Sugammadex: Use in Specific Patient Population Volkan Hancı; M.D. Dokuz Eylul University İzmir, Turkey

Sugammadex Modified gamma cyclodextrin molecule. Unique molecular structure. Encapsulates the neuromuscular blocker rocuronium and vecuronium. Removing its from the muscle-nerve junction. Selective and rapid reversal of neuromuscular blockage.

Sugammadex More effective than placebo or neostigmine Reduced all signs of residual postoperative paralysis, and minor respiratory events Reduced drug-related side-effects, Cochrane Database Syst Rev. 2009 Oct 7;(4):CD007362. Anaesthesia. 2015 Dec;70(12):1441-52.

Sugammadex Dose 2 mg/kg, 4 mg/kg, 16 mg/kg Drug interaction Steroidal drugs, endogenous steroids, oestrogens Atropine, vancomycin, gentamicin, salbutamol, aminophylline, ephedrine, phentolamine, verapamil (120–700 times lower than rocuronium) Precipitation Amiodarone, dobutamine, protamine Basic Clin Pharmacol Toxicol. 2013;113(4):280-5. Braz J Anesthesiol. 2013;63(1):163-4.

Sugammadex Special Patient Population /Special Situations

Renal Elderly Hepatic Pediatric Cardiac Obese Pulmonary Obstetric Neuro-muscular Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Special Situtations Special Diseases S p e c i a l P t n s

Renal Elderly Hepatic Pediatric Cardiac Obese Pulmonary Obstetric Neuro-muscular Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Special Situtations Special Diseases S p e c i a l P t n s

Elderly Patients Sugammadex facilitates rapid reversal from moderate rocuronium-induced neuromuscular blockade in adults of all ages Recovery of the TOF ratio to 0.9 increased with age, from 2.3 (2.0-2.6) min (adults) to 2.9 (2.7-3.2) min Slower circulation time Anesthesiology. 2011 Feb;114(2):318-29.

Renal Elderly Hepatic Pediatric Cardiac Obese Pulmonary Obstetric Neuro-muscular Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Special Situtations Special Diseases S p e c i a l P t n s

Pediatric Patients Sugammadex rapidly and effectively reverses rocuronium-induced NMB in pediatric patients Sugammadex provides safer extubation with a shorter recovery time than neostigmine in pediatric patients Sugammadex can be considered as a safe agent in order to reverse neuromuscular block in pediatric patients Saudi J Anaesth. 2015 Jul-Sep;9(3):247-52. Rev Bras Anestesiol. 2014 Nov-Dec;64(6):400-5. J Res Med Sci. 2014 Aug;19(8):762-8.

Renal Elderly Hepatic Pediatric Cardiac Obese Pulmonary Obstetric Neuro-muscular Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Special Situtations Special Diseases S p e c i a l P t n s

Obese Patients Sugammadex quickly and effectively reverses NMB in obese patients Sugammadex dosing recommendations are based on total body weight. No dose adjustments are required in the obese patient. Morbidly obese patients can safely be decurarised from rocuronium-induced neuromuscular blockade T1-T2 with sugammadex dosed at 2 mg.kg(-1) ideal body weight + 40% Sugammadex dose calculated according to IBW is insufficient for reversing both deep and moderate blockades in morbidly obese patients. Am J Ther. 2015 Sep 21. [Epub ahead of print] Anaesthesia. 2011 Aug;66(8):721-5 Anesthesiology. 2012 Jul;117(1):93-8

Renal Elderly Hepatic Pediatric Cardiac Obese Pulmonary Obstetric Neuro-muscular Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Special Situtations Special Diseases S p e c i a l P t n s

Obstetric Patients Sugammadex use in obstetric patients has also successfully reversed NMB The data regarding the teratogenicity and safety of sugammadex in pregnant women are limited. No reported teratogenicity has been found. Rocuronium 1.2 mg/kg reversed by sugammadex appears to be effective in the obstetric population Sugammadex could reverse rocuronium-induced neuromuscular blockade in a dose-response manner even in the patients treated with magnesium sulfate. Acta Anaesthesiol Scand. 2011 Jul;55(6):694-9. Masui. 2014 Mar;63(3):315-9.

