RUKİYE TÜRK, SEMRA KAYA, İlksen DÖNMEZ, İSA ÖZAYDIN, OĞUZ MERHAN, Sadık YAYLA, Celal Şahin ERMUTLU, CİHAN KAÇAR, Uğur AYDIN, ÖZGÜR AKSOY, Ürfettin HÜSEYİNOĞLU

The Effect of Rocuronium and Sugammadex on Progesterone Levels in Pregnant Rabbits Under General Anesthesia

The purpose of this study was to investigate the effect of rocuronium and sugammadex on progesterone (P4) levels in pregnant rabbits under general anesthesia. Twenty-one pregnant New Zealand rabbits were used in the study. After the rabbits were divided into three groups of three (Control, Group I and Group II), each animal was given 0.5 mg/kg midazolam and 6 mg/kg propofol and then put under general anesthesia with sevoflurane on the 21st day of pregnancy. No procedure was performed on the control group apart from anesthesia. Rocuronium was administered to GI at the onset of anesthesia, and in GII, sugammadex was administered 60 min after general anesthesia + rocuronium. All of the rabbits were monitored during the anesthesia procedure. A sample of venous blood was taken and biochemically analyzed to test P4 levels. The administration of rocuronium was determined to have caused an increase in the serum progesterone level in all recorded min. Sugammadex was found to cause a quantitative decrease in the level of progesterone. In conclusion, it was found out that rocuronium and sugammadex administration did not have a negative effect on progesterone levels in pregnant rabbits receiving general anesthesia.

Genel Anestezi Altındaki Gebe Tavşanlarda Rocuronium ve Sugammadex’in Progesteron Düzeyine Etkisi

Sunulan çalışmada, genel anestezi uygulanan gebe tavşanlarda, rocuronium ve sugammadex uygulamasının progesteron düzeyine etkisinin saptanması amaçlandı. Çalışmada, 21 adet gebe Yeni Zelanda tavşanı kullanıldı. Her grupta 7 tavşan olacak şekilde üç gruba ayrıldı (Kontrol, Grup I, Grup II). Gebeliğin 21. gününde bulunan tüm tavşanlara 0.5 mg/kg midazolam ve 6 mg/kg propofol verildi. Daha sonra Sevofluran ile genel anesteziye alındı. Kontrol (C; n=7) grubundaki tavşanlar ise yalnızca genel anesteziye alındı. Grup I’deki tavşanlara genel anestezi başladığında roküronyum verildi. Grup II’de yer alan tavşanlara ise, genel anestezi ve rocuronium uygulamasından 60 dk sonra sugammadex verildi. Tüm tavşanlar genel anestezi süresince monitorize edildi. Tüm tavşanlardan venöz kan örneği alındı ve biyokimyasal olarak progesteron düzeyi analiz edildi. Rocuronium uygulamasının serum progesteron düzeyini tüm kaydedilen dakikalarda artışa neden olduğu belirlendi. Sugammadex uygulamasının ise, progesteron düzeyinde sayısal bir azalmaya neden olduğu belirlendi. Sonuç olarak, genel anesteziye alınan gebe tavşanlarda, rocuronium ve sugammadex uygulamasının progesteron düzeyi üzerine olumsuz bir etkisinin olmadığı saptandı.

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Upadya M, Saneesh PJ: Anaesthesia for non-obstetric surgery during pregnancy. Indian J Anaesth, 60 (4): 234-241, 2016. DOI: 10.4103/0019- 5049.179445

Trikha A, Singh PM: The critically ill obstetric patient - Recent concepts. Indian J Anaesth, 54 (5): 421-427, 2010. DOI: 10.4103/0019- 5049.71041

Capuano A, Sullo MG, Rafaniello C, Sportiello L, Fusco P, Vizia MD, Ferraro F: Complete resistance after maximal dose of rocuronium. J Pharmacol Pharmacother, 6 (3): 175-178, 2015.

Bom A, Hope F, Rutherford S, Thomson K: Preclinical pharmacology of sugammadex. J Crit Care, 24 (1): 29-35, 2009. DOI: 10.1016/j.jcrc. 2008.10.010

Epemolu O, Bom A, Hope F, Mason R: Reversal of neuromuscular blockade and simultaneous increase in plasma rocuronium concentration after the intravenous infusion of the novel reversal agent Org 25969. Anesthesiology, 99 (3): 632-637, 2003.

Et T, Topal A, Erol A, Tavlan A, Kılıçaslan A, Tuncer Uzun S: The effects of sugammadex on progesterone levels in pregnant rats. Balkan Med J, 32 (2): 203-207, 2015. DOI: 10.5152/balkanmedj.2015.15502

Taşkın L: Physiology of mother in pregnancy. In, Taşkın L (Ed): Birth and Women’s Health Nursing. 13rd ed., 97, Özyurt Printing, Ankara, 2016.

Peplow PV: Effects of progesterone withdrawal on uterine prostaglandin levels in the ovariectomized pregnant rat. Prostaglandins Leukot Essent Fatty Acids, 44 (4): 259-261, 1991. DOI: 10.1016/0952-3278(91)90028-4

Bennett JP, Vallance DK, Vickery BH: The synchronization of ovulation in the adult female rat by oral administration of megestrol acetate. J Reprod Fertil, 16 (2): 159-163, 1968.

Tuzcu K, Davarcı I, Karcıoğlu M, Bozdoğan YB, Aydın S, Kekeç L: Sugammadex usage for rocuronium caused residual curarization in which neostigmine failed. Cumhuriyet Med J, 34, 226-230, 2012.

