SugammadexSpecificPatients

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Sugammadex:

Use in Specific Patient Population

Dr. Volkan Hancı

Dokuz Eylul University İzmir, Turkey

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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

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Sugammadex

• More effective than placebo or neostigmine

• Reduced all signs of residual postoperative

paralysis, and minor respiratory events

• Reduced drug-related side-effects,

Anaesthesia. 2015 Dec;70(12):1441-52. Cochrane Database Syst Rev. 2009 Oct 7; (4):CD007362.

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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.

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Sugammadex

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• Elderly

• Pediatric

• Obese

• Obstetric

• Renal

• Hepatic

• Cardiac

• Pulmonary

• Neuro-muscular

•Residual Paralysis •Reinducing Neuromuscular Blockade •Neurophysiologic Monitoring •Anaphylaxis •Experimental Studies

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• Elderly

• Pediatric

• Obese

• Obstetric

• Renal

• Hepatic

• Cardiac

• Pulmonary

• Neuro-muscular

•Residual Paralysis •Reinducing Neuromuscular Blockade •Neurophysiolog ic Monitoring •Anaphylaxis •Experimental Studies •Residual Paralysis •Reinducing Neuromuscular Blockade •Neurophysiologic Monitoring •Anaphylaxis •Experimental Studies

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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

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• Elderly

• Pediatric

• Obese

• Obstetric

• Renal

• Hepatic

• Cardiac

• Pulmonary

• Neuro-muscular

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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.

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• Elderly

• Pediatric

• Obese

• Obstetric

• Renal

• Hepatic

• Cardiac

• Pulmonary

• Neuro-muscular

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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

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• Elderly

• Pediatric

• Obese

• Obstetric

• Renal

• Hepatic

• Cardiac

• Pulmonary

• Neuro-muscular

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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.

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• Elderly

• Pediatric

• Obese

• Obstetric

• Renal

• Hepatic

• Cardiac

• Pulmonary

• Neuro-muscular

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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.

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• Elderly

• Pediatric

• Obese

• Obstetric

• Renal

• Hepatic

• Cardiac

• Pulmonary

• Neuro-muscular

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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)

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• Elderly

• Pediatric

• Obese

• Obstetric

• Renal

• Hepatic

• Cardiac

• Pulmonary

• Neuro-muscular

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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 Cir Bras. 2014;29(12):807-11. Clin Drug Investig. 2013; 33(8):545-51

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Cardiac Disease

• S

uccessfully 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

Braz J Anesthesiol. 2013;63(1):159-60 Anaesth Intensive Care. 2013 ;41(3):434

J ECT. 2012 Jun;28(2):e21-2 J Med Invest. 2011 Aug;58(3-4):273-6

Balkan Med J. 2015;32(3):327-9

Anaesth Intensive Care. 2010;38(6):1138-9

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• Elderly

• Pediatric

• Obese

• Obstetric

• Renal

• Hepatic

• Cardiac

• Pulmonary

• Neuro-muscular

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Pulmonary Disease

• No negative effects or side effects

– Pulmonary disease

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• Elderly

• Pediatric

• Obese

• Obstetric

• Renal

• Hepatic

• Cardiac

• Pulmonary

• Neuro-muscular

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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.

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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

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• Elderly

• Pediatric

• Obese

• Obstetric

• Renal

• Hepatic

• Cardiac

• Pulmonary

• Neuro-muscular

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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.

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• Elderly

• Pediatric

• Obese

• Obstetric

• Renal

• Hepatic

• Cardiac

• Pulmonary

• Neuro-muscular

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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.

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• Elderly

• Pediatric

• Obese

• Obstetric

• Renal

• Hepatic

• Cardiac

• Pulmonary

• Neuro-muscular

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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.

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• Elderly

• Pediatric

• Obese

• Obstetric

• Renal

• Hepatic

• Cardiac

• Pulmonary

• Neuro-muscular

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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.

Br J Anaesth. 2011 Feb;106(2):199-201. J Clin Anesth. 2012 Feb;24(1):62-4.

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• Elderly

• Pediatric

• Obese

• Obstetric

• Renal

• Hepatic

• Cardiac

• Pulmonary

• Neuro-muscular

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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.

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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.

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• Elderly

• Pediatric

• Obese

• Obstetric

• Renal

• Hepatic

• Cardiac

• Pulmonary

• Neuro-muscular

•Residual Paralysis •Reinducing Neuromuscular Blockade •Neurophysiolog ic Monitoring •Anaphylaxis •Experimental Studies •Other Clinical Studies •Residual Paralysis •Reinducing Neuromuscular Blockade •Neurophysiologic Monitoring •Anaphylaxis •Experimental Studies •Other Clinical Studies

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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..

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Sugammadex

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