Renal Elderly Hepatic Pediatric Cardiac Obese Pulmonary Obstetric Neuro-muscular Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Special Situtations Special Diseases S p e c i a l P t n s

Renal Disease Sugammadex-NMB complex mainly excreted by the kidneys Decreased elemination High-flux dialysis (Large pore in dialyzing membranes) Renal failure; effectively and safely reversed profound rocuronium induced neuromuscular block, but the recovery was slower than healthy patients. rapid reversal of deep rocuronium-induced NMB current safety experience is insufficient to support recommended use of sugammadex in this population Eur J Anaesthesiol. 2015;32(10):681-6. Br J Anaesth. 2015 May;114(5):777-84.

Renal Elderly Hepatic Pediatric Cardiac Obese Pulmonary Obstetric Neuro-muscular Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Special Situtations Special Diseases S p e c i a l P t n s

Hepatic Disease No hepatic metabolism No restriction use in patient whit liver disease or hepatic surgery Liver transplantation effective and safe in liver transplant recipients. may reduce the risk of pulmonary complications Hepatic Surgery rapidly reverse NMB after continuous infusion of rocuronium Anaesth Pain & Intensive Care 2015;19(3) Acta Anaesthesiol Taiwan. 2014 ;52(2):54-8.

Renal Elderly Hepatic Pediatric Cardiac Obese Pulmonary Obstetric Neuro-muscular Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Special Situtations Special Diseases S p e c i a l P t n s

Cardiac Disease Safe / efficacious Not change hemodynamic parameters Might be preferred as it provides more hemodynamic stability compared to neostigmine-atropine combination Sugammadex can adequately restore neuromuscular function in heart failure patients under hemodynamically stable conditions. Not prolong QT interval J Clin Anesth. 2016;28:30-5. Acta Anaesthesiol Belg. 2012;63(2):69-73. Clin Drug Investig. 2013; 33(8):545-51 Acta Cir Bras. 2014;29(12):807-11.

Cardiac Disease Successfully used Brugada syndrome Wolff-Parkinson-White (WPW) Syndrome Long QT syndrome On the other hand, one case report accuse one of the causative agents of cardiac arrest Anaesth Intensive Care. 2013 ;41(3):434 Braz J Anesthesiol. 2013;63(1):159-60 J Med Invest. 2011 Aug;58(3-4):273-6 J ECT. 2012 Jun;28(2):e21-2 Balkan Med J. 2015;32(3):327-9 Anaesth Intensive Care. 2010;38(6):1138-9 Masui. 2015;64(6):622-7.

Renal Elderly Hepatic Pediatric Cardiac Obese Pulmonary Obstetric Neuro-muscular Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Special Situtations Special Diseases S p e c i a l P t n s

Pulmonary Disease No negative effects or side effects Lung surgery

Renal Elderly Hepatic Pediatric Cardiac Obese Pulmonary Obstetric Neuro-muscular Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Special Situtations Special Diseases S p e c i a l P t n s

Neuromuscular Disease Myasthenia Gravis Sugammadex appears to be a safe choice to avoid prolonged action of NMBA also in patients with myasthenia gravis , MG patients - rocuronium and sugammadex not observe any signs of postoperative residual curarization and respiratory depression.

Neuromuscular Disease Other neuromuscular diseases, Duchenne Myotonic dystrophies Transverse myelitis Amyotrophic lateral sclerosis Huntington disease Spinal / Bulbar Muscular Atrophy Strumpell-Lorrain disease / familial spastic paraplegia NMB effectively reversed with sugammadex

Renal Elderly Hepatic Pediatric Cardiac Obese Pulmonary Obstetric Neuro-muscular Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Special Situtations Special Diseases S p e c i a l P t n s

Rescue of Residual Paralysis Conventional reversal of NMB by a cholinesterase inhibitor is incomplete, sugammadex may be administered to fully reverse After inadequate reversal of NMB with neostigmine and glycopyrrolate, sugammadex immediately reverse the residual paralysis Residual NMB even after reversal with anticholinesterase agents, sugammadex, a safe alternative to reverse the NMB Anesth Analg. 2007 Mar;104(3):585-6. Rev Bras Anestesiol. 2012 Jul;62(4):543-7.