Pekcan Z: How can better anaesthetic combinations be performed? A review of current knowledge. Kafkas Univ Vet Fak Derg, 22 (4): 631-638, 2016. DOI: 10.9775/kvfd.2016.15111

Gunduz Gul G, Ozer AB, Demirel İ, Aksu A, Erhan OL: The effect of sugammadex on steroid hormones: A randomized clinical study. J Clin Anesth, 34, 62-67, 2016. DOI: 10.1016/j.jclinane.2016.03.039

Berg H, Viby-Mogensen J, Roed J, Mortensen CR, Engbaek J, Skovgaard LT, Krintel JJ: Residual neuromuscular block is a risk factor for postoperative pulmonary complications. A prospective, randomised, and blinded study of postoperative pulmonary complications after atracurium, vecuronium and pancuronium. Acta Anaesthesiol Scand, 41 (9): 1095-1103, 1997. DOI: 10.1111/j.1399-6576.1997.tb04851.x

Eriksson LI, Sundman E, Olsson R, Nilsson L, Witt H, Ekberg O, Kuylenstierna R: Functional assessment of the pharynx at rest and during swallowing in partially paralyzed humans: Simultaneous videomanometry and mechanomyography of awake human volunteers. Anesthesiology, 87 (5): 1035-1043, 1997.

Üstün YB, Sarıhasan B, Kocamanoğlu IS, Yeğin S, Azar H: Use of sugammadex in myasthenia gravis and becker muscular dystrophy: Four cases. J Neurol Sci [Turkish], 29 (4): 826-831, 2012.

Kang WS, Kim KS, Shin SM: Reversal with sugammadex for rocuronium-induced deep neuromuscular block after pretreatment of magnesium sulfate in rabbits. Korean J Anesthesiol, 70 (2): 203-208, 2017. DOI: 10.4097/kjae.2017.70.2.203

de Boer HD, van Egmond J, van de Pol F, Bom A, Booij LHDJ: Chemical encapsulation of rocuronium by synthetic cyclodextrin derivatives: Reversal of neuromuscular block in anaesthetized Rhesus monkeys. Br J Anaesth, 96 (2): 201- 206, 2006. DOI: 10.1093/bja/aei306

de Boer HD, van Egmond J, van de Pol F, Bom A, Booij LHDJ: Reversal of profound rocuronium meeting abstracts by sugammadex in anesthetized Rhesus monkeys. Anesthesiology, 104 (4): 718-723, 2006.

de Boer HD, van Egmond J, van de Pol F, Bom A, Booij LHDJ: Sugammadex, a new reversal agent for neuromuscular block induced by rocuronium in the anaesthetized Rhesus monkey. Br J Anaesth, 96 (4): 473- 479, 2006. DOI: 10.1093/bja/ael013

Kizilay D, Dal D, Saracoglu KT, Eti Z, Gogus FY: Comparison of neostigmine and sugammadex for hemodynamic parameters in cardiac patients undergoing noncardiac surgery. J Clin Anesth, 28, 30-35, 2016. DOI: 10.1016/j.jclinane.2015.08.002

Bridion 100 mg/ml solution for injection. https://www.medicines. org.uk/emc/product/6409/smpc; Accessed: 25 March 2018.

Al-Asmakh M: Reproductive functions of progesterone. Middle East Fertil Soc J, 12 (3): 147-152, 2007.

Hilliard J, Scaramuzzi RJ, Penardi R, Sawyer CH: Progesterone, estradiol and testosterone levels in ovarian venous blood of pregnant rabbits. Endocrinology, 93 (5): 1235-1238, 1973. DOI: 10.1210/endo-93-5- 1235

Challis JRG, Davies IJ, Ryan KJ: The concentrations of progesterone, estrone and estradiol-17ß in the plasma of pregnant rabbits. Endocrinology, 93 (4): 971-976, 1973. DOI: 10.1210/endo-93-4-971

Mizoguchi Y, Matsuoka T, Mizuguchi H, Endoh T, Kamata R, Fukuda K, Ishikawa T, Asano Y: Changes in blood parameters in New Zealand White rabbits during pregnancy. Lab Anim, 44 (1): 33-39, 2010. DOI: 10.1258/la.2009.008002

İyilikçi L, İkiz C, Adıyaman E, Gökel E, Günerli A: Remote location anaesthesia: Our experience in pregnant patients (10 Cases). Turk J Anaesth Reanim, 41, 65-67, 2013. DOI: 10.5152/TJAR.2013.15

Esmeron (50 mg/5 ml, 5 Flakon ambalaj).https://www.ilacprospektusu. com/ilac/132/esmeron-50-mg-5-ml-5-flakon-ambalaj; Accessed: 21 March 2018.

Lobaz S, Clymer M, Sammut M: Safety and efficacy of sugammadex for neuromuscular blockade reversal. Clin Med Insights Ther, 6, 1-14, 2014. DOI: 10.4137/CMT.S10241

Mitchell C, Lobaz S, Giles E: An Overview of Sugammadex. http:// anaesthesiology.gr/media/File/pdf/WFSA%20tutorial%20332%20 An%20Overview%20of%20Sugammadex.pdf; Accessed: 02 February 2018.

Zhang MQ: Drug-specific cyclodextrins: The future of rapid neuromuscular blocks reversal? Drugs Future, 28 (4): 347-354, 2003. DOI: 10.1358/dof.2003.028.04.742715

Naguib M: Sugammadex: Another milestone in clinical neuromuscular pharmacology. Anesth Analg, 104 (3): 575-581, 2007. DOI: 10.1213/01. ane.0000244594.63318.fc