ S0190-9622(08)80468-9
23. Baronos S, Selvaraj BJ, Liang M, Ahmed K, Yarmush J. Sugammadex-induced bronchospasm during desflurane anaesthesia. Br J Anaesth. 2019;123(1):e155-6. https://doi. org/10.1016/j.bja.2019.04.001
24. Clarke RC, Sadleir PH, Platt PR. The role of sugammadex in the development and modification of an allergic response to rocuronium: evidence from a cutaneous model. Anaesthesia. 2012;67(3):266-73. https://doi. org/10.1111/j.1365-2044.2011.06995.x
25. Leysen J, Bridts CH, De Clerck LS, Ebo DG. Rocuronium-induced anaphylaxis is probably not mitigated by sugammadex: evidence from an in vitro experiment. Anaesthesia. 2011;66(6):526-7. https://doi.org/10.1111/j.1365-2044.2011.06729.x
26. Hakozaki T, Murakawa M. Rocuronium-induced anaphylaxis not improved by low dose sugammadex: a case report. Anaesth Intensive Care. 2016;44(4):522. https://doi. org/10.1177/0310057X1604400411
27. Barthel F, Stojeba N, Lyons G, Biermann C, Diemunsch P. Sugammadex in rocuroniumanaphylaxis: dosematters. Br J Anaesth. 2012;109(4):646-7. https://doi.org/10.1093/bja/ aes332
28. Platt PR, Clarke RC, Johnson GH, Sadleir PH. Efficacy of sugammadex in rocuronium-induced or antibiotic-induced ana-phylaxis. A case-control study. Anaesthesia. 2015;70(11):1264-7. https://doi.org/10.1111/anae.13178
29. Baldo BA. Anaphylaxis caused by sugammadex-rocuronium inclusion complex: What is the basis of the allergenic recognition? J Clin Anesth. 2019;54:48-9. https://doi.org/10.1016/j.jclinane.2018.10.017