Renal Elderly Hepatic Pediatric Cardiac Obese Pulmonary Obstetric Neuro-muscular Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Special Situtations Special Diseases S p e c i a l P t n s

Reinducing Neuromuscular Blockade After Sugammadex Administration After reversal by sugammadex Immediate reestablishment of NMB with an aminosteroidal NMB agent is difficult. Isoquinoline NMBAs (atracurium, cisatracurium and mivacurium) or succinylcholine should be use If the aminosteroidal NMB agent use necessary Elimination time of sugammadex should be considered. Sugammadex undergoes renal elimination It takes 8 hours after injection in individuals with normal renal function.

Renal Elderly Hepatic Pediatric Cardiac Obese Pulmonary Obstetric Neuro-muscular Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Special Situtations Special Diseases S p e c i a l P t n s

Neurophysiologic Monitoring Sugammadex has been successfully used for patients requiring neurophysiologic monitoring during brain and spinal cord surgeries Sugammadex-induced reversal of NMB restores full motor function and better reflects a patient’s true baseline motor evoked potentials Somatosensory evoked potentials are not affected by NMB. Anaesth Intensive Care. 2012;40(6):1073-4

Renal Elderly Hepatic Pediatric Cardiac Obese Pulmonary Obstetric Neuro-muscular Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Special Situtations Special Diseases S p e c i a l P t n s

Anaphylaxis Severe allergic reaction after administration of sugammadex may ocur It can be seen bi-phasic reaction Sugammadex may potentially be a useful adjunct in the management of rocuronium-induced anaphylaxis. Sugammadex does not modify the clinical course of a suspected hypersensitivity reaction. Can J Anaesth. 2013 Jul;60(7):733-4 Masui. 2015 Jun;64(6):619-21. J Clin Anesth. 2012 Feb;24(1):62-4. Br J Anaesth. 2011 Feb;106(2):199-201. Anaesthesia. 2015 Nov;70(11):1264-7.

Renal Elderly Hepatic Pediatric Cardiac Obese Pulmonary Obstetric Neuro-muscular Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Special Situtations Special Diseases S p e c i a l P t n s

Experimental Studies Sugammadex-rocuronium complexes are cause histopathological and immunohistochemical changes in testis interstitial tissues, changes sperm density, germ cell number 16 mg/kg sugammadex delayed verapamil cardiotoxicity 1000mg/kg sugammadex accelerated verapamil cardiotoxicity 16 mg/kg sugammadex delayed teophylline toxicity, and raises mean lethal dose of teophylline J Mol Histol. 2012 Apr;43(2):235-41 Basic Clin Pharmacol Toxicol. 2013 Oct;113(4):280-5. Lat. Am. J. Pharm. 33 (8): 1290-6 (2014)

Experimental Studies Administration of sugammadex and dexmedetomidine to rabbits by intra-arterial routes caused histological arterial damage. Sugammadex prevented postoperative intra-abdominal adhesions Causes neuronal apoptosis in primary cultures Rev Bras Anestesiol. 2015. http://dx.doi.org/10.1016/j.bjane.2015.01.003 Kaohsiung J Med Sci. 2015 Sep;31(9):463-7. Int J Med Sci. 2013 Aug 3;10(10):1278-85.

Renal Elderly Hepatic Pediatric Cardiac Obese Pulmonary Obstetric Neuro-muscular Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Other Clinical Studies Residual Paralysis Reinducing Neuromuscular Blockade Neurophysiologic Monitoring Anaphylaxis Experimental Studies Other Clinical Studies Special Situtations Special Diseases S p e c i a l P t n s

Other Clinical Studies

Other Clinical Studies IV dexamethasone, given after induction of anesthesia, does not substantively affect the reversal time of sugammadex Lower end-extubation IOP levels were obtained sugammadex Sugammadex produced limited, transient increases in aPTT and prothrombin time but not associated with increased risk of bleeding Pre-treatment with magnesium did not significantly affect sugammadex reversal time of moderate neuromuscular blockade induced by rocuronium. Anesth Analg. 2016 Jan 14. [Epub ahead of print] J Pak Med Assoc. 2015 Nov;65(11):1219-25. Anesthesiology. 2014 Nov;121(5):969-77.. Anaesthesia. 2015 Aug;70(8):956-61.

Sugammadex Special Patient Population /Special Situations

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